Does the Evidence Support High-Dose Liposomal Amphotericin B in the Treatment of Mucormycosis?

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ID: 321926
2026
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Abstract
Guidelines recommend liposomal amphotericin B (L-AMB) at 5-10 mg/kg/day as first-line therapy for invasive mucormycosis, but whether doses exceeding 5-6 mg/kg/day improve outcomes enough to justify added nephrotoxicity and cost remains unclear. We critically appraised pharmacokinetic, preclinical, and clinical evidence from 58 publications, defining standard-dose L-AMB as 5-6 mg/kg/day and high-dose (HD) L-AMB as >6 mg/kg/day. Animal models show dose-dependent efficacy, but the only prospective trial (Ambizygo) examining HD-L-AMB was a single-arm pilot trial whose response rates were similar to historical 5 mg/kg/day cohorts. Retrospective studies have not found survival benefit favoring HD L-AMB, with consistently higher rates of nephrotoxicity. Saturable pharmacokinetics and altered liposome distribution at doses >10 mg/kg/day may explain this lack of benefit. Routine dose escalation beyond 5-6 mg/kg/day is not supported by current evidence; early diagnosis, surgical debridement, and reversal of immunosuppression appear more critical. However, selected cases may still warrant higher L-AMB doses based on individualized risk-benefit assessment.
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openalex_W7169841524 Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors Russell E. Lewis, Dimitrios P. Kontoyiannis
Journal The Journal of infectious diseases
Year 2026
DOI
10.1093/infdis/jiag336
URL
https://doi.org/10.1093/infdis/jiag336
Keywords Keywords not found

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