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Mycoses. 2006;49 Suppl 1:2-6.

A new, broad-spectrum azole antifungal: posaconazole--mechanisms of action and resistance, spectrum of activity.

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Institute for Medical Microbiology and Hygiene, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.


Posaconazole, a new triazole antifungal, exerts principally the same mechanism of action as the other azole derivatives, i.e. it inhibits the ergosterol production by binding and inhibiting the lanosterol-14alpha-demethylase which is present in almost all fungi except Pneumocystis and Pythium. Posaconazole has an exquisitely high affinity to this target. Since posaconazole has a chemical structure different from fluconazole and voriconazole, it can interact with an additional domain of the target so that it may inhibit even mutated strains resistant to fluconazole and voriconazole. In addition posaconazole is a bad substrate for efflux pumps in fungi, so it can stay active when other azoles are already inactive. Furthermore, the spectrum of posaconazole is rather large including also some zygomycetes resistant to other azoles. In conclusion, posaconazole is actually the most potent azole derivative used in medicine. A combination of posaconazole with other groups of antifungals may have a favourable effect. There are several methods to test the in vitro activities of posaconazole including the E-test, though interpretive breakpoints are still lacking.

[Indexed for MEDLINE]

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