Polymyxin Monotherapy vs. Combination Therapy for the Treatment of Multidrug-resistant Infections: A Systematic Review and Meta-analysis

OBJECTIVES: The objective of this review was to compare the effectiveness of Colistin monotherapy and combination therapy for the treatment of multidrug-resistant gram-negative bacterial infections. DATA SOURCES: PubMed, Cochrane Library. STUDY ELIGIBILITY, INTERVENTIONS, AND EXCLUSIONS: In this systematic review, we included all retrospective and prospective studies and randomized controlled trials (RCTs) that compared intravenous polymyxin monotherapy and combination therapy with any other antibiotic for treating multidrug-resistant infections. Studies using inhaled polymyxins with 5 or less than 5 patients were excluded. The primary outcome was 30-day all-cause mortality and if not reported at day 30 we extracted and documented the closest time point. Both crude outcome rates and adjusted effect estimates were extracted for mortality. STUDY APPRAISAL, DATA EXTRACTION AND SYNTHESIS: Search string used was “(Colistin OR polymyxin) AND (Enterobacteriaceae OR Klebsiella OR Acinetobacter OR Escherichia coli OR Pseudomonas) AND (random OR prospective OR retrospective OR cohort OR observational OR blind).” Thirty-nine studies were included in our analysis; out of which 6 RCTs were included and 9 studies used carbapenem as the adjunctive antibiotic. Each study was screened and reviewed for eligibility independently by two authors and data extrapolated on an Excel sheet. RESULTS: The meta-analysis of polymyxin monotherapy vs. combination therapy in multidrug-resistant infections yielded an odds ratio (OR) of 0.81 (95% confidence interval [CI]: 0.65–1.01) with minimal heterogeneity (I(2) = 40%), whereas pooled analysis of this comparison in studies that included carbapenem as combination therapy yielded an OR of 0.64 (CI: 0.40–1.03; I(2) = 62%). Likewise, the pooled analysis of the RCTs yielded an OR of 0.82 (95% CI: 0.58–1.16, I(2) = 22%). All these showed no statistical significance. However, it was seen that polymyxin combination therapy was more effective in multidrug-resistant infections compared to polymyxin monotherapy. The effectiveness was more glaring when carbapenems were used as the combination drug instead of any other antibiotic and more so in many in vitro studies that used polymyxin combination therapy. CONCLUSION: Although statistically insignificant, it would be prudent to use polymyxin combination therapy to treat multidrug-resistant gram-negative bacilli (GNB) infection over monotherapy with preference to use carbapenem as the adjunct alongside polymyxins. HOW TO CITE THIS ARTICLE: Samal S, Mishra SB, Patra SK, Rath A, Dash A, Nayak B, et al. Polymyxin Monotherapy vs. Combination Therapy for the Treatment of Multidrug-resistant Infections: A Systematic Review and Meta-analysis. Indian J Crit Care Med 2021;25(2):199–206.