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High-dose amphotericin: yay or nay? A case series and literature review
Kayla R Stover1, Taylor E Jordan2, Jamie L Wagner1
1Department of Pharmacy Practice, University of Mississippi School of Pharmacy, Jackson, MS, USA.
Abstract:
Invasive fungal infections pose significant morbidity and mortality risks, particularly those caused by moulds. Available antifungal classes are limited by toxicities and are increasingly susceptible to resistance, particularly amongst challenging fungal pathogens. The purpose of this case series and literature review was to characterize the use of a high-dose lipid formulation of amphotericin B. A case series is presented including patients who received high-dose lipid formulation amphotericin B (≥7.5 mg/kg/day) between June 2012 and August 2021. Additionally, a systematic literature review was conducted by searching the PubMed database for English-language studies involving individuals who received high-dose amphotericin B therapy (≥7.5 mg/kg) using lipid formulations. Nine patients were included in the case series, receiving an average of 8.9 ± 1.3 mg/kg liposomal amphotericin B over a mean of 11.0 ± 10.8 days predominantly for mould infections including Mucorales, aspergillosis and Fusarium. The patients were primarily cared for in intensive care units, with varying treatment histories and outcomes. A total of 11 studies (n=260 patients) met inclusion criteria for the literature review. Responses to high-dose liposomal amphotericin B ranged from 8% to 100%, often showing favourable outcomes. High doses of liposomal amphotericin B were well tolerated both in the case series and in published literature, with serum creatinine changes being the most commonly reported adverse event. However, multi-patient studies continue to report less than favourable (range 8-62%) response rates. High-dose liposomal amphotericin B, either alone or in combination with other antifungal agents, might be a viable strategy for managing invasive fungal infections when few treatment choices exist. This article is part of the Challenges and strategies in the management of invasive fungal infections Special Issue: https://www.drugsincontext.com/special_issues/challenges-and-strategies-in-the-management-of-invasive-fungal-infections.
Insights
High-dose liposomal amphotericin B may be a viable option for invasive fungal infections. This antifungal agent showed potential benefits, though response rates varied, and it was generally well-tolerated.
Area of Science:
- Medical Mycology
- Infectious Diseases
- Pharmacology
Background:
- Invasive fungal infections (IFIs) cause significant illness and death, especially those from moulds.
- Current antifungal treatments have limitations due to toxicity and emerging resistance in difficult-to-treat fungal pathogens.
Purpose of the Study:
- To evaluate the clinical use and outcomes of high-dose lipid formulation of amphotericin B (≥7.5 mg/kg/day) for IFIs.
- To characterize safety and efficacy data from a case series and systematic literature review.
Main Methods:
- A case series of nine patients receiving high-dose liposomal amphotericin B (L-AmB) between 2012 and 2021.
- A systematic literature review of 11 studies (260 patients) on high-dose L-AmB therapy (≥7.5 mg/kg).
Main Results:
- L-AmB was used for mould infections (Mucorales, aspergillosis, Fusarium) in intensive care unit patients.
- Reported response rates to high-dose L-AmB varied widely (8%–100%), with generally favorable outcomes noted in some studies.
- Adverse events were typically mild, with serum creatinine changes being most common; however, multi-patient studies showed lower response rates (8%–62%).
Conclusions:
- High-dose L-AmB may be a valuable therapeutic option for IFIs, particularly when other treatments are limited.
- Further research is needed to optimize its use and improve response rates in diverse patient populations.
