TY - JOUR AB - The diagnosis of bacterial infections remains a major challenge in medicine. Although numerous contrast agents have been developed to image bacteria, their clinical impact has been minimal because they are unable to detect small numbers of bacteria in vivo, and cannot distinguish infections from other pathologies such as cancer and inflammation. Here, we present a family of contrast agents, termed maltodextrin-based imaging probes (MDPs), which can detect bacteria in vivo with a sensitivity two orders of magnitude higher than previously reported, and can detect bacteria using a bacteria-specific mechanism that is independent of host response and secondary pathologies. MDPs are composed of a fluorescent dye conjugated to maltohexaose, and are rapidly internalized through the bacteria-specific maltodextrin transport pathway, endowing the MDPs with a unique combination of high sensitivity and specificity for bacteria. Here, we show that MDPs selectively accumulate within bacteria at millimolar concentrations, and are a thousand-fold more specific for bacteria than mammalian cells. Furthermore, we demonstrate that MDPs can image as few as 10(5) colony-forming units in vivo and can discriminate between active bacteria and inflammation induced by either lipopolysaccharides or metabolically inactive bacteria. AU - Ning, Xinghai AU - Lee, Seungjun AU - Wang, Zhirui AU - Kim, Dongin AU - Stubblefield, Bryan AU - Gilbert, Eric AU - Murthy, Niren DO - 10.1038/nmat3074 PY - 2011 SN - 1476-1122 (Print)\r1476-1122 (Linking) TI - Maltodextrin-based imaging probes detect bacteria in vivo with high sensitivity and specificity T2 - Nature Materials ER - TY - JOUR AB - Background Currently, no single U.S. surveillance system can provide estimates of the burden of all types of health care–associated infections across acute care patient populations. We conducted a prevalence survey in 10 geographically diverse states to determine the prevalence of health care–associated infections in acute care hospitals and generate updated estimates of the national burden of such infections. Methods We defined health care–associated infections with the use of National Healthcare Safety Network criteria. One-day surveys of randomly selected inpatients were performed in participating hospitals. Hospital personnel collected demographic and limited clinical data. Trained data collectors reviewed medical records retrospectively to identify health care–associated infections active at the time of the survey. Survey data and 2010 Nationwide Inpatient Sample data, stratified according to patient age and length of hospital stay, were used to estimate the total numbers of health care–associated in... AU - Magill, Shelley S. AU - Edwards, Jonathan R. AU - Bamberg, Wendy AU - Beldavs, Zintars G. AU - Dumyati, Ghinwa AU - Kainer, Marion A. AU - Lynfield, Ruth AU - Maloney, Meghan AU - McAllister-Hollod, Laura AU - Nadle, Joelle AU - Ray, Susan M. AU - Thompson, Deborah L. AU - Wilson, Lucy E. AU - Fridkin, Scott K. DO - 10.1056/NEJMoa1306801 PY - 2014 SN - 0000000000000 TI - Multistate Point-Prevalence Survey of Health Care–Associated Infections T2 - New England Journal of Medicine ER - TY - JOUR AB - Despite advances in the field of nuclear medicine, the imaging of bacterial infections has remained a challenge. The existing reagents suffer from poor sensitivity and specificity. In this study we investigate the potential of a novel PET (positron emission tomography) tracer that overcomes these limitations. Methods: 6-[18F]-fluoromaltose was synthesized. Its behavior in vitro was evaluated in bacterial and mammalian cultures. Detailed pharmacokinetic and biodistribution profiles for the tracer were obtained from a murine model. Results: 6-[18F]-fluoromaltose is taken up by multiple strains of pathogenic bacteria. It is not taken up by mammalian cancer cell lines. 6-[18F]-fluoromaltose is retained in infected muscles in a murine model of bacterial myositis. It does not accumulate in inflamed tissue. Conclusion: We have shown that 6-[18F]-fluoromaltose can be used to image bacterial infection in vivo with high specificity. We believe that this class of agents will have a significant impact on the clinical management of patients. AU - Gowrishankar, Gayatri AU - Namavari, Mohammad AU - Jouannot, Erwan Benjamin AU - Hoehne, Aileen AU - Reeves, Robert AU - Hardy, Jonathan AU - Gambhir, Sanjiv Sam DO - 10.1371/journal.pone.0107951 PY - 2014 SN - 1932-6203 TI - Investigation of 6-[18F]-fluoromaltose as a novel PET tracer for imaging bacterial infection T2 - PLoS ONE ER - TY - JOUR AU - Ning, Xinghai AU - Seo, Wonewoo AU - Lee, Seungjun AU - Takemiya, Kiyoko AU - Rafi, Mohammad AU - Feng, Xuli AU - Weiss, Daiana AU - Wang, Xiaojian AU - Williams, Larry AU - Camp, Vernon M AU - Eugene, Malveaux AU - Taylor, W Robert DO - 10.1002/anie.201xxxxxx IS - 51 PY - 2014 SP - 14096 EP - 14101 TI - Fluorine-18 labeled maltohexaose images bacterial infections by PET HHS Public Access T2 - Angew Chem Int Ed Engl UR - http://dx.doi.org/10.1002/anie.201xxxxxx. VL - 53 ER - TY - RPRT AB - The human endogenous intestinal microflora is an essential "organ" in providing nourishment, regulating epithelial development, and instructing innate immunity; yet, surprisingly, basic features remain poorly described. We examined 13,355 prokaryotic ribosomal RNA gene sequences from multiple colonic mucosal sites and feces of healthy subjects to improve our understanding of gut microbial diversity. A majority of the bacterial sequences corresponded to uncultivated species and novel microorganisms. We discovered significant intersubject variability and differences between stool and mucosa community composition. Characterization of this immensely diverse ecosystem is the first step in elucidating its role in health and disease. AU - Eckburg, Paul B AU - Bik, Elisabeth M AU - Bernstein, Charles N AU - Purdom, Elizabeth AU - Dethlefsen, Les AU - Sargent, Michael AU - Gill, Steven R AU - Nelson, Karen E AU - Relman, David A TI - Diversity of the Human Intestinal Microbial Flora UR - www.sciencemag.org/cgi/content/full/1110591/DC1 ER - TY - JOUR AB - Background. Diarrheagenic Escherichia coli (DEC) strains are a major cause of diarrhea in children under 5 years of age worldwide. DEC pathogenicity relies on the interaction of bacteria with environmental factors, including the host’s resident gut microbiota. Previous reports have shown changes in the gut microbiota’s composition during episodes of diarrhea, which may increase the pathogenicity of DEC strains. More intense and detailed identification of microbiota strains specifically associated with DEC infections and disease is needed to pinpoint their role in DEC pathogenicity. Aim. To identify resident indicative bacterial taxa in DEC-positive diarrhea stool samples of Chilean children. Methods. We analyzed 63 diarrheal stool samples from children 1-5 years of age by FilmArray® GI in order to identify a potential pathogen and to group diarrhea episodes into those caused by DEC as sole pathogen (DEC group, 32 samples) and those caused by an enteric virus as sole pathogen (viral group, 31 samples). In addition, 30 stool samples from healthy children, negative for enteric pathogens, were evaluated (healthy group). The 16S rRNA gene was amplified and sequenced using 454 pyrosequencing. Sequences were clustered into operational taxonomic units (OTUs) at 99% identity and their representatives were used to assign them to operational phylogenetic units (OPUs) using a phylogenetic inference approach. Results. Taxa assignment using the OPU approach resulted in a lower number of units but with higher accuracy compared to the OTU approach. Data analysis indicated an increase in sequences belonging to the phylum Proteobacteria in the DEC group compared to the viral and healthy groups. Samples displayed a statistically different community structure by sample grouping by redundancy analysis and ANOVA. Escherichia albertii (p=0.001), Citrobacter werkmanii (p=0.001), Yersinia enterocolitica, subsp. paleartica (p=0.048) and Haemophilus sputorum (p=0.028) were indicative species for the DEC group as compared to the viral and healthy groups. Conclusion. Gut microbiota in Chilean children with DEC-positive diarrhea differed from microbiota associated with enteric virus and healthy children. Indicative species found in this study may prove relevant in advancing our understanding of the relationship between resident gut microbiota and DEC leading to the occurrence of disease. AU - Gallardo, Pablo AU - Izquierdo, Mariana AU - Vidal, Roberto M. AU - Chamorro-Veloso, Nayaret AU - Rosselló-Móra, Ramon AU - O'Ryan, Miguel AU - Farfán, Mauricio J. DO - 10.3389/fcimb.2017.00424 PY - 2017 SN - 2235-2988 (Electronic) 2235-2988 (Linking) TI - Distinctive Gut Microbiota Is Associated with Diarrheagenic Escherichia coli Infections in Chilean Children T2 - Frontiers in Cellular and Infection Microbiology ER - TY - JOUR AB - FDG-PET, combined with CT, is nowadays getting more and more relevant for the diagnosis of several infectious and inflammatory diseases and particularly for therapy monitoring. Thus, this paper gives special attention to the role of FDG-PET/CT in the diagnosis and therapy monitoring of infectious and inflammatory diseases. Enough evidence in the literature already exists about the usefulness of FDG-PET/CT in the diagnosis, management, and followup of patients with sarcoidosis, spondylodiscitis, and vasculitis. For other diseases, such as inflammatory bowel diseases, rheumatoid arthritis, autoimmune pancreatitis, and fungal infections, hard evidence is lacking, but studies also point out that FDG-PET/CT could be useful. It is of invaluable importance to have large prospective multicenter studies in this field to provide clear answers, not only for the status of nuclear medicine in general but also to reduce high costs of treatment. AU - Glaudemans, Andor W.J.M. AU - De Vries, Erik F.J. AU - Galli, Filippo AU - Dierckx, Rudi A.J.O. AU - Slart, Riemer H.J.A. AU - Signore, Alberto DO - 10.1155/2013/623036 PY - 2013 SN - 1740-2522 TI - The use of 18 F-FDG-PET/CT for diagnosis and treatment monitoring of inflammatory and infectious diseases T2 - Clinical and Developmental Immunology ER - TY - JOUR AB - We hypothesized that prior colonization with antibiotic-resistant Gram-negative bacteria is associated with increased risk of subsequent antibiotic-resistant Gram-negative bacteremia among cancer patients. We performed a matched case-control study. Cases were cancer patients with a blood culture positive for antibiotic-resistant Gram-negative bacteria. Controls were cancer patients with a blood culture not positive for antibiotic-resistant Gram-negative bacteria. Prior colonization was defined as any antibiotic-resistant Gram-negative bacteria in surveillance or non-sterile-site cultures obtained 2-365 days before the bacteremia. Thirty-two (37%) of 86 cases and 27 (8%) of 323 matched controls were previously colonized by any antibiotic-resistant Gram-negative bacteria. Prior colonization was strongly associated with antibiotic-resistant Gram-negative bacteremia (odds ratio [OR] 7.2, 95% confidence interval [CI] 3.5-14.7) after controlling for recent treatment with piperacillin-tazobactam (OR 2.5, 95% CI 1.3-4.8). In these patients with suspected bacteremia, prior cultures may predict increased risk of antibiotic-resistant Gram-negative bacteremia. © 2014 Elsevier Inc. AU - Hess, Aaron S. AU - Kleinberg, Michael AU - Sorkin, John D. AU - Netzer, Giora AU - Johnson, Jennifer K. AU - Shardell, Michelle AU - Thom, Kerri A. AU - Harris, Anthony D. AU - Roghmann, Mary Claire DO - 10.1016/j.diagmicrobio.2014.01.022 KW - Antimicrobial resistance KW - Neutropenic fever KW - Surveillance cultures PY - 2014 SN - 9780124201187 TI - Prior colonization is associated with increased risk of antibiotic-resistant Gram-negative bacteremia in cancer patients T2 - Diagnostic Microbiology and Infectious Disease ER - TY - RPRT AB - In the past years infections caused by multidrug-resistant Gram-negative bacteria have dramatically increased in all parts of the world. This AU - Exner, Martin AU - Bhattacharya, Sanjay AU - Christiansen, Bärbel TI - Antibiotic resistance: What is so special about multidrug-resistant Gram-negative bacteria? multiresistenten Bakterien? ER - TY - JOUR AB - Maternal sun exposure in gestation and throughout the lifetime is necessary for vitamin D synthesis, and living near the sea is a population level index of seafood consumption. The aim of this study was to estimate the incidence rate of multiple sclerosis (MS) in Wales and examine its association with sun exposure, coastal living, and latitude. The study used a database of MS hospital visits and admissions in Wales between 2002 and 2013. For the 1,909 lower layer super output areas (LSOAs) in Wales, coastal status, population, longitude/latitude, and average sunshine hours per day were obtained. Age-specific and age-standardised MS incidence were calculated and modelled using Poisson regression. The distribution of births by month was compared between MS cases and the combined England and Wales population. There were 3,557 new MS cases between 2002 and 2013, with an average annual incidence of 8.14 (95% CI: 7.69-8.59) among males and 12.97 (95% CI: 12.44-13.50) among females per 100,000 population. The female-to-male ratio was 1.86:1. For both sexes combined, the average annual incidence rate was 9.10 (95% CI: 8.80-9.40). All figures are age-standardized to the 1976 European standard population. Compared to the combined England and Wales population, more people with MS were born in April, observed-to-expected ratio: 1.21 (95% CI: 1.08-1.36). MS incidence varied directly with latitude and inversely with sunshine hours. Proximity to the coast was associated with lower MS incidence only in easterly areas. This study shows that MS incidence rate in Wales is comparable to the rate in Scotland and is associated with environmental factors that probably represent levels of vitamin D. AU - Murakami, Eri AU - Shionoya, Takao AU - Komenoi, Suguru AU - Suzuki, Yuji AU - Sakane, Fumio DO - 10.1371/journal.pone PY - 2016 SN - 0018726708094 TI - Cloning and characterization of novel testis-Specific diacylglycerol kinase η splice variants 3 and 4 T2 - PLoS ONE ER - TY - RPRT PY - 2000 SN - 9241562021 TI - Global Water Supply and Sanitation Assessment 2000 Report ER - TY - JOUR TI - 2017-OMS-Lista antimicrobianos importancia critica medicina humana ER - TY - JOUR AB - Purpose: The noninvasive imaging of bacterial infections is critical in order to reduce mortality and morbidity caused by these diseases. The recently reported18F-FDS (18F-2-fluorodeoxy sorbitol) as a PET (positron emission tomography) tracer can be used to image Enterobacteriaceae-specific infections and provides a potential alternative to this problem compared with other probes for imaging infections. In this study, automatic synthesis, validation of18F-FDS and a first-in-human study were performed and discussed. Methods: A multifunctional synthesis module was employed for the radiosynthesis of18F-FDG (18F-2-fluorodeoxy glucose) and18F-FDS starting from18F ion using two-pot three-step fully automated reactions. The behavior of18F-FDS as an in vivo imaging probe for infections was evaluated in an Escherichia coli mouse infection model. The first detailed pharmacokinetic and biodistribution parameters were obtained from healthy human volunteers. Results: The uptake of18F-FDS in an E. coli mouse-myositis infection model was easily differentiated from other organs and normal muscle. Intensive lesion uptake declined after antibiotic treatment. In the pilot human study, no adverse effects due to18F-FDS were observed up to 24 h post-injection. The radiotracer was rapidly cleared from the circulation and excreted mainly through the urinary system. Conclusion: We conclude that18F-FDS PET holds great potential for appropriate and effective for the imaging of bacterial infections in vivo. These preliminary results indicate that further clinical studies are warranted. AU - Yao, Shaobo AU - Xing, Haiqun AU - Zhu, Wenjia AU - Wu, Zhanhong AU - Zhang, Yingqiang AU - Ma, Yanru AU - Liu, Yimin AU - Huo, Li AU - Zhu, Zhaohui AU - Li, Zibo AU - Li, Fang DO - 10.1016/j.nucmedbio.2015.11.008 KW - 18F-FDS KW - Automated synthesis KW - Gram-negative bacteria KW - Infection KW - PET PY - 2016 SN - 1872-9614 (Electronic)\r0969-8051 (Linking) TI - Infection Imaging With18F-FDS and First-in-Human Evaluation T2 - Nuclear Medicine and Biology ER - TY - GEN AB - This review article covers a concise account on fludeoxyglucose (18F–FDG) synthesis and quality control procedures with emphasis on practical synthesis Currently, 18F–FDG is the most successful PET radiopharmaceutical so far. The advancement in synthesis and quality control of 18F–FDG, together with its approval by the US FDA and the availability of reimbursement, are probably the main reasons for the flourish of clinical PET over the last 20 years. 18F–FDG can be synthesised by either electrophilic fluorination or nucleophilic fluorination reaction. Nucleophilic fluorination using mannose triflate as precursor and Kryptofix or tetrabutylammonium salts (TBA) is widely used because of higher yield and shorter reaction time. The quality control requirements of 18F–FDG can be found in United States Pharmacopeia (USP), British Pharmacopeia (BP), European Pharmacopeia (EP) and the Chemistry, Manufacturing, and Controls (CMC) section from United States Food and Drug Administration (US FDA) PET draft guidance documents. Basic requirements include radionuclidic identity, radiochemical purity, chemical purity, pH, residual solvent, sterility, and bacterial endotoxin level. Some of these tests (sterility, endotoxins and radionuclidic purity) can be finished after the 18F–FDG has been released. Although USP, BP and EP do not require filter membrane integrity test, many laboratories perform this test as an indirect evident of the product sterility. It is also interesting to note that there are major differences in 18F–FDG quality requirements among USP, BP, and CMC. AU - Yu, Sidney DO - 10.2349/biij.2.4.e57 KW - Fludeoxyglucouse (18F-FDG) KW - Positron emission tomography (PET) KW - Quality control (QC) PY - 2006 TI - Review of 18F-FDG synthesis and quality control T2 - Biomedical Imaging and Intervention Journal ER - TY - JOUR AB - The carbohydrate specificity of the two enzymes that catalyze the metabolic interconversions in the sorbitol pathway, aldose reductase and sorbitol dehydrogenase, has been examined through the use of fluoro- and deoxy-substrate analogs. Hydrogen bonding has been shown to be the primary mode of interaction by which these enzymes specifically recognize and bind their respective polyol substrates. Aldose reductase has broad substrate specificity, and all of the fluoro- and deoxysugars that were examined are substrates for this enzyme. Unexpectedly, both 3-fluoro- and 4-fluoro-d-glucose were found to be better substrates, with significantly lower K(m) and higher k(cat)/K(m) values than those of D-glucose. A more discriminating pattern of substrate specificity is observed for sorbitol dehydrogenase. Neither the 2-fluoro nor the 2-deoxy analogs of D-glucitol were found to be substrates or inhibitors, suggesting that the 2-hydroxyl group of sorbitol is a hydrogen bond donor. The 4-fluoro and 4-deoxy analogs are poorer substrates than sorbitol, also implying a binding role for this hydroxyl group. In contrast, both 6-fluoro- and 6-deoxy-D-glucitol are very good substrates for sorbitol dehydrogenase, indicating that the primary hydroxyl group at this position is not involved in substrate recognition by this enzyme. Copyright (C) 1998 Elsevier Science Ltd. AU - Scott, Mary Ellen AU - Viola, Ronald E. DO - 10.1016/S0008-6215(98)00266-3 KW - Aldose reductase KW - Deoxy sugars KW - Fluoro sugars KW - Sorbitol dehydrogenase KW - Sorbitol pathway KW - Substrate specificity PY - 1998 SN - 0008-6215 TI - The use of fluoro- and deoxy-substrate analogs to examine binding specificity and catalysis in the enzymes of the sorbitol pathway T2 - Carbohydrate Research ER - TY - JOUR AB - Purpose: The noninvasive imaging of bacterial infections is critical in order to reduce mortality and morbidity caused by these diseases. The recently reported18F-FDS (18F-2-fluorodeoxy sorbitol) as a PET (positron emission tomography) tracer can be used to image Enterobacteriaceae-specific infections and provides a potential alternative to this problem compared with other probes for imaging infections. In this study, automatic synthesis, validation of18F-FDS and a first-in-human study were performed and discussed. Methods: A multifunctional synthesis module was employed for the radiosynthesis of18F-FDG (18F-2-fluorodeoxy glucose) and18F-FDS starting from18F ion using two-pot three-step fully automated reactions. The behavior of18F-FDS as an in vivo imaging probe for infections was evaluated in an Escherichia coli mouse infection model. The first detailed pharmacokinetic and biodistribution parameters were obtained from healthy human volunteers. Results: The uptake of18F-FDS in an E. coli mouse-myositis infection model was easily differentiated from other organs and normal muscle. Intensive lesion uptake declined after antibiotic treatment. In the pilot human study, no adverse effects due to18F-FDS were observed up to 24 h post-injection. The radiotracer was rapidly cleared from the circulation and excreted mainly through the urinary system. Conclusion: We conclude that18F-FDS PET holds great potential for appropriate and effective for the imaging of bacterial infections in vivo. These preliminary results indicate that further clinical studies are warranted. AU - Yao, Shaobo AU - Xing, Haiqun AU - Zhu, Wenjia AU - Wu, Zhanhong AU - Zhang, Yingqiang AU - Ma, Yanru AU - Liu, Yimin AU - Huo, Li AU - Zhu, Zhaohui AU - Li, Zibo AU - Li, Fang DO - 10.1016/j.nucmedbio.2015.11.008 KW - 18F-FDS KW - Automated synthesis KW - Gram-negative bacteria KW - Infection KW - PET PY - 2016 SN - 1872-9614 (Electronic)\r0969-8051 (Linking) TI - Infection Imaging With18F-FDS and First-in-Human Evaluation T2 - Nuclear Medicine and Biology ER - TY - JOUR AU - Li, Zi-Bo AU - Wu, Zhanhong AU - Cao, Qizhen AU - Dick, David W. AU - Tseng, Jeffrey R. AU - Gambhir, Sanjiv S. AU - Chen, Xiaoyuan DO - 10.1007/s11307-007-0125-0 PY - 2008 SN - 1536-1632 TI - The Synthesis of 18F-FDS and Its Potential Application in Molecular Imaging T2 - Molecular Imaging and Biology ER - TY - JOUR AU - Zhang, Zhuo AU - Ordonez, Alvaro A. AU - Wang, Hui AU - Li, Yong AU - Gogarty, Kayla R AU - Weinstein, Edward A AU - Daryaee, Fereidoon AU - Merino, Jonathan AU - Yoon, Grace Eunbin AU - Kalinda, Alvin S AU - Mease, Ronnie C AU - Iuliano, James N. AU - Smith-Jones, Peter AU - Jain, Sanjay K. AU - Tonge, Peter J DO - 10.1021/acsinfecdis.8b00182 PY - 2018 TI - Positron Emission Tomography Imaging with 2-[ 18 F]F- p -Aminobenzoic Acid detects Staphylococcus aureus Infections and Monitors Drug Response T2 - ACS Infectious Diseases ER - TY - JOUR AB - Imaging studies are frequently used to support the clinical diagnosis of infection. These techniques include computed tomography (CT) and magnetic resonance imaging (MRI) for structural information and single photon emission computed tomography (SPECT) or positron emission tomography (PET) for metabolic data. However, frequently, there is significant overlap in the imaging appearance of infectious and noninfectious entities using these tools. To address this concern, recent approaches have targeted bacteria-specific metabolic pathways. For example, radiolabeled sugars derived from sorbitol and maltose have been investigated as PET radiotracers, since these are efficiently incorporated into bacteria but are poor substrates for mammalian cells. We have previously shown that para-aminobenzoic acid (PABA) is an excellent candidate for development as a bacteria-specific imaging tracer as it is rapidly accumulated by a wide range of pathogenic bacteria, including metabolically quiescent bacteria and clinical strains, but not by mammalian cells. Therefore, in this study, we developed an efficient radiosynthesis for [ 11 C]PABA, investigated its accumulation into Escherichia coli and Staphylococcus aureus laboratory strains in vitro, and showed that it can distinguish between infection and sterile inflammation in a murine model of acute bacterial infection. S uspected bacterial infection is a frequent indication for imaging studies in clinical practice. Current techniques rely heavily on secondary inflammatory changes to localize disease. These changes include increased blood flow and vascular permeability in contrast-enhanced computed tomography (CT) and magnetic resonance imaging (MRI), increased glucose utilization in positron emission tomography (PET) using [ 18 F]-fluorodeoxyglucose ([ 18 F]FDG), and recruitment of leukocytes in tagged white blood cell (WBC) nuclear medicine studies. AU - Mutch, Christopher A. AU - Ordonez, Alvaro A. AU - Qin, Hecong AU - Parker, Matthew AU - Bambarger, Lauren E. AU - Villanueva-Meyer, Javier E. AU - Blecha, Joseph AU - Carroll, Valerie AU - Taglang, Celine AU - Flavell, Robert AU - Sriram, Renuka AU - Vanbrocklin, Henry AU - Rosenberg, Oren AU - Ohliger, Michael A. AU - Jain, Sanjay K. AU - Neumann, Kiel D. AU - Wilson, David M. DO - 10.1021/acsinfecdis.8b00061 KW - bacteria KW - folate KW - infection KW - metabolism KW - positron emission tomography PY - 2018 TI - Para-Aminobenzoic Acid: A Positron Emission Tomography Tracer Targeting Bacteria-Specific Metabolism T2 - ACS Infectious Diseases ER - TY - GEN AB - When serious infections are suspected, patients are often treated empirically with broad-spectrum antibiotics while awaiting results that provide information on the bacterial class and species causing the infection, as well as drug susceptibilities. For deep-seated infections, these traditional diagnostic techniques often rely on tissue biopsies to obtain clinical samples which can be expensive, dangerous, and has the potential of sampling bias. Moreover, these procedures and results can take several days and may not always provide reliable information. This combination of time and effort required for proper antibiotic selection has become a barrier leading to indiscriminate broad-spectrum antibiotic use. Exposure to nosocomial infections and indiscriminate use of broad-spectrum antibiotics are responsible for promoting bacterial drug-resistance leading to substantial morbidity and mortality, especially in hospitalized and immunosuppressed patients. Therefore, early diagnosis of infection and targeted antibiotic treatments are urgently needed to reduce morbidity and mortality caused by bacterial infections worldwide. Reliable pathogen-specific bacterial imaging techniques have the potential to provide early diagnosis and guide antibiotic treatments. AU - Ordonez, Alvaro A. AU - Jain, Sanjay K. DO - 10.1053/j.semnuclmed.2017.11.003 PY - 2018 TI - Pathogen-Specific Bacterial Imaging in Nuclear Medicine T2 - Seminars in Nuclear Medicine ER - TY - RPRT AU - Mccaughey, Betsy TI - Unnecessary Deaths: The Human and Financial Costs of Hospital Infections 2nd Edition UR - http://emerald.tufts.edu/med/apua/consumers/faqs_2_4154863510.pdf ER - TY - JOUR AB - Several advances in imaging have become part of the work-up for localization, diagnosis, and management of infectious diseases and inflammatory disorders. Utility of multiple imaging modalities is a time-consuming step, and significant numbers of patients remain undiagnosed despite utilization of series of tests. Inflammatory cells have avidity for fluorine 18-labeled fluorodeoxyglucose ((18)F-FDG), and thus positron emission tomographic-computed tomographic (PET-CT) hybrid imaging provides anatomical and metabolic information that can be used to define the extent of infectious and inflammatory diseases and assess response to treatment. PET-CT provides a "one-stop test" in which use of hybrid imaging provides anatomical and metabolic information. The extent of disease is defined quickly, and response to treatment can be assessed. This modality also helps define the metastatic and/or septic foci where there is lack of localizing symptoms. More recently, there is increasing awareness among clinicians regarding the ability of PET-CT to help in diagnosing, characterizing, and assessing inflammatory disorders. This article reviews the usefulness of this imaging modality. AU - Haroon, A. AU - Zumla, A. AU - Bomanji, J. DA - 2012/5// DO - 10.1093/cid/cis193 IS - 9 PY - 2012 SP - 1333 EP - 1341 TI - Role of Fluorine 18 Fluorodeoxyglucose Positron Emission Tomography-Computed Tomography in Focal and Generalized Infectious and Inflammatory Disorders T2 - Clinical Infectious Diseases UR - http://www.ncbi.nlm.nih.gov/pubmed/22431802 UR - https://academic.oup.com/cid/article-lookup/doi/10.1093/cid/cis193 VL - 54 ER - TY - JOUR AU - Haroon, A. AU - Zumla, A. AU - Bomanji, J. DA - 2012/5// DO - 10.1093/cid/cis193 IS - 9 PY - 2012 SP - 1333 EP - 1341 TI - Role of Fluorine 18 Fluorodeoxyglucose Positron Emission Tomography-Computed Tomography in Focal and Generalized Infectious and Inflammatory Disorders T2 - Clinical Infectious Diseases UR - https://academic.oup.com/cid/article-lookup/doi/10.1093/cid/cis193 VL - 54 ER - TY - JOUR AB - FDG-PET, combined with CT, is nowadays getting more and more relevant for the diagnosis of several infectious and inflammatory diseases and particularly for therapy monitoring. Thus, this paper gives special attention to the role of FDG-PET/CT in the diagnosis and therapy monitoring of infectious and inflammatory diseases. Enough evidence in the literature already exists about the usefulness of FDG-PET/CT in the diagnosis, management, and followup of patients with sarcoidosis, spondylodiscitis, and vasculitis. For other diseases, such as inflammatory bowel diseases, rheumatoid arthritis, autoimmune pancreatitis, and fungal infections, hard evidence is lacking, but studies also point out that FDG-PET/CT could be useful. It is of invaluable importance to have large prospective multicenter studies in this field to provide clear answers, not only for the status of nuclear medicine in general but also to reduce high costs of treatment. AU - Glaudemans, Andor W J M AU - de Vries, Erik F J AU - Galli, Filippo AU - Dierckx, Rudi A J O AU - Slart, Riemer H J A AU - Signore, Alberto DO - 10.1155/2013/623036 PY - 2013 SP - 623036 EP - 623036 TI - The use of (18)F-FDG-PET/CT for diagnosis and treatment monitoring of inflammatory and infectious diseases. T2 - Clinical & developmental immunology UR - http://www.hindawi.com/journals/jir/2013/623036/ UR - http://www.ncbi.nlm.nih.gov/pubmed/24027590 UR - http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC3763592 VL - 2013 ER - TY - JOUR AB - Inflammatory and infectious diseases are a heterogeneous class of diseases that may be divided into infections, acute inflammation and chronic inflammation. Radiological imaging techniques have, with the exception of functional MRI, high sensitivity but lack in specificity. Nuclear medicine techniques, by contrast, allow the in vivo detection in humans of different physiologic and pathologic phenomena and offer noninvasive tools to detect early pathophysiological changes before anatomical changes occur. In this review, we highlight the role of nuclear medicine in inflammation/infection with emphasis on molecular imaging for in vivo histological characterization of affected tissues for diagnostic purposes and follow-up of therapies. We also describe the clinical indications of all available radiopharmaceuticals in the light of the newly available guidelines. AU - Signore, Alberto AU - Glaudemans, Andor W J M DA - 2011/12// DO - 10.1007/s12149-011-0521-z IS - 10 PY - 2011 SP - 681 EP - 700 TI - The molecular imaging approach to image infections and inflammation by nuclear medicine techniques. T2 - Annals of nuclear medicine UR - http://link.springer.com/10.1007/s12149-011-0521-z UR - http://www.ncbi.nlm.nih.gov/pubmed/21837469 VL - 25 ER - TY - JOUR AB - Inflammatory and infectious diseases are a heterogeneous class of diseases that may be divided into infections, acute inflammation and chronic inflammation. Radiological imaging techniques have, with the exception of functional MRI, high sensitivity but lack in specificity. Nuclear medicine techniques, by contrast, allow the in vivo detection in humans of different physiologic and pathologic phenomena and offer noninvasive tools to detect early pathophysiological changes before anatomical changes occur. In this review, we highlight the role of nuclear medicine in inflammation/infection with emphasis on molecular imaging for in vivo histological characterization of affected tissues for diagnostic purposes and follow-up of therapies. We also describe the clinical indications of all available radiopharmaceuticals in the light of the newly available guidelines. AU - Signore, Alberto AU - Glaudemans, Andor W J M DA - 2011/12// DO - 10.1007/s12149-011-0521-z IS - 10 PY - 2011 SP - 681 EP - 700 TI - The molecular imaging approach to image infections and inflammation by nuclear medicine techniques. T2 - Annals of nuclear medicine UR - http://link.springer.com/10.1007/s12149-011-0521-z UR - http://www.ncbi.nlm.nih.gov/pubmed/21837469 VL - 25 ER - TY - JOUR AU - Xiaojian Wang and Niren Murthy* IS - 259 PY - 2014 SP - 1 EP - 3 TI - 2014-Xiaojian Wang-Bacterial Imaging Comes og Age T2 - Science Translational Medicine VL - 6 ER - TY - JOUR AB - FDG-PET, combined with CT, is nowadays getting more and more relevant for the diagnosis of several infectious and inflammatory diseases and particularly for therapy monitoring. Thus, this paper gives special attention to the role of FDG-PET/CT in the diagnosis and therapy monitoring of infectious and inflammatory diseases. Enough evidence in the literature already exists about the usefulness of FDG-PET/CT in the diagnosis, management, and followup of patients with sarcoidosis, spondylodiscitis, and vasculitis. For other diseases, such as inflammatory bowel diseases, rheumatoid arthritis, autoimmune pancreatitis, and fungal infections, hard evidence is lacking, but studies also point out that FDG-PET/CT could be useful. It is of invaluable importance to have large prospective multicenter studies in this field to provide clear answers, not only for the status of nuclear medicine in general but also to reduce high costs of treatment. AU - Glaudemans, Andor W J M AU - de Vries, Erik F J AU - Galli, Filippo AU - Dierckx, Rudi A J O AU - Slart, Riemer H J A AU - Signore, Alberto DO - 10.1155/2013/623036 PY - 2013 SP - 623036 EP - 623036 TI - The use of (18)F-FDG-PET/CT for diagnosis and treatment monitoring of inflammatory and infectious diseases. T2 - Clinical & developmental immunology UR - http://www.hindawi.com/journals/jir/2013/623036/ UR - http://www.ncbi.nlm.nih.gov/pubmed/24027590 UR - http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC3763592 VL - 2013 ER - TY - JOUR AB - D espite the fact that current international guidelines suggest initiation of antimicro-bial therapy within an hour of presentation with severe sepsis and septic shock, no clinical studies exist to support this recommendation (1). In reality , initiation of antimicrobial therapy for infections causing critical illness often awaits thorough clinical evaluation, resuscitative measures, initial stabilization , and investigative efforts (2-6). Relatively few studies have rigorously examined the effect of delays of antimi-crobial therapy in critically ill, infected patients (7-17). To the extent that these studies have been done, the delay has most often been timed to admission to the intensive care unit (ICU) or the emergency room. No studies have examined treatment delays in relation to defined physiologic variables such as hypoten-sion. We have recently demonstrated that the onset of hypotension is a critical Objective: To determine the prevalence and impact on mortality of delays in initiation of effective antimicrobial therapy from initial onset of recurrent/persistent hypotension of septic shock. Design: A retrospective cohort study performed between July 1989 and June 2004. Setting: Fourteen intensive care units (four medical, four surgical , six mixed medical/surgical) and ten hospitals (four academic , six community) in Canada and the United States. Patients: Medical records of 2,731 adult patients with septic shock. Interventions: None. Measurements and Main Results: The main outcome measure was survival to hospital discharge. Among the 2,154 septic shock patients (78.9% total) who received effective antimicrobial therapy only after the onset of recurrent or persistent hypotension, a strong relationship between the delay in effective antimicrobial initiation and in-hospital mortality was noted (adjusted odds ratio 1.119 [per hour delay], 95% confidence interval 1.103-1.136, p < .0001). Administration of an antimicrobial effective for isolated or suspected pathogens within the first hour of documented hypo-tension was associated with a survival rate of 79.9%. Each hour of delay in antimicrobial administration over the ensuing 6 hrs was associated with an average decrease in survival of 7.6%. By the second hour after onset of persistent/recurrent hypotension, in-hospital mortality rate was significantly increased relative to receiving therapy within the first hour (odds ratio 1.67; 95% confidence interval, 1.12-2.48). In multivariate analysis (including Acute Physiology and Chronic Health Evaluation II score and therapeutic variables), time to initiation of effective antimicrobial therapy was the single strongest predictor of outcome. Median time to effective antimicrobial therapy was 6 hrs (25-75th per-centile, 2.0-15.0 hrs). Conclusions: Effective antimicrobial administration within the first hour of documented hypotension was associated with increased survival to hospital discharge in adult patients with septic shock. Despite a progressive increase in mortality rate with increasing delays, only 50% of septic shock patients received effective antimicrobial therapy within 6 hrs of documented hypo-tension. (Crit Care Med 2006; 34:1589-1596) AU - Kumar, Anand AU - Roberts, Daniel AU - Wood, Kenneth E AU - Light, Bruce AU - Parrillo, Joseph E AU - Sharma, Satendra AU - Suppes, Robert AU - Feinstein, Daniel AU - Zanotti, Sergio AU - Taiberg, Leo AU - Gurka, David AU - Kumar, Aseem AU - Cheang, Mary DO - 10.1097/01.CCM.0000217961.75225.E9 IS - 6 KW - antimicrobial KW - delay KW - outcome KW - sepsis KW - timing PY - 2006 TI - Duration of hypotension before initiation of effective antimicrobial therapy is the critical determinant of survival in human septic shock* T2 - Crit Care Med UR - http://www.ccmpitt.com/ebm/sepsis/Kumar%20A,%20et%20al.%20%20Duration%20of%20hypotension%20before%20initiation%20o.pdf VL - 34 ER - TY - JOUR AB - Integrated positron emission tomography/computed tomography (PET/CT) with the glucose analogue, 2-[(18)F]-fluoro-2-deoxy-d-glucose (FDG), is an evolving hybrid imaging technique in the evaluation of an important and diverse group of pathological conditions, which are characterised by infection and aseptic inflammation. With a rapidly expanding body of evidence, it is being increasingly recognised that, in addition to its established role in oncological imaging, FDG PET/CT also has clinical utility in suspected infection and inflammation. The technique can identify the source of infection or inflammation in a timely fashion ahead of morphological changes on conventional anatomical imaging techniques, such as computed tomography (CT) and magnetic resonance imaging (MRI), map the extent and severity of disease, identify sites for tissue sampling, and assess therapy response. FDG PET/CT exhibits distinct advantages over traditional radionuclide imaging techniques in terms of shorter duration of examination, higher spatial resolution, non-invasive nature of acquisition, ability to perform quantitative analyses, and the provision of a synergistic combination of functional and anatomical imaging. With the use of illustrative clinico-radiological cases, this article discusses the current and emerging evidence for the use of FDG PET/CT in a broad spectrum of disorders, such as fever of unknown origin, sarcoidosis, large vessel vasculitis, musculoskeletal infections, joint prosthesis or implant-related complications, human immunodeficiency virus (HIV)-related infections, and miscellaneous indications, such as IgG4-related systemic disease. It will also briefly summarise the role of more novel tracers such as FDG-labelled leukocytes and gallium-68 PET tracers in this arena. AU - Vaidyanathan, S. AU - Patel, C.N. AU - Scarsbrook, A.F. AU - Chowdhury, F.U. DA - 2015/7// DO - 10.1016/j.crad.2015.03.010 IS - 7 PY - 2015 SP - 787 EP - 800 TI - FDG PET/CT in infection and inflammation—current and emerging clinical applications T2 - Clinical Radiology UR - http://www.ncbi.nlm.nih.gov/pubmed/25917543 UR - https://linkinghub.elsevier.com/retrieve/pii/S0009926015001063 VL - 70 ER - TY - JOUR AB - OBJECTIVES This study sought to determine the value of (18)F-fluorodeoxyglucose positron emission tomography/computed tomography ((18)F-FDG PET/CT) for diagnosing prosthetic valve endocarditis (PVE). BACKGROUND The diagnosis of PVE remains challenging. In PVE cases, initial echocardiography is normal or inconclusive in almost 30%, leading to a decreased diagnostic accuracy for the modified Duke criteria. METHODS We prospectively studied 72 consecutive patients suspected of having PVE. All of the patients were subjected to clinical, microbiological, and echocardiographic evaluation. Cardiac PET/CT was performed at admission. The final diagnosis was defined according to the clinical and/or pathological modified Duke criteria determined during a 3-month follow-up. RESULTS Thirty-six patients (50%) exhibited abnormal FDG uptake around the site of the prosthetic valve. The sensitivity, specificity, positive predictive value, negative predictive value, and global accuracy were as follows (95% confidence interval): 73% (54% to 87%), 80% (56% to 93%), 85% (64% to 95%), 67% (45% to 84%), and 76% (63% to 86%), respectively. Adding abnormal FDG uptake around the prosthetic valve as a new major criterion significantly increased the sensitivity of the modified Duke criteria at admission (70% [52% to 83%] vs. 97% [83% to 99%], p = 0.008). This result was due to a significant reduction (p < 0.0001) in the number of possible PVE cases from 40 (56%) to 23 (32%). CONCLUSIONS The use of (18)F-FDG PET/CT was helpful for diagnosing PVE. The results of this study support the addition of abnormal FDG uptake as a novel major criterion for PVE. AU - Saby, Ludivine AU - Laas, Olivia AU - Habib, Gilbert AU - Cammilleri, Serge AU - Mancini, Julien AU - Tessonnier, Laetitia AU - Casalta, Jean-Paul AU - Gouriet, Frederique AU - Riberi, Alberto AU - Avierinos, Jean-Francois AU - Collart, Frederic AU - Mundler, Olivier AU - Raoult, Didier AU - Thuny, Franck DA - 2013/6// DO - 10.1016/j.jacc.2013.01.092 IS - 23 PY - 2013 SP - 2374 EP - 2382 TI - Positron Emission Tomography/Computed Tomography for Diagnosis of Prosthetic Valve Endocarditis T2 - Journal of the American College of Cardiology UR - http://www.ncbi.nlm.nih.gov/pubmed/23583251 UR - http://linkinghub.elsevier.com/retrieve/pii/S0735109713014113 VL - 61 ER - TY - JOUR AB - OBJECTIVES This study evaluated the usefulness of fluorodesoxyglucose marked by fluorine-18 ((18)F-FDG) positron emission tomography (PET) and computed tomography (CT) in patients with suspected cardiovascular implantable electronic device (CIED) infection. BACKGROUND CIED infection is sometimes challenging to diagnose. Because extraction is associated with significant morbidity/mortality, new imaging modalities to confirm the infection and its dissemination would be of clinical value. METHODS Three groups were compared. In Group A, 42 patients with suspected CIED infection underwent (18)F-FDG PET/CT. Positive PET/CT was defined as abnormal uptake along cardiac devices. Group B included 12 patients without infection who underwent PET/CT 4 to 8 weeks post-implant. Group C included 12 patients implanted for >6 months without infection who underwent PET/CT for another indication. Semi-quantitative ratio (SQR) was obtained from the ratio between maximal uptake and lung parenchyma uptake. RESULTS In Group A, 32 of 42 patients with suspected CIED infection had positive PET/CT. Twenty-four patients with positive PET/CT underwent extraction with excellent correlation. In 7 patients with positive PET/CT, 6 were treated as superficial infection with clinical resolution. One patient with positive PET/CT but negative leukocyte scan was considered false positive due to Dacron pouch. Ten patients with negative-PET/CT were treated with antibiotics and none has relapsed at 12.9 ± 1.9 months. In Group B, patients had mild uptake seen at the level of the connector. There was no abnormal uptake in Group C patients. Median SQR was significantly higher in Group A (A = 2.02 vs. B = 1.08 vs. C = 0.57; p < 0.001). CONCLUSIONS PET/CT is useful in differentiating between CIED infection and recent post-implant changes. It may guide appropriate therapy. AU - Sarrazin, Jean-François AU - Philippon, François AU - Tessier, Michel AU - Guimond, Jean AU - Molin, Franck AU - Champagne, Jean AU - Nault, Isabelle AU - Blier, Louis AU - Nadeau, Maxime AU - Charbonneau, Lyne AU - Trottier, Mikaël AU - O'Hara, Gilles DA - 2012/5// DO - 10.1016/j.jacc.2011.11.059 IS - 18 PY - 2012 SP - 1616 EP - 1625 TI - Usefulness of Fluorine-18 Positron Emission Tomography/Computed Tomography for Identification of Cardiovascular Implantable Electronic Device Infections T2 - Journal of the American College of Cardiology UR - http://www.ncbi.nlm.nih.gov/pubmed/22538331 UR - http://linkinghub.elsevier.com/retrieve/pii/S0735109712006134 VL - 59 ER - TY - JOUR AB - Early diagnosis of infective endocarditis (IE) is based on the yielding of blood cultures and echocardiographic findings. However, they have limitations and sometimes the diagnosis is inconclusive, particularly in patients with prosthetic valves (PVs) and implantable cardiac electronic devices (ICEDs). The primary aim of this study was to evaluate the diagnostic accuracy of 18F-FDG PET/CT in patients with suspected IE and ICED infection. METHODS A prospective study with 80 consecutive patients with suspected IE and ICED infection (65 men and 15 women with a mean age of 68 ± 13 y) between June 2013 and May 2015 was performed in our hospital. The inclusion criteria were clinically suspected IE and ICED infection at the following locations: native valve (NV) (n = 21), PV (n = 29), or ICED (n = 30) (automatic implantable defibrillator [n = 11] or pacemaker [n = 19]). Whole-body 18F-FDG PET/CT with a myocardial uptake suppression protocol with unfractionated heparin was performed in all patients. The final diagnosis of infection was established by the IE Study Group according to the clinical, echocardiographic, and microbiologic findings. RESULTS A final diagnosis of infection was confirmed in 31 patients: NV (n = 6), PV (n = 12), and ICED (n = 13). Sensitivity, specificity, positive predictive value, and negative predictive value for 18F-FDG PET/CT were 82%, 96%, 94%, and 87%, respectively. 