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Human Immunodeficiency Virus Type 1 (HIV-1) presents significant challenges to the immune system, predominantly characterized by CD4 + T cell depletion, leading to Acquired Immunodeficiency Syndrome (AIDS). Antiretroviral therapy (ART) effectively suppresses the viral load in people with HIV (PWH), leading to a state of chronic infection that is associated with inflammation. This review explores the complex relationship between oxidative phosphorylation, a crucial metabolic pathway for cellular energy production, and HIV-1, emphasizing the dual impact of HIV-1 infection and the metabolic and mitochondrial effects of ART. The review highlights how HIV-1 infection disrupts oxidative phosphorylation, promoting glycolysis and fatty acid synthesis to facilitate viral replication. ART can exacerbate metabolic dysregulation despite controlling viral replication, impacting mitochondrial DNA synthesis and enhancing reactive oxygen species production. These effects collectively contribute to significant changes in oxidative phosphorylation, influencing immune cell metabolism and function. Adenosine triphosphate (ATP) generated through oxidative phosphorylation can influence the metabolic landscape of infected cells through ATP-detected purinergic signaling and contributes to immunometabolic dysfunction. Future research should focus on identifying specific targets within this pathway and exploring the role of purinergic signaling in HIV-1 pathogenesis to enhance HIV-1 treatment modalities, addressing both viral infection and its metabolic consequences., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Rodriguez, Fortune, Hegde, Weinstein, Keane, Mangold and Swartz.)

The critical nature of the microbiology laboratory in infectious disease diagnosis calls for a close, positive working relationship between the physician and the microbiologists who provide enormous value to the health care team. This document, developed by experts in both adult and pediatric laboratory and clinical medicine, provides information on which tests are valuable and in which contexts, and on tests that add little or no value for diagnostic decisions. Sections are divided into anatomic systems, including Bloodstream Infections and Infections of the Cardiovascular System, Central Nervous System Infections, Ocular Infections, Soft Tissue Infections of the Head and Neck, Upper Respiratory Infections, Lower Respiratory Tract infections, Infections of the Gastrointestinal Tract, Intraabdominal Infections, Bone and Joint Infections, Urinary Tract Infections, Genital Infections, and Skin and Soft Tissue Infections; or into etiologic agent groups, including arboviral Infections, Viral Syndromes, and Blood and Tissue Parasite Infections. Each section contains introductory concepts, a summary of key points, and detailed tables that list suspected agents; the most reliable tests to order; the samples (and volumes) to collect in order of preference; specimen transport devices, procedures, times, and temperatures; and detailed notes on specific issues regarding the test methods, such as when tests are likely to require a specialized laboratory or have prolonged turnaround times. In addition, the pediatric needs of specimen management are also addressed. There is redundancy among the tables and sections, as many agents and assay choices overlap. The document is intended to serve as a reference to guide physicians in choosing tests that will aid them to diagnose infectious diseases in their patients., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Human immunodeficiency virus type 1 (HIV-1) is a chronic disease that afflicts over 38 million people worldwide without a known cure. The advent of effective antiretroviral therapies (ART) has significantly decreased the morbidity and mortality associated with HIV-1 infection in people living with HIV-1 (PWH), thanks to durable virologic suppression. Despite this, people with HIV-1 experience chronic inflammation associated with co-morbidities. While no single known mechanism accounts for chronic inflammation, there is significant evidence to support the role of the NLRP3 inflammasome as a key driver. Numerous studies have demonstrated therapeutic impact of cannabinoids, including exerting modulatory effects on the NLRP3 inflammasome. Given the high rates of cannabinoid use in PWH, it is of great interest to understand the intersecting biology of the role of cannabinoids in HIV-1-associated inflammasome signaling. Here we describe the literature of chronic inflammation in people with HIV, the therapeutic impact of cannabinoids in PWH, endocannabinoids in inflammation, and HIV-1-associated inflammation. We describe a key interaction between cannabinoids, the NLRP3 inflammasome, and HIV-1 viral infection, which supports further investigation of the critical role of cannabinoids in HIV-1 infection and inflammasome signaling., Competing Interests: Competing Interests: The authors have completed the information regarding conflicts of interest in the requested documentation and have no conflicts of interest to disclose., (© 2023 the author(s), published by De Gruyter, Berlin/Boston.)

