Anticoagulating New-Onset Atrial Fibrillation After COVID-19: A Single-Center Experience.

Anticoagulation (AC) strategy in new-onset atrial fibrillation (NOAF) secondary to other illnesses has not been broadly studied, and society-level guidance does not provide a strong recommendation regarding outpatient continuation upon discharge. Our study focused specifically on patients experiencing NOAF secondary to COVID-19. It sought to understand whether our facility's rounding prescribers were continuing patients on AC at discharge, the presence of arrhythmia at one-year follow-up, and to observe the risk of adverse outcomes in light of this unique precipitant. A retrospective cohort analysis and chart review were conducted of 231 consecutive inpatients during the initial 19 months of the COVID-19 pandemic. Eighteen patients experiencing NOAF with an average calculated CHA2DS2-VASc score of four were included in the cohort. Four patients (22%) died during hospitalization and 14 patients were discharged. Twelve of fourteen patients (86%) were discharged on AC, and eight remained adherent at follow-up. Two discharged patients died of unknown causes prior to follow-up. At follow-up, which occurred at a median of 1.2 years, 25% of the surviving cohort remained in atrial fibrillation (AF). No major bleeding events were recorded during the studied period. This retrospective analysis of a small sample of patients admitted to a single medical center for COVID-19 and experiencing NOAF demonstrates that local prescribers are continuing AC at discharge, that the rate of recurrence of AF is similar to onset in non-COVID illness at one year, and that risk of death approximated that of COVID-19 itself rather than NOAF.

Colistin Monotherapy versus Combination Therapy for Carbapenem-Resistant Organisms.

BACKGROUND: Pneumonia and bloodstream infections (BSI) due to extensively drug-resistant (XDR) Acinetobacter baumannii, XDR Pseudomonas aeruginosa, and carbapenem-resistant Enterobacterales (CRE) are associated with high mortality rates, and therapeutic options remain limited. This trial assessed whether combination therapy with colistin and meropenem was superior to colistin monotherapy for the treatment of these infections. METHODS: The OVERCOME (Colistin Monotherapy versus Combination Therapy) trial was an international, randomized, double-blind, placebo-controlled trial. We randomly assigned participants to receive colistin (5 mg/kg once followed by 1.67 mg/kg every 8 hours) in combination with either meropenem (1000 mg every 8 hours) or matching placebo for the treatment of pneumonia and/or BSI caused by XDR A. baumannii, XDR P. aeruginosa, or CRE. The primary outcome was 28-day mortality, and secondary outcomes included clinical failure and microbiologic cure. RESULTS: Between 2012 and 2020, a total of 464 participants were randomly assigned to treatment, and 423 eligible patients comprised the modified intention-to-treat population. A. baumannii was the predominant trial pathogen (78%) and pneumonia the most common index infection (70%). Most patients were in the intensive care unit at the time of enrollment (69%). There was no difference in mortality (43 vs. 37%; P=0.17), clinical failure (65 vs. 58%; difference, 6.8 percentage points; 95% confidence interval [CI], -3.1 to 16.6), microbiologic cure (65 vs. 60%; difference, 4.8 percentage points; 95% CI, -5.6 to 15.2), or adverse events (acute kidney injury, 52 vs. 49% [P=0.55]; hypersensitivity reaction, 1 vs. 3% [P=0.22]; and neurotoxicity, 5 vs. 2% [P=0.29]) between patients receiving monotherapy and combination therapy, respectively. CONCLUSIONS: Combination therapy with colistin and meropenem was not superior to colistin monotherapy for the treatment of pneumonia or BSI caused by these pathogens. (Funded by the National Institute of Allergy and Infectious Diseases, Division of Microbiology and Infectious Diseases protocol 10-0065; ClinicalTrials.gov number, NCT01597973.).

Case-case-control study of risk factors for carbapenem-resistant Enterobacterales infections among hospitalized patients.