18F-FDG PET/CT was false-negative in all cases with infected NV. 18F-FDG PET/CT was able to reclassify 63 of 70 (90%) patients initially classified as possible IE by modified Duke criteria. In 18 of 70 cases, 18F-FDG PET/CT changed possible to definite IE (26%) and in 45 of 70 cases changed possible to rejected IE (64%). Additionally, 18F-FDG PET/CT identified 8 cases of septic embolism and 3 of colorectal cancer in patients with a final diagnosis of IE. CONCLUSION 18F-FDG PET/CT proved to be a useful diagnostic tool in suspected IE and ICED infection and should be included in the diagnostic algorithm for early diagnosis. 18F-FDG PET/CT is not useful in the diagnosis of IE in NV but should be also considered in the initial assessment of this complex scenario to rule out extracardiac complications and possible neoplasms. AU - Granados, U. AU - Fuster, D. AU - Pericas, J. M. AU - Llopis, J. L. AU - Ninot, S. AU - Quintana, E. AU - Almela, M. AU - Pare, C. AU - Tolosana, J. M. AU - Falces, C. AU - Moreno, A. AU - Pons, F. AU - Lomena, F. AU - Miro, J. M. AU - Hospital Clinic Endocarditis Study Group DA - 2016/11// DO - 10.2967/jnumed.116.173690 IS - 11 KW - 18F-FDG-PET/CT KW - implantable cardiac electronic devices KW - infective endocarditis KW - prosthetic valve KW - septic embolisms PY - 2016 SP - 1726 EP - 1732 TI - Diagnostic Accuracy of 18F-FDG PET/CT in Infective Endocarditis and Implantable Cardiac Electronic Device Infection: A Cross-Sectional Study T2 - Journal of Nuclear Medicine UR - http://www.ncbi.nlm.nih.gov/pubmed/27261514 UR - http://jnm.snmjournals.org/cgi/doi/10.2967/jnumed.116.173690 VL - 57 ER - TY - JOUR AB - BACKGROUND Injury to the airways after smoke inhalation is a major mortality risk factor in victims of burn injuries, resulting in a 15-45% increase in patient deaths. Damage to the airways by smoke may induce acute respiratory distress syndrome (ARDS), which is partly characterized by hypoxemia in the airways. While ARDS has been associated with bacterial infection, the impact of hypoxemia on airway microbiota is unknown. Our objective was to identify differences in microbiota within the airways of burn patients who develop hypoxemia early after inhalation injury and those that do not using next-generation sequencing of bacterial 16S rRNA genes. RESULTS DNA was extracted from therapeutic bronchial washings of 48 patients performed within 72 hours of hospitalization for burn and inhalation injury at the North Carolina Jaycee Burn Center. DNA was prepared for sequencing using a novel molecule tagging method and sequenced on the Illumina MiSeq platform. Bacterial species were identified using the MTToolbox pipeline. Patients with hypoxemia, as indicated by a PaO2/FiO2 ratio ≤ 300, had a 30% increase in abundance of Streptococcaceae and Enterobacteriaceae and 84% increase in Staphylococcaceae as compared to patients with a PaO2/FiO2 ratio > 300. Wilcoxon rank-sum test identified significant enrichment in abundance of OTUs identified as Prevotella melaninogenica (p = 0.042), Corynebacterium (p = 0.037) and Mogibacterium (p = 0.048). Linear discriminant effect size analysis (LefSe) confirmed significant enrichment of Prevotella melaninognica among patients with a PaO2/FiO2 ratio ≤ 300 (p<0.05). These results could not be explained by differences in antibiotic treatment. CONCLUSIONS The airway microbiota following burn and inhalation injury is altered in patients with a PaO2/FiO2 ratio ≤ 300 early after injury. Enrichment of specific taxa in patients with a PaO2/FiO2 ratio ≤ 300 may indicate airway environment and patient changes that favor these microbes. Longitudinal studies are necessary to identify stably colonizing taxa that play roles in hypoxemia and ARDS pathogenesis. AU - Walsh, Dana M AU - McCullough, Shaun D AU - Yourstone, Scott AU - Jones, Samuel W AU - Cairns, Bruce A AU - Jones, Corbin D AU - Jaspers, Ilona AU - Diaz-Sanchez, David DO - 10.1371/journal.pone.0173848 IS - 3 PB - Public Library of Science PY - 2017 SP - e0173848 EP - e0173848 TI - Alterations in airway microbiota in patients with PaO2/FiO2 ratio ≤ 300 after burn and inhalation injury. T2 - PloS one UR - http://www.ncbi.nlm.nih.gov/pubmed/28358811 UR - http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC5373524 VL - 12 ER - TY - JOUR AB - AIM Information on the epidemiology of multiresistant bacteria (MRB) with zoonotic potential is growing but still remains quite incomplete. This narrative mini-review provides a general overview of the epidemiology of the most important zoonotic MRB in cattle, swine and poultry in Europe. METHODS A literature search was conducted mainly on the PubMed website including articles published until April 2012. RESULTS Livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA) especially poses a zoonotic risk to people working in close contact with livestock. These people may become carriers themselves and the hazard of transmission into health-care facilities needs surveillance. Extended-spectrum beta-lactamases (ESBL) producing bacteria are widely spread in both humans and livestock, sharing similar genotypes, especially of the CTX-M-group, which makes a zoonotic transfer very likely. Identical strains of vancomycin-resistant enterococci (VRE) were found both in humans and animals, after ingestion of animal strains transient colonization of the human gut may be possible. Only a few data are available on the transmission of methicillin-resistant coagulase-negative staphylococci (MR-CoNS) between humans and animals. Direct contact to colonized animals may be a risk factor as well as the exchange of resistance genes between human and animal staphylococci. Clostridium difficile (C. difficile) ribotype 078 emerges in livestock and humans and a zoonotic transmission seems probable as genotypes and diseases resemble each other. CONCLUSION All discussed MRB and C. difficile are important nosocomial agents which also occur in livestock and were found in foods of animal origin. Further analysis is needed to reveal the exact transmission routes and to perform a reliable risk assessment. Zielsetzung: Die Intention des vorliegenden narrativen Mini-Reviews ist es, dem Leser einen Überblick über die Prävalenz und Epidemiologie multiresistenter Bakterien in Europa bei Rindern, Schweinen und Geflügel zu geben und deren zoonotisches Potential zu beleuchten. Methode: Es wurde eine PubMed-Literaturrecherche unter Einschluss bis April 2012 publizierter Artikel durchgeführt.Ergebnisse: Der livestock-associated Methicillin-resistente Staphylococcus aureus (LA-MRSA) ist nicht nur bei Nutztieren, sondern auch häufig bei engen Kontaktpersonen nachweisbar. Dem Eintrag durch kolonisierte und infizierte Personen ins Gesundheitswesen muss deshalb Beachtung geschenkt werden. Bakterien, die die Fähigkeit besitzen, β-Laktamasen mit einem erweitertem Wirkspektrum (ESBL) zu bilden, sind ebenfalls bei Mensch und Nutztier zu finden. Insbesondere die ESBL vom Typ CTX-M stehen im Verdacht, zwischen Mensch und Tier übertragen zu werden. Einige Studien legen nahe, dass eine Transmission von Vancomycin-resistenten Enterokokken (VRE), z.B. nach oraler Aufnahme kontaminierter tierischen Lebensmitteln, auf den Menschen möglich ist. Bezüglich des zoonotischen Potentials von multiresistenten Koagulase-negativen Staphylokokken (MR-CoNS) existieren hingegen nur wenige Publikationen. Es gibt jedoch erste Hinweise, dass eine zoonotische Übertragung möglich sein könnte und auch der Austausch von Resistenzgenen zwischen humanen und tierischen Bakterien scheint prinzipiell möglich. Die Nachweisrate von Clostridium difficile (C. difficile), v.a. des Ribotyps 078, hat bei Mensch und Tier gleichermaßen zugenommen. Nicht nur die Genotypen, auch die verursachten Infektionen weisen unabhängig von der betroffenen Spezies Gemeinsamkeiten auf. Schlussfolgerung: Alle betrachteten multiresistenten Erreger sowie C. difficile spielen eine erhebliche Rolle bei nosokomialen Infektionen in der Humanmedizin und sind ebenfalls bei Nutztieren und Lebensmitteln tierischen Ursprungs zu finden. Weitere Studien sind nötig, um die exakten Transmissionsrouten zu identifizieren und eine valide Risikobeurteilung durchzuführen. AU - Dahms, Carmen AU - Hübner, Nils-Olaf AU - Wilke, Florian AU - Kramer, Axel DO - 10.3205/dgkh000241 IS - 3 KW - Clostridium difficile KW - E. coli KW - ESBL KW - MRSA KW - VRE KW - livestock KW - multiresistant KW - vancomycin KW - zoonoses PY - 2014 SP - Doc21 EP - Doc21 TI - Mini-review: Epidemiology and zoonotic potential of multiresistant bacteria and Clostridium difficile in livestock and food. T2 - GMS hygiene and infection control UR - http://www.ncbi.nlm.nih.gov/pubmed/25285265 UR - http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC4184042 VL - 9 ER - TY - JOUR AB - Escherichia (E.) coli producing extended-spectrum beta-lactamases (ESBLs) are an increasing problem for public health. The success of ESBLs may be due to spread of ESBL-producing bacterial clones, transfer of ESBL gene-carrying plasmids or exchange of ESBL encoding genes on mobile elements. This makes it difficult to identify transmission routes and sources for ESBL-producing bacteria. The objectives of this study were to compare the distribution of genotypic and phenotypic properties of E. coli isolates from different animal and human sources collected in studies in the scope of the national research project RESET. ESBL-producing E. coli from two longitudinal and four cross-sectional studies in broiler, swine and cattle farms, a cross-sectional and a case-control study in humans and diagnostic isolates from humans and animals were used. In the RESET consortium, all laboratories followed harmonized methodologies for antimicrobial susceptibility testing, confirmation of the ESBL phenotype, specific PCR assays for the detection of bla(TEM), bla(CTX), and bla(SHV) genes and sequence analysis of the complete ESBL gene as well as a multiplex PCR for the detection of the four major phylogenetic groups of E. coli. Most ESBL genes were found in both, human and non-human populations but quantitative differences for distinct ESBL-types were detectable. The enzymes CTX-M-1 (63.3% of all animal isolates, 29.3% of all human isolates), CTX-M-15 (17.7% vs. 48.0%) and CTX-M-14 (5.3% vs. 8.7%) were the most common ones. More than 70% of the animal isolates and more than 50% of the human isolates contained the broadly distributed ESBL genes bla(CTX-M-1), bla(CTX-M-15), or the combinations bla(SHV-12)+bla(TEM) or bla(CTX-M-1)+bla(TEM). While the majority of animal isolates carried bla(CTX-M-1) (37.5%) or the combination bla(CTX-M-1)+bla(TEM) (25.8%), this was the case for only 16.7% and 12.6%, respectively, of the human isolates. In contrast, 28.2% of the human isolates carried bla(CTX-M-15) compared to 10.8% of the animal isolates. When grouping data by ESBL types and phylogroups bla(CTX-M-1) genes, mostly combined with phylogroup A or B1, were detected frequently in all settings. In contrast, bla(CTX-M-15) genes common in human and animal populations were mainly combined with phylogroup A, but not with the more virulent phylogroup B2 with the exception of companion animals, where a few isolates were detectable. When E. coli subtype definition included ESBL types, phylogenetic grouping and antimicrobial susceptibility data, the proportion of isolates allocated to common clusters was markedly reduced. Nevertheless, relevant proportions of same subtypes were detected in isolates from the human and livestock and companion animal populations included in this study, suggesting exchange of bacteria or bacterial genes between these populations or a common reservoir. In addition, these results clearly showed that there is some similarity between ESBL genes, and bacterial properties in isolates from the different populations. Finally, our current approach provides good insight into common and population-specific clusters, which can be used as a basis for the selection of ESBL-producing isolates from interesting clusters for further detailed characterizations, e.g. by whole genome sequencing. AU - Valentin, Lars AU - Sharp, Hannah AU - Hille, Katja AU - Seibt, Uwe AU - Fischer, Jennie AU - Pfeifer, Yvonne AU - Michael, Geovana Brenner AU - Nickel, Silke AU - Schmiedel, Judith AU - Falgenhauer, Linda AU - Friese, Anika AU - Bauerfeind, Rolf AU - Roesler, Uwe AU - Imirzalioglu, Can AU - Chakraborty, Trinad AU - Helmuth, Reiner AU - Valenza, Giuseppe AU - Werner, Guido AU - Schwarz, Stefan AU - Guerra, Beatriz AU - Appel, Bernd AU - Kreienbrock, Lothar AU - Käsbohrer, Annemarie DA - 2014/10// DO - 10.1016/j.ijmm.2014.07.015 IS - 7 KW - Beta-lactamases KW - CTX-M-1 KW - CTX-M-15 KW - Molecular typing KW - One Health approach PY - 2014 SP - 805 EP - 816 TI - Subgrouping of ESBL-producing Escherichia coli from animal and human sources: An approach to quantify the distribution of ESBL types between different reservoirs T2 - International Journal of Medical Microbiology UR - http://www.ncbi.nlm.nih.gov/pubmed/25213631 UR - https://linkinghub.elsevier.com/retrieve/pii/S1438422114000976 VL - 304 ER - TY - GEN AU - John E. Bennett & Raphael Dolin & Martin J. Blaser PY - 2010 SP - 2815 EP - 2833 TI - Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases - 9781455748013 | US Elsevier Health Bookshop T2 - Elsevier Inc UR - https://www.us.elsevierhealth.com/mandell-douglas-and-bennetts-principles-and-practice-of-infectious-diseases-9781455748013.html ER - TY - JOUR AB - STUDY OBJECTIVE To evaluate the relationship between inadequate antimicrobial treatment of infections (both community-acquired and nosocomial infections) and hospital mortality for patients requiring ICU admission. DESIGN Prospective cohort study. SETTING Barnes-Jewish Hospital, a university-affiliated urban teaching hospital. PATIENTS Two thousand consecutive patients requiring admission to the medical or surgical ICU. INTERVENTIONS Prospective patient surveillance and data collection. MEASUREMENTS AND RESULTS One hundred sixty-nine (8.5%) infected patients received inadequate antimicrobial treatment of their infections. This represented 25.8% of the 655 patients assessed to have either community-acquired or nosocomial infections. The occurrence of inadequate antimicrobial treatment of infection was most common among patients with nosocomial infections, which developed after treatment of a community-acquired infection (45.2%), followed by patients with nosocomial infections alone (34.3%) and patients with community-acquired infections alone (17.1%) (p < 0.001). Multiple logistic regression analysis, using only the cohort of infected patients (n = 655), demonstrated that the prior administration of antibiotics (adjusted odds ratio [OR], 3.39; 95% confidence interval [CI], 2.88 to 4.23; p < 0.001), presence of a bloodstream infection (adjusted OR, 1.88; 95% CI, 1.52 to 2.32; p = 0.003), increasing acute physiology and chronic health evaluation (APACHE) II scores (adjusted OR, 1.04; 95% CI, 1.03 to 1.05; p = 0.002), and decreasing patient age (adjusted OR, 1.01; 95% CI, 1.01 to 1.02; p = 0.012) were independently associated with the administration of inadequate antimicrobial treatment. The hospital mortality rate of infected patients receiving inadequate antimicrobial treatment (52.1%) was statistically greater than the hospital mortality rate of the remaining patients in the cohort (n = 1,831) without this risk factor (12.2%) (relative risk [RR], 4.26; 95% CI, 3.52 to 5.15; p < 0.001). Similarly, the infection-related mortality rate for infected patients receiving inadequate antimicrobial treatment (42.0%) was significantly greater than the infection-related mortality rate of infected patients receiving adequate antimicrobial treatment (17.7%) (RR, 2.37; 95% CI, 1.83 to 3.08; p < 0.001). Using a logistic regression model, inadequate antimicrobial treatment of infection was found to be the most important independent determinant of hospital mortality for the entire patient cohort (adjusted OR, 4.27; 95% CI, 3.35 to 5.44; p < 0.001). The other identified independent determinants of hospital mortality included the number of acquired organ system derangements, use of vasopressor agents, the presence of an underlying malignancy, increasing APACHE II scores, increasing age, and having a nonsurgical diagnosis at the time of ICU admission. CONCLUSIONS Inadequate treatment of infections among patients requiring ICU admission appears to be an important determinant of hospital mortality. These data suggest that clinical efforts aimed at reducing the occurrence of inadequate antimicrobial treatment could improve the outcomes of critically ill patients. Additionally, prior antimicrobial therapy should be recognized as an important risk factor for the administration of inadequate antimicrobial treatment among ICU patients with clinically suspected infections. AU - Kollef, M H AU - Sherman, G AU - Ward, S AU - Fraser, V J DA - 1999/2// IS - 2 PY - 1999 SP - 462 EP - 74 TI - Inadequate antimicrobial treatment of infections: a risk factor for hospital mortality among critically ill patients. T2 - Chest UR - http://www.ncbi.nlm.nih.gov/pubmed/10027448 VL - 115 ER - TY - JOUR AB - OBJECTIVES To examine the incidence of infections and to describe them and their outcome in intensive care unit (ICU) patients. DESIGN AND SETTING International prospective cohort study in which all patients admitted to the 28 participating units in eight countries between May 1997 and May 1998 were followed until hospital discharge. PATIENTS A total of 14,364 patients were admitted to the ICUs, 6011 of whom stayed less than 24 h and 8353 more than 24 h. RESULTS Overall 3034 infectious episodes were recorded at ICU admission (crude incidence: 21.1%). In ICU patients hospitalised longer than 24 h there were 1581 infectious episodes (crude incidence: 18.9%) including 713 (45%) in patients already infected at ICU admission. These rates varied between ICUs. Respiratory, digestive, urinary tracts, and primary bloodstream infections represented about 80% of all sites. Hospital-acquired and ICU-acquired infections were documented more frequently microbiologically than community-acquired infections (71% and 86%, respectively vs. 55%). About 28% of infections were associated with sepsis, 24% with severe sepsis and 30% with septic shock, and 18% were not classified. Crude hospital mortality rates ranged from 16.9% in non-infected patients to 53.6% in patients with hospital-acquired infections at the time of ICU admission and acquiring infection during the ICU stay. CONCLUSIONS The crude incidence of ICU infections remains high, although the rate varies between ICUs and patient subsets, illustrating the added burden of nosocomial infections in the use of ICU resources. AU - Alberti, Corinne AU - Brun-Buisson, Christian AU - Burchardi, Hilmar AU - Martin, Claudio AU - Goodman, Sergey AU - Artigas, Antonio AU - Sicignano, Alberto AU - Palazzo, Mark AU - Moreno, Rui AU - Boulmé, Ronan AU - Lepage, Eric AU - Le Gall, Jean DA - 2002/2// DO - 10.1007/s00134-001-1143-z IS - 2 PY - 2002 SP - 108 EP - 121 TI - Epidemiology of sepsis and infection in ICU patients from an international multicentre cohort study T2 - Intensive Care Medicine UR - http://www.ncbi.nlm.nih.gov/pubmed/11907653 UR - http://link.springer.com/10.1007/s00134-001-1143-z VL - 28 ER - TY - JOUR AB - The Centers for Disease Control and Prevention estimates that 2 million patients suffer from hospital-acquired infections every year and nearly 100,000 of them die. Most of these medical errors are preventable. Hospital-acquired infections result in up to $4.5 billion in additional healthcare expenses annually. The U.S. government has responded to this financial loss by focusing on healthcare quality report cards and by taking strong action to curb healthcare spending. The Medicare Program has proposed changes to the Hospital Inpatient Prospective Payment System and Fiscal Year Rates: Proposed Rule CMS 1488-P-Healthcare-associated infection. Payment will be linked to performance. Under the new rule, payment will be withheld from hospitals for care associated with treating certain catheter-associated urinary tract infections, vascular catheter-associated infections, and mediastinitis after coronary artery bypass graft surgery. Infection-prevention strategies are essential. In the healthcare setting, the infection control department is categorized as non-revenue-producing. Funds dedicated to resources such as staff, educational programs, and prevention measures are vastly limited. Hospital leaders will need to balance the upfront cost needed to prevent hospital-related infections with the non-reimbursed expense accrued secondary to potentially preventable infections. The purpose of this paper is to present case studies and cost analysis of hospital-acquired infections and present strategies that reduce infections and cost. AU - Reed, Deoine AU - Kemmerly, Sandra A IS - 1 KW - Economics KW - finance KW - healthcare KW - hospital-acquired infection KW - infection control KW - infection prevention PY - 2009 SP - 27 EP - 31 TI - Infection control and prevention: a review of hospital-acquired infections and the economic implications. T2 - The Ochsner journal UR - http://www.ncbi.nlm.nih.gov/pubmed/21603406 UR - http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC3096239 VL - 9 ER - TY - JOUR AU - Leal, Aura Lucia AU - Arturo, Carlos AU - Jorge, Álvarez AU - Cortes María, Alberto AU - Ovalle, Victoria PY - 2017 TI - Boletín informativo GREBO UR - www.grebo.org ER - TY - JOUR KW - 2003 KW - Capítulo 1: Salud mundial: retos actuales KW - health KW - report KW - world PB - World Health Organization PY - 2010 TI - OMS | Capítulo 1: Salud mundial: retos actuales T2 - WHO UR - http://www.who.int/whr/2003/chapter1/es/index3.html ER - TY - JOUR AU - Woolf, S H AU - Grol, R AU - Hutchinson, A AU - Eccles, M AU - Grimshaw, J DA - 1999/2// IS - 7182 PB - BMJ Publishing Group PY - 1999 SP - 527 EP - 30 TI - Clinical guidelines: potential benefits, limitations, and harms of clinical guidelines. T2 - BMJ (Clinical research ed.) UR - http://www.ncbi.nlm.nih.gov/pubmed/10024268 UR - http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC1114973 VL - 318 ER - TY - JOUR AU - WHO KW - financiación de la salud [subject] KW - investigación [subject] KW - servicios de salud [subject] PB - World Health Organization PY - 2013 TI - OMS | Informe sobre la salud en el mundo 2010 T2 - WHO UR - http://www.who.int/whr/2010/es/ ER - TY - JOUR AU - Signore, Alberto AU - Glaudemans, Andor W. J. M. DA - 2011/12// DO - 10.1007/s12149-011-0521-z IS - 10 KW - ANTIGRANULOCYTE ANTIBODY KW - BOWEL-DISEASE KW - CLINICAL-VALUE KW - CROHNS-DISEASE KW - IN-VIVO KW - Infection KW - Inflammation KW - MONOCLONAL-ANTIBODY FRAGMENT KW - Molecular imaging KW - Nuclear medicine KW - POSITRON-EMISSION-TOMOGRAPHY KW - Pathophysiology KW - RAT ADJUVANT ARTHRITIS KW - RHEUMATOID-ARTHRITIS KW - Radiopharmaceuticals KW - UNKNOWN ORIGIN PY - 2011 SP - 681 EP - 700 TI - The molecular imaging approach to image infections and inflammation by nuclear medicine techniques T2 - Annals of Nuclear Medicine UR - http://link.springer.com/10.1007/s12149-011-0521-z VL - 25 ER - TY - JOUR AU - WHO KW - antimicrobial resistance [subject] PB - World Health Organization PY - 2018 SP - 164 EP - 164 TI - GLASS | Global antimicrobial resistance surveillance system (GLASS) report T2 - WHO UR - https://www.who.int/glass/resources/publications/early-implementation-report/en/ ER - TY - JOUR AB - Molecular imaging allows for the remote, noninvasive sensing and measurement of cellular and molecular processes in living subjects. Drawing upon a variety of modalities, molecular imaging provides a window into the biology of cancer from the subcellular level to the patient undergoing a new, experimental therapy. As signal transduction cascades and protein interaction networks become clarified, an increasing number of relevant targets for cancer therapy--and imaging--become available. Although conventional imaging is already critical to the management of patients with cancer, molecular imaging will provide even more relevant information, such as early detection of changes with therapy, identification of patient-specific cellular and metabolic abnormalities, and the disposition of therapeutic, gene-tagged cells throughout the body--all of which will have a considerable impact on morbidity and mortality. This overview discusses molecular imaging in oncology, providing examples from a variety of modalities, with an emphasis on emerging techniques for translational imaging. AU - Higgins, Luke J. AU - Pomper, Martin G. DA - 2011/2// DO - 10.1053/j.seminoncol.2010.11.010 IS - 1 PY - 2011 SP - 3 EP - 15 TI - The Evolution of Imaging in Cancer: Current State and Future Challenges T2 - Seminars in Oncology UR - http://www.ncbi.nlm.nih.gov/pubmed/21362512 UR - http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC4313866 UR - http://linkinghub.elsevier.com/retrieve/pii/S0093775410002320 VL - 38 ER - TY - GEN AU - Ibrahim Abudakar, Ted Cohen, Helen R. Stagg, Laura C. Rodrigues PY - 2016 SP - 1 EP - 371 TI - Infectious Disease Epidemiology - Google Books T2 - OXFORD UNIVERSITY PRESS UR - https://books.google.com.co/books?id=0N8mDAAAQBAJ&pg=PA304&lpg=PA304&dq=Clostridium+difficile+(12.1%25),+Staphylococcus+aureus+(10.7%25)+y+Pseudomona+aeruginosa&source=bl&ots=XuHmmvF8ff&sig=agVCmaw32OE3RxhPPK0jp09584U&hl=es-419&sa=X&ved=2ahUKEwiTk6G5ioreA ER - TY - JOUR AB - Infectious diseases are a major threat to humanity, and it is imperative that we develop imaging tools that aid in their study, facilitate diagnosis, and guide treatment. The alarming rise of highly virulent and multi-drug-resistant pathogens, their rapid spread leading to frequent global pandemics, fears of bioterrorism, and continued life-threatening nosocomial infections in hospitals remain as major challenges to health care in the USA and worldwide. Early diagnosis and rapid monitoring are essential for appropriate management and control of infections. Tomographic molecular imaging enables rapid, noninvasive visualization, localization, and monitoring of molecular processes deep within the body and offers several advantages over traditional tools used for the study of infectious diseases. Noninvasive, longitudinal assessments could streamline animal studies, allow unique insights into disease pathogenesis, and expedite clinical translation of new therapeutics. Since molecular imaging is already in common use in the clinic, it could also become a valuable tool for clinical studies, for patient care, for public health, and for enabling precision medicine for infectious diseases. AU - Jain, Sanjay K. DO - 10.1007/S11307-017-1055-0 IS - 3 KW - Bacteria KW - Influenza KW - Microbiome KW - Optical imaging KW - PET KW - TB PB - NIH Public Access PY - 2017 SP - 341 EP - 341 TI - The Promise of Molecular Imaging in the Study and Treatment of Infectious Diseases T2 - Molecular imaging and biology : MIB : the official publication of the Academy of Molecular Imaging UR - http://www.ncbi.nlm.nih.gov/pubmed/28155078 UR - http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC5407939 VL - 19 ER - TY - JOUR AB - // Stefan Wiehr 1 , Philipp Warnke 2,7 , Anna-Maria Rolle 1 , Monika Schütz 2 , Philipp Oberhettinger 2 , Ursula Kohlhofer 3 , Leticia Quintanilla-Martinez 3 , Andreas Maurer 1 , Christopher Thornton 4 , Frederic Boschetti 5 , Gerald Reischl 1 , Ingo B. Autenrieth 2 , Bernd J. Pichler 1 and Stella E. Autenrieth 6 1 Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, Eberhard Karls University Tübingen, Tübingen, Germany 2 Institute of Medical Microbiology and Hygiene, Eberhard Karls University, Tübingen, Germany 3 Institute of Pathology, Eberhard Karls University Tübingen, Tübingen, Germany 4 Biosciences and ISCA Diagnostics Ltd., University of Exeter, Exeter, United Kingdom 5 CheMatech, Faculté des Sciences Mirande, Dijon, France 6 Department of Internal Medicine II, University Hospital Tübingen, Tübingen, Germany 7 Institute of Medical Microbiology, Virology and Hygiene, Rostock University Hospital, Rostock, Germany Correspondence to: Stella E. Autenrieth, email: // Keywords : bacteria, PET/MR, in vivo imaging, 64Cu, antibody, Immunology and Microbiology Section, Immune response, Immunity Received : October 01, 2015 Accepted : February 20, 2016 Published : February 26, 2016 Abstract The specific and rapid detection of Enterobacteriaceae, the most frequent cause of gram-negative bacterial infections in humans, remains a major challenge. We developed a non-invasive method to rapidly detect systemic Yersinia enterocolitica infections using immunoPET (antibody-targeted positron emission tomography) with [ 64 Cu]NODAGA-labeled Yersinia -specific polyclonal antibodies targeting the outer membrane protein YadA. In contrast to the tracer [ 18 F]FDG, [ 64 Cu]NODAGA-YadA uptake co-localized in a dose dependent manner with bacterial lesions of Yersinia -infected mice, as detected by magnetic resonance (MR) imaging. This was accompanied by elevated uptake of [ 64 Cu]NODAGA-YadA in infected tissues, in ex vivo biodistribution studies, whereas reduced uptake was observed following blocking with unlabeled anti-YadA antibody. We show, for the first time, a bacteria-specific, antibody-based, in vivo imaging method for the diagnosis of a Gram-negative enterobacterial infection as a proof of concept, which may provide new insights into pathogen-host interactions. AU - Wiehr, Stefan AU - Warnke, Philipp AU - Rolle, Anna-Maria AU - Schütz, Monika AU - Oberhettinger, Philipp AU - Kohlhofer, Ursula AU - Quintanilla-Martinez, Leticia AU - Maurer, Andreas AU - Thornton, Christopher AU - Boschetti, Frederic AU - Reischl, Gerald AU - Autenrieth, Ingo B. AU - Pichler, Bernd J. AU - Autenrieth, Stella E. DO - 10.18632/oncotarget.7770 PY - 2016 SN - 1949-2553|escape} TI - New pathogen-specific immunoPET/MR tracer for molecular imaging of a systemic bacterial infection T2 - Oncotarget ER - TY - JOUR AB - Metabolic imaging has come to occupy a prominent place in the diagnosis and management of microbial infection. Molecular probes available for infection imaging have undergone a rapid evolution starting with nonspecific agents that accumulate similarly in infection, sterile inflammation, and neoplastic tissue and then extending to more targeted probes that seek to identify specific microbial species. This focus review describes the metabolic and molecular imaging techniques currently available for clinical use in infection imaging and those that have demonstrated promising results in preclinical studies with the potential for clinical applications. AU - Lawal, Ismaheel AU - Zeevaart, Jan Rijn AU - Ebenhan, Thomas AU - Ankrah, Alfred AU - Vorster, Mariza AU - Kruger, Hendrick AU - Govender, Thavendran AU - Sathekge, Mike DO - 10.2967/jnumed.117.191635 PY - 2017 SN - 0161-5505 TI - Metabolic Imaging of Infection T2 - Journal of Nuclear Medicine ER - TY - JOUR AB - Both the referring clinician and the nuclear medicine specialist must be aware of the main known or potential pitfalls that can occur in infection and inflammation imaging. They must decide in consensus which tracer and which imaging protocol should be used for a specific indication. This article provides an overview of all the pitfalls and limitations of nuclear medicine techniques to image infections and inflammation. Both general pitfalls and pitfalls in specific clinical entities are discussed. AU - Glaudemans, Andor W.J.M. AU - Israel, Ora AU - Slart, Riemer H.J.A. DA - 2015/11// DO - 10.1053/J.SEMNUCLMED.2015.02.005 IS - 6 PB - W.B. Saunders PY - 2015 SP - 500 EP - 512 TI - Pitfalls and Limitations of Radionuclide and Hybrid Imaging in Infection and Inflammation T2 - Seminars in Nuclear Medicine UR - https://www.sciencedirect.com/science/article/pii/S0001299815000227?via%3Dihub VL - 45 ER - TY - JOUR AB - There is often overlap in the diagnostic features of common pathologic processes such as infection, sterile inflammation, and cancer both clinically and using conventional imaging techniques. Here, we report the development of a positron emission tomography probe for live bacterial infection based on the small-molecule antibiotic trimethoprim (TMP). [18F]fluoropropyl-trimethoprim, or [18F]FPTMP, shows a greater than 100-fold increased uptake in vitro in live bacteria (Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa) relative to controls. In a rodent myositis model, [18F]FPTMP identified live bacterial infection without demonstrating confounding increased signal in the same animal from other etiologies including chemical inflammation (turpentine) and cancer (breast carcinoma). Additionally, the biodistribution of [18F]FPTMP in a nonhuman primate shows low background in many important tissues that may be sites of infection such as the lungs and soft tissues. These results suggest that [18F]FPTMP could be a broadly useful agent for the sensitive and specific imaging of bacterial infection with strong translational potential. AU - Sellmyer, Mark A AU - Lee, Iljung AU - Hou, Catherine AU - Weng, Chi-Chang AU - Li, Shihong AU - Lieberman, Brian P AU - Zeng, Chenbo AU - Mankoff, David A AU - Mach, Robert H DA - 2017/8// DO - 10.1073/pnas.1703109114 IS - 31 KW - PET KW - bacteria KW - imaging KW - radiotracer KW - trimethoprim PB - National Academy of Sciences PY - 2017 SP - 8372 EP - 8377 TI - Bacterial infection imaging with [18F]fluoropropyl-trimethoprim. T2 - Proceedings of the National Academy of Sciences of the United States of America UR - http://www.ncbi.nlm.nih.gov/pubmed/28716936 UR - http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC5547613 VL - 114 ER - TY - JOUR AB - To facilitate oviposition, the ectoparasite Bracon hebetor, injects its venom, a paralysing toxin, to the host Corcyra larva that ultimately dies without showing any metamorphic change, even if allowed to remain unparasitised. At the initial stage of venom injection the rate of heartbeat of the host becomes abruptly high. This has been explained from the synergistic action of the substances of poison gland and calyx. The paralysed larvae subsequent to envenomization die within 240 hr. Application of hydroprene as single dose or with a booster dose after paralysation mostly increases the survival period considering heart beat as the index. The predicted value of survival period (714.4 hr), determined from a fitted equation obtained from the relationship between heart beat and survival period, indicates that a 100 microg treatment/larva with a booster dose of 50 microg/larva most effectively lengthens the period. It is concluded that the venom-induced physiological dysfunction of the immobilised larvae, as indicated in the rate of heart beat and survival period, though can be recovered to some extent after the application of juvenoids, there cannot occur any metamorphic change of these larvae. The parasitoid, therefore, succeeds in completing its development and metamorphosis by arresting the development of its host through an indirect hormonal suppression. The findings indicate an endocrine implication in host-parasite relationship in insect. AU - Chanda, Sudipta AU - Panda, R. N. AU - Chakravorty, Sanjib DO - 10.1186/s13073-016-0307-y IS - 8 PY - 2002 SN - 1756-994x SP - 918 EP - 923 TI - Hormonal implication in Bracon-venom-induced paralysation of the host larva of Corcyra cephalonica (Lepidoptera: Pyralidae) T2 - Indian Journal of Experimental Biology VL - 40 ER - TY - JOUR AU - Fisman, David AU - Patrozou, Eleni AU - Carmeli, Yehuda AU - Perencevich, Eli AU - Tuite, Ashleigh R AU - Mermel, Leonard A AU - Group, Bacteremia Study DO - 10.1371/journal.pone.0114548 IS - 12 PY - 2014 SP - 1 EP - 18 TI - Geographical Variability in the Likelihood of Bloodstream Infections Due to Gram- Negative Bacteria : Correlation with Proximity to the Equator and Health Care Expenditure T2 - PLoS Genetics VL - 9 ER - TY - JOUR AU - Hess, Aaron S AU - Kleinberg, Michael AU - Sorkin, John D AU - Netzer, Giora AU - Jennifer, K AU - Shardell, Michelle AU - Thom, Kerri A AU - Harris, Anthony D AU - Greenebaum, Stewart AU - Medicine, Geriatric DO - 10.1016/j.diagmicrobio.2014.01.022.Prior IS - 1 PY - 2015 SP - 73 EP - 76 TI - HHS Public Access T2 - Diagn Microbiol Infect Dis VL - 79 ER - TY - BOOK AB - ... GL Mandell , JE Bennett , R. Dolin Mandell , Douglas and Bennett's Principles and Practice of Infectious ... outstanding experts in the field of infectious diseases – Gerald L. Mandell , MD (Chief ... Ctr, Charlottesville, Va.), John E. Bennett , MD (Head Clin., Mycology Sect., NIH, Bethesda ... AU - Mandell, Douglas, and Bennett’s DO - 10.1016/S1473-3099(10)70089-X IS - 5 PY - 2005 SN - 9780443068393 SP - 303 EP - 304 TI - Mandell, Douglas, and Bennett's principles and practice of infectious diseases T2 - The Lancet Infectious Diseases UR - http://linkinghub.elsevier.com/retrieve/pii/S147330991070089X VL - 10 ER - TY - JOUR AB - PURPOSE: [(18)F]fluorodeoxysorbitol ([(18)F]FDS) is the first radiopharmaceutical specific for a category of bacteria and has the potential to specifically detect Enterobacteriaceae infections. The purpose of this study was to testify the safety and investigate the biodistribution and radiation dosimetry of [(18)F]FDS in healthy human bodies.\n\nPROCEDURES: Six healthy subjects were intravenously injected with 320-520 MBq [(18)F]FDS. On each subject, 21 whole-body emission scans and a brain scan were conducted at settled time points within the next 4 h. Residence time for each source organ was determined by multi-exponential regression. Absorbed doses for target organs and effective dose were calculated via OLINDA/EXM.\n\nRESULTS: No adverse events due to [(18)F]FDS injection were observed in the study. The tracer was cleared rapidly from the blood pool through the urinary system. A small portion was cleared into the gut through the hepatobiliary system. The effective dose (ED) was estimated to be 0.021 ± 0.001 mSv/MBq. The organ receiving the highest absorbed dose was the urinary bladder wall (0.25 ± 0.03 mSv/MBq).\n\nCONCLUSIONS: [(18)F]FDS is safe and well tolerated. The effective dose was comparable to that of other F-18 labeled radiotracers. [(18)F]FDS is suitable for human use from a radiation dosimetry perspective. AU - Zhu, Wenjia AU - Yao, Shaobo AU - Xing, Haiqun AU - Zhang, Hui AU - Tai, Yuan chuan AU - Zhang, Yingqiang AU - Liu, Yimin AU - Ma, Yanru AU - Wu, Chenxi AU - Wang, Hongkai AU - Li, Zibo AU - Wu, Zhanhong AU - Zhu, Zhaohui AU - Li, Fang AU - Huo, Li DO - 10.1007/s11307-016-0946-9 KW - Biodistribution KW - Enterobacteriaceae KW - PET KW - Radiation dosimetry KW - [18F] FDS PY - 2016 SN - 1860-2002 TI - Biodistribution and Radiation Dosimetry of the Enterobacteriaceae-Specific Imaging Probe [18F]Fluorodeoxysorbitol Determined by PET/CT in Healthy Human Volunteers T2 - Molecular Imaging and Biology ER - TY - JOUR AB - The aim of this study was to develop a positron emission tomography (PET) tracer to visualize and monitor therapeutic response to bacterial infections. In our continued efforts to find maltose based PET tracers that can image bacterial infections, we have designed and prepared 6′′-[18F]fluoromaltotriose as a second generation PET imaging tracer targeting the maltodextrin transporter of bacteria. We have developed methods to synthesize 6′′-deoxy-6′′-[18F]fluoro-α-D-glucopyranosyl-(1-4)-O-α-D-glucopyranosyl-(1-4)-O-D-glucopyranose (6′′-[18F]-fluoromaltotriose) as a bacterial infection PET imaging agent. 6′′-[18F]fluoromaltotriose was prepared from precursor, 2′′,3′′,4′′-tri-O-acetyl-6′′-O-nosyl-α-D-glucopyranosyl-(1-4)-O-2′,3′,6′-tri-O-acetyl-α-D-glucopyranosyl-(1-4)-1,2,3,6-tetra-O-acetyl-D-glucopyranose (per-O-acetyl-6′′-O-nosyl-maltotriose 4). This method utilizes the reaction between precursor 4 and anhydrous [18F]KF/Kryptofix 2.2.2 in dimethylformamide (DMF) at 85°C for 10 minutes to yield per-O-acetyl-6′′-deoxy-6-′′ [18F]-fluoromaltotriose (7). Successive acidic and basic hydrolysis of the acetyl protecting groups in 7 produced 6′′-[18F]fluoromaltotriose (8). Also, cold 6′′- [19F]fluoromaltotriose was prepared from per-O-acetyl-6′′-hydroxymaltotriose via a diethylaminosulfur trifluoride reaction followed by a basic hydrolysis. A successful synthesis of 6′′-[18F]-fluoromaltotriose has been accomplished in 8 ± 1.2% radiochemical yield (decay corrected). Total synthesis time was 120 minutes. Serum stability of 6′′-[18F]fluoromaltotriose at 37°C indicated that 6′′-[18F]-fluoromaltotriose remained intact up to 2 hours. In conclusion, we have successfully synthesized 6′′-[18F]-fluoromaltotriose via direct fluorination of an appropriate precursor of a protected maltotriose. AU - Namavari, Mohammad AU - Gowrishankar, Gayatri AU - Srinivasan, Ananth AU - Gambhir, Sanjiv S. AU - Haywood, Thomas AU - Beinat, Corinne DO - 10.1002/jlcr.3601 IS - 5 PY - 2018 SN - 1932-6203 TI - A novel synthesis of 6′′-[18F]-fluoromaltotriose as a PET tracer for imaging bacterial infection T2 - Journal of Labelled Compounds and Radiopharmaceuticals VL - 61 ER - TY - JOUR AB - Copyright © 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc. Accurate assessment of kidney function plays an essential role for optimal clinical decision making in a variety of diseases. The major intrinsic advantages of PET are superior spatial and temporal resolutions for quantitative tomographic renal imaging. 2-deoxy-2-18F-fluorodeoxysorbitol (18F-FDS) is an analog of sorbitol that is reported to be freely filtered at the renal glomerulus without reabsorption at the tubule. Furthermore, it can be synthesized via simple reduction of widely available18F-FDG. We tested the feasibility of18F-FDS renal PET imaging in rats. Methods: The systemic and renal distribution of18F-FDS were determined by dynamic 35-min PET imaging (15 frames x 8 s, 26 frames x 30 s, 20 frames x 60 s) with a dedicated small-animal PET system and postmortem tissue counting in healthy rats. Distribution of coinjected99mTc-diethylenetriaminepentaacetic acid (DTPA) was also estimated as a reference. Plasma binding and in vivo stability of18F-FDS were determined. Results: In vivo PET imaging visualized rapid excretion of the administrated18F-FDS from both kidneys, with minimal tracer accumulation in other organs. Initial cortical tracer uptake followed by visualization of the collecting system could be observed with high contrast. Split-function renography curves were successfully obtained in healthy rats (the time of maximal concentration [Tmax] right [R] = 2.8 ± 1.2 min, Tmaxleft [L] = 2.9 ± 1.5 min, the time of half maximal concentration [T1/2max] R = 8.8 ± 3.7 min, T1/2maxL = 11.1 ± 4.9 min). Postmortem tissue counting of18F-FDS confirmed the high kidney extraction (kidney activities at 10, 30, and 60 min after tracer injection [percentage injected dose per gram]: 1.8 ± 0.7, 1.2 ± 0.1, and 0.5 ± 0.2, respectively) in a degree comparable to99mTc-DTPA (2.5 ± 1.0, 1.5 ± 0.2, and 0.8 ± 0.3, respectively). Plasma protein binding of18F-FDS was low (<0.1%), and metabolic transformation was not detected in serum and urine. Conclusion: In rat experiments,18F-FDS demonstrated high kidney extraction and excretion, low plasma protein binding, and high metabolic stability as preferable properties for renal imaging. These preliminary results warrant further confirmatory studies in large animal models and clinical studies as a novel functional renal imaging agent, given the advantages of PET technology and broad tracer availability. AU - Wakabayashi, H. AU - Werner, R. A. AU - Hayakawa, N. AU - Javadi, M. S. AU - Xinyu, C. AU - Herrmann, K. AU - Rowe, S. P. AU - Lapa, C. AU - Higuchi, T. DO - 10.2967/jnumed.116.172718 IS - 10 PY - 2016 TI - Initial Preclinical Evaluation of 18F-Fluorodeoxysorbitol PET as a Novel Functional Renal Imaging Agent T2 - Journal of Nuclear Medicine VL - 57 ER - TY - GEN AB -

