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J Antimicrob Chemother. 2010 May;65(5):931-8. doi: 10.1093/jac/dkq046. Epub 2010 Feb 18.

Polymyxin B, in combination with fluconazole, exerts a potent fungicidal effect.

Author information

1
Department of Biology, Texas A&M University, College Station, TX, USA.

Abstract

OBJECTIVES:

The objective of this study was to identify existing clinical compounds that either possess a fungicidal activity alone or can act synergistically with fungistatic antifungals.

METHODS:

We screened a clinical compound library for drugs that exhibited anti-Aspergillus activity. Among selected compounds, the cationic peptide antibiotic polymyxin B was chosen for further characterization because it can be used parenterally and topically. The fungicidal effect of polymyxin B and its synergistic interactions with azole antifungals were tested against a variety of fungal species. The toxicity of the drug combination of polymyxin B and fluconazole was compared with that of each drug alone in mammalian cell cultures.

RESULTS:

We found that polymyxin B possesses a broad-spectrum antifungal activity at relatively high concentrations. However, because of its synergistic interactions with azole antifungals, polymyxin B at much lower concentrations exerts a potent fungicidal effect against Cryptococcus neoformans, Candida albicans and non-albicans Candida species and moulds when combined with azoles. The combination of polymyxin B and fluconazole at concentrations within susceptible breakpoints is particularly potent against C. neoformans isolates, including fluconazole-resistant strains. The drug combination displayed no additional toxicity compared with polymyxin B alone when tested in cell culture.

CONCLUSIONS:

The combination of polymyxin B and fluconazole has the potential to be used in the clinic to treat systemic cryptococcosis. Our findings suggest that combining cationic peptide antibiotics with azole antifungals could provide a new direction for developing novel antifungal therapies.

PMID:
20167587
PMCID:
PMC2851492
DOI:
10.1093/jac/dkq046
[Indexed for MEDLINE]
Free PMC Article

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