Dataset Information

Comparative Effectiveness of Exclusive Exposure to Nafcillin or Oxacillin, Cefazolin, Piperacillin/Tazobactam, and Fluoroquinolones Among a National Cohort of Veterans With Methicillin-Susceptible Staphylococcus aureus Bloodstream Infection.

ABSTRACT: Objective:Beta-lactam antibiotics are recommended as first-line for treatment of methicillin-sensitive Staphylococcus aureus (MSSA) bacteremia. The objective of this study was to compare effectiveness of anti-MSSA therapies among bacteremia patients exclusively exposed to 1 antimicrobial. Method:This was a national retrospective cohort study of patients hospitalized in Veterans Affairs medical centers with MSSA bacteremia from January 1, 2002, to October 1, 2015. Patients were included if they were treated exclusively with nafcillin, oxacillin, cefazolin, piperacillin/tazobactam, or fluoroquinolones (moxifloxacin and levofloxacin). We assessed 30-day mortality, time to discharge, inpatient mortality, 30-day readmission, and 30-day S. aureus reinfection. Hazard ratios (HRs) and 95% confidence intervals (CI) were calculated using propensity-score (PS) matched Cox proportional hazards regression model. Results:When comparing nafcillin/oxacillin (n = 105) with cefazolin (n = 107), 30-day mortality was similar between groups (PS matched n = 44; HR, 0.67; 95% CI, 0.11-4.00), as were rates of the other outcomes assessed. As clinical outcomes did not vary between nafcillin/oxacillin and cefazolin, they were combined for comparison with piperacillin/tazobactam (n = 113) and fluoroquinolones (n = 103). Mortality in the 30 days after culture was significantly lower in the nafcillin/oxacillin/cefazolin group compared with piperacillin/tazobactam (PS matched n = 48; HR, 0.10; 95% CI, 0.01-0.78), and similar when compared with fluoroquinolones (PS matched n = 32; HR, 1.33; 95% CI, 0.30-5.96). Conclusions:In hospitalized patients with MSSA bacteremia, no difference in mortality was observed between nafcillin/oxacillin and cefazolin or fluoroquinolones. However, higher mortality was observed with piperacillin/tazobactam as compared with nafcillin/oxacillin/cefazolin, suggesting it may not be as effective as a monotherapy in MSSA bacteremia.

SUBMITTER: Beganovic M

PROVIDER: S-EPMC6602898 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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Comparative Effectiveness of Exclusive Exposure to Nafcillin or Oxacillin, Cefazolin, Piperacillin/Tazobactam, and Fluoroquinolones Among a National Cohort of Veterans With Methicillin-Susceptible <i>Staphylococcus aureus</i> Bloodstream Infection.

Beganovic Maya M Cusumano Jaclyn A JA Lopes Vrishali V LaPlante Kerry L KL Caffrey Aisling R AR

Open forum infectious diseases 20190606 7

<h4>Objective</h4>Beta-lactam antibiotics are recommended as first-line for treatment of methicillin-sensitive <i>Staphylococcus aureus</i> (MSSA) bacteremia. The objective of this study was to compare effectiveness of anti-MSSA therapies among bacteremia patients exclusively exposed to 1 antimicrobial.<h4>Method</h4>This was a national retrospective cohort study of patients hospitalized in Veterans Affairs medical centers with MSSA bacteremia from January 1, 2002, to October 1, 2015. Patients w ...[more]

