Synergy effect of meropenem-based combinations against Acinetobacter baumannii: a systematic review and meta-analysis

PURPOSE: The main objective of our meta-analysis was to examine the in vitro synergistic effect of meropenem-based combination therapies against Acinetobacter baumannii through a systematic review of the existing literature. METHODS: An extensive search was performed with no restrictions on date of publication, language, and publication type. Our study evaluated the main conclusions drawn from various studies describing the synergistic activity of combination therapies in vitro. RESULTS: In this review, 56 published studies were included. Our report included data on 20 types of antibiotics combined with meropenem in 1,228 Acinetobacter baumannii isolates. In time-kill studies, meropenem combined with polymyxin B and rifampicin showed synergy rates of 98.3% (95% CI, 83.7%–100.0%) and 89.4% (95% CI, 57.2%–100.0%), respectively, for Acinetobacter baumannii, modest synergy rates were found for meropenem combined with several antibiotics such as colistin and sulbactam, and no synergy effect was displayed in the combination of meropenem and ciprofloxacin, whereas in checkerboard method, the synergy rates of polymyxin B and rifampicin were 37.0% (95% CI, 0.00%–100.0%) and 56.3% (95% CI, 8.7%–97.8%), respectively. CONCLUSION: We found that time-kill studies generally identified the greatest synergy, while checkerboard and Etest methods yielded relatively poor synergy rates. Further well-designed in vivo studies should be carried out to confirm these findings.