Objective: To identify important risk factors for carbapenem-resistant Enterobacterales (CRE) infections among hospitalized patients. Design: We utilized a case-case-control design that compared patients with CRE infections to patients with carbapenem-susceptible Enterobacterales (CSE) infections and randomly selected controls during the period from January 2011 through December 2016. Setting: The study population was selected from patients at a large metropolitan tertiary-care and instructional medical center. Patients: Cases of CRE were defined as initial admission of adults diagnosed with a bacterial infection of an Enterobacterales species resistant clinically or through sensitivity testing to carbapenems 48 hours or more after admission. Cases of CSE were selected from the same patient population as the CRE cases within a 30-day window for admission, with diagnostic pathogens identified as susceptible to carbapenems. Controls were defined as adult patients admitted to any service within a 30-day window from a CRE case for >48 hours who did not meet either of the above case definitions during that admission. Results: Antibiotic exposure within 90 days prior to admission and length of hospital stay were both associated with increased odds of CRE and CSE infections compared to controls. Patients with CRE infections had >18 times greater odds of prior antibiotic exposure compared to patients with CSE infections. Conclusions: Antibiotic exposure and increased length of hospital stay may result in increased patient risk of developing an infection resistant to carbapenems and other ß-lactams.

Antimicrobial Stewardship in the ICU.

Increasing rates of infection and multidrug-resistant pathogens, along with a high use of antimicrobial therapy, make the intensive care unit (ICU) an ideal setting for implementing and supporting antimicrobial stewardship efforts. Overuse of antimicrobial agents is common in the ICU, as practitioners are challenged daily with achieving early, appropriate empiric antimicrobial therapy to improve patient outcomes. While early antimicrobial stewardship programs focused on the financial implications of antimicrobial overuse, current goals of stewardship programs align closely with those of critical care providers-to optimize patient outcomes, reduce development of resistance, and minimize adverse outcomes associated with antibiotic overuse and misuse such as acute kidney injury and Clostridioides difficile-associated disease. Significant opportunities exist in the ICU for critical care clinicians to support stewardship practices at the bedside, including thoughtful and restrained initiation of antimicrobial therapy, use of biomarkers in addition to rapid diagnostics, Staphylococcus aureus screening, and traditional microbiologic culture and susceptibilities to guide antibiotic de-escalation, and use of the shortest duration of therapy that is clinically appropriate. Integration of critical care practitioners into the initiatives of antimicrobial stewardship programs is key to their success. This review summarizes key components of antimicrobial stewardship programs and mechanisms for critical care practitioners to share the responsibility for antimicrobial stewardship.

Predictors of respiratory bacterial co-infection in hospitalized COVID-19 patients.

The primary objectives were to determine the prevalence of and identify variables associated with respiratory bacterial co-infection in COVID-19 inpatients. Secondary outcomes included length of stay and in-hospital mortality. Eighty-two (11.2%) of 735 COVID-19 inpatients had respiratory bacterial co-infection. Fifty-seven patients met inclusion criteria and were matched to three patients lacking co-infection (N = 228 patients). Patients with co-infection were more likely to receive antibiotics [57 (100%) vs 130 (76%), P < 0.0001] and for a longer duration [19 (13-33) vs 8 (4-13) days, P < 0.0001]. The multi-variable logistic regression model revealed risk factors of respiratory bacterial co-infection to be admission from SNF/LTAC/NH (AOR 6.8, 95% CI 2.6-18.2), severe COVID-19 (AOR 3.03, 95% CI 0.78-11.9), and leukocytosis (AOR 3.03, 95% CI 0.99-1.16). Although respiratory bacterial co-infection is rare in COVID-19 inpatients, antibiotic use is common. Early recognition of respiratory bacterial coinfection predictors in COVID-19 inpatients may improve empiric antibiotic prescribing.

Synovial Fluid-Induced Aggregation Occurs across Staphylococcus aureus Clinical Isolates and is Mechanistically Independent of Attached Biofilm Formation.

