title: Multilaboratory Evaluation of In Vitro Antifungal Susceptibility Testing of Dermatophytes for ME1111.
abstract: ME1111 is a novel small molecule antifungal agent under development for the topical treatment of onychomycosis. Standardization of the susceptibility testing method for this candidate antifungal is needed. Toward this end, 8 independent laboratories determined the interlaboratory reproducibility of ME1111 susceptibility testing. In addition, we subsequently identified 2 strains as quality control (QC) isolates for the method. In the reproducibility study, 5 blinded clinical strains each of Trichophyton rubrum, Trichophyton mentagrophytes, and Epidermophyton floccosum were tested, while the QC study tested 6 blinded T. rubrum or T. mentagrophytes ATCC strains. Testing was performed in frozen microtiter panels according to the Clinical and Laboratory Standards Institute (CLSI) M38-A2 methodology. In the reproducibility study, 9 of 15 clinical strains showed interlaboratory agreement of >90% at the 80% inhibition endpoint, with a range of agreement of 76.2% to 100%. In the QC study, 4 of the 6 ATCC strains showed interlaboratory agreement of >90%. ME1111 demonstrated excellent interlaboratory agreement when tested against dermatophytes. Based on this data, the CLSI Subcommittee on Antifungal Susceptibility Tests approved the susceptibility testing of ME1111 against dermatophytes according to M38-A2 methodology, which stipulates RPMI 1640 as the test medium, an inoculum size of 1 to 3 × 10(3) CFU/ml, and an incubation time and temperature of 96 h at 35°C. The MIC endpoint should be 80% inhibition compared with the growth control. T. rubrum ATCC MYA-4438 and T. mentagrophytes ATCC 28185 were selected as QC isolates, with an acceptable range of 0.12 to 1 μg/ml for the two strains.
authors.affiliation: Case Western Reserve University, Cleveland, Ohio, USA mahmoud.ghannoum@case.edu.
authors.forename: M
authors.initials: M
authors.lastname: Ghannoum
authors.affiliation: Wadsworth Center, New York State Department of Health, Albany, New York, USA.
authors.forename: V
authors.initials: V
authors.lastname: Chaturvedi
authors.affiliation: University of Iowa Carver College of Medicine, Iowa City, Iowa, USA.
authors.forename: D
authors.initials: D
authors.lastname: Diekema
authors.affiliation: University of Texas Health Science Center at Houston, Houston, Texas, USA.
authors.forename: L
authors.initials: L
authors.lastname: Ostrosky-Zeichner
authors.affiliation: University of Alberta Hospital, Edmonton, Alberta, Canada.
authors.forename: R
authors.initials: R
authors.lastname: Rennie
authors.affiliation: Weill Cornell Medical Center, New York, New York, USA.
authors.forename: T
authors.initials: T
authors.lastname: Walsh
authors.affiliation: Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: N
authors.initials: N
authors.lastname: Wengenack
authors.affiliation: University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA.
authors.forename: A
authors.initials: A
authors.lastname: Fothergill
authors.affiliation: University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA.
authors.forename: N
authors.initials: N
authors.lastname: Wiederhold
mesh_terms: D000935:Antifungal Agents / Q000494:pharmacology*; D003883:Arthrodermataceae / Q000145:classification / Q000187:drug effects*; D003881:Dermatomycoses / Q000382:microbiology*; D006801:Humans; D008826:Microbial Sensitivity Tests; D010636:Phenols / Q000494:pharmacology*; D011720:Pyrazoles / Q000494:pharmacology*; D015203:Reproducibility of Results
chemical_list: C000611893:2-(3,5-dimethyl-1H-pyrazol-1-yl)-5-methylphenol; D000935:Antifungal Agents; D010636:Phenols; D011720:Pyrazoles