Empiric Therapy With Carbapenem-Sparing Regimens for Bloodstream Infections due to Extended-Spectrum β-Lactamase-Producing Enterobacteriaceae: Results From the INCREMENT Cohort

Clin Infect Dis. 2017 Oct 30;65(10):1615-1623. doi: 10.1093/cid/cix606.

Abstract

Background: There is little information about the efficacy of active alternative drugs to carbapenems except β-lactam/β-lactamase inhibitors for the treatment of bloodstream infections (BSIs) due to extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-E). The objective of this study was to assess the outcomes of patients with BSI due to ESBL-E who received empiric therapy with such drugs (other active drugs [OADs]) or carbapenems.

Methods: A multinational retrospective cohort study of patients with BSI due to ESBL-E who received empiric treatment with OADs or carbapenems was performed. Cox regression including a propensity score for receiving OADs was performed to analyze 30-day all-cause mortality as main outcome. Clinical failure and length of stay were also analyzed.

Results: Overall, 335 patients were included; 249 received empiric carbapenems and 86 OADs. The most frequent OADs were aminoglycosides (43 patients) and fluoroquinolones (20 patients). Empiric therapy with OADs was not associated with mortality (hazard ratio [HR], 0.75; 95% confidence interval [CI], .38-1.48) in the Cox regression analysis. Propensity score-matched pairs, subgroups, and sensitivity analyses did not show different trends; specifically, the adjusted HR for aminoglycosides was 1.05 (95% CI, .51-2.16). OADs were neither associated with 14-day clinical failure (adjusted odds ratio, 0.62; 95% CI, .29-1.36) nor length of hospital stay.

Conclusions: We were unable to show that empiric treatment with OAD was associated with a worse outcome compared with carbapenems. This information allows more options to be considered for empiric therapy, at least for some patients, depending on local susceptibility patterns of ESBL-E.

Keywords: aminoglycosides; antimicrobial resistance; bloodstream infections; extended-spectrum β-lactamase–producing Enterobacteriaceae; therapy.

MeSH terms

  • Anti-Bacterial Agents* / pharmacology
  • Anti-Bacterial Agents* / therapeutic use
  • Bacteremia* / drug therapy
  • Bacteremia* / microbiology
  • Carbapenems / pharmacology
  • Enterobacteriaceae Infections* / drug therapy
  • Enterobacteriaceae Infections* / microbiology
  • Enterobacteriaceae* / drug effects
  • Enterobacteriaceae* / enzymology
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Retrospective Studies
  • beta-Lactam Resistance*
  • beta-Lactamases

Substances

  • Anti-Bacterial Agents
  • Carbapenems
  • beta-Lactamases