Rapid synovial fluid-induced aggregation of Staphylococcus aureus is currently being investigated as an important factor in the establishment of periprosthetic joint infections (PJIs). Pathogenic advantages of aggregate formation have been well documented in vitro, including recalcitrance to antibiotics and protection from host immune defenses. The objective of the present work was to determine the strain dependency of synovial fluid-induced aggregation by measuring the degree of aggregation of 21 clinical S. aureus isolates cultured from either PJI or bloodstream infections using imaging and flow cytometry. Furthermore, by measuring attached bacterial biomass using a conventional crystal violet assay, we assessed whether there is a correlation between the aggregative phenotype and surface-associated biofilm formation. While all of the isolates were stimulated to aggregate upon exposure to bovine synovial fluid (BSF) and human serum (HS), the extent of aggregation was highly variable between individual strains. Interestingly, the PJI isolates aggregated significantly more upon BSF exposure than those isolated from bloodstream infections. While we were able to stimulate biofilm formation with all of the isolates in growth medium, supplementation with either synovial fluid or human serum inhibited bacterial surface attachment over a 24 h incubation. Surprisingly, there was no correlation between the degree of synovial fluid-induced aggregation and quantity of surface-associated biofilm as measured by a conventional biofilm assay without host fluid supplementation. Taken together, our findings suggest that synovial fluid-induced aggregation appears to be widespread among S. aureus strains and mechanistically independent of biofilm formation. IMPORTANCE Bacterial infections of hip and knee implants are rare but devastating complications of orthopedic surgery. Despite a widespread appreciation of the considerable financial, physical, and emotional burden associated with the development of a prosthetic joint infection, the establishment of bacteria in the synovial joint remains poorly understood. It has been shown that immediately upon exposure to synovial fluid, the viscous fluid in the joint, Staphylococcus aureus rapidly forms aggregates which are resistant to antibiotics and host immune cell clearance. The bacterial virulence associated with aggregate formation is likely a step in the establishment of prosthetic joint infection, and as such, it has the potential to be a potent target of prevention. We hope that this work contributes to the future development of therapeutics targeting synovial fluid-induced aggregation to better prevent and treat these infections.

Clinical Impact of an Antibiotic Time Out Initiative at an Academic Medical Center.

Background: Various strategies aimed at limiting inappropriate antimicrobial use including antibiotic time out (ATO) have been proposed to combat the development of antimicrobial resistance, yet there are limited studies that have assessed the impact of ATO on clinical outcomes. Methods: This single-center retrospective study reviewed the effect of a passive ATO strategy by comparing 100 adult patients with an ATO matched by infection type to 100 antibiotic-treated adult patients lacking an ATO note. Results: No difference in clinical outcomes was observed, however, ATO did result in improved optimization of antibiotic selection and duration, and reduction of piperacillin/tazobactam and vancomycin use. Conclusion: Further studies are warranted to evaluate the impact of ATO on clinical outcomes of a larger homogenous population with specified infectious diagnoses and clinical characteristics.

Standardizing clinical culture specimen collection in Ethiopia: a training-of-trainers.

BACKGROUND: Proper specimen collection is central to improving patient care by ensuring optimal yield of diagnostic tests, guiding appropriate management, and targeting treatment. The purpose of this article is to describe the development and implementation of a training-of-trainers educational program designed to improve clinical culture specimen collection among healthcare personnel (HCP) in Ethiopia. METHODS: A Clinical Specimen Collection training package was created consisting of a Trainer's Manual, Reference Manual, Assessment Tools, Step-by-Step Instruction Guides (i.e., job aides), and Core Module PowerPoint Slides. RESULTS: A two-day course was used in training 16 master trainers and 47 facility-based trainers responsible for cascading trainings on clinical specimen collection to HCP at the pre-service, in-service, or national-levels. The Clinical Specimen Collection Package is offered online via The Ohio State University's CANVAS online platform. CONCLUSIONS: The training-of-trainers approach may be an effective model for development of enhanced specimen collection practices in low-resource countries.

Effectiveness of fidaxomicin versus oral vancomycin in the treatment of recurrent clostridioides difficile.

WHAT IS KNOWN AND OBJECTIVE: The 2017 IDSA/SHEA Clinical Practice Guidelines for Clostridioides difficile infection (CDI) recommend treating recurrent episodes with fidaxomicin or oral vancomycin, but there is little evidence to support one strategy over another, particularly beyond the first recurrence. The aim of this study was to compare clinical outcomes in patients with recurrent CDI treated with vancomycin vs. fidaxomicin. METHODS: This retrospective study evaluated inpatients with recurrent CDI treated with vancomycin or fidaxomicin between 1 January 2013 and 1 May 2019. The primary outcome was CDI recurrence. Secondary outcomes included re-infection, treatment failure, infection-related length of stay (IRLOS) and in-hospital all-cause mortality (IHACM). The Wilcoxon rank-sum test, Pearson's chi-square test or Fisher's exact test was utilized, as appropriate. A multivariable logistic regression (MLR) model was used to estimate the adjusted odds ratio and 95% confidence interval assessing recurrence while adjusting for confounding variables. A survival analysis was also conducted. RESULTS: 135 patients met the inclusion criteria (35 fidaxomicin vs. 100 vancomycin). There was no difference in CDI recurrence [7 (20%) fidaxomicin vs. 11 (11%) vancomycin, p = 0.18]; this persisted in the MLR model (OR: 0.85 [95% CI 0.27-2.7]) and survival analysis (p = 0.1954). Additionally, there was no difference in re-infection rate (p = 0.73), treatment failure (p = 0.13), IRLOS (p = 0.19) or IHACM (p = 0.65). WHAT IS NEW AND CONCLUSION: This represents the first analysis of CDI recurrence that included patients with >2 prior episodes of CDI. The study found no difference in additional recurrences when patients were treated with oral vancomycin vs fidaxomicin for recurrent CDI. However, the current study is limited by the small sample size available for inclusion. Prospective randomized studies with larger sample sizes are needed to confirm this study's conclusions.

