Clinical outcomes and adverse events associated with intravenous polymyxin-containing therapy in hospitalized children with resistant Gram-negative infections: a systematic review and meta-analysis.

Background: Intravenous polymyxins remain salvage agents for resistant Gram-negative infections in children, but pediatric evidence on clinical outcomes and toxicity is fragmented. Methods: We systematically searched PubMed, Embase, Web of Science, the Cochrane Library, CNKI, Wanfang Data, SinoMed, and VIP from inception to 31 January 2025. Eligible studies reported intravenous polymyxin-containing therapy in hospitalized pediatric patients with documented or suspected resistant Gram-negative infections. Random-effects single-arm meta-analyses were used to estimate pooled outcome proportions. Results: Twenty-four studies comprising 1,152 reported patients or treatment units were included, most of which were single-arm observational studies. The pooled proportions were 22% [95% confidence interval (CI) 16%-27%] for all-cause mortality, 14% (95% CI 11%-17%) for infection-related mortality, 65% (95% CI 58%-72%) for clinical improvement, 13% (95% CI 9%-17%) for overall adverse events, and 10% (95% CI 7%-14%) for nephrotoxicity. Neurotoxicity and hepatotoxicity were infrequently reported. Clinical setting, dosing, outcome definitions, and units of analysis were heterogeneous. Conclusions: The available evidence describes outcomes observed during intravenous polymyxin-containing therapy in hospitalized children but does not establish comparative efficacy or causality for adverse events. Prospective multicenter pediatric studies using standardized dosing, outcome, and safety definitions are needed.