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When Azoles Cannot Be Used: The Clinical Effectiveness of Intermittent Liposomal Amphotericin Prophylaxis in

R Batchelor1, C Thomas1, B J Gardiner2,3

  • 1Department of General Medicine, Alfred Health, Melbourne, Victoria, Australia.

Open Forum Infectious Diseases
|August 2, 2021
PubMed
Abstract

Insights

Intermittent liposomal amphotericin B (L-AMB) prophylaxis showed a high rate of breakthrough-invasive fungal disease (BIFD) in hematology patients unable to take azoles. Further trials are needed to optimize L-AMB regimens.

Area of Science:

  • Hematology
  • Infectious Diseases
  • Pharmacology

Background:

  • Azole antifungals are standard prophylaxis, but patient intolerance necessitates alternatives.
  • Hematology patients often have contraindications to azoles, creating a need for alternative antifungal strategies.
  • Liposomal amphotericin B (L-AMB) is a potential option for prophylaxis in this population.

Purpose of the Study:

  • To evaluate the effectiveness and safety of intermittent liposomal amphotericin B (L-AMB) prophylaxis.
  • To assess breakthrough-invasive fungal disease (BIFD) rates and acute kidney injury in hematology patients receiving L-AMB.
  • To identify common indications for L-AMB use in this patient group.

Main Methods:

  • Retrospective cohort study of hematology patients receiving intravenous L-AMB (1 mg/kg thrice weekly) from July 2013 to June 2018.
  • Outcomes included breakthrough-invasive fungal disease (BIFD), reasons for discontinuation, and acute kidney injury.
  • Data were extracted from pharmacy records for 198 patients who received 273 L-AMB courses.

Main Results:

  • A BIFD rate of 9.6% was observed during or shortly after L-AMB prophylaxis.
  • Probable/proven BIFD occurred in 6.6% of patients, with molds and non-albicans Candida species being common pathogens.
  • Acute kidney injury occurred in 27% of courses but rarely led to discontinuation (3.3%).

Conclusions:

  • Intermittent L-AMB prophylaxis is associated with a high incidence of BIFD in hematology patients.
  • The most frequent indications for L-AMB were chemotherapy/drug interactions and intolerance to azoles.
  • Further pragmatic trials are essential to determine optimal L-AMB regimens for patients unsuitable for azoles, especially with increasing use of targeted anticancer drugs.
Keywords:
antifungal prophylaxisbreakthrough fungal infectioninvasive fungal diseaseliposomal amphotericin Bmalignant hematology

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