Correlation of invitro susceptibility based on MICs and SQLE mutations with clinical response to terbinafine in patients with tinea corporis/cruris [Clinical Therapeutics]

Recalcitrant dermatophytoses are on the rise in India. High MICs of terbinafine (TRB) and squalene epoxidase (SQLE) mutations conferring resistance in Trichophyton spp have been recently documented. However, studies correlating laboratory data with clinical response to TRB in tinea corporis/cruris are lacking. This study investigated the clinico-mycological profile of 85 tinea corporis/cruris patients, and performed antifungal susceptibility testing by CLSI micro-broth dilution and SQLE mutation analysis of isolates obtained and correlated these with the response to TRB. Cases confirmed by KOH mount of skin scrapings were started on TRB 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, 64 patients' (75.3%) skin scrapings yielded growth on culture. Strikingly all isolates were confirmed as Trichophyton interdigitale by ITS sequencing. Thirty-nine (61%) isolates had TRB MICs ≥1 µg/ml. Complete follow-up data was available for 30 culture positive patients. A highly significant difference in modal MICs to TRB among the three treatment response groups was noted (p=0.009).Interestingly, 8 of the 9 patients in group 3 harboured isolates exhibiting elevated TRB MICs (8-32µg/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.

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