PMID: 31281864

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Project description:BackgroundCeftriaxone is a convenient option for methicillin-sensitive Staphylococcus aureus (MSSA) outpatient parenteral antimicrobial therapy (OPAT), but population-based studies for its effectiveness are lacking.MethodsIn this retrospective cohort, a large insurance claims database was queried from 2010 to 2018 for adults with MSSA bloodstream infection (BSI). Patients discharged on OPAT on cefazolin or oxacillin/nafcillin were compared with ceftriaxone with respect to 90-day hospital readmission with the same infection category and 90-day all-cause readmission using logistic regression models.ResultsOf 1895 patients with MSSA BSI, 1435 (75.7%) patients received cefazolin, oxacillin, or nafcillin and 460 (24.3%) ceftriaxone. Readmission due to the same infection category occurred in 366 (19.3%), and all-cause readmission occurred in 535 (28.3%) within 90 days. Risk factors significantly associated with readmission with the same infection category were the oldest sampled age group (61-64 years: adjusted odds ratio [aOR], 1.47 [95% confidence interval {CI}, 1.01-2.14]), intensive care unit stay during index admission (aOR, 2.33 [95% CI, 1.81-3.01]), prosthetic joint infection (aOR, 1.96 [95% CI, 1.18-2.23]), central line-associated BSI (aOR, 1.72 [95% CI, 1.33-2.94]), and endocarditis (aOR, 1.63 [95% CI, 1.18-2.23]). Ceftriaxone was not associated with increased risk of readmission with the same infection category (aOR, 0.89 [95% CI, .67-1.18]), or 90-day all-cause readmission (aOR, 0.86 [95% CI, .66-1.10]) when compared with oxacillin/nafcillin/cefazolin.ConclusionsIn this cohort of MSSA BSI patients discharged on OPAT, there were no differences in outcomes of readmission with the same infection and 90-day all-cause readmission in patients treated with ceftriaxone compared to oxacillin/nafcillin or cefazolin. Patients with complicated BSIs such as endocarditis and epidural abscess were more likely to be prescribed cefazolin or oxacillin/nafcillin.

Project description:Our objective was to examine whether empirical antimicrobial therapy (EAT) against methicillin-susceptible Staphylococcus aureus bacteremia (MS-SAB) with piperacillin-tazobactam (TZP), cefuroxime or combination therapy with one of these was differentially associated with 7-, 30-, and 90- day all-cause mortality or MS-SAB relapse. A multicenter retrospective cohort study of adults with MS-SAB from 2009 through 2018 was used, and 7-, 30-, 90-day mortality and relapse within 90 days were assessed and expressed as hazard ratio (HR) with a 95% confidence interval (95% CI) using Cox proportional hazard regression analysis. Matching of the two monotherapy groups was performed using propensity score matching. In total, 1158 MS-SAB cases were included and received one of three EAT regimens: TZP (n = 429), cefuroxime (n = 337), or TZP or cefuroxime with one or more additional effective antimicrobial (n = 392). The overall 30-day mortality was 28.0% (25.5 to 30.3%). After adjustment and matching, there was no significant difference in 7-, 30-, or 90-day mortality between the therapy groups. The matched HR of death was 0.81 (95% CI, 0.38 to 1.76) at 7 days, 0.82 (95% CI, 0.47 to 1.46) at 30 days, and 0.81 (95% CI, 0.50 to 1.32) at 90 days for TZP compared with cefuroxime. Adjusted HR of 90-day relapse was insignificant between the three therapy groups: TZP: 1.55 (95% CI, 0.54 to 4.43); combination therapy: 1.73 (95% CI, 0.62 to 4.80) compared to cefuroxime. There was no significant difference in 7-, 30-, or 90-day mortality or relapse between MS-SAB patients treated with empirical TZP or cefuroxime after adjustment and matching of covariables. IMPORTANCE This multicenter retrospective matched cohort study evaluated the effect of empirical antimicrobial therapy on the clinical outcome of methicillin-susceptible Staphylococcus aureus bacteremia (MS-SAB) in >1100 adult patients. To the best of our knowledge, this is the largest study to date evaluating the effect of empirical treatment on the MS-SAB outcome. Importantly, the study found no significant difference in either short- or long-term mortality nor relapse between patients with MS-SAB receiving empirical treatment with cefuroxime or piperacillin-tazobactam. As such, this study provides crucial contemporary data supporting the widespread clinical practice of initiating empirical antimicrobial therapy of sepsis with β-lactam-β-lactamase-inhibitor.