Implementation of an antimicrobial stewardship program in a veterinary medical teaching institution.

Widespread use of antimicrobials in human and veterinary medicine drives the emergence and dissemination of resistant bacteria in human, animal, and environmental reservoirs. The AVMA and FDA Center for Veterinary Medicine have both taken public positions emphasizing the importance of incorporating antimicrobial stewardship in veterinary clinical settings; however, a model for implementing a comprehensive antimicrobial stewardship program in veterinary practice is not readily available. In 2015, The Ohio State University College of Veterinary Medicine began developing a veterinary antimicrobial stewardship program modeled on existing programs in human health-care institutions and the 7 core elements of a successful hospital antimicrobial stewardship program, as defined by the CDC. The program includes comprehensive antimicrobial use guidelines, active environmental surveillance, and enhanced infection control procedures in The Ohio State University Veterinary Medical Center, along with routine monitoring and reporting of antimicrobial prescribing practices and antimicrobial susceptibility patterns of common pathogens isolated from patients and the hospital environment. Finally, programs have been developed to educate clinicians, staff, and students on antimicrobial resistance and appropriate antimicrobial prescribing practices. The antimicrobial stewardship program has been designed to help clinicians and students confidently make judicious antimicrobial use decisions and provide them with actionable steps that can help them act as strong stewards while providing the best care for their patients. This report describes our program and the process involved in developing it, with the intent that the program could serve as a potential model for other veterinary medical institutions.

Prediction of Antibiotic Susceptibility for Urinary Tract Infection in a Hospital Setting.

Empiric antibiotic prescribing can be supported by guidelines and/or local antibiograms, but these have limitations. We sought to use data from a comprehensive electronic health record to use statistical learning to develop predictive models for individual antibiotics that incorporate patient- and hospital-specific factors. This paper reports on the development and validation of these models with a large retrospective cohort. This was a retrospective cohort study including hospitalized patients with positive urine cultures in the first 48 h of hospitalization at a 1,500-bed tertiary-care hospital over a 4.5-year period. All first urine cultures with susceptibilities were included. Statistical learning techniques, including penalized logistic regression, were used to create predictive models for cefazolin, ceftriaxone, ciprofloxacin, cefepime, and piperacillin-tazobactam. These were validated on a held-out cohort. The final data set used for analysis included 6,366 patients. Final model covariates included demographics, comorbidity score, recent antibiotic use, recent antimicrobial resistance, and antibiotic allergies. Models had acceptable to good discrimination in the training data set and acceptable performance in the validation data set, with a point estimate for area under the receiver operating characteristic curve (AUC) that ranged from 0.65 for ceftriaxone to 0.69 for cefazolin. All models had excellent calibration. We used electronic health record data to create predictive models to estimate antibiotic susceptibilities for urinary tract infections in hospitalized patients. Our models had acceptable performance in a held-out validation cohort.

Efficacy of combination therapy versus monotherapy in the treatment of Stenotrophomonas maltophilia pneumonia.

