Colistin-based combination therapy versus monotherapy for carbapenem-resistant gram-negative bacterial infections: a systematic review and meta-analysis.

Objective: The objective of this study was to summarize available data on colistin (COL) combination therapy or monotherapy for carbapenem-resistant gram-negative bacteria (CR-GNB). Methods: Two reviewers independently evaluated and extracted data from PubMed, Embase, and Cochrane Library from inception to January 31, 2025, for studies comparing COL combination therapy with monotherapy in patients with CR-GNB infections. The primary outcome was all-cause mortality, and secondary outcomes included microbiological eradication rate, clinical improvement rate, length of stay (LOS), nephrotoxicity, and neurotoxicity. Differences for dichotomous outcomes were expressed as risk ratios (RRs) with 95% confidence intervals (CIs), whereas those for continuous outcomes were expressed as mean differences (MDs) with 95% confidence intervals (CIs). The risk of bias was assessed with the Cochrane tools. Certainty of evidence was assessed using GRADE. This systematic review was registered with PROSPERO (CRD42025636727). Results: A total of 26 eligible studies were included. Moderate-quality evidence indicates that compared with COL monotherapy, COL combination therapy significantly increased microbial eradication rate (RR 1.07, 95% CI 1.00-1.13, p = 0.04), particularly in infections caused by carbapenem-resistant Acinetobacter baumannii (CRAB). However, there were no significant differences in terms of 28-day all-cause mortality (RR 0.94, 95% CI 0.85-1.05, p = 0.30). In addition, low-quality evidence suggests that there were no significant differences were observed between COL monotherapy and COL combination therapy in terms of clinical improvement rate (RR 1.00, p = 0.97), intensive care units LOS (MD 0.67 days, p = 0.80), total LOS (MD 0.84 days, p = 0.67), nephrotoxicity (RR 0.98, p = 0.64) and neurotoxicity (RR 0.51, p = 0.14). Conclusion: Moderate-quality evidence suggests that COL combination therapy improved microbiological eradication rates in CRAB infections compared to monotherapy. However, high-quality RCTs are still needed to confirm the beneficial role of colistin-based combination therapy. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/myprospero, identifier CRD42025636727.