Multilaboratory Evaluation of In Vitro Antifungal Susceptibility Testing of Dermatophytes for ME1111

Authors: M. Ghannoum, V. Chaturvedi, D. Diekema, L. Ostrosky-Zeichner, R. Rennie, T. Walsh, N. Wengenack, A. Fothergill, and N. Wiederhold

Publication Year: 2016

PMID: 26719434

Currently available topical agents for the treatment of onychomycosis have low efficacy, and thus, there is a continued need for the development of new topical antifungals (1, 2). ME1111 showed potent antifungal activity against Trichophyton rubrum and Trichophyton mentagrophytes (the major etiologic agents of onychomycosis) strains isolated in Japan and reference fungal strains with an MIC range of 0.12 to 0.5 mg/liter and with an MIC₅₀ and an MIC₉₀ of 0.5 mg/liter for both (3). ME1111 is a novel antifungal whose small molecular weight enhances its ability to penetrate the nail plate to reach the nail bed where the infection resides. ME1111 inhibits succinate dehydrogenase (complex II) (4), and the fungicidal activity of ME1111 seems to be due to its inhibition of this enzyme, which leads to the blockade of ATP production.

The standardized method for the susceptibility testing of dermatophytes was added to the Clinical and Laboratory Standards Institute (CLSI) approved standard M38-A2 following an interlaboratory study involving ciclopirox, fluconazole, griseofulvin, itraconazole, posaconazole, terbinafine, and voriconazole (5). However, this standard does not specifically reference ME1111.

Therefore, in order for ME1111 to be included in this standard, an interlaboratory study was needed to evaluate the reproducibility of the MICs of ME1111 against recent clinical isolates of dermatophytes. Additionally, in accordance with CLSI standard M23-A3, an interlaboratory study was required to identify quality control (QC) strains to monitor the precision and accuracy of the procedure, the performances of the reagents, and the performances of persons who read, interpret, and report the results (6).

In the reproducibility study, eight independent laboratories tested the in vitro antifungal activity of ME1111 against 15 clinical dermatophyte isolates. Based on these investigations, QC isolates for ME1111 were identified and were subsequently approved by the CLSI Subcommittee on Antifungal Susceptibility Tests.

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