β-Lactam/β-lactam inhibitor combinations for the treatment of bacteremia due to extended-spectrum β-lactamase-producing Escherichia coli: a post hoc analysis of prospective cohorts

Clin Infect Dis. 2012 Jan 15;54(2):167-74. doi: 10.1093/cid/cir790. Epub 2011 Nov 4.

Abstract

Background: Extended-spectrum ß-lactamase-producing Escherichia coli (ESBL-EC) is an important cause of invasive infections. Alternatives to carbapenems--considered the drugs of choice--are needed because of the emergence of carbapenemase-producing enterobacteria. The efficacy of ß-lactam/ß-lactam inhibitors (BLBLI) in such infections is controversial.

Methods: The authors performed a post hoc analysis of patients with bloodstream infections due to ESBL-EC from 6 published prospective cohorts. Mortality and length of hospital stay in patients treated with an active BLBLI (amoxicillin-clavulanic acid [AMC] and piperacillin-tazobactam [PTZ]) or carbapenem were compared in 2 cohorts: the empirical therapy cohort (ETC) and the definitive therapy cohort (DTC). Confounding was controlled by multivariate analysis; for patients in the ETC, a propensity score for receiving carbapenem was also used.

Results: The ETC included 103 patients (BLBLI, 72; carbapenem, 31), and the DTC included 174 (BLBLI, 54; carbapenem, 120). Mortality rates at day 30 for those treated with BLBLI versus carbapenems were 9.7% versus 19.4% for the ETC and 9.3% versus 16.7% for the DTC, respectively (P > .2, log-rank test). After adjustment for confounders, no association was found between either empirical therapy with BLBLI (adjusted hazard ratio [HR], 1.14; 95% confidence interval [CI], .29-4.40; P = .84) or definitive therapy (adjusted HR, 0.76; 95% CI, .28-2.07; P = .5) and increased mortality. Furthermore, BLBLI therapy, with respect to carbapenem, was not found to influence length of hospital stay.

Conclusions: These results suggest that AMC and PTZ are suitable alternatives to carbapenems for treating patients with bloodstream infections due to ESBL-EC if active in vitro and would be particularly useful as definitive therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Amoxicillin-Potassium Clavulanate Combination / therapeutic use*
  • Anti-Bacterial Agents / therapeutic use*
  • Bacteremia / drug therapy*
  • Bacteremia / epidemiology
  • Bacteremia / microbiology
  • Escherichia coli / drug effects
  • Escherichia coli / enzymology
  • Escherichia coli / isolation & purification
  • Escherichia coli Infections / drug therapy*
  • Escherichia coli Infections / epidemiology
  • Escherichia coli Infections / microbiology
  • Female
  • Humans
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Penicillanic Acid / analogs & derivatives*
  • Penicillanic Acid / therapeutic use
  • Piperacillin / therapeutic use
  • Piperacillin, Tazobactam Drug Combination
  • Proportional Hazards Models
  • Prospective Studies
  • Spain / epidemiology
  • beta-Lactam Resistance
  • beta-Lactamase Inhibitors*

Substances

  • Anti-Bacterial Agents
  • beta-Lactamase Inhibitors
  • Piperacillin, Tazobactam Drug Combination
  • Amoxicillin-Potassium Clavulanate Combination
  • Penicillanic Acid
  • Piperacillin