Background: Patients with bacteremia due to carbapenem-resistant Enterobacterales (CRE) experience delays until appropriate therapy and high mortality rates. Rapid molecular diagnostics for carbapenemases and new β-lactam/β-lactamase inhibitors may improve outcomes., Methods: We conducted an observational study of patients with CRE bacteremia from 2016 to 2018 at 8 New York and New Jersey medical centers and assessed center-specific clinical microbiology practices. We compared time to receipt of active antimicrobial therapy and mortality between patients whose positive blood cultures underwent rapid molecular testing for the Klebsiella pneumoniae carbapenemase (KPC) gene (blaKPC) and patients whose cultures did not undergo this test. CRE isolates underwent antimicrobial susceptibility testing by broth microdilution and carbapenemase profiling by whole-genome sequencing. We also assessed outcomes when ceftazidime-avibactam and polymyxins were used as targeted therapies., Results: Of 137 patients with CRE bacteremia, 89 (65%) had a KPC-producing organism. Patients whose blood cultures underwent blaKPC PCR testing (n = 51) had shorter time until receipt of active therapy (median: 24 vs 50 hours; P = .009) compared with other patients (n = 86) and decreased 14-day (16% vs 37%; P = .007) and 30-day (24% vs 47%; P = .007) mortality. blaKPC PCR testing was associated with decreased 30-day mortality (adjusted odds ratio: .37; 95% CI: .16-.84) in an adjusted model. The 30-day mortality rate was 10% with ceftazidime-avibactam monotherapy and 31% with polymyxin monotherapy (P = .08)., Conclusions: In a KPC-endemic area, blaKPC PCR testing of positive blood cultures was associated with decreased time until appropriate therapy and decreased mortality for CRE bacteremia, and ceftazidime-avibactam is a reasonable first-line therapy for these infections., Competing Interests: Potential conflicts of interest . M. J. S has received grant/contract support from Affinity Biosensors, Allergan (payments were made to his institution through an investigator-initiated grant [CAZ-IT-21]), BioFire Diagnostics, and Merck; served as consultant to Shionogi; and served on a Data Safety Monitoring Board for Spero Therapeutics. Y.-W. T. is an employee of Cepheid. T. J. W. has received grant support from Allergan, Amplyx, Astellas, Leadiant Biosciences, Medicines Company, Merck, Scynexis, Shionogi, T2 Biosystems, Tetraphase, and Viosera and has served as consultant to Amplyx, Astellas, Allergan, ContraFect, Gilead, Karyopharm, Leadiant Biosciences, Medicines Company, Merck, Methylgene, Partner Therapeutics, Pfizer, Scynexis, Shionogi, and T2 Biosystems. L. F. W. has received grant support from Accelerate Diagnostics, BioFire Diagnostics, and Roche Molecular Systems and has served as consultant to Roche Molecular Systems, Shionogi, and Talis Biomedical. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Bacteremia is a major cause of morbidity and mortality. Rapid identification of pathogens for early targeted antimicrobial therapy is crucial for detecting emergence of antibiotic resistance and improving outcomes. However, there are limited data regarding the analytical performance of a rapid identification (ID) and antimicrobial susceptibility testing (AST) method like Accelerate Pheno blood culture detection system compared with the conventional methods routinely used in microbiology laboratories. We undertook a systematic quality improvement (QI) study to compare AST results obtained with Accelerate Pheno system rapid ID/AST system with a standard reference method in a university hospital microbiology laboratory. This was a single center, retrospective (5/10/19 to 8/1/19) and prospective (8/1/19 to 1/31/20) study that evaluated all blood cultures growing Gram-negative rods (GNR). We compared AST results obtained using the reference disk diffusion (DD) susceptibility method with those obtained by the Accelerate Pheno system. We calculated the error rates and categorical agreement between the Accelerate Pheno system and DD for each organism and specific drug tested. We evaluated 355 blood cultures growing GNR, of which 284 met the inclusion criteria. We grouped all Enterobacterales ( n  =  263) for analysis (156 Escherichia coli, 60 Klebsiella spp., 20 Proteus mirabilis, 17 Enterobacter spp., and 10 Serratia marcescens ) . Twenty-one Pseudomonas aeruginosa isolates were analyzed separately. For Enterobacterales, categorical agreement (CA) was ≥90% for amikacin (AMK), aztreonam (ATM), cefepime (FEP), ceftriaxone (CRO), ertapenem (ETP), gentamicin (GEN), meropenem (MEM), and tobramycin (TOB); and very major error (VME) was <5% for ampicillin/sulbactam (SAM), GEN, MEM, TOB, CRO, and ceftazidime (CAZ). For ciprofloxacin (CIP), CA was 87% and VME was 8%. For P. aeruginosa, CA was ≥90% for AMK and TOB, and VME was ≥5% for AMK, CAZ, GEN, MEM, piperacillin-tazobactam (TZP), and TOB. Accelerate Pheno rapid ID/AST system for GNR isolated from blood culture (BCs) was reliable for some but not all agents in the panel. Based on the findings from this study, our laboratory reports Accelerate Pheno system AST results only for Enterobacterales, and we limit our reports to CRO, CAZ, TZP, CIP, ATM, and GEN. IMPORTANCE This was an 8-month retrospective and prospective study looking at the analytical performance of the Accelerate Pheno system on clinical isolates obtained from patients seen in our tertiary care hospital. Most of the published literature on the analytical performance of Accelerate Pheno System has been from clinical trials with limited data from clinical microbiology laboratories postimplementation of the system. Here we compare the AST results on 355 blood cultures growing Gram-negative bacteria in Accelerate Pheno system with the CLSI reference disk diffusion (DD) method. The findings from this study highlight the "real-world" performance of the Accelerate Pheno system for Gram-negative bacteria from blood cultures. We provide data to show the reliable susceptibility testing results of Enterobacterales for most of the commonly used antimicrobial agents and significant limitation for susceptibility testing results of Pseudomonas aeruginosa on the Accelerate Pheno system.

Recent data on polymyxin pharmacokinetics, pharmacodynamics, toxicity, and clinical outcomes suggest these agents have limited clinical utility. Pharmacokinetics-pharmacodynamics data show a steady-state concentration of 2 μg/mL is required for killing bacteria with colistin minimum inhibitory concentrations of 2 μg/mL. Less than 50% of patients with normal renal function achieve this exposure, and it is associated with high risk of nephrotoxicity. This exposure does not achieve bacterial stasis in pneumonia models. Randomized and observational studies consistently demonstrate increased mortality for polymyxins compared with alternative agents. The Clinical and Laboratory Standards Institute (CLSI) and European Committee on Antimicrobial Susceptibility Testing (EUCAST) are 2 global organizations that establish interpretive criteria for in vitro susceptibility data. CLSI has recently taken the step to eliminate the "susceptible" interpretive category for the polymyxins, whereas EUCAST maintains this interpretive category. This viewpoint describes the opinions of these organizations and the data that were used to inform their perspectives., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Vaborbactam is a novel boron-based beta-lactamase inhibitor developed to be effective against Klebsiella pneumoniae carbapenemase (KPC)-producing bacteria. This enzyme is a key driver in the global spread of β-lactam resistance among carbapenem-resistant Enterobacterales. Alone, vaborbactam has no antibacterial activity; however, the combination of meropenem-vaborbactam has enhanced activity against gram-negative organisms, particularly Enterobacterales with class A and C carbapenemases. Multiple in vitro studies evaluating isolates from various geographic regions, and over different time periods, have demonstrated the high potency of meropenem-vaborbactam against organisms containing KPC2 and KPC3. However, meropenem-vaborbactam does not have activity against OXA-48 or metallo-beta lactamases. This review covers the in vitro studies of meropenem-vaborbactam performed to date, which evaluated both large cohorts of clinical isolates and engineered isolates, to determine efficacy in various settings, including the presence of porin mutations and efflux pump upregulation.

The number of onsite clinical microbiology laboratories in hospitals is decreasing, likely related to the business model for laboratory consolidation and labor shortages, and this impacts a variety of clinical practices, including that of banking isolates for clinical or epidemiologic purposes. To determine the impact of these trends, infectious disease (ID) physicians were surveyed regarding their perceptions of offsite services. Clinical microbiology practices for retention of clinical isolates for future use were also determined. Surveys were sent to members of the Infectious Diseases Society of America's (IDSA) Emerging Infections Network (EIN). The EIN is a sentinel network of ID physicians who care for adult and/or pediatric patients in North America and who are members of IDSA. The response rate was 763 (45%) of 1,680 potential respondents. Five hundred forty (81%) respondents reported interacting with the clinical microbiology laboratory. Eighty-six percent of respondents thought an onsite laboratory very important for timely diagnostic reporting and ongoing communication with the clinical microbiologist. Thirty-five percent practiced in institutions where the core microbiology laboratory has been moved offsite, and an additional 7% ( n  = 38) reported that movement of core laboratory functions offsite was being considered. The respondents reported that only 24% of laboratories banked all isolates, with the majority saving isolates for less than 30 days. Based on these results, the trend toward centralized core laboratories negatively impacts the practice of ID physicians, potentially delays effective implementation of prompt and targeted care for patients with serious infections, and similarly adversely impacts infection control epidemiologic investigations., (Copyright © 2020 American Society for Microbiology.)