Abstract

Background

Bacterial infections are still a major global healthcare problem. To combat the increasing antimicrobial resistance, early diagnosis of bacterial infections—including the identification of bacterial species—is needed to improve antibiotic stewardship and to help reduce the use of broad-spectrum antibiotics. To aid successful targeted antibiotic treatment, specific detection and localisation of infectious organisms is warranted. Nuclear medicine imaging approaches have been successfully used to diagnose bacterial infections and to differentiate between pathogen induced infections and sterile inflammatory processes.

Aim

In this comprehensive review we present an overview of recent developments in radiolabelled bacterial imaging tracers.

Methods

The PubMed/MEDLINE and Embase (OvidSP) literature databases were systematically searched for publications on SPECT and PET on specific imaging of bacterial using specific guidelines with MeSH-terms, truncations, and completion using cross-references. Tracers in literature that was extensively reviewed before 2016 were not included in this update. Where possible, the chemical structure of the radiolabelled compounds and clinical images were shown.

Results

In 219 original articles pre-clinical and clinical imaging of bacterial infection with new tracers were included. In our view, the highest translational potential lies with tracers that are specific to target the pathogens: e.g., 99mTc- and 68Ga-labelled UBI29–41, 99mTc-vancomycin, m-[18F]-fluoro-PABA, [methyl-11C]-D-methionine, [18F]-FDS, [18F]-maltohexaose and [18F]-maltotriose. An encouraging note is that some of these tracers have already been successfully evaluated in clinical settings.

Conclusion

This review summarises updates in tracer development for specific (pre-clinical and clinical) imaging of bacterial infections. We propsed some promising tracers that are likely to become innovative standards in the clinical setting in the near feature.