Project description:Resistance to piperacillin/tazobactam (TZP) in Escherichia coli has predominantly been associated with mechanisms that confer resistance to third-generation cephalosporins. Recent reports have identified E. coli strains with phenotypic resistance to piperacillin/tazobactam but susceptibility to third-generation cephalosporins (TZP-R/3GC-S). In this study we sought to determine the genetic diversity of this phenotype in E. coli (n=58) isolated between 2014-2017 at a single tertiary hospital in Liverpool, UK, as well as the associated resistance mechanisms. We compare our findings to a UK-wide collection of invasive E. coli isolates (n=1509) with publicly available phenotypic and genotypic data. These data sets included the TZP-R/3GC-S phenotype (n=68), and piperacillin/tazobactam and third-generation cephalosporin-susceptible (TZP-S/3GC-S, n=1271) phenotypes. The TZP-R/3GC-S phenotype was displayed in a broad range of sequence types, which was mirrored in the same phenotype from the UK-wide collection, and the overall diversity of invasive E. coli isolates. The TZP-R/3GC-S isolates contained a diverse range of plasmids, indicating multiple acquisition events of TZP resistance mechanisms rather than clonal expansion of a particular plasmid or sequence type. The putative resistance mechanisms were equally diverse, including hyperproduction of TEM-1, either via strong promoters or gene amplification, carriage of inhibitor-resistant β-lactamases, and an S133G blaCTX-M-15 mutation detected for the first time in clinical isolates. Several of these mechanisms were present at a lower abundance in the TZP-S/3GC-S isolates from the UK-wide collection, but without the associated phenotypic resistance to TZP. Eleven (19%) of the isolates had no putative mechanism identified from the genomic data. Our findings highlight the complexity of this cryptic phenotype and the need for continued phenotypic monitoring, as well as further investigation to improve detection and prediction of the TZP-R/3GC-S phenotype from genomic data.

Project description:Abstract Background Escherichia coli and Klebsiella pneumoniae with a piperacillin-tazobactam–nonsusceptible/ceftriaxone-susceptible (TZP-NS/CRO-S) phenotype have been increasingly identified, with limited available literature evaluating treatment strategies. Methods This was a retrospective study of noncritically ill adults hospitalized between 2013 and 2021 and treated at least 48 hours for TZP-NS/CRO-S E coli or K pneumoniae infections. The primary composite endpoint included escalation to intensive care unit, infection- or treatment-related readmission, mortality, and infection recurrence. Outcomes were compared between groups who received carbapenem (CG) versus carbapenem-sparing agents (CSG) as targeted gram-negative therapy. Results Of 1062 patients screened, 200 were included (CG, n = 51; CSG, n = 149). Baseline characteristics, including Charlson Comorbidity Index (CCI; median [interquartile range], 6 [3–9] vs 6 [4–9]; P = .704), were similar between groups, except for more immunocompromised CG patients (29% vs 11%, P = .001). The most common infection sources were urinary (31% vs 57%, P = .002) and bloodstream (18% vs 17%, P = .887). Eighty-eight percent of the CG received meropenem, while 58% of the CSG received ceftriaxone as targeted therapy. There was no statistical difference in the primary endpoint between overall groups (27% vs 17%, P = .123), nor when stratified by infection source. More patients in the CSG switched to oral therapy (15 [29%] vs 100 [67%], P < .001). In multivariate analysis, CCI was an independent predictor of the primary outcome (odds ratio [OR], 1.199 [95% confidence interval, 1.074–1.340]; P = .001), while treatment with carbapenem-sparing therapy was not. Conclusions Our study did not find improved clinical outcomes with targeted carbapenem therapy for TZP-NS/CRO-S infections. Carbapenem-sparing agents may be considered to spare carbapenems in noncritically ill patients similar to those included in our cohort. Piperacillin-tazobactam–nonsusceptible/ceftriaxone-susceptible Enterobacterales have been increasingly identified in the New York metropolitan area. In noncritically ill patients with uncomplicated infections of this phenotype, carbapenem-sparing agents, including third-generation cephalosporins, may be considered.

Dataset Information

Comparative Effectiveness of Exclusive Exposure to Nafcillin or Oxacillin, Cefazolin, Piperacillin/Tazobactam, and Fluoroquinolones Among a National Cohort of Veterans With Methicillin-Susceptible Staphylococcus aureus Bloodstream Infection.

Publications

Comparative Effectiveness of Exclusive Exposure to Nafcillin or Oxacillin, Cefazolin, Piperacillin/Tazobactam, and Fluoroquinolones Among a National Cohort of Veterans With Methicillin-Susceptible <i>Staphylococcus aureus</i> Bloodstream Infection.

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