Daptomycin is one of the few treatment options for infections caused by enterococci that are resistant to ampicillin and vancomycin, such as vancomycin-resistant Enterococcus faecium. The emergence and clinical significance of daptomycin-resistant enterococci and evolving microbiologic, pharmacokinetic-pharmacodynamic, and clinical data indicated that the pre-2019 Clinical and Laboratory Standards Institute (CLSI) susceptible-only breakpoint of ≤4 μg/mL for daptomycin and enterococci was no longer appropriate. After analyzing data that are outlined in this article, the CLSI Subcommittee on Antimicrobial Susceptibility Testing established new breakpoints for daptomycin and enterococci. For E. faecium, a susceptible dose-dependent (SDD) breakpoint of ≤4 μg/mL was established based on an increased dosage of 8-12 mg/kg/day (≥8 μg/mL-resistant). CLSI suggests infectious diseases consultation to guide daptomycin use for the SDD category. For Enterococcus faecalis and other enterococcal species, revised breakpoints of ≤2 μg/mL-susceptible, 4 μg/mL-intermediate, and ≥8 μg/mL-resistant were established based on a standard dosage of 6 mg/kg/day., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

The Clinical and Laboratory Standards Institute (CLSI) Subcommittee on Antimicrobial Susceptibility Testing (AST SC) is a volunteer-led, multidisciplinary consensus body that develops and publishes standards and guidelines (among other products) for antimicrobial susceptibility testing (AST) methods and results interpretation in the United States and internationally. The Subcommittee (SC) meets face-to-face twice yearly, and its working groups (WGs) are active throughout the year via teleconferences. All meetings are open to the public. Participants include clinical microbiologists, infectious disease (ID) pharmacists, and infectious disease physicians representing the health care professions, government, and industry. Individuals who work for a company with a primary financial dependency on drug sales cannot serve as voting members, and well-defined conflict of interest polices are in place. In addition to developing and updating susceptibility breakpoints, the SC develops and validates new testing methods, provides guidance on how results should be interpreted and applied, sets quality control ranges, and educates users through seminars, symposia, and webinars. Based on its work, the SC publishes print and electronic standards and guidelines, including an annual update, the Performance Standards for Antimicrobial Susceptibility Testing (M100). This commentary will describe the background, organization, functions, and operational processes of the AST SC., (Copyright © 2020 American Society for Microbiology.)

In 2014, a DNA-based phylogenetic study confirming the paraphyly of the grass subtribe Sporobolinae proposed the creation of a large monophyletic genus Sporobolus, including (among others) species previously included in the genera Spartina, Calamovilfa, and Sporobolus. Spartina species have contributed substantially (and continue contributing) to our knowledge in multiple disciplines, including ecology, evolutionary biology, molecular biology, biogeography, experimental ecology, biological invasions, environmental management, restoration ecology, history, economics, and sociology. There is no rationale so compelling to subsume the name Spartina as a subgenus that could rival the striking, global iconic history and use of the name Spartina for over 200 yr. We do not agree with the subjective arguments underlying the proposal to change Spartina to Sporobolus. We understand the importance of both the objective phylogenetic insights and of the subjective formalized nomenclature and hope that by opening this debate we will encourage positive feedback that will strengthen taxonomic decisions with an interdisciplinary perspective. We consider that the strongly distinct, monophyletic clade Spartina should simply and efficiently be treated as the genus Spartina., (© 2019 by the Ecological Society of America.)

In this review, we present a comprehensive discussion of matters related to the problem of blood culture contamination. Issues addressed include the scope and magnitude of the problem, the bacteria most often recognized as contaminants, the impact of blood culture contamination on clinical microbiology laboratory function, the economic and clinical ramifications of contamination, and, perhaps most importantly, a systematic discussion of solutions to the problem. We conclude by providing a series of unanswered questions that pertain to this important issue., (Copyright © 2019 American Society for Microbiology.)

Background: Blood cultures, the gold standard for diagnosing bloodstream infections (BSIs), are insensitive and limited by prolonged time to results. The T2Bacteria Panel (T2 Biosystems) is a direct-from-blood, nonculture test that identifies the most common ESKAPE bacteria (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Escherichia coli)., Objective: To assess performance of the T2Bacteria Panel in diagnosing suspected BSIs in adults., Design: Prospective patient enrollment (8 December 2015 through 4 August 2017)., Setting: Eleven U.S. hospitals., Patients: 1427 patients for whom blood cultures were ordered as standard of care., Intervention: Paired blood culture and T2Bacteria testing., Measurements: Performance of T2Bacteria compared with a single set of blood cultures in diagnosing proven, probable, and possible BSIs caused by T2Bacteria-targeted organisms., Results: Blood culture and T2Bacteria results were positive for targeted bacteria in 3% (39 of 1427) and 13% (181 of 1427) of patients, respectively. Mean times from start of blood culture incubation to positivity and species identification were 38.5 (SD, 32.8) and 71.7 (SD, 39.3) hours, respectively. Mean times to species identification with T2Bacteria were 3.61 (SD, 0.2) to 7.70 (SD, 1.38) hours, depending on the number of samples tested. Per-patient sensitivity and specificity of T2Bacteria for proven BSIs were 90% (95% CI, 76% to 96%) and 90% (CI, 88% to 91%), respectively; the negative predictive value was 99.7% (1242 of 1246). The rate of negative blood cultures with a positive T2Bacteria result was 10% (146 of 1427); 60% (88 of 146) of such results were associated with probable (n = 62) or possible (n = 26) BSIs. If probable BSIs and both probable and possible BSIs were assumed to be true positives missed by blood culture, per-patient specificity of T2Bacteria was 94% and 96%, respectively., Limitation: Low prevalence of positive blood cultures, collection of a single set of culture specimens, and inability of T2Bacteria to detect nontargeted pathogens., Conclusion: The T2Bacteria Panel rapidly and accurately diagnoses BSIs caused by 5 common bacteria., Primary Funding Source: T2 Biosystems.

