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

Authors

Russell E Lewis, Dimitrios P Kontoyiannis

Published in

The Journal of infectious diseases. Jul 21, 2026. Epub Jul 21, 2026.

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.

PMID:
42479449
Bibliographic data and abstract were imported from PubMed on 21 Jul 2026.

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