Impact of carbapenem versus non-carbapenem treatment on the rates of superinfection: A meta-analysis of randomized controlled trials.

Imipenem and meropenem are the recommended antipseudomonal carbapenems for nosocomial pneumonia per clinical practice guidelines. However, these agents have a relatively broader spectrum of activity than other antibiotics and need to be reserved. Carbapenems might cause higher rate of superinfection. The aim of this study was to compare the rate of superinfection between patients who received imipenem or meropenem versus those who received non-carbapenem treatment. PubMed, EMBASE, Cochrane Library databases and two trial registries were searched for relevant randomized controlled trials of hospitalized adults with pneumonia through February 24, 2017 without date or language restrictions. Risk ratios (RRs) with 95% confidence intervals (CIs) were estimated using random-effects models. The primary outcome was based on the intention-to-treat analysis while clinically evaluable patients were analyzed as secondary outcome. Eight RCTs were included in this meta-analysis. A statistically higher risk of superinfection with low heterogeneity (RR = 1.690, 95% CI 1.247-2.291, p = 0.001, I2  = 0%) was associated with the two carbapenems compared to non-carbapenems. However, in comparison with non-carbapenems, superinfection with imipenem was significantly higher (RR = 1.694, 95% CI 1.234-2.325, p = 0.001, I2  = 0%), while it was non-significant with meropenem (RR = 1.647, 95% CI 0.552-4.919, p = 0.371, I2  = 0%). Superinfection was statistically higher in both double-blind and open-label studies and when carbapenems were compared to other antipseudomonal beta-lactams. This meta-analysis identified significantly higher superinfection with imipenem compared to non-carbapenems. The findings confirm the theory of higher superinfections with broader spectrum agents and provide additional support for reserving carbapenems for the treatment of infections caused by multidrug-resistant organisms.