Analysis of polysaccharide in the cyst wall of Pneumocystis carinii and therapeutic strategy for pneumocystosis using beta-1, 3-glucan biosynthesis inhibitor in vivo.

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In vivo activities of a beta-1, 3-glucan biosynthesis inhibitor, aculeacin A, against P. carinii and P. carinii pneumonia were investigated using the rat model. Intraperitoneal administration of aculeacin A at 25 mg/kg or 10 mg/kg, or even at 2 mg/kg per day for 2 weeks from 5 Weeks of steroid treatment, affected cyst wall formation, inhibited cyst maturation, and prevented severe pneumonia in steroid-treated rats. Administration of aculeacin A at 10 mg/kg, or even at 2 mg/kg per day earlier, during the initial phase of infection, was more effective suggesting that this drug can be used prophilactically. Simultaneous administration of aculeacin A (0.4 mg/kg) and trimethoprim-sulfamethoxazole (1mg/kg as a dose of sulfamethoxazole) from 5 weeks of steroid treatment showed therapeutic effects against rat pneumocystosis. This data suggested that dosages of both drugs were reduced, though distinct synergy of use of both drugs was not given in this case.Thus it is hoped that studies of beta-1, 3-glucan biosynthetic inhibitors will not only help in the understanding of the biochemical pathways of the organisms, but also lead to improved human pneumocystosis chemotherapy.