BACKGROUND: Stenotrophomonas maltophilia is intrinsically resistant to several antibiotics, making it potentially challenging to treat. Studies have demonstrated treatment failures and resistance development with monotherapy (MT); however, clinical data are limited with combination therapy (CT). OBJECTIVES: To compare clinical outcomes with CT versus MT for S. maltophilia pneumonia. METHODS: This was a retrospective cohort study of patients admitted between November 2011 and October 2017 with S. maltophilia pneumonia who received at least 48 h of effective therapy. The primary outcome was clinical response after 7 days of effective therapy with CT versus MT. Secondary outcomes included development of a non-susceptible isolate, 30 day microbiological cure, infection recurrence, infection-related mortality and all-cause mortality. The Wilcoxon rank sum test, the Pearson χ2 test and Fisher's exact test were utilized for univariate analyses. A multivariable logistic regression model was used to assess clinical response while adjusting for confounding variables. RESULTS: Of 252 patients with S. maltophilia pneumonia included, 38 received CT and 214 received MT. There was no difference in 7 day clinical response with CT versus MT (47.4% versus 39.7%, P = 0.38), even after controlling for immune status, APACHE II score and polymicrobial pneumonia (adjusted OR 1.51, 95% CI 0.63-3.65). Thirty day microbiological cure (P = 0.44), recurrence (P = 0.53), infection-related mortality (P = 0.19) and isolation of a non-susceptible isolate during or after therapy (P = 1.00 each) were also similar between both groups; however, 30 day all-cause mortality was greater with CT (P = 0.03). CONCLUSIONS: CT had similar rates of clinical efficacy and resistance development compared with MT for S. maltophilia pneumonia.

Nonspecific Symptoms Lack Diagnostic Accuracy for Infection in Older Patients in the Emergency Department.

OBJECTIVES: To determine if nonspecific symptoms and fever affect the posttest probability of acute bacterial infection in older patients in the emergency department (ED). DESIGN: Preplanned, secondary analysis of a prospective observational study. SETTING: Tertiary care, academic ED. PARTICIPANTS: A total of 424 patients in the ED, 65 years or older, including all chief complaints. MEASUREMENTS: We identified presence of altered mental status, malaise/lethargy, and fever, as reported by the patient, as documented in the chart, or both. Bacterial infection was adjudicated by agreement among two or more of three expert reviewers. Odds ratios were calculated using univariable logistic regression. Positive and negative likelihood ratios (PLR and NLR, respectively) were used to determine each symptom's effect on posttest probability of infection. RESULTS: Of 424 subjects, 77 (18%) had bacterial infection. Accounting for different reporting methods, presence of altered mental status (PLR range, 1.40-2.53) or malaise/lethargy (PLR range, 1.25-1.34) only slightly increased posttest probability of infection. Their absence did not assist with ruling out infection (NLR, greater than 0.50 for both). Fever of 38°C or higher either before or during the ED visit had moderate to large increases in probability of infection (PLR, 5.15-18.10), with initial fever in the ED perfectly predictive, but absence of fever did not rule out infection (NLR, 0.79-0.92). Results were similar when analyzing lower respiratory, gastrointestinal, and urinary tract infections (UTIs) individually. Of older adults diagnosed as having UTIs, 47% did not complain of UTI symptoms. CONCLUSIONS: The presence of either altered mental status or malaise/lethargy does not substantially increase the probability of bacterial infection in older adults in the ED and should not be used alone to indicate infection in this population. Fever of 38°C or higher is associated with increased probability of infection. J Am Geriatr Soc 67:484-492, 2019.

Establishment of a Sentinel Laboratory-Based Antimicrobial Resistance Surveillance Network in Ethiopia.

In 2014, as part of the Global Health Security Agenda, Ethiopia was provided the technical and financial resources needed to prioritize antimicrobial resistance (AMR) in the national public health sphere. Under the direction of a multi-stakeholder working group, AMR surveillance was launched in July 2017 at 4 sentinel sites across the country. The AMR surveillance initiative in Ethiopia represents one of the first systematic efforts to prospectively collect, analyze, and report national-level microbiology results from a network of hospitals and public health laboratories in the country. Baseline readiness assessments were conducted to identify potential challenges to implementation to be addressed through capacity-building efforts. As part of these efforts, the working group leveraged existing resources, initiated laboratory capacity building through mentorship, and established infrastructure and systems for quality assurance, data management, and improved coordination. As a result, AMR surveillance data are being reported and analyzed for use; data from more than 1,700 patients were collected between July 2017 and March 2018. The critical challenges and effective solutions identified through surveillance planning and implementation have provided lessons to help guide successful AMR surveillance in other settings. Ultimately, the surveillance infrastructure, laboratory expertise, and communication frameworks built specifically for AMR surveillance in Ethiopia can be extended for use with other infectious diseases and potential public health emergencies. Thus, building AMR surveillance in Ethiopia has illustrated how laying the foundation for a specific public health initiative can develop capacity for core public health functions with potential benefit.

