Comparison of the echinocandin caspofungin with amphotericin B for treatment of histoplasmosis following pulmonary challenge in a murine model

Twenty clinical isolates of Histoplasma capsulatum were tested for their in vitro susceptibilities to caspofungin in comparison to those to amphoteric in B by following National Committee for Clinical Laboratory Standards guid elines for yeasts, The mean MICs were 16.6 mu g/ml (range, 8 to 32 mu g/ml) for caspofungin and 0.56 mu g/ml (range, 0.5 to 1.0 mu g/ml) for amphoteri cin B. Survival experiments used a 10(5) dose in a pulmonary challenge mode l with B6C3F(1) mice. All mice that received amphotericin B at 2 mg/kg of b ody weight every other day (q.o.d.), 30% of mice that received caspofungin at 8 mg/kg/day, and 20% of mice that received caspofungin at 4 mg/kg/day su rvived to day lj, while mice that received caspofungin at 2 mg/kg/day and a ll control mice that received the vehicle died by day 14. Amphotericin B at 2 mg/kg q.o.d. markedly reduced the fungal burden in the lungs and spleens , as measured by Histoplasma antigen detection techniques and quantitative cultures, for each comparison. Caspofungin at 10 mg/kg twice a day (b.i.d.) did not reduce the fungal burden, as measured by antigen detection techniq ues, but slightly reduced the levels of fungi in both the lungs and spleens , as determined by quantitative cultures. Caspofungin at 5 mg/kg b.i.d. did not affect fungal burden. Overall, caspofungin had only a slight effect on survival or fungal burden.