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

Russell E Lewis1, Dimitrios P Kontoyiannis2

  • 1Department of Molecular Medicine, University of Padua, Padua, Italy.

The Journal of Infectious Diseases
|July 21, 2026
PubMed

Insights

Current guidelines suggest liposomal amphotericin B (L-AMB) for invasive mucormycosis. However, evidence does not support routine high-dose L-AMB, as it offers no survival benefit and increases nephrotoxicity.

Area of Science:

  • Mycology
  • Pharmacology
  • Infectious Diseases

Background:

  • Invasive mucormycosis is a severe fungal infection with high mortality.
  • Liposomal amphotericin B (L-AMB) is a recommended first-line treatment.
  • Optimal dosing of L-AMB remains debated, particularly regarding higher doses.

Purpose of the Study:

  • To critically appraise evidence on the efficacy and safety of high-dose (HD) L-AMB (>6 mg/kg/day) compared to standard-dose (5-6 mg/kg/day) for invasive mucormycosis.
  • To determine if increased L-AMB doses improve outcomes and justify potential toxicity and cost.

Main Methods:

  • Systematic review and critical appraisal of 58 publications.
  • Inclusion of pharmacokinetic, preclinical, and clinical evidence.
  • Definition of standard-dose L-AMB (5-6 mg/kg/day) and HD-L-AMB (>6 mg/kg/day).

Main Results:

  • Animal models suggest dose-dependent efficacy.
  • A single prospective trial showed similar response rates for HD-L-AMB compared to historical standard-dose data.
  • Retrospective studies did not demonstrate survival benefit with HD-L-AMB and reported higher nephrotoxicity.
  • Pharmacokinetic data suggest saturation at doses >10 mg/kg/day.

Conclusions:

  • Routine dose escalation of L-AMB beyond 5-6 mg/kg/day is not supported by current evidence.
  • Early diagnosis, surgical intervention, and immunosuppression reversal are critical for managing invasive mucormycosis.
  • Higher L-AMB doses may be considered in select cases based on individual risk-benefit assessment.
Keywords:
high-doseliposomal amphotericin Bmucormycosisnephrotoxicitypharmacokinetics

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