Vancomycin-resistant enterococcal bacteremia (VRE-B) is a common nosocomial infection associated with significant morbidity and mortality. Daptomycin and linezolid are primary treatment options although definitive clinical data to assess comparative therapeutic effectiveness are lacking. This study assessed the outcomes of patients with VRE-B treated with linezolid or daptomycin. This was a single-center, retrospective cohort study evaluating adult patients with VRE-B treated with either daptomycin or linezolid admitted between January 2012 and August 2016 at a tertiary care, academic medical center. The primary outcome was clinical failure, a composite outcome defined as 14-day in-hospital mortality, microbiologic failure, or relapse of VRE-B. Secondary outcomes included 14-day in-hospital mortality, microbiologic failure, relapse of VRE-B, duration of VRE-B, and antibiotic failure. A multivariate logistic regression model was performed to adjust for potential confounding variables. A total of 93 patients were included ( n = 62 for linezolid and n = 31 for daptomycin). All blood isolates were Enterococcus faecium . Overall clinical failure was 55.9% and 14-day in-hospital mortality was 21.5%. There was a significantly higher rate of clinical failure in the daptomycin group as compared with the linezolid-treated patients (74.2% versus 46.8%; p = 0.01; respectively). In multivariate logistic regression analysis, there was a significantly higher odds of clinical failure for patients treated with daptomycin as compared with linezolid (adjusted odds ratio 2.89; 95% confidence interval 1.08-7.75) after adjusting for confounders. Secondary outcomes were not statistically significantly different between study groups. Standard-dose (6 mg/kg) daptomycin treatment was associated with a higher rate of clinical failure as compared with linezolid treatment., Competing Interests: Conflict of interest statement: The authors declare that there is no conflict of interest.

Background: Rapid identification of Gram-positive cocci in clusters (GPCC) in positive blood cultures (pBC) may limit exposure to unnecessary or inappropriate antibiotics., Methods: Inpatients with pBC showing GPCC between October 2013 and December 2017 were included. In the baseline period (BL), final ID and susceptibility results were reported in the electronic medical record (EMR) within 48 h of telephoned Gram stain report. The laboratory introduced rapid phenotypic identification and direct susceptibility testing (INT1), later replaced by PCR (INT2). In the last Intervention (INT3), Antimicrobial Stewardship Response Team (ASRT) contacted providers with PCR results and recommendations., Results: Time to directed therapy (TDT) for MSSA and coagulase-negative Staphylococci (CoNS) decreased from BL to INT3 (48.5-17.9 h, 50.3-16.4 h, respectively). Time to ID from BL to INT3 for MSSA and CoNS also decreased (23.2-1.9 h, 44.7-2.8, respectively)., Conclusions: TDT can be improved by modification of reporting methods with utilization of an ASRT., (Copyright © 2018 Elsevier Inc. All rights reserved.)

The critical nature of the microbiology laboratory in infectious disease diagnosis calls for a close, positive working relationship between the physician/advanced practice provider and the microbiologists who provide enormous value to the healthcare team. This document, developed by experts in laboratory and adult and pediatric clinical medicine, provides information on which tests are valuable and in which contexts, and on tests that add little or no value for diagnostic decisions. This document presents a system-based approach rather than specimen-based approach, and includes bloodstream and cardiovascular system infections, central nervous system infections, ocular infections, soft tissue infections of the head and neck, upper and lower respiratory infections, infections of the gastrointestinal tract, intra-abdominal infections, bone and joint infections, urinary tract infections, genital infections, and other skin and soft tissue infections; or into etiologic agent groups, including arthropod-borne infections, viral syndromes, and blood and tissue parasite infections. Each section contains introductory concepts, a summary of key points, and detailed tables that list suspected agents; the most reliable tests to order; the samples (and volumes) to collect in order of preference; specimen transport devices, procedures, times, and temperatures; and detailed notes on specific issues regarding the test methods, such as when tests are likely to require a specialized laboratory or have prolonged turnaround times. In addition, the pediatric needs of specimen management are also emphasized. There is intentional redundancy among the tables and sections, as many agents and assay choices overlap. The document is intended to serve as a guidance for physicians in choosing tests that will aid them to quickly and accurately diagnose infectious diseases in their patients.

Methicillin-resistant Staphylococcus aureus (MRSA) is a leading cause of bacteremia and is associated with significant morbidity and mortality. Prior studies evaluating the association of vancomycin MICs with clinical outcomes in patients with MRSA bacteremia have been inconsistent. This study evaluated the association between vancomycin MICs and 30-day in-hospital mortality rates for patients with MRSA bacteremia. This was a retrospective cohort study of patients with MRSA bacteremia treated with vancomycin for ≥72 h from January 2013 to August 2016. Vancomycin MICs were determined by broth microdilution via automated susceptibility testing methods. Study groups consisted of patients with MRSA isolates that had vancomycin MICs of <2 μg/ml and those with vancomycin MICs of 2 μg/ml. Covariates included demographics, severity of illness, comorbidities, intensive-care unit (ICU) admission, infectious disease consultation, infectious sources, and hospital onset of bacteremia. The primary outcome was 30-day in-hospital mortality. Secondary outcomes included the duration of bacteremia, persistent bacteremia for ≥7 days, recurrence within 30 days, change to alternative antibiotic therapy, and length of hospital stay. Multivariate logistic regression models were analyzed to control for potential confounding variables. A total of 166 patients were included for analysis: 91 patients with vancomycin MICs of <2 μg/ml and 75 patients with vancomycin MICs of 2 μg/ml. In the multivariate logistic regression model, a vancomycin MIC of 2 μg/ml, compared to a MIC of <2 μg/ml, was not significantly associated with 30-day in-hospital mortality after adjustment for confounders. Additionally, all secondary outcomes were not statistically significantly different between study groups. In patients with MRSA bacteremia treated with vancomycin, the vancomycin MIC was not associated with differences in clinical outcomes., (Copyright © 2018 American Society for Microbiology.)

