Correlation of in vitro susceptibility based on MICs and SQLE mutations with clinical response to terbinafine in patients with tinea corporis/cruris

Abstract

Recalcitrant dermatophytoses are on the rise and recent publications have documented high minimum inhibitory concentrations (MICs) to TRB and squalene epoxidase (SQLE) mutations. However, literature correlating the laboratory the data with clinical response is lacking.\n\nThis study was conducted to study the clinico-mycological profile of tinea corporis and cruris, including antifungal susceptibility testing (AFST) and SQLE mutation analysis and correlate these with clinical response to TRB. Skin scrapings of patients with tinea corporis with/without tinea cruris were subjected to species identification, AFST and SQLE gene analysis (on 15 isolates). KOH confirmed cases were started on TRB 250mg once a day (OD). If >50% clinical clearance was achieved by 3 weeks; the same dose was continued.(Group 1). If clinical clearance at 3 weeks was <50%, the dose was increased to 250mg 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). Trichophyton interdigitale was confirmed on all 64 isolates obtained on culture. Forty four (68.7%) isolates had high ([&ge;]1 g/ml) MICs to TRB. Six isolates were found to have aminoacid substitution Leu393Phe in SQLE protein, while one had the substitution Phe397Leu. The difference in modal MICs to TRB between the 3 clinical response groups (1.5157g/ml, 5.0396 g/ml and 20.1587g/ml respectively for group 1,2 and 3) was highly significant. Clinical response was achieved in 68% of those resistant by MIC data, and 42.8% of SQLE mutation harboring isolates, by increasing drug (TRB) exposure.\n\nWe infer that TRB resistance in dermatophytes has reached alarming proportions in our patients. Though improved outcomes were achieved with higher drug exposure, with the high failure rate seen in the study, the case for shifting to another class of antifungals as first line agent against dermatophytoses is strong.