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Published on: February 14, 2018
Amphotericin B: an introduction
1Department of Microbiology, Bristol Royal Infirmary, UK.
Abstract:
Amphotericin B has a broad spectrum of action that includes most of the major fungal pathogens of man. This drug binds to the membrane sterols of fungal cells, causing impairment of their barrier function and loss of cell constituents. Metabolic disruption and cell death are consequent upon membrane alterations. Investigations of the sterol content of mutant strains of Candida albicans and Cryptococcus neoformans has demonstrated that resistance is often associated with alterations in membrane sterol composition. Treatment failure due to the development of amphotericin B resistance is an uncommon problem. It has tended to occur in patients receiving treatment with cytotoxic drugs. Interactions between amphotericin B and a number of other antimicrobial drugs have been observed in tests in vitro and in vivo. However, apart from one report that the combination with flucytosine is superior to amphotericin B on its own in the treatment of cryptococcal meningitis, there have been no controlled trials to support the use of drug combinations in human infections.
Insights
Amphotericin B targets fungal cell membranes, but resistance can occur. Drug combinations show potential but require further clinical trials for efficacy in treating fungal infections.
Area of Science:
- Mycology
- Pharmacology
- Infectious Diseases
Background:
- Amphotericin B is a broad-spectrum antifungal agent effective against major human fungal pathogens.
- It functions by binding to fungal cell membrane sterols, disrupting barrier integrity and leading to cell death.
Purpose of the Study:
- To review the mechanism of action, resistance patterns, and drug interactions of Amphotericin B.
- To assess the current evidence for combination antifungal therapies.
Main Methods:
- Literature review of Amphotericin B's mechanism, resistance, and interactions.
- Analysis of in vitro and in vivo studies on drug combinations.
Main Results:
- Fungal resistance to Amphotericin B is often linked to alterations in membrane sterol composition, particularly in Candida albicans and Cryptococcus neoformans.
- Treatment failure with Amphotericin B is uncommon but may occur in patients on cytotoxic drugs.
- Drug interactions have been observed, but controlled trials supporting combination therapy are limited, except for a report on Amphotericin B and flucytosine for cryptococcal meningitis.
Conclusions:
- Amphotericin B remains a crucial antifungal, but understanding resistance mechanisms is important.
- Further controlled clinical trials are needed to validate the use of combination antifungal therapies in human infections.
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