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.