Drug Combinations against Mucor irregularis In Vitro

Abstract

Combinations of terbinafine or caspofungin with amphotericin B, posaconazole, or itraconazole were studied as potential treatments against 18 isolates of Mucor irregularis in vitro. Synergism of the combinations of terbinafine with amphotericin B, posaconazole, and itraconazole against 38.9, 33.3, and 44.4% of the strains studied was observed. In contrast, synergism of the combinations of caspofungin with amphotericin B, posaconazole, and itraconazole against 99.4, 66.7, and 99.4% of the strains studied was observed. Furthermore, no antagonism was observed.C utanous zygomycosis is a fungal infection caused mainly by members of the order Mucorales that affect the skin. The most frequently reported genus in the English literature is Rhizopus, followed by Lichtheimia spp. and Rhizomucor pusillus (1). Cutaneous zygomycosis caused by Mucor irregularis (formerly Rhizomucor variabilis) is an emerging disease in China that is characterized by progressive swelling, ulceration, and destruction of involved skin at exposed sites, especially the central face, and leads to severe disfigurement and even death if left untreated (2-4). Notably, it seemed that most of the patients infected with M. irregularis were immunocompetent (2-9).Amphotericin B is the most potent drug used for the treatment of M. irregularis infection, but the toxicity of amphotericin B limits its long-term clinical application. Posaconazole has been used primarily as salvage therapy, but at present, there is no strong published clinical evidence supporting its role as a single agent for the treatment of mucormycosis (10). Itraconazole has variable effectiveness against M. irregularis in vitro (11) but was proven to be effective against some M. irregularis infections (2, 5). Terbinafine is an allylamine antifungal agent used primarily to treat dermotropic infections and onychomycosis but has potential for use in adjunct therapy in combination with azoles, polyenes, or echinocandins in the management of severe drug-resistant or refractory mycosis (12). Besides, terbinafine could reach high concentrations in the stratum corneum and sebum because of its lipophilic nature (13), which provided the possibility that terbinafine can be used in combination therapies to treat cutaneous zygomycosis.To our knowledge, with the exception of some reported cases (7, 9), no susceptibility of M. irregularis to combinations of antifungal drugs in vitro has been reported. In the present study, the combinations of terbinafine or caspofungin with amphotericin B, posaconazole, or itraconazole were assessed against M. irregularis isolates in vitro.A total of 18 M. irregularis patient isolates preserved by the Research Center for Medical Mycology at Peking University were tested. Isolates were identified by both conventional morphological methods and the internal transcribed spacer sequence analysis method (11).Drug combinations were conducted by using a checkerboard method based on Clinical and Laboratory Standards Institute document M38-A2 (14) that provided the MICs of each agen...

Evaluation of antifungal combination against Cryptococcus spp.

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ESCMID† and ECMM‡ joint clinical guidelines for the diagnosis and management of mucormycosis 2013

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