Correlation of Susceptibility Based on MICs and Squalene Epoxidase Mutations with Clinical Response to Terbinafine in Patients with Tinea Corporis/Cruris.

Ananta Khurana, Aradhana Masih, Anuradha Chowdhary, Kabir Sardana, Sagar Borker, Aastha Gupta, R K Gautam, P K Sharma, Dhruv Jain

Journal: Antimicrobial agents and chemotherapy 2019;62(12):e01038-18

PMID: 30275090

Abstract

Recalcitrant dermatophytoses are on the rise in India. High MICs of terbinafine (TRB) and squalene epoxidase () gene mutations conferring resistance in spp. have been recently documented. However, studies correlating laboratory data with clinical response to TRB in tinea corporis/cruris are lacking. For this study, we investigated the clinicomycological profile of 85 tinea corporis/cruris patients and performed antifungal susceptibility testing by CLSI microbroth dilution and SQLE mutation analysis of the isolates obtained and correlated these with the responses to TRB. Patients confirmed by potassium hydroxide (KOH) mounting of skin scrapings were started on TRB at 250 mg once a day (OD). If >50% clinical clearance was achieved by 3 weeks, the same dose was continued (group 1). If response was <50%, the dose was increased to 250 mg twice a day (BD) (group 2). If the response still remained below 50% after 3 weeks of BD, the patients were treated with itraconazole (ITR; group 3). Overall, skin scrapings from 64 (75.3%) patients yielded growth on culture. Strikingly, all isolates were confirmed to be isolates by internal transcribed spacer (ITS) sequencing. Thirty-nine (61%) of the isolates had TRB MICs of ≥1 µg/ml. Complete follow-up data were available for 30 culture-positive patients. A highly significant difference in modal MICs to TRB among the three treatment response groups was noted ( = 0.009). Interestingly, 8 of the 9 patients in group 3 harbored isolates exhibiting elevated TRB MICs (8 to 32 µg/ml) and SQLE mutations. The odds of achieving cure with TRB MIC < 1 µg/ml strains were 2.5 times the odds of achieving cure with the strain exhibiting MIC ≥1 µg/ml.

Copyright © 2018 American Society for Microbiology.

Address: Department of Dermatology, Dr Ram Manohar Lohia Hospital and Postgraduate Institute of Medical Education and Research, New Delhi, India [email protected] [email protected].; Department of Medical Mycology, Vallabhbhai Patel Chest Institute, University of Delhi, Delhi, India.; Department of Medical Mycology, Vallabhbhai Patel Chest Institute, University of Delhi, Delhi, India [email protected] [email protected].; Department of Dermatology, Dr Ram Manohar Lohia Hospital and Postgraduate Institute of Medical Education and Research, New Delhi, India.; Department of Community Medicine, Dr Ram Manohar Lohia Hospital and Postgraduate Institute of Medical Education and Research, New Delhi, India.; People's College of Medical Sciences and Research Centre, Bhopal, Madhya Pradesh, India.
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