MIC and Upper Limit of Wild-Type Distribution for 13 Antifungal Agents against a Trichophyton mentagrophytes-Trichophyton interdigitale Complex of Indian Origin

• Published in: Antimicrobial agents and chemotherapy 2020-03, Vol.64 (4)
• Main Authors: Shaw, Dipika, Singh, Shreya, Dogra, Sunil, Jayaraman, Jyothi, Bhat, Ramesh, Panda, Saumya, Chakrabarti, Arunaloke, Anjum, Nishat, Chowdappa, Aruna, Nagamoti, Mahantesh, Varshney, Umesh, Vanam, Hari Pankaj, Savio, Jayanthi, Antony, Meryl, Rudramurthy, Shivaprakash M
• Format: Article
• Language: English
• Subjects: Antifungal Agents - pharmacology; Arthrodermataceae - drug effects; Arthrodermataceae - genetics; Arthrodermataceae - isolation & purification; Dermatomycoses - drug therapy; Drug Resistance, Fungal - genetics; Humans; India; Microbial Sensitivity Tests; Susceptibility
• ISSN: 0066-4804; 1098-6596
• DOI: 10.1128/AAC.01964-19

Dermatophytosis due to the complex is being increasingly reported across India. Reports of therapeutic failure have surfaced recently, but there are no clinical break points (CBP) or epidemiological cutoffs (ECVs) available to guide the treatment of dermatophytosis. In this study, a total of 498 isolates of the complex were collected from six medical centers over a period of five years (2014 to 2018). Antifungal susceptibility testing of the isolates was carried out for itraconazole, fluconazole, ketoconazole, voriconazole, luliconazole, sertaconazole, miconazole, clotrimazole, terbinafine, amorolfine, naftifine, ciclopirox olamine, and griseofulvin. The MICs (in mg/liter) comprising >95% of the modeled populations were as follows: 0.06 for miconazole, luliconazole, and amorolfine; 0.25 for voriconazole; 0.5 for itraconazole, ketoconazole, and ciclopirox olamine; 1 for clotrimazole and sertaconazole; 8 for terbinafine; 16 for naftifine; 32 for fluconazole; and 64 for griseofulvin. A high percentage of isolates above the upper limit of the wild-type MIC (UL-WT) were observed for miconazole (29%), luliconazole (13.9%), terbinafine (11.4%), naftifine (5.2%), and voriconazole (4.8%), while they were low for itraconazole (0.2%). Since the MICs of itraconazole were low against the complex, this could be considered the choice of first-line treatment. The F397L mutation in the squalene epoxidase (SE) gene was observed in 77.1% of isolates with a terbinafine MIC of ≥1 mg/liter, but no mutation was detected in isolates with a terbinafine MIC of