Antifungal drug resistance: not all azoles are equal

Abstract

Response to: Pemán J, Cantón E, Espinel-Ingroff A. Antifungal drug resistance mechanisms. Expert Rev. Anti Infect. Ther. 7(4), 453-460 (2009).

The expert review of antifungal drug resistance mechanisms by Pemán, Cantón and Espinel-Ingroff [1] is an extremely useful and succinct reference for many agents. While it is impossible to delve into every antifungal agent and their mechanism of action, there was a rather important omission from the azole class. Miconazole, as one of the first available imidazole agents, has been used for over 30 years for the treatment of fungal infections [2,3]. While intravenous miconazole is no longer available for systemic use, other formulations are widely used for many common infections [4,5]. Miconazole is unique among azoles in that it has a dual mechanism of action [6]. Like all azoles, miconazole inhibits lanosterol demethylase, thereby inhibiting ergosterol synthesis. In addition, miconazole increases intracellular reactive oxygen species, at least in part through inhibition of fungal catalase and peroxidase [6,7]. This is probably the basis for the fungicidal activity of miconazole, whereas other azoles are fungistatic [6]. Miconazole also exhibits activity against a wide range of species including Aspergillus spp., Cryptococcus neoformans , Histoplasma capsulatum , Pseudallescheria boydii, Trichosporon spp., Candida spp. and Gram-positive bacteria [5,8,9]. The incidence of resistance to miconazole is low, both in clinical isolates [10] and laboratory experiments [5,11].

Understandably, a review of antifungal resistance mechanisms will not focus on agents with little known resistance. Nevertheless, miconazole, as a major member of the azole class of antifungal treatments with a unique mechanism of action, may warrant some mention for a more complete overview.

Financial & competing interests disclosure

The author is an employee of Strativa Pharmaceuticals, a division of Par Pharmaceutical, Inc. The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Writing assistance was supported by Strativa Pharmaceuticals and provided by Prescott Medical Communications Group.

References

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