title: Carbapenem therapy is associated with improved survival compared with piperacillin-tazobactam for patients with extended-spectrum β-lactamase bacteremia.
abstract: BACKGROUND
  The effectiveness of piperacillin-tazobactam (PTZ) for the treatment of extended-spectrum β-lactamase (ESBL) bacteremia is controversial. We compared 14-day mortality of PTZ vs carbapenems as empiric therapy in a cohort of patients with ESBL bacteremia who all received definitive therapy with a carbapenem.
  
  
  METHODS
  Patients hospitalized between January 2007 and April 2014 with monomicrobial ESBL bacteremia were included. A decrease of >3 doubling dilutions in the minimum inhibitory concentration for third-generation cephalosporins tested in combination with 4 µg/mL of clavulanic acid was used to confirm ESBL status. The primary exposure was empiric therapy, defined as antibiotic therapy administered to a patient before ESBL status was known. Patients were excluded if they did not receive a carbapenem after ESBL production was identified. The primary outcome was time to death from the first day of bacteremia. Propensity scores using inverse probability of exposure weighting (IPW) were used to estimate the probability that a patient would receive PTZ vs carbapenems empirically. We calculated overall hazard ratios for mortality censored at 14 days using Cox proportional hazards models on an IPW-adjusted cohort.
  
  
  RESULTS
  A total of 331 unique patients with ESBL bacteremia were identified. One hundred three (48%) patients received PTZ empirically and 110 (52%) received carbapenems empirically. The adjusted risk of death was 1.92 times higher for patients receiving empiric PTZ compared with empiric carbapenem therapy (95% confidence interval, 1.07-3.45).
  
  
  CONCLUSIONS
  PTZ appears inferior to carbapenems for the treatment of ESBL bacteremia. For patients at high risk of invasive ESBL infections, early carbapenem therapy should be considered. Our findings should not be extended to β-lactam/β-lactamase inhibitor combinations in development, as limited clinical data are available for these agents.
authors.affiliation: Department of Pediatrics, Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Pranita D
authors.initials: PD
authors.lastname: Tamma
authors.affiliation: Department of Medicine, Division of Infectious Diseases, University of Pennsylvania School of Medicine, Philadelphia.
authors.forename: Jennifer H
authors.initials: JH
authors.lastname: Han
authors.affiliation: Department of Epidemiology and Public Health, University of Maryland School of Medicine.
authors.forename: Clare
authors.initials: C
authors.lastname: Rock
authors.affiliation: Department of Epidemiology and Public Health, University of Maryland School of Medicine.
authors.forename: Anthony D
authors.initials: AD
authors.lastname: Harris
authors.affiliation: Department of Medicine, Division of Infectious Diseases, University of Pennsylvania School of Medicine, Philadelphia.
authors.forename: Ebbing
authors.initials: E
authors.lastname: Lautenbach
authors.affiliation: Department of Pharmacy, Johns Hopkins Hospital.
authors.forename: Alice J
authors.initials: AJ
authors.lastname: Hsu
authors.affiliation: Department of Pharmacy, Johns Hopkins Hospital.
authors.forename: Edina
authors.initials: E
authors.lastname: Avdic
authors.affiliation: Department of Medicine, Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Sara E
authors.initials: SE
authors.lastname: Cosgrove
mesh_terms: D000368:Aged; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D016470:Bacteremia / Q000188:drug therapy* / Q000382:microbiology* / Q000401:mortality; D015780:Carbapenems / Q000627:therapeutic use*; D015331:Cohort Studies; D004756:Enterobacteriaceae Infections / Q000188:drug therapy* / Q000382:microbiology / Q000401:mortality; D004926:Escherichia coli / Q000187:drug effects / Q000302:isolation & purification; D005260:Female; D006801:Humans; D041121:Klebsiella oxytoca / Q000187:drug effects / Q000302:isolation & purification; D007711:Klebsiella pneumoniae / Q000187:drug effects / Q000302:isolation & purification; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D010397:Penicillanic Acid / Q000031:analogs & derivatives* / Q000627:therapeutic use; D010878:Piperacillin / Q000627:therapeutic use; D000077725:Piperacillin, Tazobactam Drug Combination; D057216:Propensity Score; D016016:Proportional Hazards Models; D011513:Proteus mirabilis / Q000187:drug effects / Q000302:isolation & purification; D015996:Survival Rate; D013997:Time Factors; D065093:beta-Lactamase Inhibitors / Q000627:therapeutic use*; D001618:beta-Lactamases / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D015780:Carbapenems; D065093:beta-Lactamase Inhibitors; D000077725:Piperacillin, Tazobactam Drug Combination; D010397:Penicillanic Acid; D001618:beta-Lactamases; D010878:Piperacillin
keywords: ESBL; carbapenem; gram-negative; piperacillin-tazobactam; resistance