Polymyxins in resistant Gram-negative infections: 22% all-cause mortality, 10% nephrotoxicityPolymyxins For Kids: 22% Mortality In Resistant Infections

BackgroundIntravenous polymyxins remain salvage agents for resistant Gram-negative infections in children, but pediatric evidence on clinical outcomes and toxicity is fragmented.MethodsWe 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.ResultsTwenty-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.ConclusionsThe 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.