The outcomes in nephrotoxicity among therapies utilizing three distinct polymyxins: a systematic review and network meta-analysis.

OBJECTIVES

Polymyxin B (PMB), colistin sulfate, and colistimethate sodium (CMS) are key therapies for multidrug-resistant Gram-negative infections in critically ill patients. However, their comparative nephrotoxicity remains unclear with inconsistent evidence; therefore, this study used a network meta-analysis to systematically compare their renal safety and related clinical outcomes.

METHODS

Studies comparing PMB, colistin sulfate, and CMS were identified through systematic searches of PubMed, EMBASE, the Cochrane Library, Web of Science, CNKI, and Wanfang databases up to April 4, 2026. A frequentist network meta-analysis was conducted to estimate the relative risk of nephrotoxicity among the three polymyxin formulations by integrating direct and indirect evidence within a unified analytical framework. Secondary outcomes included 28-day mortality, microbiological eradication, and length of hospital stay. Data were synthesized using fixed- or random-effects models as appropriate, based on the degree of between-study heterogeneity.

RESULTS

Compared with patients receiving colistin sulfate, those receiving CMS showed higher estimated odds of nephrotoxicity in both the network analysis (OR 3.65, 95% CI 1.31-10.19) and the direct pairwise comparison (OR 2.47, 95% CI 1.44-4.22). In contrast, patients receiving PMB did not show a statistically significant difference in nephrotoxicity compared with those receiving colistin sulfate (OR 0.99, 95% CI 0.68-1.43). In direct comparisons, colistin sulfate cohort was also associated with a lower risk of nephrotoxicity than PMB cohort (OR 0.46, 95% CI 0.28-0.77). Age- and serum albumin-adjusted analysis and subgroup analysis yielded broadly similar results. For secondary outcomes, patients receiving colistin sulfate or PMB showed higher estimated odds of 28-day mortality compared with those receiving CMS, whereas no statistically significant difference in 28-day mortality was observed between colistin sulfate and PMB cohort. Across treatment comparisons, no significant differences were identified in bacterial clearance or length of hospital stay.

CONCLUSION

This network meta-analysis of observational cohort studies suggests that colistin sulfate may be associated with a lower risk of nephrotoxicity than CMS- and PMB-based therapy. Nevertheless, given the heterogeneity across studies and the potential for residual confounding inherent in observational evidence, these findings should be interpreted cautiously and regarded as hypothesis-generating until further evaluated in well-designed prospective cohort studies or randomized controlled trials.

SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD420261322516.