Sarah B. Doernberg

Does Doxycycline Protect Against Development of Clostridium difficile Infection

BACKGROUND Receipt of antibiotics is a major risk factor for Clostridium difficile infection (CDI). Doxycycline has been associated with a lower risk for CDI than other antibiotics. We investigated whether doxycycline protected against development of CDI in hospitalized patients receiving ceftriaxone, a high-risk antibiotic for CDI. METHODS We studied adults admitted to an academic county hospital between 1 June 2005 and 31 December 2010 who received ceftriaxone to determine whether the additional receipt of doxycycline decreased the risk of CDI. Patients were followed from first administration of ceftriaxone to occurrence of CDI or administrative closure 30 days later. RESULTS Two thousand three hundred five unique patients comprising 2734 hospitalizations were studied. Overall, 43 patients developed CDI within 30 days of ceftriaxone receipt, an incidence of 5.60 cases per 10 000 patient-days. The incidence of CDI was 1.67 cases per 10 000 patient-days in those receiving doxycycline, compared to 8.11 per 10 000 patient-days in those who did not receive doxycycline. In a multivariable model adjusted for age, gender, race, comorbidities, hospital duration, pneumonia diagnosis, surgical admission, and duration of ceftriaxone and other antibiotics, for each day of doxycycline receipt the rate of CDI was 27% lower than a patient who did not receive doxycycline (hazard ratio, 0.73; 95% confidence interval, .56-.96). CONCLUSIONS In this cohort of patients receiving ceftriaxone, doxycycline was associated with lower risk of CDI. Guidelines recommend this combination as a second-line regimen for some patients with community-acquired pneumonia (CAP). Further clinical studies would help define whether doxycycline-containing regimens should be a preferred therapy for CAP.

Association of macrophage migration inhibitory factor (MIF) polymorphisms with risk of meningitis from Streptococcus pneumoniae

Macrophage migration inhibitory factor (MIF) is an upstream proinflammatory cytokine encoded by a functionally polymorphic locus. This study of 119 patients explored the potential relationship between MIF genotype and invasive Streptococcus pneumoniae infections. We observed an association between a high-expression MIF allele and occurrence of pneumococcal meningitis.

Cefazolin versus Nafcillin for Methicillin-Sensitive Staphylococcus aureus Bloodstream Infection in a California Tertiary Medical Center

ABSTRACT Recent observational studies have suggested possible reductions in mortality in patients receiving cefazolin versus antistaphylococcal penicillins. We examined 90-day mortality in patients receiving cefazolin compared to nafcillin for methicillin-susceptible Staphylococcus aureus (MSSA) bloodstream infection (BSI). We identified persons with MSSA BSI admitted to San Francisco General Hospital from January 2008 to July 2013 through a hospital-wide infection surveillance system and confirmed 90-day mortality using U.S. national vital registries. We included persons receiving cefazolin or nafcillin as the predominant intravenous antimicrobial agent; all participants received inpatient Infectious Diseases service consultation. We estimated the association between receipt of cefazolin and 90-day risk of death by multivariate logistic regression, including a propensity score for receiving cefazolin as the second predictor. Of 230 MSSA BSI cases, 30 received nafcillin and 70 received cefazolin as the predominant antimicrobial; 10 died within 90 days, 5 from each group. Unadjusted analysis showed substantial but not statistically significant reduced odds of death in those receiving cefazolin (odds ratio, 0.38; 95% confidence interval [CI], 0.10 to 1.44). Multivariate analysis with propensity scores found a similar adjusted odds ratio (0.40; 95% CI, 0.09 to 1.74; P = 0.22). We found a large reduction in 90-day mortality in those receiving cefazolin compared to nafcillin for MSSA BSI, but this finding was not statistically significant. The magnitude of effect seen in this and other studies justifies further study.

Risk factors for acquisition of extended-spectrum β-lactamase-producing Escherichia coli in an urban county hospital.