AU - Welling, Mick M. AU - Hensbergen, Albertus W. AU - Bunschoten, Anton AU - Velders, Aldrik H. AU - Roestenberg, Meta AU - van Leeuwen, Fijs W.B. DO - 10.1007/s40336-019-00317-4 IS - 2 PY - 2019 TI - An update on radiotracer development for molecular imaging of bacterial infections T2 - Clinical and Translational Imaging VL - 7 ER - TY - GEN AB - Humans are virtually identical in their genetic makeup, yet the small differences in our DNA give rise to tremendous phenotypic diversity across the human population. By contrast, the metagenome of the human microbiome—the total DNA content of microbes inhabiting our bodies—is quite a bit more variable, with only a third of its constituent genes found in a majority of healthy individuals. Understanding this variability in the “healthy microbiome” has thus been a major challenge in microbiome research, dating back at least to the 1960s, continuing through the Human Microbiome Project and beyond. Cataloguing the necessary and sufficient sets of microbiome features that support health, and the normal ranges of these features in healthy populations, is an essential first step to identifying and correcting microbial configurations that are implicated in disease. Toward this goal, several population-scale studies have documented the ranges and diversity of both taxonomic compositions and functional potentials normally observed in the microbiomes of healthy populations, along with possible driving factors such as geography, diet, and lifestyle. Here, we review several definitions of a ‘healthy microbiome’ that have emerged, the current understanding of the ranges of healthy microbial diversity, and gaps such as the characterization of molecular function and the development of ecological therapies to be addressed in the future. AU - Lloyd-Price, Jason AU - Abu-Ali, Galeb AU - Huttenhower, Curtis DO - 10.1186/s13073-016-0307-y PY - 2016 SN - 1756-994x TI - The healthy human microbiome T2 - Genome Medicine ER - TY - JOUR AB - Molecular imaging is revolutionizing the way we study the inner workings of the human body, diagnose diseases, approach drug design, and assess therapies. The field as a whole is making possible the visualization of complex biochemical processes involved in normal physiology and disease states, in real time, in living cells, tissues, and intact subjects. In this review, we focus specifically on molecular imaging of intact living subjects. We provide a basic primer for those who are new to molecular imaging, and a resource for those involved in the field. We begin by describing classical molecular imaging techniques together with their key strengths and limitations, after which we introduce some of the latest emerging imaging modalities. We provide an overview of the main classes of molecular imaging agents (i.e., small molecules, peptides, aptamers, engineered proteins, and nanoparticles) and cite examples of how molecular imaging is being applied in oncology, neuroscience, cardiology, gene therapy, cell tracking, and theranostics (therapy combined with diagnostics). A step-by-step guide to answering biological and/or clinical questions using the tools of molecular imaging is also provided. We conclude by discussing the grand challenges of the field, its future directions, and enormous potential for further impacting how we approach research and medicine. AU - James, Michelle L. AU - Gambhir, Sanjiv S. DA - 2012/4// DO - 10.1152/physrev.00049.2010 IS - 2 PY - 2012 SP - 897 EP - 965 TI - A Molecular Imaging Primer: Modalities, Imaging Agents, and Applications T2 - Physiological Reviews UR - http://www.ncbi.nlm.nih.gov/pubmed/22535898 UR - http://www.physiology.org/doi/10.1152/physrev.00049.2010 VL - 92 ER - TY - JOUR AB - The Enterobacteriaceae are a family of rod-shaped Gram-negative bacteria that normally inhabit the gastrointestinal tract and are the most common cause of Gram-negative bacterial infections in humans. In addition to causing serious multidrug-resistant, hospital-acquired infections, a number of Enterobacteriaceae species are also recognized as biothreat pathogens. As a consequence, new tools are urgently needed to specifically identify and localize infections due to Enterobacteriaceae and to monitor antimicrobial efficacy. In this report, we used commercially available 2-[(18)F]-fluorodeoxyglucose ((18)F-FDG) to produce 2-[(18)F]-fluorodeoxysorbitol ((18)F-FDS), a radioactive probe for Enterobacteriaceae, in 30 min. (18)F-FDS selectively accumulated in Enterobacteriaceae, but not in Gram-positive bacteria or healthy mammalian or cancer cells in vitro. In a murine myositis model, (18)F-FDS positron emission tomography (PET) rapidly differentiated true infection from sterile inflammation with a limit of detection of 6.2 ± 0.2 log10 colony-forming units (CFU) for Escherichia coli. Our findings were extended to models of mixed Gram-positive and Gram-negative thigh co-infections, brain infection, Klebsiella pneumonia, and mice undergoing immunosuppressive chemotherapy. This technique rapidly and specifically localized infections due to Enterobacteriaceae, providing a three-dimensional holistic view within the animal. Last, (18)F-FDS PET monitored the efficacy of antimicrobial treatment, demonstrating a PET signal proportionate to the bacterial burden. Therapeutic failures associated with multidrug-resistant, extended-spectrum β-lactamase (ESBL)-producing E. coli infections were detected in real time. Together, these data show that (18)F-FDS is a candidate imaging probe for translation to human clinical cases of known or suspected infections owing to Enterobacteriaceae. AU - Weinstein, E. A. AU - Ordonez, A. A. AU - DeMarco, V. P. AU - Murawski, A. M. AU - Pokkali, S. AU - MacDonald, E. M. AU - Klunk, M. AU - Mease, R. C. AU - Pomper, M. G. AU - Jain, S. K. DO - 10.1126/scitranslmed.3009815 IS - 259 PY - 2014 SN - 1946-6234 SP - 259ra146 EP - 259ra146 TI - Imaging Enterobacteriaceae infection in vivo with 18F-fluorodeoxysorbitol positron emission tomography T2 - Science Translational Medicine VL - 6 ER - TY - JOUR AB - Context: Infection is a major cause of morbidity and mortality in intensive care units (ICUs) worldwide. However, relatively little information is available about the global epidemiology of such infections. Objective: To provide an up-to-date, international picture of the extent and patterns of infection in ICUs. Design, Setting, and Patients: The Extended Prevalence of Infection in Intensive Care (EPIC II) study, a 1-day, prospective, point prevalence study with follow-up conducted on May 8, 2007. Demographic, physiological, bacteriological, therapeutic, and outcome data were collected for 14 414 patients in 1265 participating ICUs from 75 countries on the study day. Analyses focused on the data from the 13 796 adult (>18 years) patients. Results: On the day of the study, 7087 of 13 796 patients (51%) were considered infected; 9084 (71%) were receiving antibiotics. The infection was of respiratory origin in 4503 (64%), and microbiological culture results were positive in 4947 (70%) of the infected patients; 62% of the positive isolates were gram-negative organisms, 47% were gram-positive, and 19% were fungi. Patients who had longer ICU stays prior to the study day had higher rates of infection, especially infections due to resistant staphylococci, Acinetobacter, Pseudomonas species, and Candida species. The ICU mortality rate of infected patients was more than twice that of noninfected patients (25% [1688/6659] vs 11% [682/6352], respectively; P<.001), as was the hospital mortality rate (33% [2201/6659] vs 15% [942/6352], respectively; P<.001) (adjusted odds ratio for risk of hospital mortality, 1.51; 95% confidence interval, 1.36-1.68; P<.001). Conclusions: Infections are common in patients in contemporary ICUs, and risk of infection increases with duration of ICU stay. In this large cohort, infection was independently associated with an increased risk of hospital death. ©2009 American Medical Association. All rights reserved. AU - Vincent, Jean Louis AU - Rello, Jordi AU - Marshall, John AU - Silva, Eliezer AU - Anzueto, Antonio AU - Martin, Claude D AU - Moreno, Rui AU - Lipman, Jeffrey AU - Gomersall, Charles AU - Sakr, Yasser AU - Reinhart, Konrad DO - 10.1001/jama.2009.1754 IS - 21 PY - 2009 SP - 2323 EP - 2329 TI - International study of the prevalence and outcomes of infection in intensive care units T2 - JAMA - Journal of the American Medical Association UR - http://jama.jamanetwork.com/ VL - 302 ER - TY - JOUR AB - Carbapenem-resistant Enterobacteriaceae (CRE) are a serious public health threat. Infections due to these organisms are associated with significant morbidity and mortality. Mechanisms of drug resistance in gram-negative bacteria (GNB) are numerous; β-lactamase genes carried on mobile genetic elements are a key mechanism for the rapid spread of antibiotic-resistant GNB worldwide. Transmissible carbapenem-resistance in Enterobacteriaceae has been recognized for the last 2 decades, but global dissemination of carbapenemase-producing Enterobacteriaceae (CPE) is a more recent problem that, once initiated, has been occurring at an alarming pace. In this article, we discuss the evolution of CRE, with a focus on the epidemiology of the CPE pandemic; review risk factors for colonization and infection with the most common transmissible CPE worldwide, Klebsiella pneumoniae carbapenemase-producing K. pneumoniae; and present strategies used to halt the striking spread of these deadly pathogens. AU - Logan, Latania K. AU - Weinstein, Robert A. DO - 10.1093/infdis/jiw282 IS - 1 KW - Adult KW - Antibacterial agents KW - Carbapenemases KW - Carbapenems KW - Child KW - Drug resistance KW - Enterobacteriaceae infections KW - Epidemiology KW - Global health KW - Gram-negative bacteria PY - 2017 SN - 0022-1899 TI - The epidemiology of Carbapenem-resistant enterobacteriaceae: The impact and evolution of a global menace T2 - Journal of Infectious Diseases VL - 2015 ER - TY - JOUR AU - Fleming A IS - 8 PY - 2001 SP - 780 EP - 790 TI - 1929 On the actibacterial action Penicillium T2 - Bull World Health Organ VL - 79 ER - TY - JOUR AB - The modern patient is increasingly susceptible to bacterial infections including those due to multidrug-resistant organisms (MDROs). Noninvasive whole-body analysis with pathogen-specific imaging technologies can significantly improve patient outcomes by rapidly identifying a source of infection and monitoring the response to treatment, but no such technology exists clinically. Methods: We systematically screened 961 random radiolabeled molecules in silico as substrates for essential metabolic pathways in bacteria, followed by in vitro uptake in representative bacteria-Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, and mycobacteria. Fluorine-labeled analogs, that could be developed as PET-based imaging tracers, were evaluated in a murine myositis model. Results: We identified 3 novel, nontoxic molecules demonstrating selective bacterial uptake: para-Aminobenzoic acid (PABA), with uptake in all representative bacteria including Mycobacterium tuberculosis; mannitol, with selective uptake in S. aureus and E. coli; and sorbitol, accumulating only in E. coli. None accumulated in mammalian cells or heat-killed bacteria, suggesting metabolism-derived specificity. In addition to an extended bacterial panel of laboratory strains, all 3 molecules rapidly accumulated in respective clinical isolates of interest including MDROs such as methicillin-resistant S. aureus, extended-spectrum b-lactamase-producing, and carbapenem-resistant Enterobacteriaceae. In a murine myositis model, fluorine-labeled analogs of all 3 molecules could rapidly detect and differentiate infection sites from sterile inflammation in mice (P 5 0.03). Finally, 2-deoxy-2-[F-18]fluoro-D-sorbitol (18F-FDS) can be easily synthesized from 18F-FDG. PET, with 18F-FDS synthesized using current good manufacturing practice, could rapidly differentiate true infection from sterile inflammation to selectively localize E. coli infection in mice. Conclusion: We have developed a systematic approach that exploits unique biochemical pathways in bacteria to develop novel pathogen-specific imaging tracers. These tracers have significant potential for clinical translation to specifically detect and localize a broad range of bacteria, including MDROs. AU - Ordonez, Alvaro A. AU - Weinstein, Edward A. AU - Bambarger, Lauren E. AU - Saini, Vikram AU - Chang, Yong S. AU - DeMarco, Vincent P. AU - Klunk, Mariah H. AU - Urbanowski, Michael E. AU - Moulton, Kimberly L. AU - Murawski, Allison M. AU - Pokkali, Supriya AU - Kalinda, Alvin S. AU - Jain, Sanjay K. DO - 10.2967/jnumed.116.181792 IS - 1 KW - Bacteria KW - Drug-resistance KW - Imaging KW - PET KW - Translational PY - 2017 SN - 1535-5667 (Electronic)\r0161-5505 (Linking) SP - 144 EP - 150 TI - A systematic approach for developing bacteria-specific imaging tracers T2 - Journal of Nuclear Medicine VL - 58 ER - TY - JOUR AB - Objectives: To evaluate environmental contamination with methotrexate, cyclophosphamide, and ifosfamide in Quebec, Canada, community pharmacies and to describe hazardous drug handling practices in these pharmacies. Methods: Three standardized sites were sampled in each participating community pharmacy. Samples were analyzed for the presence of cyclophosphamide, ifosfamide, and methotrexate by high-performance liquid chromatography tandem mass spectrometry. The limits of detection were 0.10, 0.12, and 0.41 ng/mL for cyclophosphamide, ifosfamide, and methotrexate, respectively. Nine working practices were assessed. Results: 20 community pharmacies participated in the study, and 60 samples were analyzed. No traces of cyclophosphamide or ifosfamide were detected. Traces of methotrexate were found in 12 of 20 pharmacies (60%). Of the 20 pharmacies, 8 (40%) had a storage space reserved for hazardous drugs and none had a preparation area reserved for handling methotrexate tablets. All of the participating community pharmacies had a tablet counter reserved for the handling of hazardous drugs, and all pharmacies cleaned their tablet counter reserved for handling hazardous drugs after use. None of the pharmacies cut or crushed methotrexate tablets. Conclusion: The growing number of hazardous drugs represents a challenge for community pharmacies. Community pharmacists must be made aware of their presence and the need to comply with personal protection measures to reduce staff occupational exposure to hazardous drugs. AU - Merger, Delphine AU - Tanguay, Cynthia AU - Langlois, Éric AU - Lefebvre, Michel AU - Bussières, Jean Franco̧is DO - 10.1331/JAPhA.2013.12245 IS - 4 KW - Community pharmacies KW - Environmental monitoring KW - Methotrexate KW - Occupational exposure PB - Elsevier Masson SAS PY - 2013 SP - 423 EP - 426 TI - Environmental contamination with methotrexate in Canadian community pharmacies T2 - Journal of the American Pharmacists Association UR - http://dx.doi.org/10.1331/JAPhA.2013.12245 VL - 53 ER - TY - JOUR AB - Healthcare associated infections (HAI) are among the major complications of modern medical therapy. The most important HAIs are those related to invasive devices: central line-associated bloodstream infections (CLABSI), catheter-associated urinary tract infections (CAUTI), ventilator-associated pneumonia (VAP) as well as surgical site infections (SSI). HAIs are associated with significant mortality, morbidities and increasing healthcare cost. The cited case-fatality rate ranges from 2.3% to 14.4% depending on the type of infection. In this mini-review, we shed light on these aspects as well as drivers to decrease HAIs. © 2014 King Saud Bin Abdulaziz University for Health Sciences. AU - Al-Tawfiq, Jaffar A. AU - Tambyah, Paul A. DO - 10.1016/j.jiph.2014.04.003 IS - 4 KW - Hand hygiene KW - Healthcare associated infection PB - King Saud Bin Abdulaziz University for Health Sciences PY - 2014 SP - 339 EP - 344 TI - Healthcare associated infections (HAI) perspectives T2 - Journal of Infection and Public Health UR - http://dx.doi.org/10.1016/j.jiph.2014.04.003 VL - 7 ER - TY - JOUR AB - The frequency of antimicrobial resistance has increased globally due to misuse and overuse of antibiotics, and multi-drug resistant (MDR) bacteria are now recognized as a major cause of hospital-acquired infections (HAI). Our aim was to investigate the prevalence, distribution, and antimicrobial susceptibility rates of MDR bacteria in patients with HAI from a tertiary hospital in China. We retrospectively evaluated all patients with a confirmed diagnosis of bacterial infection at a tertiary general hospital in Jining, for the period between January 2012 and December 2014. The following clinical and demographic data were collected: age, sex, specimens, treatment, microbiology results, and antibiotic resistance patterns of isolates. Bacterial identification and susceptibility testing were performed using VITEK 2 COMPACT system. We screened a total of 15,588 patients, out of which 7579 (48.6%) had an HAI. MDR showed 3223 out of 7579 isolates (42.5%). The most frequently isolated MDR bacteria in patients with HAI were extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli (n = 1216/3223, 37.7%), MDR Pseudomonas aeruginosa (n = 627/3223, 19.5%) and MDR Acinetobacter baumannii (n = 588/3223, 18.2%). MDR-HAI were more common in males (2074/3223, 64.4%) and in elderly patients (≥60 years; 1196/3223, 37.1%). Sputum was the main source of MDR isolates (2056/3223, 63.8%). Patients with MDR-HAI were predominantly distributed in different types of intensive care units. MDR strains in our study showed resistance to most current antibiotics. Overall, patients with HAI infections attributed to MDR bacteria were widely distributed in our hospital. Enhanced surveillance of MDR bacteria is critical for guiding the rational use of antibiotics and reducing the incidence of HAI. AU - Wang, Meng AU - Wei, Hongyan AU - Zhao, Yaxin AU - Shang, Linlin AU - Di, Linlin AU - Lyu, Chuanfeng AU - Liu, Jun DO - 10.17305/BJBMS.2018.3826 IS - 1 PY - 2019 TI - Analysis of multidrug-resistant bacteria in 3223 patients with hospital-acquired infections (HAI) from a tertiary general hospital in China T2 - Bosnian Journal of Basic Medical Sciences VL - 19 ER - TY - JOUR AB - Background: Sustainable systematic interventions are important for infection prevention and control (IPC). Data from surveillance of healthcare-associated infections (HAI) provides feedback for implementation of IPC programs. To address the paucity of such data in Asia, we searched for national HAI surveillance and IPC programs in this region. Methods: Data were analysed from open access national surveillance reports of three Asian countries: Taiwan, South Korea and Japan from 2008 to 2015. National IPC programs were identified. Results: There were differences among the countries in surveillance protocols, hospital coverage rates, and national IPC policies and programs. Nevertheless, there was a 53.0% reduction in overall HAI over the 8-year period. This consisted of a decrease from 9.34 to 5.03 infections per 1000 patient-days in Taiwan, from 7.56 to 2.76 in Korea, and from 4.41 to 2.74 in Japan (Poisson regression, all p < 0.05). Across the three countries, Escherichia coli and Candida albicans were the major pathogens for urinary tract infection. Staphylococcus aureus, Acinetobacter baumannii and Enterococcus faecium were common bloodstream pathogens. For pneumonia, S. aureus, A. baumannii, Pseudomonas aeruginosa, and Klebsiella pneumoniae were the predominant pathogens, with considerable country differences. There was a 64.6% decrease in the number of isolates of methicillin-resistant S. aureus, 38.4% decrease in carbapenem-resistant P. aeruginosa and 49.2% decrease in carbapenem-resistant A. baumannii (CRAB) in Taiwan (all p < 0.05), and similarly in Korea with the exception of CRAB (30.5 and 50.4% reduction, respectively, both p < 0.05). Conclusion: We found a significant decrease in HAI across the three countries in association with sequential multifaceted interventions such as hand hygiene, care bundles, and antimicrobial stewardships. Further regional collaboration could be forged to develop joint strategies to prevent HAI. AU - Chiang, Cho Han AU - Pan, Sung Ching AU - Yang, Tyan Shin AU - Matsuda, Keisuke AU - Kim, Hong Bin AU - Choi, Young Hwa AU - Hori, Satoshi AU - Wang, Jann Tay AU - Sheng, Wang Huei AU - Chen, Yee Chun AU - Chang, Feng Yee AU - Chang, Shan Chwen DO - 10.1186/s13756-018-0422-1 IS - 1 KW - Antimicrobial resistance KW - Healthcare-associated infections KW - Infection prevention and control program KW - National policy KW - National surveillance PB - Antimicrobial Resistance & Infection Control PY - 2018 SP - 1 EP - 12 TI - Healthcare-associated infections in intensive care units in Taiwan, South Korea, and Japan: Recent trends based on national surveillance reports T2 - Antimicrobial Resistance and Infection Control VL - 7 ER - TY - JOUR AB - Journal homepage: http://www.ijcmas.com Hospitals and other health care institutions are engaged in essential and intensive efforts to prevent health care associated infections (HAI). HAIs are of particular concern to infection prevention professionals because many of these are caused by rapidly developing strains of multidrug resistant organisms. The preventive aspect of hospital acquired infection (HAI) surveillance is difficult to assess. Experts agree that careful cleaning and disinfection of environmental surfaces are essential elements of effective infection prevention programs. Many different hospital staff is involved in monitoring the minimum levels of hospital infection and should be aware of their role in surveillance. Our aim was to investigate the effect of HAI surveillance on frequently handled surfaces from high risk areas and from wards in a tertiary care new teaching hospital. A prospective study was done for a period of 3 months from Jan-Apr 2017. Active surveillance was done on frequently handled surfaces like front desk, door handle, telephone, monitor, cot railings and patients' bedside tables. About 6 swabs were taken from each of these surfaces in various wards and intensive care units (High risk areas) every week. (i.e. 60 swabs per week). Active surveillance of the study showed Staphylococcus aureus and Klebsiella pneumoniae and aerobic spore bearers in places like front desk, telephone, and injection trolleys which are frequently handled by HCWs and the patients. There is no easy way to keep a hospital clean, though we may claim that it is 100% clean. There is need for a more integrated approach to infection and occupational acquired illness prevention. Removing invisible dirt from today's hospitals and the future ones requires sufficiently trained staff, continuous surveillance of environmental hygiene and bioburden education, constant upgrading of practice and two-way communication between those responsible for cleaning and those responsible for infection control. Staphylococcus aureus and Klebsiella pneumoniae, the common causative agents of hospital acquired infections, present in frequently handled surfaces can be prevented by effective disinfection. Environmental service departments should consider the use of newer disinfectants and no-touch decontamination technologies to improve disinfection of surfaces in health care centres. Regular surface cleaning with 1% hypochlorite helped in prevention of infection in our hospital which was proved in our study, since there was no growth found if surface cleaning was done twice every day in high risk areas, and daily in wards. AU - Subbalakshmi, E. DO - 10.20546/ijcmas.2018.702.108 IS - 2 PY - 2018 TI - Surveillance of Hospital Acquired Infection from Frequently Handled Surfaces in a Tertiary Care Teaching Hospital T2 - International Journal of Current Microbiology and Applied Sciences VL - 7 ER - TY - JOUR AB - Hospital-acquired infections (HAIs), including emerging multi-drug resistant organisms, threaten healthcare systems worldwide. Efficient containment measures of HAIs must mobilize the entire healthcare network. Thus, to best understand how to reduce the potential scale of HAI epidemic spread, we explore patient transfer patterns in the French healthcare system. Using an exhaustive database of all hospital discharge summaries in France in 2014, we construct and analyze three patient networks based on the following: transfers of patients with HAI (HAI-specific network); patients with suspected HAI (suspected-HAI net-work); and all patients (general network). All three networks have heterogeneous patient flow and demonstrate small-world and scale-free characteristics. Patient populations that comprise these networks are also heterogeneous in their movement patterns. Ranking of hospitals by centrality measures and comparing community clustering using community detection algorithms shows that despite the differences in patient population, the HAI-specific and suspected-HAI networks rely on the same underlying structure as that of the general network. As a result, the general network may be more reliable in studying potential spread of HAIs. Finally, we identify transfer patterns at both the French regional and departmental (county) levels that are important in the identification of key hospital centers, patient flow trajectories, and regional clusters that may serve as a basis for novel wide-scale infection control strategies. AU - Nekkab, Narimane AU - Astagneau, Pascal AU - Temime, Laura AU - Crépey, Pascal DO - 10.1371/journal.pcbi.1005666 IS - 8 PY - 2017 SN - 1111111111 TI - Spread of hospital-acquired infections: A comparison of healthcare networks T2 - PLoS Computational Biology VL - 13 ER - TY - JOUR AU - Irene, Wendy AU - Dragan, Tatiana AU - Wrenn, Stephanie DO - 10.1016/j.ijid.2015.06.024 PB - International Society for Infectious Diseases PY - 2015 SN - 7804921500 SP - 129 EP - 134 TI - International Journal of Infectious Diseases Nosocomial Gram-negative bacteremia in intensive care : epidemiology , antimicrobial susceptibilities , and outcomes T2 - International Journal of Infectious Diseases UR - http://dx.doi.org/10.1016/j.ijid.2015.06.024 VL - 37 ER - TY - JOUR AU - Luna, Carlos M AU - Rodriguez-noriega, Eduardo AU - Bavestrello, Luis AU - Guzmán-blanco, Manuel DO - 10.1155/2014/480463 PY - 2014 SP - 1 EP - 12 TI - Gram-Negative Infections in Adult Intensive Care Units of Latin America and the Caribbean T2 - Critical Care Research and Practice VL - 2014 ER - TY - JOUR AB - Bloodstream infection (BSI) is a serious complication of critical illness but it is uncertain whether acquisition of BSI in the intensive care unit (ICU) increases the risk of death. A study was conducted among all Calgary health region (population approximately 1 million) adults admitted to ICUs for 48 h or more during a three-year period to investigate the occurrence, microbiology and risk factors for developing an ICU-acquired BSI and to determine whether these infections independently predict mortality. One hundred and ninety-nine ICU-acquired BSI episodes occurred during 4933 ICU admissions for a cumulative incidence of 4% and an incidence density of 5.4 per 1000 ICU days. The most common isolates were Staphylococcus aureus (18%), coagulase-negative staphylococci (11%), and Enterococcus faecalis (8%); 12% of infections were due to antimicrobial-resistant bacteria. Admission to the regional neurosurgery/trauma ICU [odds ratio (OR) 2.86; 95% confidence interval (CI) 2.10-3.90] and increasing Acute Physiology and Chronic Health Evaluation II (APACHE II) score (OR 1.05 per point, 95% CI 1.03-1.07) were associated with higher risk, whereas a surgical diagnosis (OR 0.69; 95% CI 0.52-0.93) was associated with lower risk of developing ICU-acquired BSI in logistic regression analysis. The crude in-hospital death rate was 45% for patients with ICU-acquired BSI compared with 21% for those without (P < 0.0001) Development of an ICU-acquired BSI was an independent risk factor for death (OR 1.79; 95% CI 1.3-2.5) and increases the risk of dying from critical illness. AU - Laupland, K.B. AU - Kirkpatrick, A.W. AU - Church, D.L. AU - Ross, T. AU - Gregson, D.B. DA - 2004/10// DO - 10.1016/j.jhin.2004.06.007 IS - 2 PY - 2004 SP - 137 EP - 145 TI - Intensive-care-unit-acquired bloodstream infections in a regional critically ill population T2 - Journal of Hospital Infection UR - http://www.ncbi.nlm.nih.gov/pubmed/15474185 UR - http://linkinghub.elsevier.com/retrieve/pii/S0195670104002488 VL - 58 ER - TY - JOUR AB - OBJECTIVE The purpose of this study was to provide a national estimate of the number of healthcare-associated infections (HAI) and deaths in United States hospitals. METHODS No single source of nationally representative data on HAIs is currently available. The authors used a multi-step approach and three data sources. The main source of data was the National Nosocomial Infections Surveillance (NNIS) system, data from 1990-2002, conducted by the Centers for Disease Control and Prevention. Data from the National Hospital Discharge Survey (for 2002) and the American Hospital Association Survey (for 2000) were used to supplement NNIS data. The percentage of patients with an HAI whose death was determined to be caused or associated with the HAI from NNIS data was used to estimate the number of deaths. RESULTS In 2002, the estimated number of HAIs in U.S. hospitals, adjusted to include federal facilities, was approximately 1.7 million: 33,269 HAIs among newborns in high-risk nurseries, 19,059 among newborns in well-baby nurseries, 417,946 among adults and children in ICUs, and 1,266,851 among adults and children outside of ICUs. The estimated deaths associated with HAIs in U.S. hospitals were 98,987: of these, 35,967 were for pneumonia, 30,665 for bloodstream infections, 13,088 for urinary tract infections, 8,205 for surgical site infections, and 11,062 for infections of other sites. CONCLUSION HAIs in hospitals are a significant cause of morbidity and mortality in the United States. The method described for estimating the number of HAIs makes the best use of existing data at the national level. AU - Klevens, R. Monina AU - Edwards, Jonathan R. AU - Richards, Chesley L. AU - Horan, Teresa C. AU - Gaynes, Robert P. AU - Pollock, Daniel A. AU - Cardo, Denise M. DA - 2007/3// DO - 10.1177/003335490712200205 IS - 2 PY - 2007 SP - 160 EP - 166 TI - Estimating Health Care-Associated Infections and Deaths in U.S. Hospitals, 2002 T2 - Public Health Reports UR - http://www.ncbi.nlm.nih.gov/pubmed/17357358 UR - http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC1820440 UR - http://journals.sagepub.com/doi/10.1177/003335490712200205 VL - 122 ER - TY - JOUR AU - Chelazzi, Cosimo AU - Pettini, Eleonora AU - Villa, Gianluca AU - Gaudio, A Raffaele De DO - 10.1186/s12871-015-0106-9 PB - BMC Anesthesiology PY - 2015 SP - 1 EP - 7 TI - Epidemiology , associated factors and outcomes of ICU-acquired infections caused by Gram-negative bacteria in critically ill patients : an observational , retrospective study T2 - BMC Anesthesiology UR - http://dx.doi.org/10.1186/s12871-015-0106-9 ER - TY - JOUR AU - Maria, Ricarda KW - agriculture KW - biocides KW - disinfection KW - epidemiology KW - infection control KW - measures KW - multidrug-resistant gram-negative bacteria KW - reservoirs KW - resistance patterns KW - surveillance KW - therapy PY - 2017 SP - 1 EP - 24 TI - Antibiotic resistance : What is so special about multidrug-resistant Gram-negative bacteria ? Antibiotikaresistenz : Was ist so besonders an den Gram-negativen T2 - GMS Hygiene and Infection Control VL - 12 ER - TY - GEN AB -

This review summarizes recent epidemiology of Gram-negative infections in selected countries from Latin American and Caribbean adult intensive care units (ICUs). A systematic search of the biomedical literature (PubMed) was performed to identify articles published over the last decade. Where appropriate, data also were collected from the reference list of published articles, health departments of specific countries, and registries. Independent cohort data from all countries (Argentina, Brazil, Chile, Colombia, Cuba, Mexico, Trinidad and Tobago, and Venezuela) signified a high rate of ICU infections (prevalence: Argentina, 24%; Brazil, 57%). Gram-negative pathogens, predominantly Acinetobacter baumannii, Klebsiella pneumoniae, Pseudomonas aeruginosa , and Escherichia coli , accounted for > 50% of ICU infections, which were often complicated by the presence of multidrug-resistant strains and clonal outbreaks. Empirical use of antimicrobial agents was identified as a strong risk factor for resistance development and excessive mortality. Infection control strategies utilizing hygiene measures and antimicrobial stewardship programs reduced the rate of device-associated infections. To mitigate the poor health outcomes associated with infections by multidrug-resistant Gram-negative bacteria, urgent focus must be placed on infection control strategies and local surveillance programs.