The use of nature-based infrastructure (NBI) has attracted increasing attention in the context of protection against coastal flooding. This review is focused on NBI approaches to improve coastal resilience in the face of extreme storm events, including hurricanes. We not only consider the role of NBI as a measure to protect people and property but also in the context of other ecological goods and services provided by tidal wetlands including production of fish and shellfish. Although the results of many studies suggest that populated areas protected by coastal marshes were less likely to experience damage when exposed to the full force of storm surge, it was absolutely critical to place the role of coastal wetlands into perspective by noting that while tidal marshes can reduce wave energy from low-to-moderate-energy storms, their capacity to substantially reduce storm surge remains poorly quantified. Moreover, although tidal marshes can reduce storm surge from fast moving storms, very large expanses of habitat are needed to be most effective, and for most urban settings, there is insufficient space to rely on nature-based risk reduction strategies alone. The success of a given NBI method is also context dependent on local conditions, with potentially confounding influences from substrate characteristics, topography, near shore bathymetry, distance from the shore and other physical factors and human drivers such as development patterns. Furthermore, it is important to better understand the strengths and weaknesses of newly developed NBI projects through rigorous evaluations and characterize the local specificities of the particular built and natural environments surrounding these coastal areas. In order for the relevant science to better inform policy, and assist in land-use challenges, scientists must clearly state the likelihood of success in a particular circumstance and set of conditions. We conclude that "caution is advised" before selecting a particular NBI method as there is no "one size fits all" solution to address site-specific conditions., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Blood cultures (BCs) are the standard method for diagnosis of bloodstream infections (BSIs). However, the average BC contamination rate (CR) in U.S. hospitals is 2.9%, potentially resulting in unnecessary antibiotic use and excessive therapy costs. Several studies have compared various skin antisepsis agents without a clear consensus as to which agent is most effective in reducing contamination. A prospective, randomized crossover study directly comparing blood culture contamination rates using chlorhexidine versus iodine tincture for skin antisepsis was performed at Robert Wood Johnson University Hospital (RWJUH). Eight nursing units at RWJUH were provided with blood culture kits containing either chlorhexidine (CH) or iodine tincture (IT) for skin antisepsis prior to all blood culture venipunctures, which were obtained by nurses or clinical care technicians. At quarterly intervals, the antiseptic agent used on each nursing unit was switched. Analyses of positive BCs were performed to distinguish true BSIs from contaminants. Of the 6,095 total BC sets obtained from the participating nursing units, 667 (10.94%) were positive and 238 (3.90%) were judged by the investigators to be contaminated. Of the 3,130 BCs obtained using IT, 340 (10.86%) were positive and 123 (3.93%) were contaminated. Of 2,965 BCs obtained using CH, 327 (11.03%) were positive and 115 (3.88%) were contaminated. The rates of contaminated BCs were not statistically significant between the two antiseptic agents (P = 1.0). We conclude that CH and IT are equivalent agents for blood culture skin antisepsis., (Copyright © 2016, American Society for Microbiology. All Rights Reserved.)

The importance of blood culture (BC) volume for detection of bloodstream infections (BSIs) is documented. Recently, improved diagnostic sensitivity was demonstrated for 30- versus 20-ml BCs in adults (Cockerill FR, Wilson JW, Vetter EA, Goodman KM, Torgerson CA, Harmsen WS, Schleck CD, IIstrup DM, Washington JA, Wilson WR. Clin Infect Dis 38:1724-1730, 2004, http://dx.doi.org/10.1128/JCM.01314-11). Hospitals receive higher reimbursement for patients with documented septicemia. We determined the cost-effectiveness of 30-ml versus 20-ml BCs using results from our institution and previously published data. Positive BC results from 292 bacteremic episodes were reviewed. The costs of the reagents, equipment, phlebotomist, and technologist time were determined. The medical records department provided Medicare reimbursement (MR) data for patients with selected ICD-9 codes. These data provided an estimate of the annualized increase in MR versus costs associated with conversion to 30-ml BCs. MR for 464 annual primary BSIs was $24,808/episode. An expected 7.2% increase in BSIs detected using 30-ml BCs would add 34 additional cases annually and increase MR by $843,472. Comparative MR data for cases where septicemia complicated another diagnosis were available for 4 International Classification of Diseases, Ninth Revision (ICD-9) codes: laparoscopic cholecystectomy, biliary tract disorders, pneumonia, and cellulitis. The mean incremental MR was $9,667 per episode, which projected to a $483,350 revenue increase annually. The annual cost associated with conversion to 30-ml BCs was estimated to be $157,798. Thus, the potential net increase in hospital revenue would be $1,169,031 for 30-ml versus 20-ml BCs. Our results suggest that conversion to 30-ml BCs may not only improve patient care by detecting more BSIs but also increase hospital revenue substantially., (Copyright © 2015, American Society for Microbiology. All Rights Reserved.)

Background: Bloodstream infection (BSI) is a major cause of morbidity and mortality throughout the world. Rapid identification of bloodstream pathogens is a laboratory practice that supports strategies for rapid transition to direct targeted therapy by providing for timely and effective patient care. In fact, the more rapidly that appropriate antimicrobials are prescribed, the lower the mortality for patients with sepsis. Rapid identification methods may have multiple positive impacts on patient outcomes, including reductions in mortality, morbidity, hospital lengths of stay, and antibiotic use. In addition, the strategy can reduce the cost of care for patients with BSIs., Objectives: The purpose of this review is to evaluate the evidence for the effectiveness of three rapid diagnostic practices in decreasing the time to targeted therapy for hospitalized patients with BSIs. The review was performed by applying the Centers for Disease Control and Prevention's (CDC's) Laboratory Medicine Best Practices Initiative (LMBP) systematic review methods for quality improvement (QI) practices and translating the results into evidence-based guidance (R. H. Christenson et al., Clin Chem 57:816-825, 2011, http://dx.doi.org/10.1373/clinchem.2010.157131)., Search Strategy: A comprehensive literature search was conducted to identify studies with measurable outcomes. A search of three electronic bibliographic databases (PubMed, Embase, and CINAHL), databases containing "gray" literature (unpublished academic, government, or industry evidence not governed by commercial publishing) (CIHI, NIHR, SIGN, and other databases), and the Cochrane database for English-language articles published between 1990 and 2011 was conducted in July 2011., Dates of Search: The dates of our search were from 1990 to July 2011., Selection Criteria: Animal studies and non-English publications were excluded. The search contained the following medical subject headings: bacteremia; bloodstream infection; time factors; health care costs; length of stay; morbidity; mortality; antimicrobial therapy; rapid molecular techniques, polymerase chain reaction (PCR); in situ hybridization, fluorescence; treatment outcome; drug therapy; patient care team; pharmacy service, hospital; hospital information systems; Gram stain; pharmacy service; and spectrometry, mass, matrix-assisted laser desorption-ionization. Phenotypic as well as the following key words were searched: targeted therapy; rapid identification; rapid; Gram positive; Gram negative; reduce(ed); cost(s); pneumoslide; PBP2; tube coagulase; matrix-assisted laser desorption/ionization time of flight; MALDI TOF; blood culture; EMR; electronic reporting; call to provider; collaboration; pharmacy; laboratory; bacteria; yeast; ICU; and others. In addition to the electronic search being performed, a request for unpublished quality improvement data was made to the clinical laboratory community., Main Results: Rapid molecular testing with direct communication significantly improves timeliness compared to standard testing. Rapid phenotypic techniques with direct communication likely improve the timeliness of targeted therapy. Studies show a significant and homogeneous reduction in mortality associated with rapid molecular testing combined with direct communication., Authors' Conclusions: No recommendation is made for or against the use of the three assessed practices of this review due to insufficient evidence. The overall strength of evidence is suggestive; the data suggest that each of these three practices has the potential to improve the time required to initiate targeted therapy and possibly improve other patient outcomes, such as mortality. The meta-analysis results suggest that the implementation of any of the three practices may be more effective at increasing timeliness to targeted therapy than routine microbiology techniques for identification of the microorganisms causing BSIs. Based on the included studies, results for all three practices appear applicable across multiple microorganisms, including methicillin-resistant Staphylococcus aureus (MRSA), methicillin-sensitive S. aureus (MSSA), Candida species, and Enterococcus species., (Copyright © 2015 Buehler et al.)

