Prophylactic effect of FK463, a novel antifungal lipopeptide, against Pneumocystis carinii infection in mice

The prophylactic effect of FK463, a new water-soluble echinocandin-like lip opeptide with inhibitory activity against 1,3-beta-D-glucan synthase, again st Pneumocystis carinii infection was investigated with the severe combined immunodeficient (SCID) mouse model. Treatment with FK463, pentamidine, and saline only was performed for 6 weeks from the day after the SCID mice wer e inoculated intranasally with infected lung homogenates. FK463 at 0.2 or 1 .0 mg/kg of body weight, pentamidine at 4 mg/kg, or saline was subcutaneous ly administered daily into the backs of the SCID mice. The effects of the d rugs were evaluated by detection of P. carinii cysts in mouse lung homogena tes by toluidine blue O staining, lung histology, and PCR amplification of a P, carinii-specific DNA fragment from the lungs. P, carinii cysts were de tected in the lungs of all mice administered saline. In contrast, no cysts were detected in mice administered both doses of FK463 and pentamidine. A s pecific DNA fragment was amplified from all mice administered saline and at least half or more of the mice administered FK463 and pentamidine. These r esults indicate that FK463 acts on cyst walt formation but not on trophozoi te proliferation and is extremely effective in preventing P. carinii-associ ated pneumonia, These results suggest that FK463 is potentially useful as a prophylactic agent against P, carinii infection.