Need for alternative trial designs and evaluation strategies for therapeutic studies of invasive mycoses.

Studies of invasive fungal infections have been and remain difficult to implement. Randomized clinical trials of fungal infections are especially slow and expensive to perform because it is difficult to identify eligible patients in a timely fashion, to prove the presence of the fungal infection in an unequivocal fashion, and to evaluate outcome in a convincing fashion. Because of these challenges, licensing decisions for antifungal agents have to date depended heavily on historical control comparisons and secondary advantages of the new agent. Although the availability of newer and potentially more effective agents makes these approaches less desirable, the fundamental difficulties of trials of invasive fungal infections have not changed. Therefore, there is a need for alternative trial designs and evaluation strategies for therapeutic studies of invasive mycoses, and this article summarizes the possible strategies in this area.

Comparative study of antifungal activity of sertaconazole, terbinafine, and bifonazole against clinical isolates of Candida spp., Cryptococcus neoformans and dermatophytes.

The in vitro activity of sertaconazole was compared with that of terbinafine and bifonazole against 180 Candida spp., Cryptococcus neoformans yeasts and 53 dermatophytes. Minimum inhibitory concentrations (MICs) were determined by a microdilution method in Sabouraud's buffered liquid medium (pH 5.6). Sertaconazole (arithmetic mean MIC 1.24 mg/l) was statistically more active than bifonazole (MIC 6.54 mg/l) and terbinafine (MIC 12.61 mg/l) against yeasts strains, MIC values for sertaconazole being generally and specifically lower for each tested yeast species. MIC for C. parapsilosis (0.26 mg/l) demonstrated a higher activity of sertaconazole against this species, in contrast to C. tropicalis (MIC 1.49 mg/l). Against dermatophytes, MIC for terbinafine (0.05 mg/l) was lower than sertaconazole (MIC 0.41 mg/l) and bifonazole (MIC 1.04 mg/l). These results, obtained under the same experimental conditions, confirm the good antifungal activity of sertaconazole against both yeasts and dermatophytes with lower MICs obtained in the topical application. This in vitro activity correlates with the clinical efficacy of sertaconazole compared with other antifungal agents.