AU - Luna, Carlos M. AU - Rodriguez-Noriega, Eduardo AU - Bavestrello, Luis AU - Guzmán-Blanco, Manuel DO - 10.1155/2014/480463 PY - 2014 TI - Gram-negative infections in adult intensive care units of latin america and the caribbean T2 - Critical Care Research and Practice ER - TY - JOUR AB - Objectives: To describe the epidemiology, antimicrobial susceptibilities, treatment, and outcomes of intensive care unit (ICU)-acquired Gram-negative bacteremia. Methods: Patients with ICU-acquired Gram-negative bacteremia from 2004 to 2012 were reviewed retrospectively. Independent predictors of mortality were examined using multivariable Cox regression. Results: Seventy-eight cases of ICU-acquired Gram-negative bacteremia occurred in 74 patients. The infection rate was 0.97/1000 patient-days. Mean patient age was 55 years, 62% were male. The most common admission diagnoses were respiratory failure (34%) and sepsis/septic shock (45%). Mortality was 35% at 30 days. The most common source of bacteremia was pneumonia (33%). Of 83 Gram-negative isolates, Escherichia coli (20%) and Pseudomonas aeruginosa (18%) were most common. For aerobic isolates, susceptibilities to ciprofloxacin (61%) and piperacillin/tazobactam (68%) were low. For pseudomonal isolates, susceptibilities to ciprofloxacin (53%), piperacillin/tazobactam (67%), and imipenem (53%) were equally disappointing. Adequate empiric antimicrobial therapy was prescribed in 85% of bacteremia cases. On multivariable analysis, adequate empiric therapy (adjusted hazard ratio (aHR) 0.38, 95% confidence interval (CI) 0.16-0.89), immune suppression (aHR 3.4, 95% CI 1.4-8.3), and coronary artery disease (aHR 4.5, 95% CI 1.7-11.9) were independently associated with 30-day mortality. Conclusions: ICU-acquired Gram-negative bacteremia is associated with high mortality. Resistance to ciprofloxacin, piperacillin/tazobactam, and carbapenems was common. Coronary artery disease, immune suppression, and inadequate empiric antimicrobial therapy were independently associated with increased mortality. AU - Sligl, Wendy Irene AU - Dragan, Tatiana AU - Smith, Stephanie Wrenn DO - 10.1016/j.ijid.2015.06.024 KW - Antimicrobial resistance KW - Bacteremia KW - Critical care KW - Gram-negative KW - Intensive care KW - Nosocomial infection PY - 2015 SN - 1878-3511; 1201-9712 TI - Nosocomial Gram-negative bacteremia in intensive care: Epidemiology, antimicrobial susceptibilities, and outcomes T2 - International Journal of Infectious Diseases ER - TY - JOUR AB - Background: Gram-negative bacteria are increasingly responsible for nosocomial infections, including ICU-acquired infections. Due to high virulence, rate of multi-drug resistance and limited availability of new agents, these infections create cumbersome clinical burdens, making it important to reduce the risk of their occurrence. The aim of the study was to assess epidemiology-related factors and outcomes of Gram-negative, ICU-acquired infections in a cohort of medical-surgical patients. Methods: A retrospective survey was conducted on all patients admitted to a mixed ICU from January 2012 to December 2013. 'ICU-acquired infections' were defined as new infections acquired no less than 48h after ICU admission. Diagnosis was made according to the Centers for Disease Control and Prevention National Healthcare Safety Network (CDC/NHSN) criteria. Differences across patients who did and did not acquire a Gram-negative infection were tested regarding age, sex, body mass index, medical or surgical admission, cardiovascular comorbidities, chronic obstructive pulmonary disease, diabetes, end-stage renal failure, co-existing tumours and prophylactic anti-fungal treatment. Multivariate analysis was used to assess the independency of these associations. Finally, differences in ICU-mortality, ICU-length of stay and duration of mechanical ventilation were tested across patients with and without new, ICU-acquired, Gram-negative infections. Results: Of 494 patients admitted to the ICU, 46 (9.3%) acquired an infection 48 or more hours after admittance. In 30/46 patients (65.2%) the isolated bacterium was Gram-negative. Univariate analysis showed that clinical factors associated with new ICU-acquired Gram-negative infections were medical admission (p < 0.001, 95% CI 0.59 - 0.29, OR = 0.13), chronic kidney disease (p = 0.018, 95% CI 1.20 - 7.34, OR = 2.98) and prophylactic antifungal therapy (p < 0.001, 95% CI 1.91 - 9.79, OR = 4.33). At multivariate analysis, only medical admission and prophylactic antifungal therapy were significantly associated with ICU-acquired Gram-negative infections. Higher ICU-length of stay and longer duration of mechanical ventilation were associated with these infections while ICU-mortality did not significantly differ. Conclusions: ICU-acquired Gram-negative infections were common in a cohort of mixed medical-surgical patients. Only medical admission and anti-fungal prophylaxis were found to be independently associated with these infections; they were not found to have a significant effect on ICU-mortality. AU - Chelazzi, Cosimo AU - Pettini, Eleonora AU - Villa, Gianluca AU - De Gaudio, A. Raffaele DO - 10.1186/s12871-015-0106-9 PY - 2015 SN - 1471-2253 TI - Epidemiology, associated factors and outcomes of ICU-acquired infections caused by Gram-negative bacteria in critically ill patients: An observational, retrospective study T2 - BMC Anesthesiology ER - TY - JOUR AB - In 2014, a total of 2,976 Enterobacteriaceae isolates with decreased susceptibility to carbapenems were received at the French Associated National Reference Center for Antibiotic Resistance (NRC) and were char-acterised for their molecular resistance mechanism to carbapenems and compared with results obtained during 2012 and 2013.The overall number of entero-bacterial isolates with decreased susceptibility to carbapenems received at the NRC rapidly increased (more than twofold in two years) with a growing pro-portion of carbapenemase producers (23.1% in 2012 vs 28.6% in 2013 vs 36.2% in 2014). Between 2012 and 2014, the main carbapenemase type was OXA-48, with an increase in OXA-48 variants (mostly OXA-181) and NDM producers, whereas the number KPC producers decreased. We identified a potential spread of OXA-181 producers in the tropical region of Africa. Finally, OXA-48 and OXA-48-related enzymes remained the predominant carbapenemases in France. The number of carbapenemase-producing Escherischia coli iso-lates was multiplied by fivefold between 2012 and 2014, suggesting a possible dissemination in the community. AU - Dortet, Laurent AU - Cuzon, G. AU - Ponties, V. AU - Nordmann, P. DO - 10.2807/1560-7917.ES.2017.22.6.30461 IS - 6 PY - 2017 SP - 30461 EP - 30461 TI - Trends in carbapenemase-producing Enterobacteriaceae, France, 2012 to 2014 T2 - Eurosurveillance VL - 22 ER - TY - JOUR AB - Health-care-associated infection is the most frequent result of unsafe patient care worldwide, but few data are available from the developing world. We aimed to assess the epidemiology of endemic health-care-associated infection in developing countries. We searched electronic databases and reference lists of relevant papers for articles published 1995-2008. Studies containing full or partial data from developing countries related to infection prevalence or incidence - including overall health-care-associated infection and major infection sites, and their microbiological cause - were selected. We classified studies as low-quality or high-quality according to predefined criteria. Data were pooled for analysis. Of 271 selected articles, 220 were included in the final analysis. Limited data were retrieved from some regions and many countries were not represented. 118 (54) studies were low quality. In general, infection frequencies reported in high-quality studies were greater than those from low-quality studies. Prevalence of health-care-associated infection (pooled prevalence in high-quality studies, 15·5 per 100 patients [95 CI 12·6-18·9]) was much higher than proportions reported from Europe and the USA. Pooled overall health-care-associated infection density in adult intensive-care units was 47·9 per 1000 patient-days (95 CI 36·7-59·1), at least three times as high as densities reported from the USA. Surgical-site infection was the leading infection in hospitals (pooled cumulative incidence 5·6 per 100 surgical procedures), strikingly higher than proportions recorded in developed countries. Gram-negative bacilli represented the most common nosocomial isolates. Apart from meticillin resistance, noted in 158 of 290 (54) Staphylococcus aureus isolates (in eight studies), very few articles reported antimicrobial resistance. The burden of health-care-associated infection in developing countries is high. Our findings indicate a need to improve surveillance and infection-control practices. World Health Organization. © 2011 Elsevier Ltd. AU - Allegranzi, Benedetta AU - Nejad, Sepideh Bagheri AU - Combescure, Christophe AU - Graafmans, Wilco AU - Attar, Homa AU - Donaldson, Liam AU - Pittet, Didier DO - 10.1016/S0140-6736(10)61458-4 IS - 9761 PB - Elsevier Ltd PY - 2011 SP - 228 EP - 241 TI - Burden of endemic health-care-associated infection in developing countries: Systematic review and meta-analysis T2 - The Lancet UR - http://dx.doi.org/10.1016/S0140-6736(10)61458-4 VL - 377 ER - TY - JOUR AB - PURPOSE Infective endocarditis (IE) is widely underdiagnosed or diagnosed after a major delay. The diagnosis is currently based on the modified DUKE criteria, where the only validated imaging technique is echocardiography, and remains challenging especially in patients with an implantable cardiac device. The aim of this study was to assess the incremental diagnostic role of (18)F-FDG PET/CT in patients with an implanted cardiac device and suspected IE. METHODS We prospectively analysed 27 consecutive patients with an implantable device evaluated for suspected device-related IE between January 2011 and June 2013. The diagnostic probability of IE was defined at presentation according to the modified DUKE criteria. PET/CT was performed as soon as possible following the clinical suspicion of IE. Patients then underwent medical or surgical treatment based on the overall clinical evaluation. During follow-up, we considered: lead cultures in patients who underwent extraction, direct inspection and lead cultures in those who underwent surgery, and a clinical/instrumental reevaluation after at least 6 months in patients who received antimicrobial treatment or had an alternative diagnosis and were not treated for IE. After the follow-up period, the diagnosis was systematically reviewed by the multidisciplinary team using the modified DUKE criteria and considering the new findings. RESULTS Among the ten patients with a positive PET/CT scan, seven received a final diagnosis of "definite IE", one of "possible IE" and two of "IE rejected". Among the 17 patients with a negative PET/CT scan, four were false-negative and received a final diagnosis of definite IE. These patients underwent PET/CT after having started antibiotic therapy (≥48 h) or had a technically suboptimal examination. CONCLUSION In patients with a cardiac device, PET/CT increases the diagnostic accuracy of the modified Duke criteria for IE, particularly in the subset of patients with possible IE in whom it may help the clinician manage a challenging situation. AU - Graziosi, Maddalena AU - Nanni, Cristina AU - Lorenzini, Massimiliano AU - Diemberger, Igor AU - Bonfiglioli, Rachele AU - Pasquale, Ferdinando AU - Ziacchi, Matteo AU - Biffi, Mauro AU - Martignani, Cristian AU - Bartoletti, Michele AU - Tumietto, Fabio AU - Boriani, Giuseppe AU - Viale, Pier Luigi AU - Fanti, Stefano AU - Rapezzi, Claudio DA - 2014/8// DO - 10.1007/s00259-014-2773-z IS - 8 PY - 2014 SP - 1617 EP - 1623 TI - Role of 18F-FDG PET/CT in the diagnosis of infective endocarditis in patients with an implanted cardiac device: a prospective study T2 - European Journal of Nuclear Medicine and Molecular Imaging UR - http://www.ncbi.nlm.nih.gov/pubmed/24802193 UR - http://link.springer.com/10.1007/s00259-014-2773-z VL - 41 ER - TY - JOUR AB - Nosocomial infections are also known as hospital-acquired/associated infections. National Healthcare Safety Network along with Centers for Disease Control for surveillance has classified nosocomial infection sites into 13 types with 50 infection sites, which are specific on the basis of biological and clinical criteria. The agents that are usually involved in hospital-acquired infections include Streptococcus spp., Acinetobacter spp., enterococci, Pseudomonas aeruginosa, coagulase-negative staphylococci, Staphylococcus aureus, Bacillus cereus, Legionella and Enterobacteriaceae family members, namely, Proteus mirablis, Klebsiella pneumonia, Escherichia coli, Serratia marcescens. Nosocomial pathogens can be transmitted through person to person, environment or contaminated water and food, infected individuals, contaminated healthcare personnel's skin or contact via shared items and surfaces. Mainly, multi-drug-resistant nosocomial organisms include methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci, Pseudomonas aeruginosa and Klebsiella pneumonia, whereas Clostridium difficile shows natural resistance. Excessive and improper use of broad-spectrum antibiotics, especially in healthcare settings, is elevating nosocomial infections, which not only becomes a big health care problem but also causes great economic and production loss in the community. Nosocomial infections can be controlled by measuring and comparing the infection rates within healthcare settings and sticking to the best healthcare practices. Centers for Disease Control and Prevention provides the methodology for surveillance of nosocomial infections along with investigation of major outbreaks. By means of this surveillance, hospitals can devise a strategy comprising of infection control practices. AU - Khan, Hassan Ahmed AU - Ahmad, Aftab AU - Mehboob, Riffat DO - 10.1016/j.apjtb.2015.05.001 IS - 7 KW - Antibiotics KW - Control strategies KW - Hospital-acquired infection KW - Surveillance PB - Elsevier PY - 2015 SP - 509 EP - 514 TI - Nosocomial infections and their control strategies T2 - Asian Pacific Journal of Tropical Biomedicine UR - http://dx.doi.org/10.1016/j.apjtb.2015.05.001 VL - 5 ER - TY - GEN AU - John E. Bennett & Raphael Dolin & Martin J. Blaser PY - 2010 SP - 2815 EP - 2833 TI - Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases - 9781455748013 | US Elsevier Health Bookshop T2 - Elsevier Inc UR - https://www.us.elsevierhealth.com/mandell-douglas-and-bennetts-principles-and-practice-of-infectious-diseases-9781455748013.html ER - TY - JOUR AU - Maria, Ricarda KW - agriculture KW - biocides KW - disinfection KW - epidemiology KW - infection control KW - measures KW - multidrug-resistant gram-negative bacteria KW - reservoirs KW - resistance patterns KW - surveillance KW - therapy PY - 2017 SP - 1 EP - 24 TI - Antibiotic resistance : What is so special about multidrug-resistant Gram-negative bacteria ? Antibiotikaresistenz : Was ist so besonders an den Gram-negativen T2 - GMS Hygiene and Infection Control VL - 12 ER - TY - JOUR AB - Objectives: To describe the epidemiology, antimicrobial susceptibilities, treatment, and outcomes of intensive care unit (ICU)-acquired Gram-negative bacteremia. Methods: Patients with ICU-acquired Gram-negative bacteremia from 2004 to 2012 were reviewed retrospectively. Independent predictors of mortality were examined using multivariable Cox regression. Results: Seventy-eight cases of ICU-acquired Gram-negative bacteremia occurred in 74 patients. The infection rate was 0.97/1000 patient-days. Mean patient age was 55 years, 62% were male. The most common admission diagnoses were respiratory failure (34%) and sepsis/septic shock (45%). Mortality was 35% at 30 days. The most common source of bacteremia was pneumonia (33%). Of 83 Gram-negative isolates, Escherichia coli (20%) and Pseudomonas aeruginosa (18%) were most common. For aerobic isolates, susceptibilities to ciprofloxacin (61%) and piperacillin/tazobactam (68%) were low. For pseudomonal isolates, susceptibilities to ciprofloxacin (53%), piperacillin/tazobactam (67%), and imipenem (53%) were equally disappointing. Adequate empiric antimicrobial therapy was prescribed in 85% of bacteremia cases. On multivariable analysis, adequate empiric therapy (adjusted hazard ratio (aHR) 0.38, 95% confidence interval (CI) 0.16-0.89), immune suppression (aHR 3.4, 95% CI 1.4-8.3), and coronary artery disease (aHR 4.5, 95% CI 1.7-11.9) were independently associated with 30-day mortality. Conclusions: ICU-acquired Gram-negative bacteremia is associated with high mortality. Resistance to ciprofloxacin, piperacillin/tazobactam, and carbapenems was common. Coronary artery disease, immune suppression, and inadequate empiric antimicrobial therapy were independently associated with increased mortality. AU - Sligl, Wendy Irene AU - Dragan, Tatiana AU - Smith, Stephanie Wrenn DO - 10.1016/j.ijid.2015.06.024 KW - Antimicrobial resistance KW - Bacteremia KW - Critical care KW - Gram-negative KW - Intensive care KW - Nosocomial infection PY - 2015 SN - 1878-3511; 1201-9712 TI - Nosocomial Gram-negative bacteremia in intensive care: Epidemiology, antimicrobial susceptibilities, and outcomes T2 - International Journal of Infectious Diseases ER - TY - GEN AU - Ibrahim Abudakar, Ted Cohen, Helen R. Stagg, Laura C. Rodrigues PY - 2016 SP - 1 EP - 371 TI - Infectious Disease Epidemiology - Google Books T2 - OXFORD UNIVERSITY PRESS UR - https://books.google.com.co/books?id=0N8mDAAAQBAJ&pg=PA304&lpg=PA304&dq=Clostridium+difficile+(12.1%25),+Staphylococcus+aureus+(10.7%25)+y+Pseudomona+aeruginosa&source=bl&ots=XuHmmvF8ff&sig=agVCmaw32OE3RxhPPK0jp09584U&hl=es-419&sa=X&ved=2ahUKEwiTk6G5ioreA ER - TY - JOUR AB - Bloodstream infection (BSI) is a serious complication of critical illness but it is uncertain whether acquisition of BSI in the intensive care unit (ICU) increases the risk of death. A study was conducted among all Calgary health region (population approximately 1 million) adults admitted to ICUs for 48 h or more during a three-year period to investigate the occurrence, microbiology and risk factors for developing an ICU-acquired BSI and to determine whether these infections independently predict mortality. One hundred and ninety-nine ICU-acquired BSI episodes occurred during 4933 ICU admissions for a cumulative incidence of 4% and an incidence density of 5.4 per 1000 ICU days. The most common isolates were Staphylococcus aureus (18%), coagulase-negative staphylococci (11%), and Enterococcus faecalis (8%); 12% of infections were due to antimicrobial-resistant bacteria. Admission to the regional neurosurgery/trauma ICU [odds ratio (OR) 2.86; 95% confidence interval (CI) 2.10-3.90] and increasing Acute Physiology and Chronic Health Evaluation II (APACHE II) score (OR 1.05 per point, 95% CI 1.03-1.07) were associated with higher risk, whereas a surgical diagnosis (OR 0.69; 95% CI 0.52-0.93) was associated with lower risk of developing ICU-acquired BSI in logistic regression analysis. The crude in-hospital death rate was 45% for patients with ICU-acquired BSI compared with 21% for those without (P < 0.0001) Development of an ICU-acquired BSI was an independent risk factor for death (OR 1.79; 95% CI 1.3-2.5) and increases the risk of dying from critical illness. AU - Laupland, K.B. AU - Kirkpatrick, A.W. AU - Church, D.L. AU - Ross, T. AU - Gregson, D.B. DA - 2004/10// DO - 10.1016/j.jhin.2004.06.007 IS - 2 PY - 2004 SP - 137 EP - 145 TI - Intensive-care-unit-acquired bloodstream infections in a regional critically ill population T2 - Journal of Hospital Infection UR - http://www.ncbi.nlm.nih.gov/pubmed/15474185 UR - http://linkinghub.elsevier.com/retrieve/pii/S0195670104002488 VL - 58 ER - TY - JOUR AU - Fisman, David AU - Patrozou, Eleni AU - Carmeli, Yehuda AU - Perencevich, Eli AU - Tuite, Ashleigh R AU - Mermel, Leonard A AU - Group, Bacteremia Study DO - 10.1371/journal.pone.0114548 IS - 12 PY - 2014 SP - 1 EP - 18 TI - Geographical Variability in the Likelihood of Bloodstream Infections Due to Gram- Negative Bacteria : Correlation with Proximity to the Equator and Health Care Expenditure T2 - PLoS Genetics VL - 9 ER - TY - RPRT PY - 2000 SN - 9241562021 TI - Global Water Supply and Sanitation Assessment 2000 Report ER - TY - JOUR AB - FDG-PET, combined with CT, is nowadays getting more and more relevant for the diagnosis of several infectious and inflammatory diseases and particularly for therapy monitoring. Thus, this paper gives special attention to the role of FDG-PET/CT in the diagnosis and therapy monitoring of infectious and inflammatory diseases. Enough evidence in the literature already exists about the usefulness of FDG-PET/CT in the diagnosis, management, and followup of patients with sarcoidosis, spondylodiscitis, and vasculitis. For other diseases, such as inflammatory bowel diseases, rheumatoid arthritis, autoimmune pancreatitis, and fungal infections, hard evidence is lacking, but studies also point out that FDG-PET/CT could be useful. It is of invaluable importance to have large prospective multicenter studies in this field to provide clear answers, not only for the status of nuclear medicine in general but also to reduce high costs of treatment. AU - Glaudemans, Andor W.J.M. AU - De Vries, Erik F.J. AU - Galli, Filippo AU - Dierckx, Rudi A.J.O. AU - Slart, Riemer H.J.A. AU - Signore, Alberto DO - 10.1155/2013/623036 PY - 2013 SN - 1740-2522 TI - The use of 18 F-FDG-PET/CT for diagnosis and treatment monitoring of inflammatory and infectious diseases T2 - Clinical and Developmental Immunology ER - TY - JOUR AB - In 2014, a total of 2,976 Enterobacteriaceae isolates with decreased susceptibility to carbapenems were received at the French Associated National Reference Center for Antibiotic Resistance (NRC) and were char-acterised for their molecular resistance mechanism to carbapenems and compared with results obtained during 2012 and 2013.The overall number of entero-bacterial isolates with decreased susceptibility to carbapenems received at the NRC rapidly increased (more than twofold in two years) with a growing pro-portion of carbapenemase producers (23.1% in 2012 vs 28.6% in 2013 vs 36.2% in 2014). Between 2012 and 2014, the main carbapenemase type was OXA-48, with an increase in OXA-48 variants (mostly OXA-181) and NDM producers, whereas the number KPC producers decreased. We identified a potential spread of OXA-181 producers in the tropical region of Africa. Finally, OXA-48 and OXA-48-related enzymes remained the predominant carbapenemases in France. The number of carbapenemase-producing Escherischia coli iso-lates was multiplied by fivefold between 2012 and 2014, suggesting a possible dissemination in the community. AU - Dortet, Laurent AU - Cuzon, G. AU - Ponties, V. AU - Nordmann, P. DO - 10.2807/1560-7917.ES.2017.22.6.30461 IS - 6 PY - 2017 SP - 30461 EP - 30461 TI - Trends in carbapenemase-producing Enterobacteriaceae, France, 2012 to 2014 T2 - Eurosurveillance VL - 22 ER - TY - JOUR AB - STUDY OBJECTIVE To evaluate the relationship between inadequate antimicrobial treatment of infections (both community-acquired and nosocomial infections) and hospital mortality for patients requiring ICU admission. DESIGN Prospective cohort study. SETTING Barnes-Jewish Hospital, a university-affiliated urban teaching hospital. PATIENTS Two thousand consecutive patients requiring admission to the medical or surgical ICU. INTERVENTIONS Prospective patient surveillance and data collection. MEASUREMENTS AND RESULTS One hundred sixty-nine (8.5%) infected patients received inadequate antimicrobial treatment of their infections. This represented 25.8% of the 655 patients assessed to have either community-acquired or nosocomial infections. The occurrence of inadequate antimicrobial treatment of infection was most common among patients with nosocomial infections, which developed after treatment of a community-acquired infection (45.2%), followed by patients with nosocomial infections alone (34.3%) and patients with community-acquired infections alone (17.1%) (p < 0.001). Multiple logistic regression analysis, using only the cohort of infected patients (n = 655), demonstrated that the prior administration of antibiotics (adjusted odds ratio [OR], 3.39; 95% confidence interval [CI], 2.88 to 4.23; p < 0.001), presence of a bloodstream infection (adjusted OR, 1.88; 95% CI, 1.52 to 2.32; p = 0.003), increasing acute physiology and chronic health evaluation (APACHE) II scores (adjusted OR, 1.04; 95% CI, 1.03 to 1.05; p = 0.002), and decreasing patient age (adjusted OR, 1.01; 95% CI, 1.01 to 1.02; p = 0.012) were independently associated with the administration of inadequate antimicrobial treatment. The hospital mortality rate of infected patients receiving inadequate antimicrobial treatment (52.1%) was statistically greater than the hospital mortality rate of the remaining patients in the cohort (n = 1,831) without this risk factor (12.2%) (relative risk [RR], 4.26; 95% CI, 3.52 to 5.15; p < 0.001). Similarly, the infection-related mortality rate for infected patients receiving inadequate antimicrobial treatment (42.0%) was significantly greater than the infection-related mortality rate of infected patients receiving adequate antimicrobial treatment (17.7%) (RR, 2.37; 95% CI, 1.83 to 3.08; p < 0.001). Using a logistic regression model, inadequate antimicrobial treatment of infection was found to be the most important independent determinant of hospital mortality for the entire patient cohort (adjusted OR, 4.27; 95% CI, 3.35 to 5.44; p < 0.001). The other identified independent determinants of hospital mortality included the number of acquired organ system derangements, use of vasopressor agents, the presence of an underlying malignancy, increasing APACHE II scores, increasing age, and having a nonsurgical diagnosis at the time of ICU admission. CONCLUSIONS Inadequate treatment of infections among patients requiring ICU admission appears to be an important determinant of hospital mortality. These data suggest that clinical efforts aimed at reducing the occurrence of inadequate antimicrobial treatment could improve the outcomes of critically ill patients. Additionally, prior antimicrobial therapy should be recognized as an important risk factor for the administration of inadequate antimicrobial treatment among ICU patients with clinically suspected infections. AU - Kollef, M H AU - Sherman, G AU - Ward, S AU - Fraser, V J DA - 1999/2// IS - 2 PY - 1999 SP - 462 EP - 74 TI - Inadequate antimicrobial treatment of infections: a risk factor for hospital mortality among critically ill patients. T2 - Chest UR - http://www.ncbi.nlm.nih.gov/pubmed/10027448 VL - 115 ER - TY - JOUR AB - Metabolic imaging has come to occupy a prominent place in the diagnosis and management of microbial infection. Molecular probes available for infection imaging have undergone a rapid evolution starting with nonspecific agents that accumulate similarly in infection, sterile inflammation, and neoplastic tissue and then extending to more targeted probes that seek to identify specific microbial species. This focus review describes the metabolic and molecular imaging techniques currently available for clinical use in infection imaging and those that have demonstrated promising results in preclinical studies with the potential for clinical applications. AU - Lawal, Ismaheel AU - Zeevaart, Jan Rijn AU - Ebenhan, Thomas AU - Ankrah, Alfred AU - Vorster, Mariza AU - Kruger, Hendrick AU - Govender, Thavendran AU - Sathekge, Mike DO - 10.2967/jnumed.117.191635 PY - 2017 SN - 0161-5505 TI - Metabolic Imaging of Infection T2 - Journal of Nuclear Medicine ER - TY - JOUR AB - The carbohydrate specificity of the two enzymes that catalyze the metabolic interconversions in the sorbitol pathway, aldose reductase and sorbitol dehydrogenase, has been examined through the use of fluoro- and deoxy-substrate analogs. Hydrogen bonding has been shown to be the primary mode of interaction by which these enzymes specifically recognize and bind their respective polyol substrates. Aldose reductase has broad substrate specificity, and all of the fluoro- and deoxysugars that were examined are substrates for this enzyme. Unexpectedly, both 3-fluoro- and 4-fluoro-d-glucose were found to be better substrates, with significantly lower K(m) and higher k(cat)/K(m) values than those of D-glucose. A more discriminating pattern of substrate specificity is observed for sorbitol dehydrogenase. Neither the 2-fluoro nor the 2-deoxy analogs of D-glucitol were found to be substrates or inhibitors, suggesting that the 2-hydroxyl group of sorbitol is a hydrogen bond donor. The 4-fluoro and 4-deoxy analogs are poorer substrates than sorbitol, also implying a binding role for this hydroxyl group. In contrast, both 6-fluoro- and 6-deoxy-D-glucitol are very good substrates for sorbitol dehydrogenase, indicating that the primary hydroxyl group at this position is not involved in substrate recognition by this enzyme. Copyright (C) 1998 Elsevier Science Ltd. AU - Scott, Mary Ellen AU - Viola, Ronald E. DO - 10.1016/S0008-6215(98)00266-3 KW - Aldose reductase KW - Deoxy sugars KW - Fluoro sugars KW - Sorbitol dehydrogenase KW - Sorbitol pathway KW - Substrate specificity PY - 1998 SN - 0008-6215 TI - The use of fluoro- and deoxy-substrate analogs to examine binding specificity and catalysis in the enzymes of the sorbitol pathway T2 - Carbohydrate Research ER - TY - JOUR AB - Inflammatory and infectious diseases are a heterogeneous class of diseases that may be divided into infections, acute inflammation and chronic inflammation. Radiological imaging techniques have, with the exception of functional MRI, high sensitivity but lack in specificity. Nuclear medicine techniques, by contrast, allow the in vivo detection in humans of different physiologic and pathologic phenomena and offer noninvasive tools to detect early pathophysiological changes before anatomical changes occur. In this review, we highlight the role of nuclear medicine in inflammation/infection with emphasis on molecular imaging for in vivo histological characterization of affected tissues for diagnostic purposes and follow-up of therapies. We also describe the clinical indications of all available radiopharmaceuticals in the light of the newly available guidelines. AU - Signore, Alberto AU - Glaudemans, Andor W J M DA - 2011/12// DO - 10.1007/s12149-011-0521-z IS - 10 PY - 2011 SP - 681 EP - 700 TI - The molecular imaging approach to image infections and inflammation by nuclear medicine techniques. T2 - Annals of nuclear medicine UR - http://link.springer.com/10.1007/s12149-011-0521-z UR - http://www.ncbi.nlm.nih.gov/pubmed/21837469 VL - 25 ER - TY - RPRT AB - The human endogenous intestinal microflora is an essential "organ" in providing nourishment, regulating epithelial development, and instructing innate immunity; yet, surprisingly, basic features remain poorly described. We examined 13,355 prokaryotic ribosomal RNA gene sequences from multiple colonic mucosal sites and feces of healthy subjects to improve our understanding of gut microbial diversity. A majority of the bacterial sequences corresponded to uncultivated species and novel microorganisms. We discovered significant intersubject variability and differences between stool and mucosa community composition. Characterization of this immensely diverse ecosystem is the first step in elucidating its role in health and disease. AU - Eckburg, Paul B AU - Bik, Elisabeth M AU - Bernstein, Charles N AU - Purdom, Elizabeth AU - Dethlefsen, Les AU - Sargent, Michael AU - Gill, Steven R AU - Nelson, Karen E AU - Relman, David A TI - Diversity of the Human Intestinal Microbial Flora UR - www.sciencemag.org/cgi/content/full/1110591/DC1 ER - TY - GEN AB - This review article covers a concise account on fludeoxyglucose (18F–FDG) synthesis and quality control procedures with emphasis on practical synthesis Currently, 18F–FDG is the most successful PET radiopharmaceutical so far. The advancement in synthesis and quality control of 18F–FDG, together with its approval by the US FDA and the availability of reimbursement, are probably the main reasons for the flourish of clinical PET over the last 20 years. 18F–FDG can be synthesised by either electrophilic fluorination or nucleophilic fluorination reaction. Nucleophilic fluorination using mannose triflate as precursor and Kryptofix or tetrabutylammonium salts (TBA) is widely used because of higher yield and shorter reaction time. The quality control requirements of 18F–FDG can be found in United States Pharmacopeia (USP), British Pharmacopeia (BP), European Pharmacopeia (EP) and the Chemistry, Manufacturing, and Controls (CMC) section from United States Food and Drug Administration (US FDA) PET draft guidance documents. Basic requirements include radionuclidic identity, radiochemical purity, chemical purity, pH, residual solvent, sterility, and bacterial endotoxin level. Some of these tests (sterility, endotoxins and radionuclidic purity) can be finished after the 18F–FDG has been released. Although USP, BP and EP do not require filter membrane integrity test, many laboratories perform this test as an indirect evident of the product sterility. It is also interesting to note that there are major differences in 18F–FDG quality requirements among USP, BP, and CMC. AU - Yu, Sidney DO - 10.2349/biij.2.4.e57 KW - Fludeoxyglucouse (18F-FDG) KW - Positron emission tomography (PET) KW - Quality control (QC) PY - 2006 TI - Review of 18F-FDG synthesis and quality control T2 - Biomedical Imaging and Intervention Journal ER - TY - JOUR AB - Molecular imaging is revolutionizing the way we study the inner workings of the human body, diagnose diseases, approach drug design, and assess therapies. The field as a whole is making possible the visualization of complex biochemical processes involved in normal physiology and disease states, in real time, in living cells, tissues, and intact subjects. In this review, we focus specifically on molecular imaging of intact living subjects. We provide a basic primer for those who are new to molecular imaging, and a resource for those involved in the field. We begin by describing classical molecular imaging techniques together with their key strengths and limitations, after which we introduce some of the latest emerging imaging modalities. We provide an overview of the main classes of molecular imaging agents (i.e., small molecules, peptides, aptamers, engineered proteins, and nanoparticles) and cite examples of how molecular imaging is being applied in oncology, neuroscience, cardiology, gene therapy, cell tracking, and theranostics (therapy combined with diagnostics). A step-by-step guide to answering biological and/or clinical questions using the tools of molecular imaging is also provided. We conclude by discussing the grand challenges of the field, its future directions, and enormous potential for further impacting how we approach research and medicine. AU - James, Michelle L. AU - Gambhir, Sanjiv S. DA - 2012/4// DO - 10.1152/physrev.00049.2010 IS - 2 PY - 2012 SP - 897 EP - 965 TI - A Molecular Imaging Primer: Modalities, Imaging Agents, and Applications T2 - Physiological Reviews UR - http://www.ncbi.nlm.nih.gov/pubmed/22535898 UR - http://www.physiology.org/doi/10.1152/physrev.00049.2010 VL - 92 ER - TY - JOUR AU - Luna, Carlos M AU - Rodriguez-noriega, Eduardo AU - Bavestrello, Luis AU - Guzmán-blanco, Manuel DO - 10.1155/2014/480463 PY - 2014 SP - 1 EP - 12 TI - Gram-Negative Infections in Adult Intensive Care Units of Latin America and the Caribbean T2 - Critical Care Research and Practice VL - 2014 ER - TY - JOUR AB - Infectious diseases are a major threat to humanity, and it is imperative that we develop imaging tools that aid in their study, facilitate diagnosis, and guide treatment. The alarming rise of highly virulent and multi-drug-resistant pathogens, their rapid spread leading to frequent global pandemics, fears of bioterrorism, and continued life-threatening nosocomial infections in hospitals remain as major challenges to health care in the USA and worldwide. Early diagnosis and rapid monitoring are essential for appropriate management and control of infections. Tomographic molecular imaging enables rapid, noninvasive visualization, localization, and monitoring of molecular processes deep within the body and offers several advantages over traditional tools used for the study of infectious diseases. Noninvasive, longitudinal assessments could streamline animal studies, allow unique insights into disease pathogenesis, and expedite clinical translation of new therapeutics. Since molecular imaging is already in common use in the clinic, it could also become a valuable tool for clinical studies, for patient care, for public health, and for enabling precision medicine for infectious diseases. AU - Jain, Sanjay K. DO - 10.1007/S11307-017-1055-0 IS - 3 KW - Bacteria KW - Influenza KW - Microbiome KW - Optical imaging KW - PET KW - TB PB - NIH Public Access PY - 2017 SP - 341 EP - 341 TI - The Promise of Molecular Imaging in the Study and Treatment of Infectious Diseases T2 - Molecular imaging and biology : MIB : the official publication of the Academy of Molecular Imaging UR - http://www.ncbi.nlm.nih.gov/pubmed/28155078 UR - http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC5407939 VL - 19 ER - TY - JOUR AB - OBJECTIVES To examine the incidence of infections and to describe them and their outcome in intensive care unit (ICU) patients. DESIGN AND SETTING International prospective cohort study in which all patients admitted to the 28 participating units in eight countries between May 1997 and May 1998 were followed until hospital discharge. PATIENTS A total of 14,364 patients were admitted to the ICUs, 6011 of whom stayed less than 24 h and 8353 more than 24 h. RESULTS Overall 3034 infectious episodes were recorded at ICU admission (crude incidence: 21.1%). In ICU patients hospitalised longer than 24 h there were 1581 infectious episodes (crude incidence: 18.9%) including 713 (45%) in patients already infected at ICU admission. These rates varied between ICUs. Respiratory, digestive, urinary tracts, and primary bloodstream infections represented about 80% of all sites. Hospital-acquired and ICU-acquired infections were documented more frequently microbiologically than community-acquired infections (71% and 86%, respectively vs. 55%). About 28% of infections were associated with sepsis, 24% with severe sepsis and 30% with septic shock, and 18% were not classified. Crude hospital mortality rates ranged from 16.9% in non-infected patients to 53.6% in patients with hospital-acquired infections at the time of ICU admission and acquiring infection during the ICU stay. CONCLUSIONS The crude incidence of ICU infections remains high, although the rate varies between ICUs and patient subsets, illustrating the added burden of nosocomial infections in the use of ICU resources. AU - Alberti, Corinne AU - Brun-Buisson, Christian AU - Burchardi, Hilmar AU - Martin, Claudio AU - Goodman, Sergey AU - Artigas, Antonio AU - Sicignano, Alberto AU - Palazzo, Mark AU - Moreno, Rui AU - Boulmé, Ronan AU - Lepage, Eric AU - Le Gall, Jean DA - 2002/2// DO - 10.1007/s00134-001-1143-z IS - 2 PY - 2002 SP - 108 EP - 121 TI - Epidemiology of sepsis and infection in ICU patients from an international multicentre cohort study T2 - Intensive Care Medicine UR - http://www.ncbi.nlm.nih.gov/pubmed/11907653 UR - http://link.springer.com/10.1007/s00134-001-1143-z VL - 28 ER - TY - JOUR AB - Molecular imaging allows for the remote, noninvasive sensing and measurement of cellular and molecular processes in living subjects. Drawing upon a variety of modalities, molecular imaging provides a window into the biology of cancer from the subcellular level to the patient undergoing a new, experimental therapy. As signal transduction cascades and protein interaction networks become clarified, an increasing number of relevant targets for cancer therapy--and imaging--become available. Although conventional imaging is already critical to the management of patients with cancer, molecular imaging will provide even more relevant information, such as early detection of changes with therapy, identification of patient-specific cellular and metabolic abnormalities, and the disposition of therapeutic, gene-tagged cells throughout the body--all of which will have a considerable impact on morbidity and mortality. This overview discusses molecular imaging in oncology, providing examples from a variety of modalities, with an emphasis on emerging techniques for translational imaging. AU - Higgins, Luke J. AU - Pomper, Martin G. DA - 2011/2// DO - 10.1053/j.seminoncol.2010.11.010 IS - 1 PY - 2011 SP - 3 EP - 15 TI - The Evolution of Imaging in Cancer: Current State and Future Challenges T2 - Seminars in Oncology UR - http://www.ncbi.nlm.nih.gov/pubmed/21362512 UR - http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC4313866 UR - http://linkinghub.elsevier.com/retrieve/pii/S0093775410002320 VL - 38 ER - TY - JOUR AU - Woolf, S H AU - Grol, R AU - Hutchinson, A AU - Eccles, M AU - Grimshaw, J DA - 1999/2// IS - 7182 PB - BMJ Publishing Group PY - 1999 SP - 527 EP - 30 TI - Clinical guidelines: potential benefits, limitations, and harms of clinical guidelines. T2 - BMJ (Clinical research ed.) UR - http://www.ncbi.nlm.nih.gov/pubmed/10024268 UR - http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC1114973 VL - 318 ER - TY - JOUR AU - Chelazzi, Cosimo AU - Pettini, Eleonora AU - Villa, Gianluca AU - Gaudio, A Raffaele De DO - 10.1186/s12871-015-0106-9 PB - BMC Anesthesiology PY - 2015 SP - 1 EP - 7 TI - Epidemiology , associated factors and outcomes of ICU-acquired infections caused by Gram-negative bacteria in critically ill patients : an observational , retrospective study T2 - BMC Anesthesiology UR - http://dx.doi.org/10.1186/s12871-015-0106-9 ER - TY - JOUR AB - To facilitate oviposition, the ectoparasite Bracon hebetor, injects its venom, a paralysing toxin, to the host Corcyra larva that ultimately dies without showing any metamorphic change, even if allowed to remain unparasitised. At the initial stage of venom injection the rate of heartbeat of the host becomes abruptly high. This has been explained from the synergistic action of the substances of poison gland and calyx. The paralysed larvae subsequent to envenomization die within 240 hr. Application of hydroprene as single dose or with a booster dose after paralysation mostly increases the survival period considering heart beat as the index. The predicted value of survival period (714.4 hr), determined from a fitted equation obtained from the relationship between heart beat and survival period, indicates that a 100 microg treatment/larva with a booster dose of 50 microg/larva most effectively lengthens the period. It is concluded that the venom-induced physiological dysfunction of the immobilised larvae, as indicated in the rate of heart beat and survival period, though can be recovered to some extent after the application of juvenoids, there cannot occur any metamorphic change of these larvae. The parasitoid, therefore, succeeds in completing its development and metamorphosis by arresting the development of its host through an indirect hormonal suppression. The findings indicate an endocrine implication in host-parasite relationship in insect. AU - Chanda, Sudipta AU - Panda, R. N. AU - Chakravorty, Sanjib DO - 10.1186/s13073-016-0307-y IS - 8 PY - 2002 SN - 1756-994x SP - 918 EP - 923 TI - Hormonal implication in Bracon-venom-induced paralysation of the host larva of Corcyra cephalonica (Lepidoptera: Pyralidae) T2 - Indian Journal of Experimental Biology VL - 40 ER - TY - JOUR AB - We hypothesized that prior colonization with antibiotic-resistant Gram-negative bacteria is associated with increased risk of subsequent antibiotic-resistant Gram-negative bacteremia among cancer patients. We performed a matched case-control study. Cases were cancer patients with a blood culture positive for antibiotic-resistant Gram-negative bacteria. Controls were cancer patients with a blood culture not positive for antibiotic-resistant Gram-negative bacteria. Prior colonization was defined as any antibiotic-resistant Gram-negative bacteria in surveillance or non-sterile-site cultures obtained 2-365 days before the bacteremia. Thirty-two (37%) of 86 cases and 27 (8%) of 323 matched controls were previously colonized by any antibiotic-resistant Gram-negative bacteria. Prior colonization was strongly associated with antibiotic-resistant Gram-negative bacteremia (odds ratio [OR] 7.2, 95% confidence interval [CI] 3.5-14.7) after controlling for recent treatment with piperacillin-tazobactam (OR 2.5, 95% CI 1.3-4.8). In these patients with suspected bacteremia, prior cultures may predict increased risk of antibiotic-resistant Gram-negative bacteremia. © 2014 Elsevier Inc. AU - Hess, Aaron S. AU - Kleinberg, Michael AU - Sorkin, John D. AU - Netzer, Giora AU - Johnson, Jennifer K. AU - Shardell, Michelle AU - Thom, Kerri A. AU - Harris, Anthony D. AU - Roghmann, Mary Claire DO - 10.1016/j.diagmicrobio.2014.01.022 KW - Antimicrobial resistance KW - Neutropenic fever KW - Surveillance cultures PY - 2014 SN - 9780124201187 TI - Prior colonization is associated with increased risk of antibiotic-resistant Gram-negative bacteremia in cancer patients T2 - Diagnostic Microbiology and Infectious Disease ER - TY - JOUR AB - Copyright © 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc. Accurate assessment of kidney function plays an essential role for optimal clinical decision making in a variety of diseases. The major intrinsic advantages of PET are superior spatial and temporal resolutions for quantitative tomographic renal imaging. 2-deoxy-2-18F-fluorodeoxysorbitol (18F-FDS) is an analog of sorbitol that is reported to be freely filtered at the renal glomerulus without reabsorption at the tubule. Furthermore, it can be synthesized via simple reduction of widely available18F-FDG. We tested the feasibility of18F-FDS renal PET imaging in rats. Methods: The systemic and renal distribution of18F-FDS were determined by dynamic 35-min PET imaging (15 frames x 8 s, 26 frames x 30 s, 20 frames x 60 s) with a dedicated small-animal PET system and postmortem tissue counting in healthy rats. Distribution of coinjected99mTc-diethylenetriaminepentaacetic acid (DTPA) was also estimated as a reference. Plasma binding and in vivo stability of18F-FDS were determined. Results: In vivo PET imaging visualized rapid excretion of the administrated18F-FDS from both kidneys, with minimal tracer accumulation in other organs. Initial cortical tracer uptake followed by visualization of the collecting system could be observed with high contrast. Split-function renography curves were successfully obtained in healthy rats (the time of maximal concentration [Tmax] right [R] = 2.8 ± 1.2 min, Tmaxleft [L] = 2.9 ± 1.5 min, the time of half maximal concentration [T1/2max] R = 8.8 ± 3.7 min, T1/2maxL = 11.1 ± 4.9 min). Postmortem tissue counting of18F-FDS confirmed the high kidney extraction (kidney activities at 10, 30, and 60 min after tracer injection [percentage injected dose per gram]: 1.8 ± 0.7, 1.2 ± 0.1, and 0.5 ± 0.2, respectively) in a degree comparable to99mTc-DTPA (2.5 ± 1.0, 1.5 ± 0.2, and 0.8 ± 0.3, respectively). Plasma protein binding of18F-FDS was low (<0.1%), and metabolic transformation was not detected in serum and urine. Conclusion: In rat experiments,18F-FDS demonstrated high kidney extraction and excretion, low plasma protein binding, and high metabolic stability as preferable properties for renal imaging. These preliminary results warrant further confirmatory studies in large animal models and clinical studies as a novel functional renal imaging agent, given the advantages of PET technology and broad tracer availability. AU - Wakabayashi, H. AU - Werner, R. A. AU - Hayakawa, N. AU - Javadi, M. S. AU - Xinyu, C. AU - Herrmann, K. AU - Rowe, S. P. AU - Lapa, C. AU - Higuchi, T. DO - 10.2967/jnumed.116.172718 IS - 10 PY - 2016 TI - Initial Preclinical Evaluation of 18F-Fluorodeoxysorbitol PET as a Novel Functional Renal Imaging Agent T2 - Journal of Nuclear Medicine VL - 57 ER - TY - GEN AU - John E. Bennett & Raphael Dolin & Martin J. Blaser PY - 2010 SP - 2815 EP - 2833 TI - Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases - 9781455748013 | US Elsevier Health Bookshop T2 - Elsevier Inc UR - https://www.us.elsevierhealth.com/mandell-douglas-and-bennetts-principles-and-practice-of-infectious-diseases-9781455748013.html ER - TY - GEN AB - Humans are virtually identical in their genetic makeup, yet the small differences in our DNA give rise to tremendous phenotypic diversity across the human population. By contrast, the metagenome of the human microbiome—the total DNA content of microbes inhabiting our bodies—is quite a bit more variable, with only a third of its constituent genes found in a majority of healthy individuals. Understanding this variability in the “healthy microbiome” has thus been a major challenge in microbiome research, dating back at least to the 1960s, continuing through the Human Microbiome Project and beyond. Cataloguing the necessary and sufficient sets of microbiome features that support health, and the normal ranges of these features in healthy populations, is an essential first step to identifying and correcting microbial configurations that are implicated in disease. Toward this goal, several population-scale studies have documented the ranges and diversity of both taxonomic compositions and functional potentials normally observed in the microbiomes of healthy populations, along with possible driving factors such as geography, diet, and lifestyle. Here, we review several definitions of a ‘healthy microbiome’ that have emerged, the current understanding of the ranges of healthy microbial diversity, and gaps such as the characterization of molecular function and the development of ecological therapies to be addressed in the future. AU - Lloyd-Price, Jason AU - Abu-Ali, Galeb AU - Huttenhower, Curtis DO - 10.1186/s13073-016-0307-y PY - 2016 SN - 1756-994x TI - The healthy human microbiome T2 - Genome Medicine ER - TY - JOUR AU - WHO KW - financiación de la salud [subject] KW - investigación [subject] KW - servicios de salud [subject] PB - World Health Organization PY - 2013 TI - OMS | Informe sobre la salud en el mundo 2010 T2 - WHO UR - http://www.who.int/whr/2010/es/ ER - TY - JOUR AB - Carbapenem-resistant Enterobacteriaceae (CRE) are a serious public health threat. Infections due to these organisms are associated with significant morbidity and mortality. Mechanisms of drug resistance in gram-negative bacteria (GNB) are numerous; β-lactamase genes carried on mobile genetic elements are a key mechanism for the rapid spread of antibiotic-resistant GNB worldwide. Transmissible carbapenem-resistance in Enterobacteriaceae has been recognized for the last 2 decades, but global dissemination of carbapenemase-producing Enterobacteriaceae (CPE) is a more recent problem that, once initiated, has been occurring at an alarming pace. In this article, we discuss the evolution of CRE, with a focus on the epidemiology of the CPE pandemic; review risk factors for colonization and infection with the most common transmissible CPE worldwide, Klebsiella pneumoniae carbapenemase-producing K. pneumoniae; and present strategies used to halt the striking spread of these deadly pathogens. AU - Logan, Latania K. AU - Weinstein, Robert A. DO - 10.1093/infdis/jiw282 IS - 1 KW - Adult KW - Antibacterial agents KW - Carbapenemases KW - Carbapenems KW - Child KW - Drug resistance KW - Enterobacteriaceae infections KW - Epidemiology KW - Global health KW - Gram-negative bacteria PY - 2017 SN - 0022-1899 TI - The epidemiology of Carbapenem-resistant enterobacteriaceae: The impact and evolution of a global menace T2 - Journal of Infectious Diseases VL - 2015 ER - TY - JOUR AB - Imaging studies are frequently used to support the clinical diagnosis of infection. These techniques include computed tomography (CT) and magnetic resonance imaging (MRI) for structural information and single photon emission computed tomography (SPECT) or positron emission tomography (PET) for metabolic data. However, frequently, there is significant overlap in the imaging appearance of infectious and noninfectious entities using these tools. To address this concern, recent approaches have targeted bacteria-specific metabolic pathways. For example, radiolabeled sugars derived from sorbitol and maltose have been investigated as PET radiotracers, since these are efficiently incorporated into bacteria but are poor substrates for mammalian cells. We have previously shown that para-aminobenzoic acid (PABA) is an excellent candidate for development as a bacteria-specific imaging tracer as it is rapidly accumulated by a wide range of pathogenic bacteria, including metabolically quiescent bacteria and clinical strains, but not by mammalian cells. Therefore, in this study, we developed an efficient radiosynthesis for [ 11 C]PABA, investigated its accumulation into Escherichia coli and Staphylococcus aureus laboratory strains in vitro, and showed that it can distinguish between infection and sterile inflammation in a murine model of acute bacterial infection. S uspected bacterial infection is a frequent indication for imaging studies in clinical practice. Current techniques rely heavily on secondary inflammatory changes to localize disease. These changes include increased blood flow and vascular permeability in contrast-enhanced computed tomography (CT) and magnetic resonance imaging (MRI), increased glucose utilization in positron emission tomography (PET) using [ 18 F]-fluorodeoxyglucose ([ 18 F]FDG), and recruitment of leukocytes in tagged white blood cell (WBC) nuclear medicine studies. AU - Mutch, Christopher A. AU - Ordonez, Alvaro A. AU - Qin, Hecong AU - Parker, Matthew AU - Bambarger, Lauren E. AU - Villanueva-Meyer, Javier E. AU - Blecha, Joseph AU - Carroll, Valerie AU - Taglang, Celine AU - Flavell, Robert AU - Sriram, Renuka AU - Vanbrocklin, Henry AU - Rosenberg, Oren AU - Ohliger, Michael A. AU - Jain, Sanjay K. AU - Neumann, Kiel D. AU - Wilson, David M. DO - 10.1021/acsinfecdis.8b00061 KW - bacteria KW - folate KW - infection KW - metabolism KW - positron emission tomography PY - 2018 TI - Para-Aminobenzoic Acid: A Positron Emission Tomography Tracer Targeting Bacteria-Specific Metabolism T2 - ACS Infectious Diseases ER - TY - JOUR AB - OBJECTIVES This study evaluated the usefulness of fluorodesoxyglucose marked by fluorine-18 ((18)F-FDG) positron emission tomography (PET) and computed tomography (CT) in patients with suspected cardiovascular implantable electronic device (CIED) infection. BACKGROUND CIED infection is sometimes challenging to diagnose. Because extraction is associated with significant morbidity/mortality, new imaging modalities to confirm the infection and its dissemination would be of clinical value. METHODS Three groups were compared. In Group A, 42 patients with suspected CIED infection underwent (18)F-FDG PET/CT. Positive PET/CT was defined as abnormal uptake along cardiac devices. Group B included 12 patients without infection who underwent PET/CT 4 to 8 weeks post-implant. Group C included 12 patients implanted for >6 months without infection who underwent PET/CT for another indication. Semi-quantitative ratio (SQR) was obtained from the ratio between maximal uptake and lung parenchyma uptake. RESULTS In Group A, 32 of 42 patients with suspected CIED infection had positive PET/CT. Twenty-four patients with positive PET/CT underwent extraction with excellent correlation. In 7 patients with positive PET/CT, 6 were treated as superficial infection with clinical resolution. One patient with positive PET/CT but negative leukocyte scan was considered false positive due to Dacron pouch. Ten patients with negative-PET/CT were treated with antibiotics and none has relapsed at 12.9 ± 1.9 months. In Group B, patients had mild uptake seen at the level of the connector. There was no abnormal uptake in Group C patients. Median SQR was significantly higher in Group A (A = 2.02 vs. B = 1.08 vs. C = 0.57; p < 0.001). CONCLUSIONS PET/CT is useful in differentiating between CIED infection and recent post-implant changes. It may guide appropriate therapy. AU - Sarrazin, Jean-François AU - Philippon, François AU - Tessier, Michel AU - Guimond, Jean AU - Molin, Franck AU - Champagne, Jean AU - Nault, Isabelle AU - Blier, Louis AU - Nadeau, Maxime AU - Charbonneau, Lyne AU - Trottier, Mikaël AU - O'Hara, Gilles DA - 2012/5// DO - 10.1016/j.jacc.2011.11.059 IS - 18 PY - 2012 SP - 1616 EP - 1625 TI - Usefulness of Fluorine-18 Positron Emission Tomography/Computed Tomography for Identification of Cardiovascular Implantable Electronic Device Infections T2 - Journal of the American College of Cardiology UR - http://www.ncbi.nlm.nih.gov/pubmed/22538331 UR - http://linkinghub.elsevier.com/retrieve/pii/S0735109712006134 VL - 59 ER - TY - JOUR AB - Early diagnosis of infective endocarditis (IE) is based on the yielding of blood cultures and echocardiographic findings. However, they have limitations and sometimes the diagnosis is inconclusive, particularly in patients with prosthetic valves (PVs) and implantable cardiac electronic devices (ICEDs). The primary aim of this study was to evaluate the diagnostic accuracy of 18F-FDG PET/CT in patients with suspected IE and ICED infection. METHODS A prospective study with 80 consecutive patients with suspected IE and ICED infection (65 men and 15 women with a mean age of 68 ± 13 y) between June 2013 and May 2015 was performed in our hospital. The inclusion criteria were clinically suspected IE and ICED infection at the following locations: native valve (NV) (n = 21), PV (n = 29), or ICED (n = 30) (automatic implantable defibrillator [n = 11] or pacemaker [n = 19]). Whole-body 18F-FDG PET/CT with a myocardial uptake suppression protocol with unfractionated heparin was performed in all patients. The final diagnosis of infection was established by the IE Study Group according to the clinical, echocardiographic, and microbiologic findings. RESULTS A final diagnosis of infection was confirmed in 31 patients: NV (n = 6), PV (n = 12), and ICED (n = 13). Sensitivity, specificity, positive predictive value, and negative predictive value for 18F-FDG PET/CT were 82%, 96%, 94%, and 87%, respectively. 18F-FDG PET/CT was false-negative in all cases with infected NV. 18F-FDG PET/CT was able to reclassify 63 of 70 (90%) patients initially classified as possible IE by modified Duke criteria. In 18 of 70 cases, 18F-FDG PET/CT changed possible to definite IE (26%) and in 45 of 70 cases changed possible to rejected IE (64%). Additionally, 18F-FDG PET/CT identified 8 cases of septic embolism and 3 of colorectal cancer in patients with a final diagnosis of IE. CONCLUSION 18F-FDG PET/CT proved to be a useful diagnostic tool in suspected IE and ICED infection and should be included in the diagnostic algorithm for early diagnosis. 18F-FDG PET/CT is not useful in the diagnosis of IE in NV but should be also considered in the initial assessment of this complex scenario to rule out extracardiac complications and possible neoplasms. AU - Granados, U. AU - Fuster, D. AU - Pericas, J. M. AU - Llopis, J. L. AU - Ninot, S. AU - Quintana, E. AU - Almela, M. AU - Pare, C. AU - Tolosana, J. M. AU - Falces, C. AU - Moreno, A. AU - Pons, F. AU - Lomena, F. AU - Miro, J. M. AU - Hospital Clinic Endocarditis Study Group DA - 2016/11// DO - 10.2967/jnumed.116.173690 IS - 11 KW - 18F-FDG-PET/CT KW - implantable cardiac electronic devices KW - infective endocarditis KW - prosthetic valve KW - septic embolisms PY - 2016 SP - 1726 EP - 1732 TI - Diagnostic Accuracy of 18F-FDG PET/CT in Infective Endocarditis and Implantable Cardiac Electronic Device Infection: A Cross-Sectional Study T2 - Journal of Nuclear Medicine UR - http://www.ncbi.nlm.nih.gov/pubmed/27261514 UR - http://jnm.snmjournals.org/cgi/doi/10.2967/jnumed.116.173690 VL - 57 ER - TY - JOUR AB - Despite advances in the field of nuclear medicine, the imaging of bacterial infections has remained a challenge. The existing reagents suffer from poor sensitivity and specificity. In this study we investigate the potential of a novel PET (positron emission tomography) tracer that overcomes these limitations. Methods: 6-[18F]-fluoromaltose was synthesized. Its behavior in vitro was evaluated in bacterial and mammalian cultures. Detailed pharmacokinetic and biodistribution profiles for the tracer were obtained from a murine model. Results: 6-[18F]-fluoromaltose is taken up by multiple strains of pathogenic bacteria. It is not taken up by mammalian cancer cell lines. 6-[18F]-fluoromaltose is retained in infected muscles in a murine model of bacterial myositis. It does not accumulate in inflamed tissue. Conclusion: We have shown that 6-[18F]-fluoromaltose can be used to image bacterial infection in vivo with high specificity. We believe that this class of agents will have a significant impact on the clinical management of patients. AU - Gowrishankar, Gayatri AU - Namavari, Mohammad AU - Jouannot, Erwan Benjamin AU - Hoehne, Aileen AU - Reeves, Robert AU - Hardy, Jonathan AU - Gambhir, Sanjiv Sam DO - 10.1371/journal.pone.0107951 PY - 2014 SN - 1932-6203 TI - Investigation of 6-[18F]-fluoromaltose as a novel PET tracer for imaging bacterial infection T2 - PLoS ONE ER - TY - BOOK AB - ... GL Mandell , JE Bennett , R. Dolin Mandell , Douglas and Bennett's Principles and Practice of Infectious ... outstanding experts in the field of infectious diseases – Gerald L. Mandell , MD (Chief ... Ctr, Charlottesville, Va.), John E. Bennett , MD (Head Clin., Mycology Sect., NIH, Bethesda ... AU - Mandell, Douglas, and Bennett’s DO - 10.1016/S1473-3099(10)70089-X IS - 5 PY - 2005 SN - 9780443068393 SP - 303 EP - 304 TI - Mandell, Douglas, and Bennett's principles and practice of infectious diseases T2 - The Lancet Infectious Diseases UR - http://linkinghub.elsevier.com/retrieve/pii/S147330991070089X VL - 10 ER - TY - JOUR AU - Ning, Xinghai AU - Seo, Wonewoo AU - Lee, Seungjun AU - Takemiya, Kiyoko AU - Rafi, Mohammad AU - Feng, Xuli AU - Weiss, Daiana AU - Wang, Xiaojian AU - Williams, Larry AU - Camp, Vernon M AU - Eugene, Malveaux AU - Taylor, W Robert DO - 10.1002/anie.201xxxxxx IS - 51 PY - 2014 SP - 14096 EP - 14101 TI - Fluorine-18 labeled maltohexaose images bacterial infections by PET HHS Public Access T2 - Angew Chem Int Ed Engl UR - http://dx.doi.org/10.1002/anie.201xxxxxx. VL - 53 ER - TY - JOUR AU - Leal, Aura Lucia AU - Arturo, Carlos AU - Jorge, Álvarez AU - Cortes María, Alberto AU - Ovalle, Victoria PY - 2017 TI - Boletín informativo GREBO UR - www.grebo.org ER - TY - JOUR AU - Fleming A IS - 8 PY - 2001 SP - 780 EP - 790 TI - 1929 On the actibacterial action Penicillium T2 - Bull World Health Organ VL - 79 ER - TY - JOUR AB - AIM Information on the epidemiology of multiresistant bacteria (MRB) with zoonotic potential is growing but still remains quite incomplete. This narrative mini-review provides a general overview of the epidemiology of the most important zoonotic MRB in cattle, swine and poultry in Europe. METHODS A literature search was conducted mainly on the PubMed website including articles published until April 2012. RESULTS Livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA) especially poses a zoonotic risk to people working in close contact with livestock. These people may become carriers themselves and the hazard of transmission into health-care facilities needs surveillance. Extended-spectrum beta-lactamases (ESBL) producing bacteria are widely spread in both humans and livestock, sharing similar genotypes, especially of the CTX-M-group, which makes a zoonotic transfer very likely. Identical strains of vancomycin-resistant enterococci (VRE) were found both in humans and animals, after ingestion of animal strains transient colonization of the human gut may be possible. Only a few data are available on the transmission of methicillin-resistant coagulase-negative staphylococci (MR-CoNS) between humans and animals. Direct contact to colonized animals may be a risk factor as well as the exchange of resistance genes between human and animal staphylococci. Clostridium difficile (C. difficile) ribotype 078 emerges in livestock and humans and a zoonotic transmission seems probable as genotypes and diseases resemble each other. CONCLUSION All discussed MRB and C. difficile are important nosocomial agents which also occur in livestock and were found in foods of animal origin. Further analysis is needed to reveal the exact transmission routes and to perform a reliable risk assessment. Zielsetzung: Die Intention des vorliegenden narrativen Mini-Reviews ist es, dem Leser einen Überblick über die Prävalenz und Epidemiologie multiresistenter Bakterien in Europa bei Rindern, Schweinen und Geflügel zu geben und deren zoonotisches Potential zu beleuchten. Methode: Es wurde eine PubMed-Literaturrecherche unter Einschluss bis April 2012 publizierter Artikel durchgeführt.Ergebnisse: Der livestock-associated Methicillin-resistente Staphylococcus aureus (LA-MRSA) ist nicht nur bei Nutztieren, sondern auch häufig bei engen Kontaktpersonen nachweisbar. Dem Eintrag durch kolonisierte und infizierte Personen ins Gesundheitswesen muss deshalb Beachtung geschenkt werden. Bakterien, die die Fähigkeit besitzen, β-Laktamasen mit einem erweitertem Wirkspektrum (ESBL) zu bilden, sind ebenfalls bei Mensch und Nutztier zu finden. Insbesondere die ESBL vom Typ CTX-M stehen im Verdacht, zwischen Mensch und Tier übertragen zu werden. Einige Studien legen nahe, dass eine Transmission von Vancomycin-resistenten Enterokokken (VRE), z.B. nach oraler Aufnahme kontaminierter tierischen Lebensmitteln, auf den Menschen möglich ist. Bezüglich des zoonotischen Potentials von multiresistenten Koagulase-negativen Staphylokokken (MR-CoNS) existieren hingegen nur wenige Publikationen. Es gibt jedoch erste Hinweise, dass eine zoonotische Übertragung möglich sein könnte und auch der Austausch von Resistenzgenen zwischen humanen und tierischen Bakterien scheint prinzipiell möglich. Die Nachweisrate von Clostridium difficile (C. difficile), v.a. des Ribotyps 078, hat bei Mensch und Tier gleichermaßen zugenommen. Nicht nur die Genotypen, auch die verursachten Infektionen weisen unabhängig von der betroffenen Spezies Gemeinsamkeiten auf. Schlussfolgerung: Alle betrachteten multiresistenten Erreger sowie C. difficile spielen eine erhebliche Rolle bei nosokomialen Infektionen in der Humanmedizin und sind ebenfalls bei Nutztieren und Lebensmitteln tierischen Ursprungs zu finden. Weitere Studien sind nötig, um die exakten Transmissionsrouten zu identifizieren und eine valide Risikobeurteilung durchzuführen. AU - Dahms, Carmen AU - Hübner, Nils-Olaf AU - Wilke, Florian AU - Kramer, Axel DO - 10.3205/dgkh000241 IS - 3 KW - Clostridium difficile KW - E. coli KW - ESBL KW - MRSA KW - VRE KW - livestock KW - multiresistant KW - vancomycin KW - zoonoses PY - 2014 SP - Doc21 EP - Doc21 TI - Mini-review: Epidemiology and zoonotic potential of multiresistant bacteria and Clostridium difficile in livestock and food. T2 - GMS hygiene and infection control UR - http://www.ncbi.nlm.nih.gov/pubmed/25285265 UR - http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC4184042 VL - 9 ER - TY - JOUR AB - Background Currently, no single U.S. surveillance system can provide estimates of the burden of all types of health care–associated infections across acute care patient populations. We conducted a prevalence survey in 10 geographically diverse states to determine the prevalence of health care–associated infections in acute care hospitals and generate updated estimates of the national burden of such infections. Methods We defined health care–associated infections with the use of National Healthcare Safety Network criteria. One-day surveys of randomly selected inpatients were performed in participating hospitals. Hospital personnel collected demographic and limited clinical data. Trained data collectors reviewed medical records retrospectively to identify health care–associated infections active at the time of the survey. Survey data and 2010 Nationwide Inpatient Sample data, stratified according to patient age and length of hospital stay, were used to estimate the total numbers of health care–associated in... AU - Magill, Shelley S. AU - Edwards, Jonathan R. AU - Bamberg, Wendy AU - Beldavs, Zintars G. AU - Dumyati, Ghinwa AU - Kainer, Marion A. AU - Lynfield, Ruth AU - Maloney, Meghan AU - McAllister-Hollod, Laura AU - Nadle, Joelle AU - Ray, Susan M. AU - Thompson, Deborah L. AU - Wilson, Lucy E. AU - Fridkin, Scott K. DO - 10.1056/NEJMoa1306801 PY - 2014 SN - 0000000000000 TI - Multistate Point-Prevalence Survey of Health Care–Associated Infections T2 - New England Journal of Medicine ER - TY - JOUR TI - 2017-OMS-Lista antimicrobianos importancia critica medicina humana ER - TY - GEN AB -