The clinical development of FtsZ-targeting benzamide compounds like PC190723 has been limited by poor drug-like and pharmacokinetic properties. Development of prodrugs of PC190723 (e.g., TXY541) resulted in enhanced pharmaceutical properties, which, in turn, led to improved intravenous efficacy as well as the first demonstration of oral efficacy in vivo against both methicillin-sensitive Staphylococcus aureus (MSSA) and methicillin-resistant S. aureus (MRSA). Despite being efficacious in vivo, TXY541 still suffered from suboptimal pharmacokinetics and the requirement of high efficacious doses. We describe here the design of a new prodrug (TXA709) in which the Cl group on the pyridyl ring has been replaced with a CF3 functionality that is resistant to metabolic attack. As a result of this enhanced metabolic stability, the product of the TXA709 prodrug (TXA707) is associated with improved pharmacokinetic properties (a 6.5-fold-longer half-life and a 3-fold-greater oral bioavailability) and superior in vivo antistaphylococcal efficacy relative to PC190723. We validate FtsZ as the antibacterial target of TXA707 and demonstrate that the compound retains potent bactericidal activity against S. aureus strains resistant to the current standard-of-care drugs vancomycin, daptomycin, and linezolid. These collective properties, coupled with minimal observed toxicity to mammalian cells, establish the prodrug TXA709 as an antistaphylococcal agent worthy of clinical development., (Copyright © 2015, American Society for Microbiology. All Rights Reserved.)

The bioaccumulation and biomagnification of sediment-bound hydrophobic organic contaminants (HOCs) are of major concern for environmental and human health. In dynamic estuaries, HOCs can be taken up from sediments, porewater, or the overlying water column concentrations directly or via the diet. The transfer of HOCs including polycyclic aromatic hydrocarbons (PAHs), polychlorinated biphenyls (PCBs), and polychlorinated dibenzo-p-dioxins/furans (PCDD/Fs) to resident/migratory biota was investigated in 11 finfish species and blue crabs (Callinectes sapidus) in the Passaic River estuary. Concurrently, passive samplers were deployed to assess porewater and overlying water column concentrations. Biota were assigned to three trophic levels based on their tissue 15N isotope values and published life history strategies. There were no significant differences in trophic magnification factors (TMFs) calculated based on life-history scenarios, implying that the migratory species, mostly juveniles, had equilibrated with in situ sources of pollutants at the time they were sampled. Bioaccumulation factors and TMFs were >1 for most PCBs and tetra- and penta-CDD/DFs, indicating that they underwent biomagnification in the food web. All PAHs, PCB 11, and other lower chlorinated PCBs and PCDD/Fs did not magnify. Results from the analysis of HOC profiles implied that biota accumulated HOCs from sediments, porewater, and diet but not from overlying water.

We systematically evaluated 5 methods for testing daptomycin versus 48 Enterococcus faecalis, 51 Enterococcus faecium, and 50 Staphylococcus aureus isolates using (i and ii) broth microdilution (BMD) with 50-mg/liter calcium medium supplementation (reference method) and 30-mg/liter calcium medium supplementation (BMD30 method), (iii) Etest, and (iv and v) MicroScan panel 33 using 2 methods to prepare the bacterial inoculum (MicroScan turbidity and MicroScan Prompt). Isolates were categorized as susceptible (S) or nonsusceptible (NS) based on measured MICs. Essential (± 1 dilution) agreement (EA) and categorical (S/NS) agreement (CA) for each method were compared to the reference method. For E. faecium, categorical agreement was poor between the reference method and BMD30 as well as with the three commercial methods, with frequent false-NS results (30 for BMD30, 18 for Etest, 22 for MicroScan Prompt, and 25 for MicroScan turbidity). All E. faecalis isolates were judged to be S by the reference method; two of these isolates were categorized as NS using the BMD30 method, and one was categorized as NS by all three commercial methods. All S. aureus isolates were judged to be S using all five methods. MIC values determined by the comparator methods tended to be higher than those for the reference method, especially for E. faecium isolates. EAs between the reference BMD and BMD30, Etest, MicroScan Prompt, and MicroScan turbidity were 63%, 63%, 63%, and 56%, respectively, for E. faecium, 87%, 83%, 98%, and 80%, respectively, for E. faecalis, and all 100% for S. aureus., (Copyright © 2014, American Society for Microbiology. All Rights Reserved.)

New blood culture media containing antibiotic-binding polymeric beads have been developed for the BacT/Alert (bioMérieux, Inc., Durham, NC) blood culture system. To assess the performance of these new media, we compared the new BacT/Alert aerobic medium (FA Plus) with resins to BacT/Alert FA medium with activated charcoal and the new BacT/Alert anaerobic medium (FN Plus) to BacT/Alert FN medium at 3 tertiary care medical centers. Study bottle pairs were inoculated with a target volume of 6 to 10 ml of blood from adults and incubated in the BacT/Alert 3D blood culture instrument. In the FA Plus versus FA comparison, there were 1,507 study pairs. Among 170 isolates causing true bloodstream infections (BSIs), significantly more Staphylococcus aureus (P<0.001) and total microorganisms (P<0.01) grew in the FA Plus bottle than in the FA bottle. Fewer coagulase-negative staphylococcal (CoNS) contaminants grew in the FA Plus bottle than in the FA bottle (10 versus 22; P=0.05). In addition, growth was detected earlier in the FA Plus bottle than in the FA bottle (P<0.001). In the FN Plus versus FN comparison, there were 2,386 study pairs. Among 201 isolates causing true BSIs, significantly more S. aureus (P<0.001), CoNS (P<0.005), and total microorganisms (P<0.001) grew in the FN Plus bottle than in the FN bottle. Also, significantly more CoNS contaminants grew in the FN Plus bottle than in the FN bottle (P<0.001). Overall, microorganisms were detected earlier in the FN Plus than in the FN bottle (P<0.001). Medical technologists at all 3 study sites preferred the new media for Gram stain interpretation. We conclude that the FA Plus and FN Plus media provide improved and earlier detection of microorganisms compared with the FA and FN media and are preferable for Gram stain interpretation as well.