BACKGROUND Better characterization of risk factors for extended-spectrum β-lactamase (ESBL)-producing bacteria is important for prevention, control, and treatment. This study aimed to identify risk factors for ESBL-producing Escherichia coli in a population of patients at an acute care urban teaching hospital. METHODS A matched case-control study was performed. Cases comprised adults with ESBL E coli isolated from any source and matched with controls on year of hospitalization. One control group included patients with non-ESBL E coli, and a second control group consisted of patients with another resistant bacterium with well-characterized risk factors, Pseudomonas aeruginosa. RESULTS There were 93 subjects in each group. Risk factors associated with ESBL cases compared with both control groups in a univariate model included sex, age, comorbidity, health care facility residence, recent hospitalization, and hemodialysis. In multivariate analysis, only Charlson comorbidity score remained significant between the cases and both control groups. Recent receipt of antibiotics was a risk factor for ESBL E coli versus non-ESBL E coli but not versus P aeruginosa. CONCLUSIONS Underlying comorbid illness appears to be a robust risk factor for acquisition of ESBL-producing E coli. Antibiotic use is a less clear risk factor and may be a surrogate for health care exposure in general.

Vancomycin MIC Does Not Predict 90-Day Mortality, Readmission, or Recurrence in a Prospective Cohort of Adults with Staphylococcus aureus Bacteremia

ABSTRACT Staphylococcus aureus bacteremia (SAB) is a tremendous health burden. Previous studies examining the association of vancomycin MIC and outcomes in patients with SAB have been inconclusive. This study evaluated the association between vancomycin MICs and 30- or 90-day mortality in individuals with SAB. This was a prospective cohort study of adults presenting from 2008 to 2013 with a first episode of SAB. Subjects were identified by an infection surveillance system. The main predictor was vancomycin MIC by MicroScan. The primary outcomes were death at 30 and 90 days, and secondary outcomes included recurrence, readmission, or a composite of death, recurrence, and readmission at 30 and 90 days. Covariates included methicillin susceptibility, demographics, illness severity, comorbidities, infectious source, and antibiotic use. Cox proportional-hazards models with propensity score adjustment were used to estimate 30- and 90-day outcomes. Of 429 unique first episodes of SAB, 11 were excluded, leaving 418 individuals for analysis. Eighty-three (19.9%) participants had a vancomycin MIC of 2 μg/ml. In the propensity-adjusted Cox model, a vancomycin MIC of 2 μg/ml compared to <2 μg/ml was not associated with a greater hazard of mortality or composite outcome of mortality, readmission, and recurrence at either 30 days (hazard ratios [HRs] of 0.86 [95% confidence interval {CI}, 0.41, 1.80] [P = 0.70] and 0.94 [95% CI, 0.55, 1.58] [P = 0.80], respectively) or 90 days (HRs of 0.91 [95% CI, 0.49, 1.69] [P = 0.77] and 0.69 [95% CI, 0.46, 1.04] [P = 0.08], respectively) after SAB diagnosis. In a prospective cohort of patients with SAB, vancomycin MIC was not associated with 30- or 90-day mortality or a composite of mortality, disease recurrence, or hospital readmission.

Chronic Meningitis Investigated via Metagenomic Next-Generation Sequencing

Importance Identifying infectious causes of subacute or chronic meningitis can be challenging. Enhanced, unbiased diagnostic approaches are needed. Objective To present a case series of patients with diagnostically challenging subacute or chronic meningitis using metagenomic next-generation sequencing (mNGS) of cerebrospinal fluid (CSF) supported by a statistical framework generated from mNGS of control samples from the environment and from patients who were noninfectious. Design, Setting, and Participants In this case series, mNGS data obtained from the CSF of 94 patients with noninfectious neuroinflammatory disorders and from 24 water and reagent control samples were used to develop and implement a weighted scoring metric based on z scores at the species and genus levels for both nucleotide and protein alignments to prioritize and rank the mNGS results. Total RNA was extracted for mNGS from the CSF of 7 participants with subacute or chronic meningitis who were recruited between September 2013 and March 2017 as part of a multicenter study of mNGS pathogen discovery among patients with suspected neuroinflammatory conditions. The neurologic infections identified by mNGS in these 7 participants represented a diverse array of pathogens. The patients were referred from the University of California, San Francisco Medical Center (n = 2), Zuckerberg San Francisco General Hospital and Trauma Center (n = 2), Cleveland Clinic (n = 1), University of Washington (n = 1), and Kaiser Permanente (n = 1). A weighted z score was used to filter out environmental contaminants and facilitate efficient data triage and analysis. Main Outcomes and Measures Pathogens identified by mNGS and the ability of a statistical model to prioritize, rank, and simplify mNGS results. Results The 7 participants ranged in age from 10 to 55 years, and 3 (43%) were female. A parasitic worm (Taenia solium, in 2 participants), a virus (HIV-1), and 4 fungi (Cryptococcus neoformans, Aspergillus oryzae, Histoplasma capsulatum, and Candida dubliniensis) were identified among the 7 participants by using mNGS. Evaluating mNGS data with a weighted z score–based scoring algorithm reduced the reported microbial taxa by a mean of 87% (range, 41%-99%) when taxa with a combined score of 0 or less were removed, effectively separating bona fide pathogen sequences from spurious environmental sequences so that, in each case, the causative pathogen was found within the top 2 scoring microbes identified using the algorithm. Conclusions and Relevance Diverse microbial pathogens were identified by mNGS in the CSF of patients with diagnostically challenging subacute or chronic meningitis, including a case of subarachnoid neurocysticercosis that defied diagnosis for 1 year, the first reported case of CNS vasculitis caused by Aspergillus oryzae, and the fourth reported case of C dubliniensis meningitis. Prioritizing metagenomic data with a scoring algorithm greatly clarified data interpretation and highlighted the problem of attributing biological significance to organisms present in control samples used for metagenomic sequencing studies.