Abstract

Background

Bacterial infections are still a major global healthcare problem. To combat the increasing antimicrobial resistance, early diagnosis of bacterial infections—including the identification of bacterial species—is needed to improve antibiotic stewardship and to help reduce the use of broad-spectrum antibiotics. To aid successful targeted antibiotic treatment, specific detection and localisation of infectious organisms is warranted. Nuclear medicine imaging approaches have been successfully used to diagnose bacterial infections and to differentiate between pathogen induced infections and sterile inflammatory processes.

Aim

In this comprehensive review we present an overview of recent developments in radiolabelled bacterial imaging tracers.

Methods

The PubMed/MEDLINE and Embase (OvidSP) literature databases were systematically searched for publications on SPECT and PET on specific imaging of bacterial using specific guidelines with MeSH-terms, truncations, and completion using cross-references. Tracers in literature that was extensively reviewed before 2016 were not included in this update. Where possible, the chemical structure of the radiolabelled compounds and clinical images were shown.

Results

In 219 original articles pre-clinical and clinical imaging of bacterial infection with new tracers were included. In our view, the highest translational potential lies with tracers that are specific to target the pathogens: e.g., 99mTc- and 68Ga-labelled UBI29–41, 99mTc-vancomycin, m-[18F]-fluoro-PABA, [methyl-11C]-D-methionine, [18F]-FDS, [18F]-maltohexaose and [18F]-maltotriose. An encouraging note is that some of these tracers have already been successfully evaluated in clinical settings.

Conclusion

This review summarises updates in tracer development for specific (pre-clinical and clinical) imaging of bacterial infections. We propsed some promising tracers that are likely to become innovative standards in the clinical setting in the near feature.

