Fluconazole in the treatment of tinea capitis

Abstract

Twenty white children (8 girls; 12 boys), ranging in age from 2 to 12 years (most in the age range 5–9 years), were enrolled in a clinical trial with their parents consent to assess the efficacy, safety, and tolerability of a single oral dose of fluconazole given once weekly for 4–8 weeks for the treatment of outpatients with mycologically proven tinea capitis. Ten children had previously undergone an unsuccessful course of treatment with griseofulvin liquid suspension or the ultramicronized formulation and desired alternative therapy. Factors possibly contributing to the lack of success of griseofulvin included living in a tropical area, poor hygiene, insufficient dosages, and malnutrition. Adverse reactions to griseofulvin included skin eruption, nausea, photosensitivity, and drug interactions. Furthermore, the patients became exasperated with the long duration of griseofulvin therapy. The diagnosis of tinea capitis was confirmed on the basis of microscopic examination of arthrospores of the infecting fungus located outside or inside the affected hairs. The primary isolation of the causative pathogens in culture was accomplished using Mycosel (BBL, Baltimore, MD) and Sabouraud dextrose agar. The pathogens recovered were Microsporum canis (13), M. gypseum (5), and Trichophyton tonsurans (2). All cases caused by M. canis were positive under Wood’s light. Patients underwent a physical examination, laboratory tests were performed, and a medical history was obtained from the mother or father of each patient. Any medications taken by the patients at study entry or during the study were recorded. Fluconazole therapy was administered once a week in the presence of the investigator. The dosage was based on body weight. Initially, the fluconazole dose was 6 mg/kg. The dose subsequently was increased to 8 mg/kg based on safety information, including laboratory test results. All patients, except for four, were treated at the higher dose. Shampoos were not used as adjunctive therapy. Patients were assessed weekly for clinical and mycologic response and for the occurrence of adverse events. Adverse event information included the date of onset, duration, severity, and relationship to drug therapy.

A randomized controlled trial assessing the efficacy of fluconazole in the treatment of pediatric tinea capitis

“…Relatively low sample sizes in earlier trials, ranging from only 20 to 61 patients per study, [14][15][16][17] may have resulted in overestimation of the efficacy of fluconazole. Furthermore, some earlier trials were conducted in populations living in underdeveloped tropical countries with a different spectrum of causative organisms, 15,17 and these species apparently had more favorable response rates to fluconazole. More permissive definitions of ''cure'' in earlier studies [14][15][16][17] were also contributing factors to the favorable clinical cure rates reported previously.…”

“…First, priority was given to test other hypotheses. On the basis of the apparent success of fluconazole in previous studies, [14][15][16][17] it was hypothesized that a 3-week course of fluconazole might also be comparable or superior in efficacy to a 6-week course of griseofulvin at the labeled dose. A third arm (fluconazole 6 mg/kg/day for 3 weeks followed by placebo for 3 weeks) was employed to test this hypothesis.…”

“…Similarly, a once-weekly dose of fluconazole, 6 or 8 mg/kg for 4 to 8 weeks, resulted in a mycological cure in 100% of patients. 15 Gupta et al 16 showed that fluconazole at 6 mg/kg per day for 2 to 3 weeks resulted in a mycological and clinical cure in 88.1% of patients and was well tolerated without clinical AEs. The same group subsequently showed that fluconazole 8 mg/kg once weekly for 8 to 16 weeks was curative in 60 of 61 patients with tinea capitis caused by Trichophyton or Microsporum spp.…”

“…Furthermore, some earlier trials were conducted in populations living in underdeveloped tropical countries with a different spectrum of causative organisms, 15,17 and these species apparently had more favorable response rates to fluconazole. More permissive definitions of ''cure'' in earlier studies [14][15][16][17] were also contributing factors to the favorable clinical cure rates reported previously. Finally, our trial may not have been of sufficient duration to detect a subset of mycological cures that would have eventually occurred had the study had been extended to 12 or 16 weeks, as in previous studies.…”

“…On the basis of its apparent success in previous studies, [14][15][16][17] it was hypothesized that fluconazole might have a therapeutic effect that was superior to that of griseofulvin. We used a randomized, multicenter, third-party-blind superiority study to test this hypothesis; to verify the safety, efficacy, and optimal duration of fluconazole therapy in children with tinea capitis; and to compare the efficacy of fluconazole to that of standard-dose griseofulvin.…”