The critical role of the microbiology laboratory in infectious disease diagnosis calls for a close, positive working relationship between the physician and the microbiologists who provide enormous value to the health care team. This document, developed by both laboratory and clinical experts, provides information on which tests are valuable and in which contexts, and on tests that add little or no value for diagnostic decisions. Sections are divided into anatomic systems, including Bloodstream Infections and Infections of the Cardiovascular System, Central Nervous System Infections, Ocular Infections, Soft Tissue Infections of the Head and Neck, Upper Respiratory Infections, Lower Respiratory Tract infections, Infections of the Gastrointestinal Tract, Intraabdominal Infections, Bone and Joint Infections, Urinary Tract Infections, Genital Infections, and Skin and Soft Tissue Infections; or into etiologic agent groups, including Tickborne Infections, Viral Syndromes, and Blood and Tissue Parasite Infections. Each section contains introductory concepts, a summary of key points, and detailed tables that list suspected agents; the most reliable tests to order; the samples (and volumes) to collect in order of preference; specimen transport devices, procedures, times, and temperatures; and detailed notes on specific issues regarding the test methods, such as when tests are likely to require a specialized laboratory or have prolonged turnaround times. There is redundancy among the tables and sections, as many agents and assay choices overlap. The document is intended to serve as a reference to guide physicians in choosing tests that will aid them to diagnose infectious diseases in their patients.

The critical role of the microbiology laboratory in infectious disease diagnosis calls for a close, positive working relationship between the physician and the microbiologists who provide enormous value to the health care team. This document, developed by both laboratory and clinical experts, provides information on which tests are valuable and in which contexts, and on tests that add little or no value for diagnostic decisions. Sections are divided into anatomic systems, including Bloodstream Infections and Infections of the Cardiovascular System, Central Nervous System Infections, Ocular Infections, Soft Tissue Infections of the Head and Neck, Upper Respiratory Infections, Lower Respiratory Tract infections, Infections of the Gastrointestinal Tract, Intraabdominal Infections, Bone and Joint Infections, Urinary Tract Infections, Genital Infections, and Skin and Soft Tissue Infections; or into etiologic agent groups, including Tickborne Infections, Viral Syndromes, and Blood and Tissue Parasite Infections. Each section contains introductory concepts, a summary of key points, and detailed tables that list suspected agents; the most reliable tests to order; the samples (and volumes) to collect in order of preference; specimen transport devices, procedures, times, and temperatures; and detailed notes on specific issues regarding the test methods, such as when tests are likely to require a specialized laboratory or have prolonged turnaround times. There is redundancy among the tables and sections, as many agents and assay choices overlap. The document is intended to serve as a reference to guide physicians in choosing tests that will aid them to diagnose infectious diseases in their patients.

Objective: To mathematically assess drug losses due to infusion line residuals and evaluate methods to compensate for drug loss due to residual volumes in intravenous pump tubing., Data Sources: Literature was accessed through Ovid MEDLINE (1996-February 2013), using combinations of the search terms tubing residuals, residual volume, residual medication, intravenous infusions, intravenous injections, piperacillin, piperacillin-tazobactam, β-lactams, equipment design, infusion pumps, extended infusion, extended administration, and prolonged infusion. In addition, select reference citations from publications identified were reviewed., Study Selection and Data Extraction: All articles that involved extended-infusion piperacillin-tazobactam implementation strategies were included in the review., Data Synthesis: Infusion pump characteristics and tubing residuals can affect extended-infusion piperacillin-tazobactam dosing strategies. Two studies addressing tubing residuals were identified. Both studies recommended increasing infusion volumes to compensate for tubing residuals. One study also recommended decreasing infusion-line dead space by using alternative infusion pump systems. Study calculations suggest that higher doses of piperacillin-tazobactam may be used to account for medication left in tubing residuals if alternative infusion pump systems cannot be obtained, and increased infusion volumes are not an option., Conclusions: Extended-infusion piperacillin-tazobactam has been used as a method of maximizing pharmacodynamic target attainment. Use of higher doses of piperacillin-tazobactam may be a reasonable method to compensate for drug loss due to residual volumes in large-bore intravenous pump tubing.

The detection and identification of microorganisms circulating in the bloodstream of patients is arguably one of the most important functions of the clinical microbiology laboratory. Effective implementation of this function requires careful consideration of specimen collection and processing, culture techniques, result reporting, and, perhaps most importantly, result interpretation by the physician. The purpose of this review is to provide a synopsis of the current state of the art for each of these areas, with the intention of providing adequate information to enable clinical laboratory personnel and physicians to critically evaluate and, if required, improve their current blood culture practices., (© 2013 The Authors Clinical Microbiology and Infection © 2013 European Society of Clinical Microbiology and Infectious Diseases.)

Tetracycline class agents vary widely in their activity against emerging important antimicrobial-resistant pathogens such as methicillin-resistant Staphylococcus aureus (MRSA) and Acinetobacter spp. Also, published susceptibility breakpoints are discordant between the Clinical and Laboratory Standards Institute (CLSI), the European Committee on Antimicrobial Susceptibility Testing (EUCAST), and regulatory-approved documents. We have assessed the impact of these differences for tetracycline HCL and minocycline when tested against contemporary Gram-positive pathogens. The SENTRY Antimicrobial Surveillance Program (2011) compared minocycline and tetracycline HCL activity via reference methods (M07-A9) using a worldwide collection of S. aureus (SA; 4917 strains with 1955 MRSA), Streptococcus pneumoniae (SPN; 1899), S. pyogenes (GRA; 246), and S. agalactiae (GRB; 217). Regardless of applied categorical breakpoints, minocycline exhibited wider coverage (% susceptible) than tetracycline HCL of 4.5-11.8/0.5-2.6/1.4-2.3/0.4-0.4% for MRSA/SPN/GRB/GRA, respectively. Lower EUCAST susceptible breakpoints produced reduced susceptibility rates for minocycline ranging from no difference (≤0.5 μg/mL) for GRA to -8.9% (≤1 μg/mL) for MRSA (97.2% susceptible by CLSI; 88.3% by EUCAST). Use of tetracycline HCL-susceptible results to predict minocycline susceptibility was very accurate (99.0-100.0%), with absolute categorical agreement rates ranging from 92.1% to 98.4% (CLSI) to 98.4% to 99.6% (EUCAST) for streptococci; greatest predictive error was noted using the CLSI breakpoints (14.7%) compared to EUCAST criteria (only 5.0%; acceptable), both for MRSA testing dominated by false-resistant results for minocycline. In conclusion, minocycline demonstrates continued superior in vitro activity compared to tetracycline HCL when testing SA (especially MRSA) and pathogenic streptococci. When testing tetracyclines, laboratories must recognize the expanded spectrum of minocycline against certain pathogens and utilize methods minimizing interpretive error. We conclude that EUCAST breakpoint criteria (≤0.5 or ≤1 μg/mL) represent the most conservative (better recognize strains with tet resistance mechanisms) and accurate tetracycline breakpoint guidelines for testing contemporary isolates of Gram-positive cocci., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Yokenella regensburgei is a member of the family Enterobacteriaceae that has rarely been implicated in clinical disease. We report here a case of septicemia with a skin and soft tissue source caused by Y. regensburgei in an immunocompromised host.

