Carbapenems versus alternative antibiotics for the treatment of bacteraemia due to Enterobacteriaceae producing extended-spectrum β-lactamases: a systematic review and meta-analysis

J Antimicrob Chemother. 2012 Dec;67(12):2793-803. doi: 10.1093/jac/dks301. Epub 2012 Aug 21.


Objectives: To study the comparative mortality associated with carbapenems and alternative antibiotics for the treatment of patients with extended-spectrum β-lactamase (ESBL)-positive Enterobacteriaceae bacteraemia.

Methods: We searched systematically PubMed and Scopus databases for studies providing data for mortality among patients treated with carbapenems, β-lactam/β-lactamase inhibitor combinations (BL/BLIs) or non-BL/BLIs (mainly cephalosporins and fluoroquinolones), preferably as monotherapy. Studies focusing on patients of all ages with community- and healthcare-associated bacteraemia were eligible. Data were pooled using the technique of meta-analysis.

Results: Twenty-one articles, studying 1584 patients, were included. Escherichia coli and Klebsiella pneumoniae were the most commonly studied bacteria. Delay in appropriate treatment up to 6 days was reported. Carbapenems were used mainly as definitive therapy. Carbapenems were associated with lower mortality than non- BL/BLIs for definitive [risk ratio (RR) 0.65, 95% CI 0.47-0.91] and empirical (RR 0.50, 95% CI 0.33-0.77) treatment. No statistically significant differences in mortality were found between carbapenems and BL/BLIs administered as definitive (RR 0.52, 95% 0.23-1.13) or empirical (RR 0.91, 95% CI 0.66-1.25) treatment. BL/BLIs were not associated with lower mortality than non-BL/BLIs administered either definitively (RR 1.59, 95% 0.83-3.06) or empirically (RR 0.82, 95% 0.48-1.41). Data regarding subgroups according to the setting, comorbidity and bacterial species could not be extracted.

Conclusions: Based on data from non-randomized studies, carbapenems may be considered the treatment of choice for empirical treatment of patients with ESBL-producing Enterobacteriaceae bacteraemia. The role of BL/BLIs should be further evaluated for definitive treatment. Further research should focus on faster identification of ESBL-positive pathogens and potential differences in the treatment of each bacterial species.

Publication types

  • Comparative Study
  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Anti-Bacterial Agents / therapeutic use*
  • Carbapenems / therapeutic use*
  • Enterobacteriaceae / drug effects*
  • Enterobacteriaceae / enzymology
  • Enterobacteriaceae / isolation & purification
  • Enterobacteriaceae Infections / drug therapy*
  • Enterobacteriaceae Infections / microbiology
  • Enterobacteriaceae Infections / mortality*
  • Humans
  • Survival Analysis
  • Treatment Outcome
  • beta-Lactam Resistance*
  • beta-Lactamases / metabolism*


  • Anti-Bacterial Agents
  • Carbapenems
  • beta-Lactamases