{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T04:49:30Z","timestamp":1782103770575,"version":"3.54.5"},"reference-count":33,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T00:00:00Z","timestamp":1782086400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>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\u201310.19) and the direct pairwise comparison (OR 2.47, 95% CI 1.44\u20134.22). 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\u20131.43). 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\u20130.77). 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Systematic review registration<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link>https:\/\/www.crd.york.ac.uk\/PROSPERO\/<\/jats:ext-link>\n                      , identifier CRD420261322516.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmed.2026.1869822","type":"journal-article","created":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T04:32:08Z","timestamp":1782102728000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["The outcomes in nephrotoxicity among therapies utilizing three distinct polymyxins: a systematic review and network meta-analysis"],"prefix":"10.3389","volume":"13","author":[{"given":"Huan","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Critical Care Medicine, West China Hospital of Sichuan University, Chengdu","place":["Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Critical Care Medicine, West China Hospital of Sichuan University, Chengdu","place":["Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zheng","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Critical Care Medicine, West China Hospital of Sichuan University, Chengdu","place":["Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haiqing","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Critical Care Medicine, West China Hospital of Sichuan University, Chengdu","place":["Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianbo","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Critical Care Medicine, West China Hospital of Sichuan University, Chengdu","place":["Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xue","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Critical Care Medicine, West China Hospital of Sichuan University, Chengdu","place":["Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sipan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Critical Care Medicine, West China Hospital of Sichuan University, Chengdu","place":["Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuelian","family":"Liao","sequence":"additional","affiliation":[{"name":"Department of Critical Care Medicine, West China Hospital of Sichuan University, Chengdu","place":["Sichuan, China"]},{"name":"Department of Critical Care Medicine, West China Tianfu Hospital of Sichuan University, Chengdu","place":["Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,22]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1186\/s13054-024-05031-w","article-title":"Efficacy and safety of different polymyxin-containing regimens for the treatment of pneumonia caused by multidrug-resistant gram-negative bacteria: a systematic review and network meta-analysis.","volume":"28","author":"Zhou","year":"2024","journal-title":"Crit 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