A MIXED METHODS APPROACH TO TAILORING EVIDENCE-BASED GUIDANCE FOR ANTIBIOTIC STEWARDSHIP TO ONE MEDICAL SYSTEM.

Our objective is to operationalize a novel antibiotic advisor, called the personalized weighted incidence syndromic combination antibiogram (pWISCA), intended to help physicians with initial antibiotic choice in hospitals. Clinical decision support tools are a promising technology for providing evidence-based guidance that incorporates data about patients from electronic health records. Nevertheless, congruence with policies and procedures and local experts' opinions, as well as taking into account local resistance data for the medical center's patient population, is needed when selecting and ordering the antibiotic medication options provided by pWISCA. This paper presents findings from applying a mixed methods approach to identify and prioritize antibiotic medications and associated contextual data to display in a CDS tailored to the local hospital. We discuss implications of these findings.

Clinical Outcomes with Penicillin Versus Alternative ß-Lactams in the Treatment of Penicillin-Susceptible Staphylococcus aureus Bacteremia.

OBJECTIVES: To identify the impact of penicillin versus alternative ß-lactams on clinical outcomes in patients with penicillin-susceptible Staphylococcus aureus (PSSA) bacteremia. DESIGN: Retrospective cohort study. SETTING: Academic medical center. PATIENTS: Adult patients with PSSA bacteremia treated with a ß-lactam as definitive therapy. MEASUREMENTS: The primary outcome was a composite end point of 30-day clinical failure (change in PSSA therapy due to persistent or worsening signs and symptoms, PSSA bacteremia recurrence or persistence, and/or infection-related mortality) in patients treated with penicillin versus alternative ß-lactams. Secondary outcomes included infection-related and hospital length of stay (LOS), 90-day recurrence, 90-day infection-related readmission, 30-day all-cause mortality, adverse drug events (ADEs), and 30-day change in PSSA therapy due to ADEs. A subgroup analysis comparing penicillin, nafcillin, and cefazolin was also conducted. MAIN RESULTS: For the 122 patients who were included, the most common definitive therapies were nafcillin (37%), cefazolin (29%), and penicillin (21%). No difference was found in 30-day clinical failure (4% vs 11%, p=0.46), infection-related LOS (12 days vs 11 days, p=0.39), hospital LOS (12.5 days vs 12 days, p=0.69), 90-day recurrence (p=1.00), 90-day infection-related readmission (p=1.00), or 30-day all-cause mortality (p=0.45) between penicillin and other ß-lactams. The prevalence of ADEs was different among penicillin, nafcillin, and cefazolin (p=0.049), with nafcillin requiring more changes in therapy (p=0.005). CONCLUSIONS: Definitive therapy with penicillin had similar efficacy compared with alternative ß-lactams for the treatment of PSSA bacteremia. However, nafcillin was associated with more ADEs requiring a change in therapy.

Risk of acute kidney injury in critically ill surgical patients with presumed pneumonia is not impacted by choice of methicillin-resistant staphylococcus aureus therapy.

BACKGROUND: Vancomycin and linezolid are standard treatment options for nosocomial methicillin-resistant Staphylococcus aureus (MRSA) pneumonia. While acute kidney injury (AKI) is commonly attributed to vancomycin, existing data has not definitely confirmed vancomycin as an independent risk factor for AKI. AIMS: This study aimed to quantify the incidence of AKI in Surgical Intensive Care Unit (ICU) patients receiving empiric vancomycin or linezolid for nosocomial pneumonia and to identify risk factors for AKI with a focus on MRSA antibiotic therapy. MATERIALS AND METHODS: A retrospective cohort analysis of surgical ICU patients who received at least 48 h of vancomycin or linezolid for pneumonia was performed. Patients who received vancomycin were compared to those who received linezolid with a primary endpoint of AKI as defined by the risk/injury/failure/loss/end-stage renal disease (RIFLE) criteria. A modified RIFLE criteria assessing only changes in serum creatinine was also used. RESULTS: One hundred one patients were evaluated (63 vancomycin and 38 linezolid). AKI occurred in 51 (81.0%) and 32 (84.2%) patients in the vancomycin and linezolid groups (P = 0.79), respectively. Using the modified RIFLE criteria, AKI occurred in 19 (30.2%) and 14 (36.8%) patients in the vancomycin and linezolid groups (P = 0.448). After adjustment for age, diabetes mellitus, Charlson comorbidity index, and concomitant nephrotoxins, there was no difference in risk of AKI between groups (P = 0.773). CONCLUSIONS: Patients who received empiric vancomycin or linezolid for nosocomial pneumonia experienced high, but similar rates of AKI. The results suggest MRSA antibacterial therapy in this setting may not be independently indicative of AKI risk, rather the risk is likely multifactorial.

