In vitro activities of antifungal drugs against environmental Exophiala isolates and review of the literature

Abstract

Exophiala is a genus of black fungi isolated worldwide from environmental and clinical specimens. Data on antifungal susceptibility of Exophiala isolates are limited and the methodology on susceptibility testing is not yet standardised. In this study, we investigated in vitro antifungal susceptibilities of environmental Exophiala isolates. A total of 87 Exophiala isolated from dishwashers or railway ties were included. A CLSI M38-A2 microdilution method with modifications was used to determine antifungal susceptibility for fluconazole, voriconazole, posaconazole, itraconazole, amphotericin B and terbinafine. Minimum inhibitory concentration (MIC) values were determined visually at 48 hours, 72 hours and 96 hours. MIC-0 endpoint (complete inhibition of growth) was used for amphotericin B and azoles, except fluconazole, for which MIC-2 endpoint (~50% inhibition compared to growth control) was used. Both MIC-0 and MIC-1 (~80% inhibition compared to growth control) results were analysed for terbinafine to enable comparison with previous studies. Fungal growth was sufficient for determination of MICs at 48 hours for all isolates except two Exophiala dermatitidis strains. At 72 hours, most active antifungal agents according to GM MIC were voriconazole and terbinafine, followed by posaconazole, itraconazole and amphotericin B in rank order of decreasing activity. While amphotericin B displayed adequate in vitro activity despite relatively high MICs, fluconazole showed no meaningful antifungal activity against Exophiala.

Orbital abscess caused by Exophiala dermatitidis following posterior subtenon injection of triamcinolone acetonide: a case report and a review of literature related to Exophiala eye infections

“…As shown in Table 2, bacterial orbital abscess develops within 4-6 weeks, whereas fungal [36,37]. The study of in vitro antifungal susceptibilities of environmental Exophiala isolates has shown that the most active antifungal agents are voriconazole and terbinafine, followed by posaconazole, itraconazole and amphotericin B, and that fluconazole has no meaningful antifungal activity against Exophiala [38]. In the current case, the recurrence of orbital abscess was observed without antifungal systemic treatment in the postoperative period of the first surgery.…”

Exophiala dermatitidis: Key issues of an opportunistic fungal pathogen

“…Currently there are no available standardized broth microdilution methodologies or validated MIC breakpoints for in vitro resistance testing for E. dermatitidis. However, numerous studies dealing with susceptibility patterns of the black yeast-like fungus exist [21,29,41,45,123,130,[132][133][134][135][136][137][138][139][140].…”

“…The antibiotic colistin which is also used for inhalation therapy in CF patients exhibited antifungal activity [148] and was able to reduce mature biofilm [130]. Future research in - [134][135][136][137] developing novel anti-infective agents for the treatment of E. dermatitidis infection is warranted. In CNS infections with E. dermatitidis, therapeutic studies suggest the complete excision of the brain abscess.…”

<i>Exophiala dermatitidis</i> Fungemia Diagnosed Using Time-of-flight Mass Spectrometry during Chemotherapy for Malignant Lymphoma and Successful Treatment with Voriconazole

“…However, it is difficult to decide on the appropriate breakpoint for Candida species (24). In practice, voriconazole shows good results when administered at appropriate concentrations, according to therapeutic drug monitoring (25); the appropriate breakpoint for E. dermatitidis is still being investigated (26).…”