AU - Welling, Mick M. AU - Hensbergen, Albertus W. AU - Bunschoten, Anton AU - Velders, Aldrik H. AU - Roestenberg, Meta AU - van Leeuwen, Fijs W.B. DO - 10.1007/s40336-019-00317-4 IS - 2 PY - 2019 TI - An update on radiotracer development for molecular imaging of bacterial infections T2 - Clinical and Translational Imaging VL - 7 ER - TY - JOUR AU - Xiaojian Wang and Niren Murthy* IS - 259 PY - 2014 SP - 1 EP - 3 TI - 2014-Xiaojian Wang-Bacterial Imaging Comes og Age T2 - Science Translational Medicine VL - 6 ER - TY - JOUR AB - OBJECTIVE The purpose of this study was to provide a national estimate of the number of healthcare-associated infections (HAI) and deaths in United States hospitals. METHODS No single source of nationally representative data on HAIs is currently available. The authors used a multi-step approach and three data sources. The main source of data was the National Nosocomial Infections Surveillance (NNIS) system, data from 1990-2002, conducted by the Centers for Disease Control and Prevention. Data from the National Hospital Discharge Survey (for 2002) and the American Hospital Association Survey (for 2000) were used to supplement NNIS data. The percentage of patients with an HAI whose death was determined to be caused or associated with the HAI from NNIS data was used to estimate the number of deaths. RESULTS In 2002, the estimated number of HAIs in U.S. hospitals, adjusted to include federal facilities, was approximately 1.7 million: 33,269 HAIs among newborns in high-risk nurseries, 19,059 among newborns in well-baby nurseries, 417,946 among adults and children in ICUs, and 1,266,851 among adults and children outside of ICUs. The estimated deaths associated with HAIs in U.S. hospitals were 98,987: of these, 35,967 were for pneumonia, 30,665 for bloodstream infections, 13,088 for urinary tract infections, 8,205 for surgical site infections, and 11,062 for infections of other sites. CONCLUSION HAIs in hospitals are a significant cause of morbidity and mortality in the United States. The method described for estimating the number of HAIs makes the best use of existing data at the national level. AU - Klevens, R. Monina AU - Edwards, Jonathan R. AU - Richards, Chesley L. AU - Horan, Teresa C. AU - Gaynes, Robert P. AU - Pollock, Daniel A. AU - Cardo, Denise M. DA - 2007/3// DO - 10.1177/003335490712200205 IS - 2 PY - 2007 SP - 160 EP - 166 TI - Estimating Health Care-Associated Infections and Deaths in U.S. Hospitals, 2002 T2 - Public Health Reports UR - http://www.ncbi.nlm.nih.gov/pubmed/17357358 UR - http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC1820440 UR - http://journals.sagepub.com/doi/10.1177/003335490712200205 VL - 122 ER - TY - JOUR AB - Both the referring clinician and the nuclear medicine specialist must be aware of the main known or potential pitfalls that can occur in infection and inflammation imaging. They must decide in consensus which tracer and which imaging protocol should be used for a specific indication. This article provides an overview of all the pitfalls and limitations of nuclear medicine techniques to image infections and inflammation. Both general pitfalls and pitfalls in specific clinical entities are discussed. AU - Glaudemans, Andor W.J.M. AU - Israel, Ora AU - Slart, Riemer H.J.A. DA - 2015/11// DO - 10.1053/J.SEMNUCLMED.2015.02.005 IS - 6 PB - W.B. Saunders PY - 2015 SP - 500 EP - 512 TI - Pitfalls and Limitations of Radionuclide and Hybrid Imaging in Infection and Inflammation T2 - Seminars in Nuclear Medicine UR - https://www.sciencedirect.com/science/article/pii/S0001299815000227?via%3Dihub VL - 45 ER - TY - JOUR AU - Irene, Wendy AU - Dragan, Tatiana AU - Wrenn, Stephanie DO - 10.1016/j.ijid.2015.06.024 PB - International Society for Infectious Diseases PY - 2015 SN - 7804921500 SP - 129 EP - 134 TI - International Journal of Infectious Diseases Nosocomial Gram-negative bacteremia in intensive care : epidemiology , antimicrobial susceptibilities , and outcomes T2 - International Journal of Infectious Diseases UR - http://dx.doi.org/10.1016/j.ijid.2015.06.024 VL - 37 ER - TY - JOUR AB - Integrated positron emission tomography/computed tomography (PET/CT) with the glucose analogue, 2-[(18)F]-fluoro-2-deoxy-d-glucose (FDG), is an evolving hybrid imaging technique in the evaluation of an important and diverse group of pathological conditions, which are characterised by infection and aseptic inflammation. With a rapidly expanding body of evidence, it is being increasingly recognised that, in addition to its established role in oncological imaging, FDG PET/CT also has clinical utility in suspected infection and inflammation. The technique can identify the source of infection or inflammation in a timely fashion ahead of morphological changes on conventional anatomical imaging techniques, such as computed tomography (CT) and magnetic resonance imaging (MRI), map the extent and severity of disease, identify sites for tissue sampling, and assess therapy response. FDG PET/CT exhibits distinct advantages over traditional radionuclide imaging techniques in terms of shorter duration of examination, higher spatial resolution, non-invasive nature of acquisition, ability to perform quantitative analyses, and the provision of a synergistic combination of functional and anatomical imaging. With the use of illustrative clinico-radiological cases, this article discusses the current and emerging evidence for the use of FDG PET/CT in a broad spectrum of disorders, such as fever of unknown origin, sarcoidosis, large vessel vasculitis, musculoskeletal infections, joint prosthesis or implant-related complications, human immunodeficiency virus (HIV)-related infections, and miscellaneous indications, such as IgG4-related systemic disease. It will also briefly summarise the role of more novel tracers such as FDG-labelled leukocytes and gallium-68 PET tracers in this arena. AU - Vaidyanathan, S. AU - Patel, C.N. AU - Scarsbrook, A.F. AU - Chowdhury, F.U. DA - 2015/7// DO - 10.1016/j.crad.2015.03.010 IS - 7 PY - 2015 SP - 787 EP - 800 TI - FDG PET/CT in infection and inflammation—current and emerging clinical applications T2 - Clinical Radiology UR - http://www.ncbi.nlm.nih.gov/pubmed/25917543 UR - https://linkinghub.elsevier.com/retrieve/pii/S0009926015001063 VL - 70 ER - TY - JOUR AU - WHO KW - antimicrobial resistance [subject] PB - World Health Organization PY - 2018 SP - 164 EP - 164 TI - GLASS | Global antimicrobial resistance surveillance system (GLASS) report T2 - WHO UR - https://www.who.int/glass/resources/publications/early-implementation-report/en/ ER - TY - JOUR AB - There is often overlap in the diagnostic features of common pathologic processes such as infection, sterile inflammation, and cancer both clinically and using conventional imaging techniques. Here, we report the development of a positron emission tomography probe for live bacterial infection based on the small-molecule antibiotic trimethoprim (TMP). [18F]fluoropropyl-trimethoprim, or [18F]FPTMP, shows a greater than 100-fold increased uptake in vitro in live bacteria (Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa) relative to controls. In a rodent myositis model, [18F]FPTMP identified live bacterial infection without demonstrating confounding increased signal in the same animal from other etiologies including chemical inflammation (turpentine) and cancer (breast carcinoma). Additionally, the biodistribution of [18F]FPTMP in a nonhuman primate shows low background in many important tissues that may be sites of infection such as the lungs and soft tissues. These results suggest that [18F]FPTMP could be a broadly useful agent for the sensitive and specific imaging of bacterial infection with strong translational potential. AU - Sellmyer, Mark A AU - Lee, Iljung AU - Hou, Catherine AU - Weng, Chi-Chang AU - Li, Shihong AU - Lieberman, Brian P AU - Zeng, Chenbo AU - Mankoff, David A AU - Mach, Robert H DA - 2017/8// DO - 10.1073/pnas.1703109114 IS - 31 KW - PET KW - bacteria KW - imaging KW - radiotracer KW - trimethoprim PB - National Academy of Sciences PY - 2017 SP - 8372 EP - 8377 TI - Bacterial infection imaging with [18F]fluoropropyl-trimethoprim. T2 - Proceedings of the National Academy of Sciences of the United States of America UR - http://www.ncbi.nlm.nih.gov/pubmed/28716936 UR - http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC5547613 VL - 114 ER - TY - JOUR AU - Hess, Aaron S AU - Kleinberg, Michael AU - Sorkin, John D AU - Netzer, Giora AU - Jennifer, K AU - Shardell, Michelle AU - Thom, Kerri A AU - Harris, Anthony D AU - Greenebaum, Stewart AU - Medicine, Geriatric DO - 10.1016/j.diagmicrobio.2014.01.022.Prior IS - 1 PY - 2015 SP - 73 EP - 76 TI - HHS Public Access T2 - Diagn Microbiol Infect Dis VL - 79 ER - TY - JOUR AB - FDG-PET, combined with CT, is nowadays getting more and more relevant for the diagnosis of several infectious and inflammatory diseases and particularly for therapy monitoring. Thus, this paper gives special attention to the role of FDG-PET/CT in the diagnosis and therapy monitoring of infectious and inflammatory diseases. Enough evidence in the literature already exists about the usefulness of FDG-PET/CT in the diagnosis, management, and followup of patients with sarcoidosis, spondylodiscitis, and vasculitis. For other diseases, such as inflammatory bowel diseases, rheumatoid arthritis, autoimmune pancreatitis, and fungal infections, hard evidence is lacking, but studies also point out that FDG-PET/CT could be useful. It is of invaluable importance to have large prospective multicenter studies in this field to provide clear answers, not only for the status of nuclear medicine in general but also to reduce high costs of treatment. AU - Glaudemans, Andor W J M AU - de Vries, Erik F J AU - Galli, Filippo AU - Dierckx, Rudi A J O AU - Slart, Riemer H J A AU - Signore, Alberto DO - 10.1155/2013/623036 PY - 2013 SP - 623036 EP - 623036 TI - The use of (18)F-FDG-PET/CT for diagnosis and treatment monitoring of inflammatory and infectious diseases. T2 - Clinical & developmental immunology UR - http://www.hindawi.com/journals/jir/2013/623036/ UR - http://www.ncbi.nlm.nih.gov/pubmed/24027590 UR - http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC3763592 VL - 2013 ER - TY - JOUR AU - Haroon, A. AU - Zumla, A. AU - Bomanji, J. DA - 2012/5// DO - 10.1093/cid/cis193 IS - 9 PY - 2012 SP - 1333 EP - 1341 TI - Role of Fluorine 18 Fluorodeoxyglucose Positron Emission Tomography-Computed Tomography in Focal and Generalized Infectious and Inflammatory Disorders T2 - Clinical Infectious Diseases UR - https://academic.oup.com/cid/article-lookup/doi/10.1093/cid/cis193 VL - 54 ER - TY - JOUR AB - The Centers for Disease Control and Prevention estimates that 2 million patients suffer from hospital-acquired infections every year and nearly 100,000 of them die. Most of these medical errors are preventable. Hospital-acquired infections result in up to $4.5 billion in additional healthcare expenses annually. The U.S. government has responded to this financial loss by focusing on healthcare quality report cards and by taking strong action to curb healthcare spending. The Medicare Program has proposed changes to the Hospital Inpatient Prospective Payment System and Fiscal Year Rates: Proposed Rule CMS 1488-P-Healthcare-associated infection. Payment will be linked to performance. Under the new rule, payment will be withheld from hospitals for care associated with treating certain catheter-associated urinary tract infections, vascular catheter-associated infections, and mediastinitis after coronary artery bypass graft surgery. Infection-prevention strategies are essential. In the healthcare setting, the infection control department is categorized as non-revenue-producing. Funds dedicated to resources such as staff, educational programs, and prevention measures are vastly limited. Hospital leaders will need to balance the upfront cost needed to prevent hospital-related infections with the non-reimbursed expense accrued secondary to potentially preventable infections. The purpose of this paper is to present case studies and cost analysis of hospital-acquired infections and present strategies that reduce infections and cost. AU - Reed, Deoine AU - Kemmerly, Sandra A IS - 1 KW - Economics KW - finance KW - healthcare KW - hospital-acquired infection KW - infection control KW - infection prevention PY - 2009 SP - 27 EP - 31 TI - Infection control and prevention: a review of hospital-acquired infections and the economic implications. T2 - The Ochsner journal UR - http://www.ncbi.nlm.nih.gov/pubmed/21603406 UR - http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC3096239 VL - 9 ER - TY - JOUR KW - 2003 KW - Capítulo 1: Salud mundial: retos actuales KW - health KW - report KW - world PB - World Health Organization PY - 2010 TI - OMS | Capítulo 1: Salud mundial: retos actuales T2 - WHO UR - http://www.who.int/whr/2003/chapter1/es/index3.html ER - TY - JOUR AB - Several advances in imaging have become part of the work-up for localization, diagnosis, and management of infectious diseases and inflammatory disorders. Utility of multiple imaging modalities is a time-consuming step, and significant numbers of patients remain undiagnosed despite utilization of series of tests. Inflammatory cells have avidity for fluorine 18-labeled fluorodeoxyglucose ((18)F-FDG), and thus positron emission tomographic-computed tomographic (PET-CT) hybrid imaging provides anatomical and metabolic information that can be used to define the extent of infectious and inflammatory diseases and assess response to treatment. PET-CT provides a "one-stop test" in which use of hybrid imaging provides anatomical and metabolic information. The extent of disease is defined quickly, and response to treatment can be assessed. This modality also helps define the metastatic and/or septic foci where there is lack of localizing symptoms. More recently, there is increasing awareness among clinicians regarding the ability of PET-CT to help in diagnosing, characterizing, and assessing inflammatory disorders. This article reviews the usefulness of this imaging modality. AU - Haroon, A. AU - Zumla, A. AU - Bomanji, J. DA - 2012/5// DO - 10.1093/cid/cis193 IS - 9 PY - 2012 SP - 1333 EP - 1341 TI - Role of Fluorine 18 Fluorodeoxyglucose Positron Emission Tomography-Computed Tomography in Focal and Generalized Infectious and Inflammatory Disorders T2 - Clinical Infectious Diseases UR - http://www.ncbi.nlm.nih.gov/pubmed/22431802 UR - https://academic.oup.com/cid/article-lookup/doi/10.1093/cid/cis193 VL - 54 ER - TY - GEN AB - When serious infections are suspected, patients are often treated empirically with broad-spectrum antibiotics while awaiting results that provide information on the bacterial class and species causing the infection, as well as drug susceptibilities. For deep-seated infections, these traditional diagnostic techniques often rely on tissue biopsies to obtain clinical samples which can be expensive, dangerous, and has the potential of sampling bias. Moreover, these procedures and results can take several days and may not always provide reliable information. This combination of time and effort required for proper antibiotic selection has become a barrier leading to indiscriminate broad-spectrum antibiotic use. Exposure to nosocomial infections and indiscriminate use of broad-spectrum antibiotics are responsible for promoting bacterial drug-resistance leading to substantial morbidity and mortality, especially in hospitalized and immunosuppressed patients. Therefore, early diagnosis of infection and targeted antibiotic treatments are urgently needed to reduce morbidity and mortality caused by bacterial infections worldwide. Reliable pathogen-specific bacterial imaging techniques have the potential to provide early diagnosis and guide antibiotic treatments. AU - Ordonez, Alvaro A. AU - Jain, Sanjay K. DO - 10.1053/j.semnuclmed.2017.11.003 PY - 2018 TI - Pathogen-Specific Bacterial Imaging in Nuclear Medicine T2 - Seminars in Nuclear Medicine ER - TY - JOUR AB - Escherichia (E.) coli producing extended-spectrum beta-lactamases (ESBLs) are an increasing problem for public health. The success of ESBLs may be due to spread of ESBL-producing bacterial clones, transfer of ESBL gene-carrying plasmids or exchange of ESBL encoding genes on mobile elements. This makes it difficult to identify transmission routes and sources for ESBL-producing bacteria. The objectives of this study were to compare the distribution of genotypic and phenotypic properties of E. coli isolates from different animal and human sources collected in studies in the scope of the national research project RESET. ESBL-producing E. coli from two longitudinal and four cross-sectional studies in broiler, swine and cattle farms, a cross-sectional and a case-control study in humans and diagnostic isolates from humans and animals were used. In the RESET consortium, all laboratories followed harmonized methodologies for antimicrobial susceptibility testing, confirmation of the ESBL phenotype, specific PCR assays for the detection of bla(TEM), bla(CTX), and bla(SHV) genes and sequence analysis of the complete ESBL gene as well as a multiplex PCR for the detection of the four major phylogenetic groups of E. coli. Most ESBL genes were found in both, human and non-human populations but quantitative differences for distinct ESBL-types were detectable. The enzymes CTX-M-1 (63.3% of all animal isolates, 29.3% of all human isolates), CTX-M-15 (17.7% vs. 48.0%) and CTX-M-14 (5.3% vs. 8.7%) were the most common ones. More than 70% of the animal isolates and more than 50% of the human isolates contained the broadly distributed ESBL genes bla(CTX-M-1), bla(CTX-M-15), or the combinations bla(SHV-12)+bla(TEM) or bla(CTX-M-1)+bla(TEM). While the majority of animal isolates carried bla(CTX-M-1) (37.5%) or the combination bla(CTX-M-1)+bla(TEM) (25.8%), this was the case for only 16.7% and 12.6%, respectively, of the human isolates. In contrast, 28.2% of the human isolates carried bla(CTX-M-15) compared to 10.8% of the animal isolates. When grouping data by ESBL types and phylogroups bla(CTX-M-1) genes, mostly combined with phylogroup A or B1, were detected frequently in all settings. In contrast, bla(CTX-M-15) genes common in human and animal populations were mainly combined with phylogroup A, but not with the more virulent phylogroup B2 with the exception of companion animals, where a few isolates were detectable. When E. coli subtype definition included ESBL types, phylogenetic grouping and antimicrobial susceptibility data, the proportion of isolates allocated to common clusters was markedly reduced. Nevertheless, relevant proportions of same subtypes were detected in isolates from the human and livestock and companion animal populations included in this study, suggesting exchange of bacteria or bacterial genes between these populations or a common reservoir. In addition, these results clearly showed that there is some similarity between ESBL genes, and bacterial properties in isolates from the different populations. Finally, our current approach provides good insight into common and population-specific clusters, which can be used as a basis for the selection of ESBL-producing isolates from interesting clusters for further detailed characterizations, e.g. by whole genome sequencing. AU - Valentin, Lars AU - Sharp, Hannah AU - Hille, Katja AU - Seibt, Uwe AU - Fischer, Jennie AU - Pfeifer, Yvonne AU - Michael, Geovana Brenner AU - Nickel, Silke AU - Schmiedel, Judith AU - Falgenhauer, Linda AU - Friese, Anika AU - Bauerfeind, Rolf AU - Roesler, Uwe AU - Imirzalioglu, Can AU - Chakraborty, Trinad AU - Helmuth, Reiner AU - Valenza, Giuseppe AU - Werner, Guido AU - Schwarz, Stefan AU - Guerra, Beatriz AU - Appel, Bernd AU - Kreienbrock, Lothar AU - Käsbohrer, Annemarie DA - 2014/10// DO - 10.1016/j.ijmm.2014.07.015 IS - 7 KW - Beta-lactamases KW - CTX-M-1 KW - CTX-M-15 KW - Molecular typing KW - One Health approach PY - 2014 SP - 805 EP - 816 TI - Subgrouping of ESBL-producing Escherichia coli from animal and human sources: An approach to quantify the distribution of ESBL types between different reservoirs T2 - International Journal of Medical Microbiology UR - http://www.ncbi.nlm.nih.gov/pubmed/25213631 UR - https://linkinghub.elsevier.com/retrieve/pii/S1438422114000976 VL - 304 ER - TY - JOUR AU - Zhang, Zhuo AU - Ordonez, Alvaro A. AU - Wang, Hui AU - Li, Yong AU - Gogarty, Kayla R AU - Weinstein, Edward A AU - Daryaee, Fereidoon AU - Merino, Jonathan AU - Yoon, Grace Eunbin AU - Kalinda, Alvin S AU - Mease, Ronnie C AU - Iuliano, James N. AU - Smith-Jones, Peter AU - Jain, Sanjay K. AU - Tonge, Peter J DO - 10.1021/acsinfecdis.8b00182 PY - 2018 TI - Positron Emission Tomography Imaging with 2-[ 18 F]F- p -Aminobenzoic Acid detects Staphylococcus aureus Infections and Monitors Drug Response T2 - ACS Infectious Diseases ER - TY - JOUR AB - Journal homepage: http://www.ijcmas.com Hospitals and other health care institutions are engaged in essential and intensive efforts to prevent health care associated infections (HAI). HAIs are of particular concern to infection prevention professionals because many of these are caused by rapidly developing strains of multidrug resistant organisms. The preventive aspect of hospital acquired infection (HAI) surveillance is difficult to assess. Experts agree that careful cleaning and disinfection of environmental surfaces are essential elements of effective infection prevention programs. Many different hospital staff is involved in monitoring the minimum levels of hospital infection and should be aware of their role in surveillance. Our aim was to investigate the effect of HAI surveillance on frequently handled surfaces from high risk areas and from wards in a tertiary care new teaching hospital. A prospective study was done for a period of 3 months from Jan-Apr 2017. Active surveillance was done on frequently handled surfaces like front desk, door handle, telephone, monitor, cot railings and patients' bedside tables. About 6 swabs were taken from each of these surfaces in various wards and intensive care units (High risk areas) every week. (i.e. 60 swabs per week). Active surveillance of the study showed Staphylococcus aureus and Klebsiella pneumoniae and aerobic spore bearers in places like front desk, telephone, and injection trolleys which are frequently handled by HCWs and the patients. There is no easy way to keep a hospital clean, though we may claim that it is 100% clean. There is need for a more integrated approach to infection and occupational acquired illness prevention. Removing invisible dirt from today's hospitals and the future ones requires sufficiently trained staff, continuous surveillance of environmental hygiene and bioburden education, constant upgrading of practice and two-way communication between those responsible for cleaning and those responsible for infection control. Staphylococcus aureus and Klebsiella pneumoniae, the common causative agents of hospital acquired infections, present in frequently handled surfaces can be prevented by effective disinfection. Environmental service departments should consider the use of newer disinfectants and no-touch decontamination technologies to improve disinfection of surfaces in health care centres. Regular surface cleaning with 1% hypochlorite helped in prevention of infection in our hospital which was proved in our study, since there was no growth found if surface cleaning was done twice every day in high risk areas, and daily in wards. AU - Subbalakshmi, E. DO - 10.20546/ijcmas.2018.702.108 IS - 2 PY - 2018 TI - Surveillance of Hospital Acquired Infection from Frequently Handled Surfaces in a Tertiary Care Teaching Hospital T2 - International Journal of Current Microbiology and Applied Sciences VL - 7 ER - TY - JOUR AB - D espite the fact that current international guidelines suggest initiation of antimicro-bial therapy within an hour of presentation with severe sepsis and septic shock, no clinical studies exist to support this recommendation (1). In reality , initiation of antimicrobial therapy for infections causing critical illness often awaits thorough clinical evaluation, resuscitative measures, initial stabilization , and investigative efforts (2-6). Relatively few studies have rigorously examined the effect of delays of antimi-crobial therapy in critically ill, infected patients (7-17). To the extent that these studies have been done, the delay has most often been timed to admission to the intensive care unit (ICU) or the emergency room. No studies have examined treatment delays in relation to defined physiologic variables such as hypoten-sion. We have recently demonstrated that the onset of hypotension is a critical Objective: To determine the prevalence and impact on mortality of delays in initiation of effective antimicrobial therapy from initial onset of recurrent/persistent hypotension of septic shock. Design: A retrospective cohort study performed between July 1989 and June 2004. Setting: Fourteen intensive care units (four medical, four surgical , six mixed medical/surgical) and ten hospitals (four academic , six community) in Canada and the United States. Patients: Medical records of 2,731 adult patients with septic shock. Interventions: None. Measurements and Main Results: The main outcome measure was survival to hospital discharge. Among the 2,154 septic shock patients (78.9% total) who received effective antimicrobial therapy only after the onset of recurrent or persistent hypotension, a strong relationship between the delay in effective antimicrobial initiation and in-hospital mortality was noted (adjusted odds ratio 1.119 [per hour delay], 95% confidence interval 1.103-1.136, p < .0001). Administration of an antimicrobial effective for isolated or suspected pathogens within the first hour of documented hypo-tension was associated with a survival rate of 79.9%. Each hour of delay in antimicrobial administration over the ensuing 6 hrs was associated with an average decrease in survival of 7.6%. By the second hour after onset of persistent/recurrent hypotension, in-hospital mortality rate was significantly increased relative to receiving therapy within the first hour (odds ratio 1.67; 95% confidence interval, 1.12-2.48). In multivariate analysis (including Acute Physiology and Chronic Health Evaluation II score and therapeutic variables), time to initiation of effective antimicrobial therapy was the single strongest predictor of outcome. Median time to effective antimicrobial therapy was 6 hrs (25-75th per-centile, 2.0-15.0 hrs). Conclusions: Effective antimicrobial administration within the first hour of documented hypotension was associated with increased survival to hospital discharge in adult patients with septic shock. Despite a progressive increase in mortality rate with increasing delays, only 50% of septic shock patients received effective antimicrobial therapy within 6 hrs of documented hypo-tension. (Crit Care Med 2006; 34:1589-1596) AU - Kumar, Anand AU - Roberts, Daniel AU - Wood, Kenneth E AU - Light, Bruce AU - Parrillo, Joseph E AU - Sharma, Satendra AU - Suppes, Robert AU - Feinstein, Daniel AU - Zanotti, Sergio AU - Taiberg, Leo AU - Gurka, David AU - Kumar, Aseem AU - Cheang, Mary DO - 10.1097/01.CCM.0000217961.75225.E9 IS - 6 KW - antimicrobial KW - delay KW - outcome KW - sepsis KW - timing PY - 2006 TI - Duration of hypotension before initiation of effective antimicrobial therapy is the critical determinant of survival in human septic shock* T2 - Crit Care Med UR - http://www.ccmpitt.com/ebm/sepsis/Kumar A, et al. Duration of hypotension before initiation o.pdf VL - 34 ER - TY - JOUR AB - Inflammatory and infectious diseases are a heterogeneous class of diseases that may be divided into infections, acute inflammation and chronic inflammation. Radiological imaging techniques have, with the exception of functional MRI, high sensitivity but lack in specificity. Nuclear medicine techniques, by contrast, allow the in vivo detection in humans of different physiologic and pathologic phenomena and offer noninvasive tools to detect early pathophysiological changes before anatomical changes occur. In this review, we highlight the role of nuclear medicine in inflammation/infection with emphasis on molecular imaging for in vivo histological characterization of affected tissues for diagnostic purposes and follow-up of therapies. We also describe the clinical indications of all available radiopharmaceuticals in the light of the newly available guidelines. AU - Signore, Alberto AU - Glaudemans, Andor W J M DA - 2011/12// DO - 10.1007/s12149-011-0521-z IS - 10 PY - 2011 SP - 681 EP - 700 TI - The molecular imaging approach to image infections and inflammation by nuclear medicine techniques. T2 - Annals of nuclear medicine UR - http://link.springer.com/10.1007/s12149-011-0521-z UR - http://www.ncbi.nlm.nih.gov/pubmed/21837469 VL - 25 ER - TY - JOUR AB - The aim of this study was to develop a positron emission tomography (PET) tracer to visualize and monitor therapeutic response to bacterial infections. In our continued efforts to find maltose based PET tracers that can image bacterial infections, we have designed and prepared 6′′-[18F]fluoromaltotriose as a second generation PET imaging tracer targeting the maltodextrin transporter of bacteria. We have developed methods to synthesize 6′′-deoxy-6′′-[18F]fluoro-α-D-glucopyranosyl-(1-4)-O-α-D-glucopyranosyl-(1-4)-O-D-glucopyranose (6′′-[18F]-fluoromaltotriose) as a bacterial infection PET imaging agent. 6′′-[18F]fluoromaltotriose was prepared from precursor, 2′′,3′′,4′′-tri-O-acetyl-6′′-O-nosyl-α-D-glucopyranosyl-(1-4)-O-2′,3′,6′-tri-O-acetyl-α-D-glucopyranosyl-(1-4)-1,2,3,6-tetra-O-acetyl-D-glucopyranose (per-O-acetyl-6′′-O-nosyl-maltotriose 4). This method utilizes the reaction between precursor 4 and anhydrous [18F]KF/Kryptofix 2.2.2 in dimethylformamide (DMF) at 85°C for 10 minutes to yield per-O-acetyl-6′′-deoxy-6-′′ [18F]-fluoromaltotriose (7). Successive acidic and basic hydrolysis of the acetyl protecting groups in 7 produced 6′′-[18F]fluoromaltotriose (8). Also, cold 6′′- [19F]fluoromaltotriose was prepared from per-O-acetyl-6′′-hydroxymaltotriose via a diethylaminosulfur trifluoride reaction followed by a basic hydrolysis. A successful synthesis of 6′′-[18F]-fluoromaltotriose has been accomplished in 8 ± 1.2% radiochemical yield (decay corrected). Total synthesis time was 120 minutes. Serum stability of 6′′-[18F]fluoromaltotriose at 37°C indicated that 6′′-[18F]-fluoromaltotriose remained intact up to 2 hours. In conclusion, we have successfully synthesized 6′′-[18F]-fluoromaltotriose via direct fluorination of an appropriate precursor of a protected maltotriose. AU - Namavari, Mohammad AU - Gowrishankar, Gayatri AU - Srinivasan, Ananth AU - Gambhir, Sanjiv S. AU - Haywood, Thomas AU - Beinat, Corinne DO - 10.1002/jlcr.3601 IS - 5 PY - 2018 SN - 1932-6203 TI - A novel synthesis of 6′′-[18F]-fluoromaltotriose as a PET tracer for imaging bacterial infection T2 - Journal of Labelled Compounds and Radiopharmaceuticals VL - 61 ER - TY - JOUR AB - The diagnosis of bacterial infections remains a major challenge in medicine. Although numerous contrast agents have been developed to image bacteria, their clinical impact has been minimal because they are unable to detect small numbers of bacteria in vivo, and cannot distinguish infections from other pathologies such as cancer and inflammation. Here, we present a family of contrast agents, termed maltodextrin-based imaging probes (MDPs), which can detect bacteria in vivo with a sensitivity two orders of magnitude higher than previously reported, and can detect bacteria using a bacteria-specific mechanism that is independent of host response and secondary pathologies. MDPs are composed of a fluorescent dye conjugated to maltohexaose, and are rapidly internalized through the bacteria-specific maltodextrin transport pathway, endowing the MDPs with a unique combination of high sensitivity and specificity for bacteria. Here, we show that MDPs selectively accumulate within bacteria at millimolar concentrations, and are a thousand-fold more specific for bacteria than mammalian cells. Furthermore, we demonstrate that MDPs can image as few as 10(5) colony-forming units in vivo and can discriminate between active bacteria and inflammation induced by either lipopolysaccharides or metabolically inactive bacteria. AU - Ning, Xinghai AU - Lee, Seungjun AU - Wang, Zhirui AU - Kim, Dongin AU - Stubblefield, Bryan AU - Gilbert, Eric AU - Murthy, Niren DO - 10.1038/nmat3074 PY - 2011 SN - 1476-1122 (Print)\r1476-1122 (Linking) TI - Maltodextrin-based imaging probes detect bacteria in vivo with high sensitivity and specificity T2 - Nature Materials ER - TY - JOUR AU - Signore, Alberto AU - Glaudemans, Andor W. J. M. DA - 2011/12// DO - 10.1007/s12149-011-0521-z IS - 10 KW - ANTIGRANULOCYTE ANTIBODY KW - BOWEL-DISEASE KW - CLINICAL-VALUE KW - CROHNS-DISEASE KW - IN-VIVO KW - Infection KW - Inflammation KW - MONOCLONAL-ANTIBODY FRAGMENT KW - Molecular imaging KW - Nuclear medicine KW - POSITRON-EMISSION-TOMOGRAPHY KW - Pathophysiology KW - RAT ADJUVANT ARTHRITIS KW - RHEUMATOID-ARTHRITIS KW - Radiopharmaceuticals KW - UNKNOWN ORIGIN PY - 2011 SP - 681 EP - 700 TI - The molecular imaging approach to image infections and inflammation by nuclear medicine techniques T2 - Annals of Nuclear Medicine UR - http://link.springer.com/10.1007/s12149-011-0521-z VL - 25 ER - TY - JOUR AB - // Stefan Wiehr 1 , Philipp Warnke 2,7 , Anna-Maria Rolle 1 , Monika Schütz 2 , Philipp Oberhettinger 2 , Ursula Kohlhofer 3 , Leticia Quintanilla-Martinez 3 , Andreas Maurer 1 , Christopher Thornton 4 , Frederic Boschetti 5 , Gerald Reischl 1 , Ingo B. Autenrieth 2 , Bernd J. Pichler 1 and Stella E. Autenrieth 6 1 Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, Eberhard Karls University Tübingen, Tübingen, Germany 2 Institute of Medical Microbiology and Hygiene, Eberhard Karls University, Tübingen, Germany 3 Institute of Pathology, Eberhard Karls University Tübingen, Tübingen, Germany 4 Biosciences and ISCA Diagnostics Ltd., University of Exeter, Exeter, United Kingdom 5 CheMatech, Faculté des Sciences Mirande, Dijon, France 6 Department of Internal Medicine II, University Hospital Tübingen, Tübingen, Germany 7 Institute of Medical Microbiology, Virology and Hygiene, Rostock University Hospital, Rostock, Germany Correspondence to: Stella E. Autenrieth, email: // Keywords : bacteria, PET/MR, in vivo imaging, 64Cu, antibody, Immunology and Microbiology Section, Immune response, Immunity Received : October 01, 2015 Accepted : February 20, 2016 Published : February 26, 2016 Abstract The specific and rapid detection of Enterobacteriaceae, the most frequent cause of gram-negative bacterial infections in humans, remains a major challenge. We developed a non-invasive method to rapidly detect systemic Yersinia enterocolitica infections using immunoPET (antibody-targeted positron emission tomography) with [ 64 Cu]NODAGA-labeled Yersinia -specific polyclonal antibodies targeting the outer membrane protein YadA. In contrast to the tracer [ 18 F]FDG, [ 64 Cu]NODAGA-YadA uptake co-localized in a dose dependent manner with bacterial lesions of Yersinia -infected mice, as detected by magnetic resonance (MR) imaging. This was accompanied by elevated uptake of [ 64 Cu]NODAGA-YadA in infected tissues, in ex vivo biodistribution studies, whereas reduced uptake was observed following blocking with unlabeled anti-YadA antibody. We show, for the first time, a bacteria-specific, antibody-based, in vivo imaging method for the diagnosis of a Gram-negative enterobacterial infection as a proof of concept, which may provide new insights into pathogen-host interactions. AU - Wiehr, Stefan AU - Warnke, Philipp AU - Rolle, Anna-Maria AU - Schütz, Monika AU - Oberhettinger, Philipp AU - Kohlhofer, Ursula AU - Quintanilla-Martinez, Leticia AU - Maurer, Andreas AU - Thornton, Christopher AU - Boschetti, Frederic AU - Reischl, Gerald AU - Autenrieth, Ingo B. AU - Pichler, Bernd J. AU - Autenrieth, Stella E. DO - 10.18632/oncotarget.7770 PY - 2016 SN - 1949-2553|escape} TI - New pathogen-specific immunoPET/MR tracer for molecular imaging of a systemic bacterial infection T2 - Oncotarget ER - TY - JOUR AB - The modern patient is increasingly susceptible to bacterial infections including those due to multidrug-resistant organisms (MDROs). Noninvasive whole-body analysis with pathogen-specific imaging technologies can significantly improve patient outcomes by rapidly identifying a source of infection and monitoring the response to treatment, but no such technology exists clinically. Methods: We systematically screened 961 random radiolabeled molecules in silico as substrates for essential metabolic pathways in bacteria, followed by in vitro uptake in representative bacteria-Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, and mycobacteria. Fluorine-labeled analogs, that could be developed as PET-based imaging tracers, were evaluated in a murine myositis model. Results: We identified 3 novel, nontoxic molecules demonstrating selective bacterial uptake: para-Aminobenzoic acid (PABA), with uptake in all representative bacteria including Mycobacterium tuberculosis; mannitol, with selective uptake in S. aureus and E. coli; and sorbitol, accumulating only in E. coli. None accumulated in mammalian cells or heat-killed bacteria, suggesting metabolism-derived specificity. In addition to an extended bacterial panel of laboratory strains, all 3 molecules rapidly accumulated in respective clinical isolates of interest including MDROs such as methicillin-resistant S. aureus, extended-spectrum b-lactamase-producing, and carbapenem-resistant Enterobacteriaceae. In a murine myositis model, fluorine-labeled analogs of all 3 molecules could rapidly detect and differentiate infection sites from sterile inflammation in mice (P 5 0.03). Finally, 2-deoxy-2-[F-18]fluoro-D-sorbitol (18F-FDS) can be easily synthesized from 18F-FDG. PET, with 18F-FDS synthesized using current good manufacturing practice, could rapidly differentiate true infection from sterile inflammation to selectively localize E. coli infection in mice. Conclusion: We have developed a systematic approach that exploits unique biochemical pathways in bacteria to develop novel pathogen-specific imaging tracers. These tracers have significant potential for clinical translation to specifically detect and localize a broad range of bacteria, including MDROs. AU - Ordonez, Alvaro A. AU - Weinstein, Edward A. AU - Bambarger, Lauren E. AU - Saini, Vikram AU - Chang, Yong S. AU - DeMarco, Vincent P. AU - Klunk, Mariah H. AU - Urbanowski, Michael E. AU - Moulton, Kimberly L. AU - Murawski, Allison M. AU - Pokkali, Supriya AU - Kalinda, Alvin S. AU - Jain, Sanjay K. DO - 10.2967/jnumed.116.181792 IS - 1 KW - Bacteria KW - Drug-resistance KW - Imaging KW - PET KW - Translational PY - 2017 SN - 1535-5667 (Electronic)\r0161-5505 (Linking) SP - 144 EP - 150 TI - A systematic approach for developing bacteria-specific imaging tracers T2 - Journal of Nuclear Medicine VL - 58 ER - TY - JOUR AB - Context: Infection is a major cause of morbidity and mortality in intensive care units (ICUs) worldwide. However, relatively little information is available about the global epidemiology of such infections. Objective: To provide an up-to-date, international picture of the extent and patterns of infection in ICUs. Design, Setting, and Patients: The Extended Prevalence of Infection in Intensive Care (EPIC II) study, a 1-day, prospective, point prevalence study with follow-up conducted on May 8, 2007. Demographic, physiological, bacteriological, therapeutic, and outcome data were collected for 14 414 patients in 1265 participating ICUs from 75 countries on the study day. Analyses focused on the data from the 13 796 adult (>18 years) patients. Results: On the day of the study, 7087 of 13 796 patients (51%) were considered infected; 9084 (71%) were receiving antibiotics. The infection was of respiratory origin in 4503 (64%), and microbiological culture results were positive in 4947 (70%) of the infected patients; 62% of the positive isolates were gram-negative organisms, 47% were gram-positive, and 19% were fungi. Patients who had longer ICU stays prior to the study day had higher rates of infection, especially infections due to resistant staphylococci, Acinetobacter, Pseudomonas species, and Candida species. The ICU mortality rate of infected patients was more than twice that of noninfected patients (25% [1688/6659] vs 11% [682/6352], respectively; P<.001), as was the hospital mortality rate (33% [2201/6659] vs 15% [942/6352], respectively; P<.001) (adjusted odds ratio for risk of hospital mortality, 1.51; 95% confidence interval, 1.36-1.68; P<.001). Conclusions: Infections are common in patients in contemporary ICUs, and risk of infection increases with duration of ICU stay. In this large cohort, infection was independently associated with an increased risk of hospital death. ©2009 American Medical Association. All rights reserved. AU - Vincent, Jean Louis AU - Rello, Jordi AU - Marshall, John AU - Silva, Eliezer AU - Anzueto, Antonio AU - Martin, Claude D AU - Moreno, Rui AU - Lipman, Jeffrey AU - Gomersall, Charles AU - Sakr, Yasser AU - Reinhart, Konrad DO - 10.1001/jama.2009.1754 IS - 21 PY - 2009 SP - 2323 EP - 2329 TI - International study of the prevalence and outcomes of infection in intensive care units T2 - JAMA - Journal of the American Medical Association UR - http://jama.jamanetwork.com/ VL - 302 ER - TY - JOUR AB - FDG-PET, combined with CT, is nowadays getting more and more relevant for the diagnosis of several infectious and inflammatory diseases and particularly for therapy monitoring. Thus, this paper gives special attention to the role of FDG-PET/CT in the diagnosis and therapy monitoring of infectious and inflammatory diseases. Enough evidence in the literature already exists about the usefulness of FDG-PET/CT in the diagnosis, management, and followup of patients with sarcoidosis, spondylodiscitis, and vasculitis. For other diseases, such as inflammatory bowel diseases, rheumatoid arthritis, autoimmune pancreatitis, and fungal infections, hard evidence is lacking, but studies also point out that FDG-PET/CT could be useful. It is of invaluable importance to have large prospective multicenter studies in this field to provide clear answers, not only for the status of nuclear medicine in general but also to reduce high costs of treatment. AU - Glaudemans, Andor W J M AU - de Vries, Erik F J AU - Galli, Filippo AU - Dierckx, Rudi A J O AU - Slart, Riemer H J A AU - Signore, Alberto DO - 10.1155/2013/623036 PY - 2013 SP - 623036 EP - 623036 TI - The use of (18)F-FDG-PET/CT for diagnosis and treatment monitoring of inflammatory and infectious diseases. T2 - Clinical & developmental immunology UR - http://www.hindawi.com/journals/jir/2013/623036/ UR - http://www.ncbi.nlm.nih.gov/pubmed/24027590 UR - http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC3763592 VL - 2013 ER - TY - RPRT AB - In the past years infections caused by multidrug-resistant Gram-negative bacteria have dramatically increased in all parts of the world. This AU - Exner, Martin AU - Bhattacharya, Sanjay AU - Christiansen, Bärbel TI - Antibiotic resistance: What is so special about multidrug-resistant Gram-negative bacteria? multiresistenten Bakterien? ER - TY - RPRT AU - Mccaughey, Betsy TI - Unnecessary Deaths: The Human and Financial Costs of Hospital Infections 2nd Edition UR - http://emerald.tufts.edu/med/apua/consumers/faqs_2_4154863510.pdf ER - TY - JOUR AB - Background. Diarrheagenic Escherichia coli (DEC) strains are a major cause of diarrhea in children under 5 years of age worldwide. DEC pathogenicity relies on the interaction of bacteria with environmental factors, including the host’s resident gut microbiota. Previous reports have shown changes in the gut microbiota’s composition during episodes of diarrhea, which may increase the pathogenicity of DEC strains. More intense and detailed identification of microbiota strains specifically associated with DEC infections and disease is needed to pinpoint their role in DEC pathogenicity. Aim. To identify resident indicative bacterial taxa in DEC-positive diarrhea stool samples of Chilean children. Methods. We analyzed 63 diarrheal stool samples from children 1-5 years of age by FilmArray® GI in order to identify a potential pathogen and to group diarrhea episodes into those caused by DEC as sole pathogen (DEC group, 32 samples) and those caused by an enteric virus as sole pathogen (viral group, 31 samples). In addition, 30 stool samples from healthy children, negative for enteric pathogens, were evaluated (healthy group). The 16S rRNA gene was amplified and sequenced using 454 pyrosequencing. Sequences were clustered into operational taxonomic units (OTUs) at 99% identity and their representatives were used to assign them to operational phylogenetic units (OPUs) using a phylogenetic inference approach. Results. Taxa assignment using the OPU approach resulted in a lower number of units but with higher accuracy compared to the OTU approach. Data analysis indicated an increase in sequences belonging to the phylum Proteobacteria in the DEC group compared to the viral and healthy groups. Samples displayed a statistically different community structure by sample grouping by redundancy analysis and ANOVA. Escherichia albertii (p=0.001), Citrobacter werkmanii (p=0.001), Yersinia enterocolitica, subsp. paleartica (p=0.048) and Haemophilus sputorum (p=0.028) were indicative species for the DEC group as compared to the viral and healthy groups. Conclusion. Gut microbiota in Chilean children with DEC-positive diarrhea differed from microbiota associated with enteric virus and healthy children. Indicative species found in this study may prove relevant in advancing our understanding of the relationship between resident gut microbiota and DEC leading to the occurrence of disease. AU - Gallardo, Pablo AU - Izquierdo, Mariana AU - Vidal, Roberto M. AU - Chamorro-Veloso, Nayaret AU - Rosselló-Móra, Ramon AU - O'Ryan, Miguel AU - Farfán, Mauricio J. DO - 10.3389/fcimb.2017.00424 PY - 2017 SN - 2235-2988 (Electronic) 2235-2988 (Linking) TI - Distinctive Gut Microbiota Is Associated with Diarrheagenic Escherichia coli Infections in Chilean Children T2 - Frontiers in Cellular and Infection Microbiology ER - TY - JOUR AU - Li, Zi-Bo AU - Wu, Zhanhong AU - Cao, Qizhen AU - Dick, David W. AU - Tseng, Jeffrey R. AU - Gambhir, Sanjiv S. AU - Chen, Xiaoyuan DO - 10.1007/s11307-007-0125-0 PY - 2008 SN - 1536-1632 TI - The Synthesis of 18F-FDS and Its Potential Application in Molecular Imaging T2 - Molecular Imaging and Biology ER - TY - JOUR AB - OBJECTIVES This study sought to determine the value of (18)F-fluorodeoxyglucose positron emission tomography/computed tomography ((18)F-FDG PET/CT) for diagnosing prosthetic valve endocarditis (PVE). BACKGROUND The diagnosis of PVE remains challenging. In PVE cases, initial echocardiography is normal or inconclusive in almost 30%, leading to a decreased diagnostic accuracy for the modified Duke criteria. METHODS We prospectively studied 72 consecutive patients suspected of having PVE. All of the patients were subjected to clinical, microbiological, and echocardiographic evaluation. Cardiac PET/CT was performed at admission. The final diagnosis was defined according to the clinical and/or pathological modified Duke criteria determined during a 3-month follow-up. RESULTS Thirty-six patients (50%) exhibited abnormal FDG uptake around the site of the prosthetic valve. The sensitivity, specificity, positive predictive value, negative predictive value, and global accuracy were as follows (95% confidence interval): 73% (54% to 87%), 80% (56% to 93%), 85% (64% to 95%), 67% (45% to 84%), and 76% (63% to 86%), respectively. Adding abnormal FDG uptake around the prosthetic valve as a new major criterion significantly increased the sensitivity of the modified Duke criteria at admission (70% [52% to 83%] vs. 97% [83% to 99%], p = 0.008). This result was due to a significant reduction (p < 0.0001) in the number of possible PVE cases from 40 (56%) to 23 (32%). CONCLUSIONS The use of (18)F-FDG PET/CT was helpful for diagnosing PVE. The results of this study support the addition of abnormal FDG uptake as a novel major criterion for PVE. AU - Saby, Ludivine AU - Laas, Olivia AU - Habib, Gilbert AU - Cammilleri, Serge AU - Mancini, Julien AU - Tessonnier, Laetitia AU - Casalta, Jean-Paul AU - Gouriet, Frederique AU - Riberi, Alberto AU - Avierinos, Jean-Francois AU - Collart, Frederic AU - Mundler, Olivier AU - Raoult, Didier AU - Thuny, Franck DA - 2013/6// DO - 10.1016/j.jacc.2013.01.092 IS - 23 PY - 2013 SP - 2374 EP - 2382 TI - Positron Emission Tomography/Computed Tomography for Diagnosis of Prosthetic Valve Endocarditis T2 - Journal of the American College of Cardiology UR - http://www.ncbi.nlm.nih.gov/pubmed/23583251 UR - http://linkinghub.elsevier.com/retrieve/pii/S0735109713014113 VL - 61 ER - TY - JOUR AB - Purpose: The noninvasive imaging of bacterial infections is critical in order to reduce mortality and morbidity caused by these diseases. The recently reported18F-FDS (18F-2-fluorodeoxy sorbitol) as a PET (positron emission tomography) tracer can be used to image Enterobacteriaceae-specific infections and provides a potential alternative to this problem compared with other probes for imaging infections. In this study, automatic synthesis, validation of18F-FDS and a first-in-human study were performed and discussed. Methods: A multifunctional synthesis module was employed for the radiosynthesis of18F-FDG (18F-2-fluorodeoxy glucose) and18F-FDS starting from18F ion using two-pot three-step fully automated reactions. The behavior of18F-FDS as an in vivo imaging probe for infections was evaluated in an Escherichia coli mouse infection model. The first detailed pharmacokinetic and biodistribution parameters were obtained from healthy human volunteers. Results: The uptake of18F-FDS in an E. coli mouse-myositis infection model was easily differentiated from other organs and normal muscle. Intensive lesion uptake declined after antibiotic treatment. In the pilot human study, no adverse effects due to18F-FDS were observed up to 24 h post-injection. The radiotracer was rapidly cleared from the circulation and excreted mainly through the urinary system. Conclusion: We conclude that18F-FDS PET holds great potential for appropriate and effective for the imaging of bacterial infections in vivo. These preliminary results indicate that further clinical studies are warranted. AU - Yao, Shaobo AU - Xing, Haiqun AU - Zhu, Wenjia AU - Wu, Zhanhong AU - Zhang, Yingqiang AU - Ma, Yanru AU - Liu, Yimin AU - Huo, Li AU - Zhu, Zhaohui AU - Li, Zibo AU - Li, Fang DO - 10.1016/j.nucmedbio.2015.11.008 KW - 18F-FDS KW - Automated synthesis KW - Gram-negative bacteria KW - Infection KW - PET PY - 2016 SN - 1872-9614 (Electronic)\r0969-8051 (Linking) TI - Infection Imaging With18F-FDS and First-in-Human Evaluation T2 - Nuclear Medicine and Biology ER - TY - JOUR AB - The Enterobacteriaceae are a family of rod-shaped Gram-negative bacteria that normally inhabit the gastrointestinal tract and are the most common cause of Gram-negative bacterial infections in humans. In addition to causing serious multidrug-resistant, hospital-acquired infections, a number of Enterobacteriaceae species are also recognized as biothreat pathogens. As a consequence, new tools are urgently needed to specifically identify and localize infections due to Enterobacteriaceae and to monitor antimicrobial efficacy. In this report, we used commercially available 2-[(18)F]-fluorodeoxyglucose ((18)F-FDG) to produce 2-[(18)F]-fluorodeoxysorbitol ((18)F-FDS), a radioactive probe for Enterobacteriaceae, in 30 min. (18)F-FDS selectively accumulated in Enterobacteriaceae, but not in Gram-positive bacteria or healthy mammalian or cancer cells in vitro. In a murine myositis model, (18)F-FDS positron emission tomography (PET) rapidly differentiated true infection from sterile inflammation with a limit of detection of 6.2 ± 0.2 log10 colony-forming units (CFU) for Escherichia coli. Our findings were extended to models of mixed Gram-positive and Gram-negative thigh co-infections, brain infection, Klebsiella pneumonia, and mice undergoing immunosuppressive chemotherapy. This technique rapidly and specifically localized infections due to Enterobacteriaceae, providing a three-dimensional holistic view within the animal. Last, (18)F-FDS PET monitored the efficacy of antimicrobial treatment, demonstrating a PET signal proportionate to the bacterial burden. Therapeutic failures associated with multidrug-resistant, extended-spectrum β-lactamase (ESBL)-producing E. coli infections were detected in real time. Together, these data show that (18)F-FDS is a candidate imaging probe for translation to human clinical cases of known or suspected infections owing to Enterobacteriaceae. AU - Weinstein, E. A. AU - Ordonez, A. A. AU - DeMarco, V. P. AU - Murawski, A. M. AU - Pokkali, S. AU - MacDonald, E. M. AU - Klunk, M. AU - Mease, R. C. AU - Pomper, M. G. AU - Jain, S. K. DO - 10.1126/scitranslmed.3009815 IS - 259 PY - 2014 SN - 1946-6234 SP - 259ra146 EP - 259ra146 TI - Imaging Enterobacteriaceae infection in vivo with 18F-fluorodeoxysorbitol positron emission tomography T2 - Science Translational Medicine VL - 6 ER - TY - JOUR AB - Nosocomial infections are also known as hospital-acquired/associated infections. National Healthcare Safety Network along with Centers for Disease Control for surveillance has classified nosocomial infection sites into 13 types with 50 infection sites, which are specific on the basis of biological and clinical criteria. The agents that are usually involved in hospital-acquired infections include Streptococcus spp., Acinetobacter spp., enterococci, Pseudomonas aeruginosa, coagulase-negative staphylococci, Staphylococcus aureus, Bacillus cereus, Legionella and Enterobacteriaceae family members, namely, Proteus mirablis, Klebsiella pneumonia, Escherichia coli, Serratia marcescens. Nosocomial pathogens can be transmitted through person to person, environment or contaminated water and food, infected individuals, contaminated healthcare personnel's skin or contact via shared items and surfaces. Mainly, multi-drug-resistant nosocomial organisms include methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci, Pseudomonas aeruginosa and Klebsiella pneumonia, whereas Clostridium difficile shows natural resistance. Excessive and improper use of broad-spectrum antibiotics, especially in healthcare settings, is elevating nosocomial infections, which not only becomes a big health care problem but also causes great economic and production loss in the community. Nosocomial infections can be controlled by measuring and comparing the infection rates within healthcare settings and sticking to the best healthcare practices. Centers for Disease Control and Prevention provides the methodology for surveillance of nosocomial infections along with investigation of major outbreaks. By means of this surveillance, hospitals can devise a strategy comprising of infection control practices. AU - Khan, Hassan Ahmed AU - Ahmad, Aftab AU - Mehboob, Riffat DO - 10.1016/j.apjtb.2015.05.001 IS - 7 KW - Antibiotics KW - Control strategies KW - Hospital-acquired infection KW - Surveillance PB - Elsevier PY - 2015 SP - 509 EP - 514 TI - Nosocomial infections and their control strategies T2 - Asian Pacific Journal of Tropical Biomedicine UR - http://dx.doi.org/10.1016/j.apjtb.2015.05.001 VL - 5 ER - TY - JOUR AB - PURPOSE: [(18)F]fluorodeoxysorbitol ([(18)F]FDS) is the first radiopharmaceutical specific for a category of bacteria and has the potential to specifically detect Enterobacteriaceae infections. The purpose of this study was to testify the safety and investigate the biodistribution and radiation dosimetry of [(18)F]FDS in healthy human bodies.\n\nPROCEDURES: Six healthy subjects were intravenously injected with 320-520 MBq [(18)F]FDS. On each subject, 21 whole-body emission scans and a brain scan were conducted at settled time points within the next 4 h. Residence time for each source organ was determined by multi-exponential regression. Absorbed doses for target organs and effective dose were calculated via OLINDA/EXM.\n\nRESULTS: No adverse events due to [(18)F]FDS injection were observed in the study. The tracer was cleared rapidly from the blood pool through the urinary system. A small portion was cleared into the gut through the hepatobiliary system. The effective dose (ED) was estimated to be 0.021 ± 0.001 mSv/MBq. The organ receiving the highest absorbed dose was the urinary bladder wall (0.25 ± 0.03 mSv/MBq).\n\nCONCLUSIONS: [(18)F]FDS is safe and well tolerated. The effective dose was comparable to that of other F-18 labeled radiotracers. [(18)F]FDS is suitable for human use from a radiation dosimetry perspective. AU - Zhu, Wenjia AU - Yao, Shaobo AU - Xing, Haiqun AU - Zhang, Hui AU - Tai, Yuan chuan AU - Zhang, Yingqiang AU - Liu, Yimin AU - Ma, Yanru AU - Wu, Chenxi AU - Wang, Hongkai AU - Li, Zibo AU - Wu, Zhanhong AU - Zhu, Zhaohui AU - Li, Fang AU - Huo, Li DO - 10.1007/s11307-016-0946-9 KW - Biodistribution KW - Enterobacteriaceae KW - PET KW - Radiation dosimetry KW - [18F] FDS PY - 2016 SN - 1860-2002 TI - Biodistribution and Radiation Dosimetry of the Enterobacteriaceae-Specific Imaging Probe [18F]Fluorodeoxysorbitol Determined by PET/CT in Healthy Human Volunteers T2 - Molecular Imaging and Biology ER - TY - JOUR AB - Hospital-acquired infections (HAIs), including emerging multi-drug resistant organisms, threaten healthcare systems worldwide. Efficient containment measures of HAIs must mobilize the entire healthcare network. Thus, to best understand how to reduce the potential scale of HAI epidemic spread, we explore patient transfer patterns in the French healthcare system. Using an exhaustive database of all hospital discharge summaries in France in 2014, we construct and analyze three patient networks based on the following: transfers of patients with HAI (HAI-specific network); patients with suspected HAI (suspected-HAI net-work); and all patients (general network). All three networks have heterogeneous patient flow and demonstrate small-world and scale-free characteristics. Patient populations that comprise these networks are also heterogeneous in their movement patterns. Ranking of hospitals by centrality measures and comparing community clustering using community detection algorithms shows that despite the differences in patient population, the HAI-specific and suspected-HAI networks rely on the same underlying structure as that of the general network. As a result, the general network may be more reliable in studying potential spread of HAIs. Finally, we identify transfer patterns at both the French regional and departmental (county) levels that are important in the identification of key hospital centers, patient flow trajectories, and regional clusters that may serve as a basis for novel wide-scale infection control strategies. AU - Nekkab, Narimane AU - Astagneau, Pascal AU - Temime, Laura AU - Crépey, Pascal DO - 10.1371/journal.pcbi.1005666 IS - 8 PY - 2017 SN - 1111111111 TI - Spread of hospital-acquired infections: A comparison of healthcare networks T2 - PLoS Computational Biology VL - 13 ER - TY - JOUR AB - BACKGROUND Injury to the airways after smoke inhalation is a major mortality risk factor in victims of burn injuries, resulting in a 15-45% increase in patient deaths. Damage to the airways by smoke may induce acute respiratory distress syndrome (ARDS), which is partly characterized by hypoxemia in the airways. While ARDS has been associated with bacterial infection, the impact of hypoxemia on airway microbiota is unknown. Our objective was to identify differences in microbiota within the airways of burn patients who develop hypoxemia early after inhalation injury and those that do not using next-generation sequencing of bacterial 16S rRNA genes. RESULTS DNA was extracted from therapeutic bronchial washings of 48 patients performed within 72 hours of hospitalization for burn and inhalation injury at the North Carolina Jaycee Burn Center. DNA was prepared for sequencing using a novel molecule tagging method and sequenced on the Illumina MiSeq platform. Bacterial species were identified using the MTToolbox pipeline. Patients with hypoxemia, as indicated by a PaO2/FiO2 ratio ≤ 300, had a 30% increase in abundance of Streptococcaceae and Enterobacteriaceae and 84% increase in Staphylococcaceae as compared to patients with a PaO2/FiO2 ratio > 300. Wilcoxon rank-sum test identified significant enrichment in abundance of OTUs identified as Prevotella melaninogenica (p = 0.042), Corynebacterium (p = 0.037) and Mogibacterium (p = 0.048). Linear discriminant effect size analysis (LefSe) confirmed significant enrichment of Prevotella melaninognica among patients with a PaO2/FiO2 ratio ≤ 300 (p<0.05). These results could not be explained by differences in antibiotic treatment. CONCLUSIONS The airway microbiota following burn and inhalation injury is altered in patients with a PaO2/FiO2 ratio ≤ 300 early after injury. Enrichment of specific taxa in patients with a PaO2/FiO2 ratio ≤ 300 may indicate airway environment and patient changes that favor these microbes. Longitudinal studies are necessary to identify stably colonizing taxa that play roles in hypoxemia and ARDS pathogenesis. AU - Walsh, Dana M AU - McCullough, Shaun D AU - Yourstone, Scott AU - Jones, Samuel W AU - Cairns, Bruce A AU - Jones, Corbin D AU - Jaspers, Ilona AU - Diaz-Sanchez, David DO - 10.1371/journal.pone.0173848 IS - 3 PB - Public Library of Science PY - 2017 SP - e0173848 EP - e0173848 TI - Alterations in airway microbiota in patients with PaO2/FiO2 ratio ≤ 300 after burn and inhalation injury. T2 - PloS one UR - http://www.ncbi.nlm.nih.gov/pubmed/28358811 UR - http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC5373524 VL - 12 ER - TY - JOUR AB - The frequency of antimicrobial resistance has increased globally due to misuse and overuse of antibiotics, and multi-drug resistant (MDR) bacteria are now recognized as a major cause of hospital-acquired infections (HAI). Our aim was to investigate the prevalence, distribution, and antimicrobial susceptibility rates of MDR bacteria in patients with HAI from a tertiary hospital in China. We retrospectively evaluated all patients with a confirmed diagnosis of bacterial infection at a tertiary general hospital in Jining, for the period between January 2012 and December 2014. The following clinical and demographic data were collected: age, sex, specimens, treatment, microbiology results, and antibiotic resistance patterns of isolates. Bacterial identification and susceptibility testing were performed using VITEK 2 COMPACT system. We screened a total of 15,588 patients, out of which 7579 (48.6%) had an HAI. MDR showed 3223 out of 7579 isolates (42.5%). The most frequently isolated MDR bacteria in patients with HAI were extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli (n = 1216/3223, 37.7%), MDR Pseudomonas aeruginosa (n = 627/3223, 19.5%) and MDR Acinetobacter baumannii (n = 588/3223, 18.2%). MDR-HAI were more common in males (2074/3223, 64.4%) and in elderly patients (≥60 years; 1196/3223, 37.1%). Sputum was the main source of MDR isolates (2056/3223, 63.8%). Patients with MDR-HAI were predominantly distributed in different types of intensive care units. MDR strains in our study showed resistance to most current antibiotics. Overall, patients with HAI infections attributed to MDR bacteria were widely distributed in our hospital. Enhanced surveillance of MDR bacteria is critical for guiding the rational use of antibiotics and reducing the incidence of HAI. AU - Wang, Meng AU - Wei, Hongyan AU - Zhao, Yaxin AU - Shang, Linlin AU - Di, Linlin AU - Lyu, Chuanfeng AU - Liu, Jun DO - 10.17305/BJBMS.2018.3826 IS - 1 PY - 2019 TI - Analysis of multidrug-resistant bacteria in 3223 patients with hospital-acquired infections (HAI) from a tertiary general hospital in China T2 - Bosnian Journal of Basic Medical Sciences VL - 19 ER - TY - JOUR AB - Background: Sustainable systematic interventions are important for infection prevention and control (IPC). Data from surveillance of healthcare-associated infections (HAI) provides feedback for implementation of IPC programs. To address the paucity of such data in Asia, we searched for national HAI surveillance and IPC programs in this region. Methods: Data were analysed from open access national surveillance reports of three Asian countries: Taiwan, South Korea and Japan from 2008 to 2015. National IPC programs were identified. Results: There were differences among the countries in surveillance protocols, hospital coverage rates, and national IPC policies and programs. Nevertheless, there was a 53.0% reduction in overall HAI over the 8-year period. This consisted of a decrease from 9.34 to 5.03 infections per 1000 patient-days in Taiwan, from 7.56 to 2.76 in Korea, and from 4.41 to 2.74 in Japan (Poisson regression, all p < 0.05). Across the three countries, Escherichia coli and Candida albicans were the major pathogens for urinary tract infection. Staphylococcus aureus, Acinetobacter baumannii and Enterococcus faecium were common bloodstream pathogens. For pneumonia, S. aureus, A. baumannii, Pseudomonas aeruginosa, and Klebsiella pneumoniae were the predominant pathogens, with considerable country differences. There was a 64.6% decrease in the number of isolates of methicillin-resistant S. aureus, 38.4% decrease in carbapenem-resistant P. aeruginosa and 49.2% decrease in carbapenem-resistant A. baumannii (CRAB) in Taiwan (all p < 0.05), and similarly in Korea with the exception of CRAB (30.5 and 50.4% reduction, respectively, both p < 0.05). Conclusion: We found a significant decrease in HAI across the three countries in association with sequential multifaceted interventions such as hand hygiene, care bundles, and antimicrobial stewardships. Further regional collaboration could be forged to develop joint strategies to prevent HAI. AU - Chiang, Cho Han AU - Pan, Sung Ching AU - Yang, Tyan Shin AU - Matsuda, Keisuke AU - Kim, Hong Bin AU - Choi, Young Hwa AU - Hori, Satoshi AU - Wang, Jann Tay AU - Sheng, Wang Huei AU - Chen, Yee Chun AU - Chang, Feng Yee AU - Chang, Shan Chwen DO - 10.1186/s13756-018-0422-1 IS - 1 KW - Antimicrobial resistance KW - Healthcare-associated infections KW - Infection prevention and control program KW - National policy KW - National surveillance PB - Antimicrobial Resistance & Infection Control PY - 2018 SP - 1 EP - 12 TI - Healthcare-associated infections in intensive care units in Taiwan, South Korea, and Japan: Recent trends based on national surveillance reports T2 - Antimicrobial Resistance and Infection Control VL - 7 ER - TY - JOUR AB - Background: Gram-negative bacteria are increasingly responsible for nosocomial infections, including ICU-acquired infections. Due to high virulence, rate of multi-drug resistance and limited availability of new agents, these infections create cumbersome clinical burdens, making it important to reduce the risk of their occurrence. The aim of the study was to assess epidemiology-related factors and outcomes of Gram-negative, ICU-acquired infections in a cohort of medical-surgical patients. Methods: A retrospective survey was conducted on all patients admitted to a mixed ICU from January 2012 to December 2013. 'ICU-acquired infections' were defined as new infections acquired no less than 48h after ICU admission. Diagnosis was made according to the Centers for Disease Control and Prevention National Healthcare Safety Network (CDC/NHSN) criteria. Differences across patients who did and did not acquire a Gram-negative infection were tested regarding age, sex, body mass index, medical or surgical admission, cardiovascular comorbidities, chronic obstructive pulmonary disease, diabetes, end-stage renal failure, co-existing tumours and prophylactic anti-fungal treatment. Multivariate analysis was used to assess the independency of these associations. Finally, differences in ICU-mortality, ICU-length of stay and duration of mechanical ventilation were tested across patients with and without new, ICU-acquired, Gram-negative infections. Results: Of 494 patients admitted to the ICU, 46 (9.3%) acquired an infection 48 or more hours after admittance. In 30/46 patients (65.2%) the isolated bacterium was Gram-negative. Univariate analysis showed that clinical factors associated with new ICU-acquired Gram-negative infections were medical admission (p < 0.001, 95% CI 0.59 - 0.29, OR = 0.13), chronic kidney disease (p = 0.018, 95% CI 1.20 - 7.34, OR = 2.98) and prophylactic antifungal therapy (p < 0.001, 95% CI 1.91 - 9.79, OR = 4.33). At multivariate analysis, only medical admission and prophylactic antifungal therapy were significantly associated with ICU-acquired Gram-negative infections. Higher ICU-length of stay and longer duration of mechanical ventilation were associated with these infections while ICU-mortality did not significantly differ. Conclusions: ICU-acquired Gram-negative infections were common in a cohort of mixed medical-surgical patients. Only medical admission and anti-fungal prophylaxis were found to be independently associated with these infections; they were not found to have a significant effect on ICU-mortality. AU - Chelazzi, Cosimo AU - Pettini, Eleonora AU - Villa, Gianluca AU - De Gaudio, A. Raffaele DO - 10.1186/s12871-015-0106-9 PY - 2015 SN - 1471-2253 TI - Epidemiology, associated factors and outcomes of ICU-acquired infections caused by Gram-negative bacteria in critically ill patients: An observational, retrospective study T2 - BMC Anesthesiology ER - TY - JOUR AB - Healthcare associated infections (HAI) are among the major complications of modern medical therapy. The most important HAIs are those related to invasive devices: central line-associated bloodstream infections (CLABSI), catheter-associated urinary tract infections (CAUTI), ventilator-associated pneumonia (VAP) as well as surgical site infections (SSI). HAIs are associated with significant mortality, morbidities and increasing healthcare cost. The cited case-fatality rate ranges from 2.3% to 14.4% depending on the type of infection. In this mini-review, we shed light on these aspects as well as drivers to decrease HAIs. © 2014 King Saud Bin Abdulaziz University for Health Sciences. AU - Al-Tawfiq, Jaffar A. AU - Tambyah, Paul A. DO - 10.1016/j.jiph.2014.04.003 IS - 4 KW - Hand hygiene KW - Healthcare associated infection PB - King Saud Bin Abdulaziz University for Health Sciences PY - 2014 SP - 339 EP - 344 TI - Healthcare associated infections (HAI) perspectives T2 - Journal of Infection and Public Health UR - http://dx.doi.org/10.1016/j.jiph.2014.04.003 VL - 7 ER - TY - JOUR AB - Health-care-associated infection is the most frequent result of unsafe patient care worldwide, but few data are available from the developing world. We aimed to assess the epidemiology of endemic health-care-associated infection in developing countries. We searched electronic databases and reference lists of relevant papers for articles published 1995-2008. Studies containing full or partial data from developing countries related to infection prevalence or incidence - including overall health-care-associated infection and major infection sites, and their microbiological cause - were selected. We classified studies as low-quality or high-quality according to predefined criteria. Data were pooled for analysis. Of 271 selected articles, 220 were included in the final analysis. Limited data were retrieved from some regions and many countries were not represented. 118 (54) studies were low quality. In general, infection frequencies reported in high-quality studies were greater than those from low-quality studies. Prevalence of health-care-associated infection (pooled prevalence in high-quality studies, 15·5 per 100 patients [95 CI 12·6-18·9]) was much higher than proportions reported from Europe and the USA. Pooled overall health-care-associated infection density in adult intensive-care units was 47·9 per 1000 patient-days (95 CI 36·7-59·1), at least three times as high as densities reported from the USA. Surgical-site infection was the leading infection in hospitals (pooled cumulative incidence 5·6 per 100 surgical procedures), strikingly higher than proportions recorded in developed countries. Gram-negative bacilli represented the most common nosocomial isolates. Apart from meticillin resistance, noted in 158 of 290 (54) Staphylococcus aureus isolates (in eight studies), very few articles reported antimicrobial resistance. The burden of health-care-associated infection in developing countries is high. Our findings indicate a need to improve surveillance and infection-control practices. World Health Organization. © 2011 Elsevier Ltd. AU - Allegranzi, Benedetta AU - Nejad, Sepideh Bagheri AU - Combescure, Christophe AU - Graafmans, Wilco AU - Attar, Homa AU - Donaldson, Liam AU - Pittet, Didier DO - 10.1016/S0140-6736(10)61458-4 IS - 9761 PB - Elsevier Ltd PY - 2011 SP - 228 EP - 241 TI - Burden of endemic health-care-associated infection in developing countries: Systematic review and meta-analysis T2 - The Lancet UR - http://dx.doi.org/10.1016/S0140-6736(10)61458-4 VL - 377 ER - TY - JOUR AB - Objectives: To evaluate environmental contamination with methotrexate, cyclophosphamide, and ifosfamide in Quebec, Canada, community pharmacies and to describe hazardous drug handling practices in these pharmacies. Methods: Three standardized sites were sampled in each participating community pharmacy. Samples were analyzed for the presence of cyclophosphamide, ifosfamide, and methotrexate by high-performance liquid chromatography tandem mass spectrometry. The limits of detection were 0.10, 0.12, and 0.41 ng/mL for cyclophosphamide, ifosfamide, and methotrexate, respectively. Nine working practices were assessed. Results: 20 community pharmacies participated in the study, and 60 samples were analyzed. No traces of cyclophosphamide or ifosfamide were detected. Traces of methotrexate were found in 12 of 20 pharmacies (60%). Of the 20 pharmacies, 8 (40%) had a storage space reserved for hazardous drugs and none had a preparation area reserved for handling methotrexate tablets. All of the participating community pharmacies had a tablet counter reserved for the handling of hazardous drugs, and all pharmacies cleaned their tablet counter reserved for handling hazardous drugs after use. None of the pharmacies cut or crushed methotrexate tablets. Conclusion: The growing number of hazardous drugs represents a challenge for community pharmacies. Community pharmacists must be made aware of their presence and the need to comply with personal protection measures to reduce staff occupational exposure to hazardous drugs. AU - Merger, Delphine AU - Tanguay, Cynthia AU - Langlois, Éric AU - Lefebvre, Michel AU - Bussières, Jean Franco̧is DO - 10.1331/JAPhA.2013.12245 IS - 4 KW - Community pharmacies KW - Environmental monitoring KW - Methotrexate KW - Occupational exposure PB - Elsevier Masson SAS PY - 2013 SP - 423 EP - 426 TI - Environmental contamination with methotrexate in Canadian community pharmacies T2 - Journal of the American Pharmacists Association UR - http://dx.doi.org/10.1331/JAPhA.2013.12245 VL - 53 ER - TY - GEN AB -