Range Expansion and the Origin of USA300 North American Epidemic Methicillin-Resistant Staphylococcus aureus.

The USA300 North American epidemic (USA300-NAE) clone of methicillin-resistant Staphylococcus aureus has caused a wave of severe skin and soft tissue infections in the United States since it emerged in the early 2000s, but its geographic origin is obscure. Here we use the population genomic signatures expected from the serial founder effects of a geographic range expansion to infer the origin of USA300-NAE and identify polymorphisms associated with its spread. Genome sequences from 357 isolates from 22 U.S. states and territories and seven other countries are compared. We observe two significant signatures of range expansion, including decreases in genetic diversity and increases in derived allele frequency with geographic distance from the Pennsylvania region. These signatures account for approximately half of the core nucleotide variation of this clone, occur genome wide, and are robust to heterogeneity in temporal sampling of isolates, human population density, and recombination detection methods. The potential for positive selection of a gyrA fluoroquinolone resistance allele and several intergenic regions, along with a 2.4 times higher recombination rate in a resistant subclade, is noted. These results are the first to show a pattern of genetic variation that is consistent with a range expansion of an epidemic bacterial clone, and they highlight a rarely considered but potentially common mechanism by which genetic drift may profoundly influence bacterial genetic variation.IMPORTANCE The process of geographic spread of an origin population by a series of smaller populations can result in distinctive patterns of genetic variation. We detect these patterns for the first time with an epidemic bacterial clone and use them to uncover the clone's geographic origin and variants associated with its spread. We study the USA300 clone of methicillin-resistant Staphylococcus aureus, which was first noticed in the early 2000s and subsequently became the leading cause of skin and soft tissue infections in the United States. The eastern United States is the most likely origin of epidemic USA300. Relatively few variants, which include an antibiotic resistance mutation, have persisted during this clone's spread. Our study suggests that an early chapter in the genetic history of this epidemic bacterial clone was greatly influenced by random subsampling of isolates during the clone's geographic spread.

Accuracy of Current Diagnostic Criteria for Acute Bacterial Infection in Older Adults in the Emergency Department.

OBJECTIVES: To compare the accuracy of the Loeb criteria, emergency department (ED) physicians' diagnoses, and Centers for Disease Control and Prevention (CDC) guidelines for acute bacterial infection in older adults with a criterion standard expert review. DESIGN: Prospective, observational study. SETTING: Urban, tertiary-care ED. PARTICIPANTS: Individuals aged 65 and older in the ED, excluding those who were incarcerated, underwent a trauma, did not speak English, or were unable to consent. MEASUREMENTS: Two physician experts identified bacterial infections using clinical judgement, participant surveys, and medical records; a third adjudicated in cases of disagreement. Agreement and test characteristics were measured for ED physician diagnosis, Loeb criteria, and CDC surveillance guidelines. RESULTS: Criterion-standard review identified bacterial infection in 77 of 424 participants (18%) (18 (4.2%) lower respiratory, 19 (4.5%) urinary tract (UTI), 22 (5.2%) gastrointestinal, 15 (3.5%) skin and soft tissue). ED physicians diagnosed infection in 71 (17%), but there were 33 with under- and 27 with overdiagnosis. Physician agreement with the criterion standard was moderate for infection overall and each infection type (κ = 0.48-0.59), but sensitivity was low (<67%), and the negative likelihood ratio (LR(-)) was greater than 0.30 for all infections. The Loeb criteria had poor sensitivity, agreement, and LR(-) for lower respiratory (50%, κ = 0.55; 0.51) and urinary tract infection (26%, κ = 0.34; 0.74), but 87% sensitivity (κ = 0.78; LR(-) 0.14) for skin and soft tissue infections. CDC guidelines had moderate agreement but poor sensitivity and LR(-). CONCLUSION: Emergency physicians often under- and overdiagnose infections in older adults. The Loeb criteria are useful only for diagnosing skin and soft tissue infections. CDC guidelines are inadequate in the ED. New criteria are needed to aid ED physicians in accurately diagnosing infection in older adults.