In vitro pharmacodynamic characteristics of griseofulvin against dermatophyte isolates of Trichophyton tonsurans from tinea capitis patients.

Tinea capitis is the most commonly observed fungal infection in childhood and is primarily caused by the dermatophyte species Trichophyton tonsurans, Microsporum canis, and Trichophyton violaceum. In North America and the United Kingdom T. tonsurans is responsible for more than 90% of cases. Griseofulvin has been the treatment of choice for tinea capitis for more than 40 years and is the sole oral antifungal agent approved by the FDA for the management of tinea capitis. Some researchers have expressed concern about the possibility of emerging resistance in tinea capitis isolates, especially when there is clinical failure to treatment. A total of 151 isolates of T. tonsurans (142), M. canis (7), and T. violaceum (2) collected from tinea capitis patients were evaluated for their susceptibility to griseofulvin using the CLSI M38-A method. MIC ranges and geometric means in parenthesis were observed for T. tonsurans 0.125-16 microg/ml (1.1 microg/ml), M. canis 0.25-2 microg/ml (0.61 microg/ml), and T. violaceum 2-4 microg/ml (2.82 microg/ml), respectively. In a time kill assay with T. tonsurans UAMH 9334, 50% and 90% reduction was observed in the number of colony forming units with >2x MIC after 6 h and 12 h of exposure to the griseofulvin, respectively. Of 142 T. tonsurans isolates studied, only three could grow on SDA containing 4 times to their griseofulvin MIC, representing resistance frequencies of 1.3 x 10(-6), 6.9 x 10(-7), and 9.7 x 10(-7). Furthermore a two-fold increase in MIC was observed in isolates collected at two time intervals in only one of eight patients. Interestingly, these isolates did not show the same increase in their in vitro resistance as exhibited by the three isolated mentioned above. In light of this data, we could not confirm any correlation between increased MIC and therapy failure.