This review summarizes recent epidemiology of Gram-negative infections in selected countries from Latin American and Caribbean adult intensive care units (ICUs). A systematic search of the biomedical literature (PubMed) was performed to identify articles published over the last decade. Where appropriate, data also were collected from the reference list of published articles, health departments of specific countries, and registries. Independent cohort data from all countries (Argentina, Brazil, Chile, Colombia, Cuba, Mexico, Trinidad and Tobago, and Venezuela) signified a high rate of ICU infections (prevalence: Argentina, 24%; Brazil, 57%). Gram-negative pathogens, predominantly Acinetobacter baumannii, Klebsiella pneumoniae, Pseudomonas aeruginosa , and Escherichia coli , accounted for > 50% of ICU infections, which were often complicated by the presence of multidrug-resistant strains and clonal outbreaks. Empirical use of antimicrobial agents was identified as a strong risk factor for resistance development and excessive mortality. Infection control strategies utilizing hygiene measures and antimicrobial stewardship programs reduced the rate of device-associated infections. To mitigate the poor health outcomes associated with infections by multidrug-resistant Gram-negative bacteria, urgent focus must be placed on infection control strategies and local surveillance programs.

AU - Luna, Carlos M. AU - Rodriguez-Noriega, Eduardo AU - Bavestrello, Luis AU - Guzmán-Blanco, Manuel DO - 10.1155/2014/480463 PY - 2014 TI - Gram-negative infections in adult intensive care units of latin america and the caribbean T2 - Critical Care Research and Practice ER - TY - JOUR AB - Maternal sun exposure in gestation and throughout the lifetime is necessary for vitamin D synthesis, and living near the sea is a population level index of seafood consumption. The aim of this study was to estimate the incidence rate of multiple sclerosis (MS) in Wales and examine its association with sun exposure, coastal living, and latitude. The study used a database of MS hospital visits and admissions in Wales between 2002 and 2013. For the 1,909 lower layer super output areas (LSOAs) in Wales, coastal status, population, longitude/latitude, and average sunshine hours per day were obtained. Age-specific and age-standardised MS incidence were calculated and modelled using Poisson regression. The distribution of births by month was compared between MS cases and the combined England and Wales population. There were 3,557 new MS cases between 2002 and 2013, with an average annual incidence of 8.14 (95% CI: 7.69-8.59) among males and 12.97 (95% CI: 12.44-13.50) among females per 100,000 population. The female-to-male ratio was 1.86:1. For both sexes combined, the average annual incidence rate was 9.10 (95% CI: 8.80-9.40). All figures are age-standardized to the 1976 European standard population. Compared to the combined England and Wales population, more people with MS were born in April, observed-to-expected ratio: 1.21 (95% CI: 1.08-1.36). MS incidence varied directly with latitude and inversely with sunshine hours. Proximity to the coast was associated with lower MS incidence only in easterly areas. This study shows that MS incidence rate in Wales is comparable to the rate in Scotland and is associated with environmental factors that probably represent levels of vitamin D. AU - Murakami, Eri AU - Shionoya, Takao AU - Komenoi, Suguru AU - Suzuki, Yuji AU - Sakane, Fumio DO - 10.1371/journal.pone PY - 2016 SN - 0018726708094 TI - Cloning and characterization of novel testis-Specific diacylglycerol kinase η splice variants 3 and 4 T2 - PLoS ONE ER - TY - JOUR AB - PURPOSE Infective endocarditis (IE) is widely underdiagnosed or diagnosed after a major delay. The diagnosis is currently based on the modified DUKE criteria, where the only validated imaging technique is echocardiography, and remains challenging especially in patients with an implantable cardiac device. The aim of this study was to assess the incremental diagnostic role of (18)F-FDG PET/CT in patients with an implanted cardiac device and suspected IE. METHODS We prospectively analysed 27 consecutive patients with an implantable device evaluated for suspected device-related IE between January 2011 and June 2013. The diagnostic probability of IE was defined at presentation according to the modified DUKE criteria. PET/CT was performed as soon as possible following the clinical suspicion of IE. Patients then underwent medical or surgical treatment based on the overall clinical evaluation. During follow-up, we considered: lead cultures in patients who underwent extraction, direct inspection and lead cultures in those who underwent surgery, and a clinical/instrumental reevaluation after at least 6 months in patients who received antimicrobial treatment or had an alternative diagnosis and were not treated for IE. After the follow-up period, the diagnosis was systematically reviewed by the multidisciplinary team using the modified DUKE criteria and considering the new findings. RESULTS Among the ten patients with a positive PET/CT scan, seven received a final diagnosis of "definite IE", one of "possible IE" and two of "IE rejected". Among the 17 patients with a negative PET/CT scan, four were false-negative and received a final diagnosis of definite IE. These patients underwent PET/CT after having started antibiotic therapy (≥48 h) or had a technically suboptimal examination. CONCLUSION In patients with a cardiac device, PET/CT increases the diagnostic accuracy of the modified Duke criteria for IE, particularly in the subset of patients with possible IE in whom it may help the clinician manage a challenging situation. AU - Graziosi, Maddalena AU - Nanni, Cristina AU - Lorenzini, Massimiliano AU - Diemberger, Igor AU - Bonfiglioli, Rachele AU - Pasquale, Ferdinando AU - Ziacchi, Matteo AU - Biffi, Mauro AU - Martignani, Cristian AU - Bartoletti, Michele AU - Tumietto, Fabio AU - Boriani, Giuseppe AU - Viale, Pier Luigi AU - Fanti, Stefano AU - Rapezzi, Claudio DA - 2014/8// DO - 10.1007/s00259-014-2773-z IS - 8 PY - 2014 SP - 1617 EP - 1623 TI - Role of 18F-FDG PET/CT in the diagnosis of infective endocarditis in patients with an implanted cardiac device: a prospective study T2 - European Journal of Nuclear Medicine and Molecular Imaging UR - http://www.ncbi.nlm.nih.gov/pubmed/24802193 UR - http://link.springer.com/10.1007/s00259-014-2773-z VL - 41 ER - TY - JOUR AB - Purpose: The noninvasive imaging of bacterial infections is critical in order to reduce mortality and morbidity caused by these diseases. The recently reported18F-FDS (18F-2-fluorodeoxy sorbitol) as a PET (positron emission tomography) tracer can be used to image Enterobacteriaceae-specific infections and provides a potential alternative to this problem compared with other probes for imaging infections. In this study, automatic synthesis, validation of18F-FDS and a first-in-human study were performed and discussed. Methods: A multifunctional synthesis module was employed for the radiosynthesis of18F-FDG (18F-2-fluorodeoxy glucose) and18F-FDS starting from18F ion using two-pot three-step fully automated reactions. The behavior of18F-FDS as an in vivo imaging probe for infections was evaluated in an Escherichia coli mouse infection model. The first detailed pharmacokinetic and biodistribution parameters were obtained from healthy human volunteers. Results: The uptake of18F-FDS in an E. coli mouse-myositis infection model was easily differentiated from other organs and normal muscle. Intensive lesion uptake declined after antibiotic treatment. In the pilot human study, no adverse effects due to18F-FDS were observed up to 24 h post-injection. The radiotracer was rapidly cleared from the circulation and excreted mainly through the urinary system. Conclusion: We conclude that18F-FDS PET holds great potential for appropriate and effective for the imaging of bacterial infections in vivo. These preliminary results indicate that further clinical studies are warranted. AU - Yao, Shaobo AU - Xing, Haiqun AU - Zhu, Wenjia AU - Wu, Zhanhong AU - Zhang, Yingqiang AU - Ma, Yanru AU - Liu, Yimin AU - Huo, Li AU - Zhu, Zhaohui AU - Li, Zibo AU - Li, Fang DO - 10.1016/j.nucmedbio.2015.11.008 KW - 18F-FDS KW - Automated synthesis KW - Gram-negative bacteria KW - Infection KW - PET PY - 2016 SN - 1872-9614 (Electronic)\r0969-8051 (Linking) TI - Infection Imaging With18F-FDS and First-in-Human Evaluation T2 - Nuclear Medicine and Biology ER -