Carbapenems versus other beta-lactams in the treatment of hospitalised patients with infection: a mixed treatment comparison

OBJECTIVE: To compare the effectiveness of meropenem with cefepime and piperacillin/tazobactam in the absence of direct comparisons in randomised controlled trials. DATA SOURCES: Two previously conducted systematic reviews, one comparing the carbapenems (ertapenem and imipenem/cilastatin) versus 4th-generation cephalosporins (cefepime) or antipseudomonal penicillins (piperacillin/tazobactam), and the other comparing the carbapenems (imipenem/cilastatin versus meropenem), were updated to provide the basis for this mixed treatment comparison. Searching was completed in April 2007. No restriction was placed on language of publication. STUDY SELECTION AND DATA EXTRACTION: Randomised controlled trials of adult patients hospitalised with infection and treated with a carbapenem or cefepime or piperacillin/tazobactam. Two reviewers independently assessed the papers against the inclusion/exclusion criteria and for methodological quality with any differences in opinion adjudicated by a third party. Two reviewers independently extracted data on clinical response, bacteriological response, mortality, and adverse events. DATA SYNTHESIS: A mixed treatment comparison meta-analysis using Bayesian Markov Chain Monte Carlo simulation was used to perform the indirect comparison. The dataset comprised 34 trials: four comparing ertapenem versus piperacillin/tazobactam, one imipenem/cilastatin versus cefepime, 26 imipenem/cilastatin versus meropenem, three imipenem/cilastatin versus piperacillin/tazobactam. We calculated odds ratios (OR) using imipenem/cilastatin as the common comparator. Meropenem was associated with the highest probability of being the most effective treatment for clinical response (OR 1.52, 95% credible interval [CrI] 1.23-1.87) and bacteriological response (OR 1.45, 95% CrI 1.15-1.80) with a reduced risk of serious adverse events (overall: OR 0.88, 95% CrI 0.76-1.02; serious adverse events leading to withdrawal: OR 0.73, 95% CrI 0.42-1.20; and GI-related: OR 0.76, 95% CrI 0.55-1.02). There was little difference between the three carbapenems and cefepime on all-cause mortality. CONCLUSIONS: This mixed treatment comparison suggests meropenem has substantial advantages over cefepime, ertapenem, imipenem/cilastatin and piperacillin/tazobactam in the treatment of hospitalised patients with infection.