Predicting a therapeutic cut-off serum level of itraconazole in recalcitrant tinea corporis and cruris-A prospective trial.

ABSTRACT

BACKGROUND: With rising resistance to terbinafine, and consistently high MICs to fluconazole and griseofulvin, itraconazole is being increasingly used as a first line drug for tinea corporis/cruris. However, inadequate clinical responses are often seen with it in spite of in vitro susceptibility. This is possibly related to a variable pharmacokinetic profile of itraconazole. The drug serum levels associated with the therapeutic outcome have not been defined in dermatophytic infections. METHODS: Forty treatment naïve patients with tinea corporis/cruris were randomised to one of the three dose groups (100, 200 and 400 mg/day) of itraconazole. The drug serum levels of 21 of these patients were obtained after 2 weeks of treatment and correlated with the final clinical outcome and in vitro antifungal susceptibility data. RESULTS: Trichophyton indotineae was identified by sequencing of ITS region of rDNA and TEF1α. All isolates were sensitive to itraconazole (Minimum Inhibitory Concentration (MICs) range 0.06-0.5 µg/ml), while MICs to terbinafine were uniformly high (range 8-32 µg/ml). Thirty-seven patients (92.5%) achieved complete cure, while three failed treatment. Serum levels achieved with 400 mg/day were significantly higher than levels with 100 or 200 mg dose. All patients with itraconazole serum levels of >0.2 µg/ml were cured, while two out of the 10 patients with serum levels <0.2 µg/ml failed treatment. CONCLUSIONS: Therapeutic failures are uncommon with itraconazole, and the prevalent strain in India has low itraconazole MICs. Treatment failure is likely with itraconazole serum levels of <0.2 µg/ml, while levels >0.2 µg/ml are consistently associated with a positive therapeutic outcome.