Safety and efficacy of colistin monotherapy versus combination therapy against carbapenem-resistant gram-negative bacteria infection: a systematic review and meta-analysis

Objective To study the safety and efficacy of colistin monotherapy versus combination therapy against carbapenem-resistant gram-negative bacteria infection. Methods CNKI, Wanfang database, PubMed, Embase and Cochrane library were systematically searched. Randomized controlled trials about colistin monotherapy versus combination therapy against carbapenem-resistant gram-negative bacteria infection were enrolled. The Cochrane Reviewers′ Handbook 5.2 was employed to evaluate the quality of the enrolled studies.The primary outcome was all-cause mortality.The secondary outcomes included infection-related mortality, clinical response, bacterial clearance, nephrotoxicity and hepatotoxicity.Meta-analysis was conducted by RevMan 5.3 software. Results Seven articles containing 859 patients were finally included.There were no significantly statistical differences in all-cause mortality rate (relative risk [RR]=1.07, 95%CI: 0.93-1.24, P>0.05), infection-related mortality rate (RR=1.35, 95%CI: 0.98-1.87, P>0.05), bacterial clearance rate (RR=0.85, 95%CI: 0.71-1.02, P=0.08), hepatotoxicity development rate (RR=0.68, 95%CI: 0.41-1.13, P=0.14), and nephrotoxicity development rate (RR=1.01, 95%CI: 0.85-1.22, P>0.05) between colistin monotherapy and combination therapy. The clinical response rate was higher in combination therapy than that in colistin monotherapy (RR=0.81, 95%CI: 0.66-0.98, P=0.03). In the subgroup analysis, no statistical differences were found in all-cause mortality rate between colistin monotherapy and combination therapy for carbapenem-resistant Acinetobacter baumannii infection (RR=1.00, 95%CI: 0.86-1.12, P>0.05). The dosage of colistin with or without loading dose was not associated with the treatment response. Conclusions Although colistin-based combination therapy has a better clinical response against carbapenem-resistant bacteria infection, especially for Acinetobacter baumannii infection, the mortality rate dose not decline compared to colistin monotherapy.Large-scale randomized controlled trials are needed to evaluate the effect in the future. Key words: Colistin; Meta-analysis; Carbapenem-resistant gram-negative bacteria; Systematic review