Successful Treatment of Fluconazole-Resistant Oropharyngeal Candidiasis by a Combination of Fluconazole and Terbinafine

Authors: Mahmoud A. Ghannoum and Boni Elewski

Publication Year: 1999

PMID: 10548586

The approvals of the azoles and the triazoles in late 1980s and early 1990s were major advances in our ability to treat safely and effectively local and systemic fungal infections. The highly safe profile of triazoles, in particular, fluconazole, led to extensive use. Fluconazole has been used to treat in excess of 16 million patients, including over 400,000 AIDS patients. Concomitant with this widespread use, there have been increasing reports of fluconazole-resistant Candida albicans strains, many of which are cross-resistant to other antimycotics (for a review, see the work of Ghannoum and Rice [6]). The likelihood of resistance development and patients becoming refractory increases when these patients are on azoles for an extended period (13). Alternative therapies for the treatment of resistant Candida isolates are currently being sought. Combining fluconazole with other antifungal agents has been suggested as an approach to achieve synergy and broaden the spectrum of activity to include fluconazole-resistant fungi (12). Use of terbinafine in combination with azoles has been suggested as a potential therapeutic option (16). Terbinafine is a clinical antimycotic which was first introduced in 1991 and is now marketed worldwide in both oral and topical formulations primarily for the treatment of fungal infections of the skin, nails, and hair. In humans, terbinafine is well absorbed after oral administration and maximal concentrations in plasma are reached within 2 h following oral administration. It binds strongly to plasma proteins, with more than 90% of proteins being bound. Terbinafine is extensively metabolized, and 15 metabolites have been identified (17). Importantly, it has been shown recently that terbinafine displays potent synergy with fluconazole in vitro against azole-resistant Candida strains (5, 8, 15). In spite of these encouraging in vitro data demonstrating synergy against fluconazole-resistant Candida, use of terbinafine and fluconazole clinically to treat patients with oropharyngeal candidiasis who are refractory to fluconazole has not been reported. This report describes the successful treatment with a combination therapy of terbinafine plus fluconazole of a patient with oropharyngeal candidiasis who failed to respond to fluconazole.

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