Staphylococci are a frequent cause of bloodstream infections (BSIs). Appropriate antibiotic treatment for BSIs may be delayed because conventional laboratory testing methods take 48 to 72 h to identify and characterize isolates from positive blood cultures. We evaluated a novel assay based on bacteriophage amplification that identifies Staphylococcus aureus and differentiates between methicillin-susceptible and methicillin-resistant S. aureus (MSSA and MRSA, respectively) in samples taken directly from signal-positive Bactec blood culture bottles within 24 h of positive signal, with results available within 5 h. The performance of the MicroPhage KeyPath MRSA/MSSA blood culture test was compared to conventional identification and susceptibility testing methods. At four sites, we collectively tested a total of 1,165 specimens, of which 1,116 were included in our analysis. Compared to standard methods, the KeyPath MRSA/MSSA blood culture test demonstrated a sensitivity, specificity, positive predictive value, and negative predictive value of 91.8%, 98.3%, 96.3%, and 96.1%, respectively, for correctly identifying S. aureus. Of those correctly identified as S. aureus (n = 334), 99.1% were correctly categorized as either MSSA or MRSA. Analysis of a subset of the data revealed that the KeyPath MRSA/MSSA blood culture test delivered results a median of 30 h sooner than conventional methods (a median of 46.9 h versus a median of 16.9 h). Although the sensitivity of the test in detecting S. aureus-positive samples is not high, its accuracy in determining methicillin resistance and susceptibility among positives is very high. These characteristics may enable earlier implementation of appropriate antibiotic treatment for many S. aureus BSI patients.

Lipid class dynamics, the pattern of change in the primary form and location of lipid stores and their relationship with standard length (L(S) ), were investigated in collections of young-of-the-year weakfish Cynoscion regalis for the purpose of determining the utility of this analysis as an indication of condition. The separation of total lipids into individual classes and the analysis of potential storage depots revealed the general patterns of lipid class dynamics and energy storage in C. regalis during their period of juvenile estuarine residency. Phospholipid and cholesterol exhibited moderate but variable (8·1-40·0 and 1·3-21·5 mg g(-1) , respectively) concentrations across the entire juvenile period and were the predominant lipid classes in juveniles <100 mm L(S) , while wax ester concentrations were low (c. 1 mg g(-1) ) and exhibited the least amount of variability among lipid classes. Triacylglycerols (TAG) and free fatty acids (FFA) exhibited similar dynamics, with relatively low concentrations (<15 mg g(-1) ) in individuals ≤100 mm L(S) . In larger juveniles both TAG and FFA concentrations generally increased rapidly, though there was considerable variability in both measures (0·0-199·7 and 0·0-49·7 mg g(-1) , respectively). Increasing levels of lipids, primarily in the form of TAG, with size indicated an accumulation of energy reserves with growth, thus providing an indication of individual condition for larger juveniles. Separate analysis of liver, viscera and the remaining carcass indicated that liver and viscera did not represent a significant depot of TAG reserves. Analysis of samples derived from whole juvenile C. regalis thus provided an accurate estimate of energy reserves., (© 2011 The Authors. Journal of Fish Biology © 2011 The Fisheries Society of the British Isles.)

Twelve sediment cores were collected in July 2007 in open waters of western Bohai Bay, the Port of Tianjin, and the adjacent estuaries of the Haihe and Yongding Rivers. While overall concentrations of trace metals at incremental depths in these cores met the Marine Sediment Quality (GB18668-2002) criteria of China, the magnitude of both metal enrichment factors (EF) and geoaccumulation indices (I(geo)) suggested that pollution with Ag, Cd, Cr, Cu and Zn was occurring in the estuaries and Port. Risk analysis also suggested that Ag and Ni concentrations were sufficiently elevated as to cause adverse biological effects in the study area. Although metal concentrations in western Bohai Bay were of less concern, a positive relationship between EF values and excess (210)Pb activity for several metals suggested that their concentrations were increasing over time., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Clinical microbiology laboratory directors come from diverse backgrounds with overlapping but not identical training experiences. Although director responsibilities are defined by CLIA legislation, there is no standardization of job descriptions among hospital or university settings. One job that would make the microbiology director indispensable, if done well, is clinical consultation. Other challenges include attracting and educating future directors, expanding income opportunities through novel business plans and research funding, increasing doctoral-level professional staffing to provide clinical, administrative, educational, and scientific competencies, cooperating with fellow laboratory directors to merge novel technical methods with appropriate clinical interpretation, and participating in the political process to drive legislation toward excellence in patient care. Conversation among medical microbiologists is needed to focus efforts on defining, standardizing, and improving our performance as CML directors.

Background: Bloodstream infections are a major cause of morbidity and mortality in adults. Bloodstream infections should be reassessed periodically because of increased antibiotic resistance, more patients receiving immunomodulatory therapy, improved antiretroviral therapy, and acquisition of infection in health care settings other than hospitals., Methods: We conducted retrospective assessment by infectious disease physicians of hospitalized adults with positive blood cultures at 3 academic medical centers., Results: Two thousand two hundred seventy positive blood culture episodes occurred in 1706 patients. Of 2669 isolates, 51% represented true infection, 41% contamination, and 8% unknown clinical significance. Although coagulase-negative staphylococci were most common, only 10% were clinically significant. Among 1225 true bloodstream infections, the most frequent isolates were Staphylococcus aureus, Escherichia coli, Enterococcus spp., Klebsiella pneumoniae, coagulase-negative staphylococci, Pseudomonas aeruginosa, Candida albicans, Enterobacter cloacae, and Serratia marcescens. Intravenous catheters were the most common primary source of bloodstream infection (23% of episodes). Most (81%) bloodstream infections were acquired in the hospital or other health care settings. Crude and attributable in-hospital case-fatality ratios were 20% and 12%, respectively, lower than in previous studies. Increasing age, hypotension, absence of fever, hospital acquisition, extreme white blood cell count values, and the presence of the acquired immunodeficiency syndrome, malignancy, or renal disease were significantly associated with an increased risk of in-hospital attributable death in multivariable analysis., Conclusions: The proportion of bloodstream infections due to intravenous catheters is continuing to increase. Most episodes were acquired in the hospital or other health care setting. In-hospital case-fatality ratios have decreased compared with previous studies. Several previously identified factors associated with an increased mortality remain statistically significant.

Two strains of Raoultella planticola and one of Raoultella ornithinolytica showing carbapenem resistance were recovered from patients hospitalized in New Jersey and Ohio. All patients had received previous antimicrobial treatment, including carbapenems. These strains harbored bla(KPC-2) and bla(KPC-3). Carbapenemase genes were embedded in isoforms of Tn4401 and were plasmidic and chromosomal in location.