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Published on: October 21, 2010
Antifungal combination therapy: where we stand
1Evans Memorial Department of Clinical Research and Department of Medicine, Boston Medical Center, Boston, Massachusetts 02181, USA. asugar@med-medl.bu.edu
Summary
Combining amphotericin B with fluconazole shows potential additive antifungal effects, unlike itraconazole, which appears antagonistic. Clinical data are needed to guide optimal use of these antifungal drug combinations.
Area of Science:
- Mycology
- Pharmacology
- Infectious Diseases
Background:
- Amphotericin B, fluconazole, and itraconazole are key antifungal agents.
- Combination therapy is used clinically, but optimal strategies are unclear.
- In vitro and animal models provide conflicting data on drug interactions.
Purpose of the Study:
- To review current data on the combined use of amphotericin B with azole antifungals.
- To clarify the interactions between amphotericin B and hydrophilic vs. lipophilic azoles.
- To discuss implications for clinical practice in treating fungal infections.
Main Methods:
- Review of in vitro studies on antifungal drug combinations.
- Analysis of experimental animal studies in models of candidiasis and aspergillosis.
- Discussion of clinical strategies and recent concepts in antifungal combination therapy.
Main Results:
- In vitro studies suggest antagonism between amphotericin B and lipophilic azoles (itraconazole, ketoconazole).
- Hydrophilic azoles (fluconazole) may not antagonize amphotericin B.
- Animal models show additive effects for fluconazole-amphotericin B but antagonism for itraconazole-amphotericin B.
Conclusions:
- The interaction between amphotericin B and azoles depends on the specific azole's properties (hydrophilic vs. lipophilic).
- Clinical trials are essential to establish evidence-based guidelines for antifungal combination therapy.
- Current clinical practice, such as sequential use of amphotericin B and itraconazole, requires further investigation.
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