Essential Resources and Strategies for Antibiotic Stewardship Programs in the Acute Care Setting

Background Antibiotic stewardship programs improve clinical outcomes and patient safety and help combat antibiotic resistance. Specific guidance on resources needed to structure stewardship programs is lacking. This manuscript describes results of a survey of US stewardship programs and resultant recommendations regarding potential staffing structures in the acute care setting. Methods A cross-sectional survey of members of 3 infectious diseases subspecialty societies actively involved in antibiotic stewardship was conducted. Survey responses were analyzed with descriptive statistics. Logistic regression models were used to investigate the relationship between stewardship program staffing levels and self-reported effectiveness and to determine which strategies mediate effectiveness. Results Two-hundred forty-four respondents from a variety of acute care settings completed the survey. Prior authorization for select antibiotics, antibiotic reviews with prospective audit and feedback, and guideline development were common strategies. Eighty-five percent of surveyed programs demonstrated effectiveness in at least 1 outcome in the prior 2 years. Each 0.50 increase in pharmacist and physician full-time equivalent (FTE) support predicted a 1.48-fold increase in the odds of demonstrating effectiveness. The effect was mediated by the ability to perform prospective audit and feedback. Most programs noted significant barriers to success. Conclusions Based on our surveys results, we propose an FTE-to-bed ratio that can be used as a starting point to guide discussions regarding necessary resources for antibiotic stewardship programs with executive leadership. Prospective audit and feedback should be the cornerstone of stewardship programs, and both physician leadership and pharmacists with expertise in stewardship are crucial for success.

Disseminated Acanthamoeba infection in a heart transplant recipient treated successfully with a miltefosine-containing regimen: case report and review of the literature

Disseminated acanthamoebiasis is a rare, often fatal, infection most commonly affecting immunocompromised patients. We report a case involving sinuses, skin, and bone in a 60‐year‐old woman 5 months after heart transplantation. She improved with a combination of flucytosine, fluconazole, miltefosine, and decreased immunosuppression. To our knowledge, this is the first case of successfully treated disseminated acanthamoebiasis in a heart transplant recipient and only the second successful use of miltefosine for this infection among solid organ transplant recipients. Acanthamoeba infection should be considered in transplant recipients with evidence of skin, central nervous system, and sinus infections that are unresponsive to antibiotics. Miltefosine may represent an effective component of a multidrug therapeutic regimen for the treatment of this amoebic infection.

Antimicrobial Stewardship Approaches in the Intensive Care Unit

Antimicrobial stewardship programs aim to monitor, improve, and measure responsible antibiotic use. The intensive care unit (ICU), with its critically ill patients and prevalence of multiple drug-resistant pathogens, presents unique challenges. This article reviews approaches to stewardship with application to the ICU, including the value of diagnostics, principles of empirical and definitive therapy, and measures of effectiveness. There is good evidence that antimicrobial stewardship results in more appropriate antimicrobial use, shorter therapy durations, and lower resistance rates. Data demonstrating hard clinical outcomes, such as adverse events and mortality, are more limited but encouraging; further studies are needed.

Comparative effectiveness of aerosolized versus oral ribavirin for the treatment of respiratory syncytial virus infections: A single-center retrospective cohort study and review of the literature

Respiratory syncytial virus (RSV) is a leading cause of viral infections in immunocompromised hosts and is associated with significant morbidity and mortality. In January 2015, our institution switched from aerosolized to oral ribavirin (RBV) for primary treatment of RSV infection among high‐risk immunocompromised adult patients. The objective of the study was to evaluate the clinical and economic outcomes associated with this switch.