CLINICALLY USED ANTIMICROBIAL DRUGS AGAINST EXPERIMENTAL PNEUMOCYSTOSIS, SINGLY AND IN COMBINATION - ANALYSIS OF DRUG-INTERACTIONS AND EFFICACIES

We analyzed single drugs and combinations of drugs used clinically in the treatment of opportunistic infections and other conditions for the ir activities against Pneumocystis carinii pneumonia In immunosuppress ed rats, When they were used alone, atovaquone, rifabutin, and dapsone were more active than clarithromycin or trimethoprim. Drug combinatio ns were evaluated far synergistic activity by an analysis of variance model for two-way factorial experiments and a response surface model, Atovaquone combined with trimethoprim and some combinations of dapsone and clarithromycin was synergistic; however, the activities of combin ations of atovaquone and rifabutin, atovaquone and clarithromycin, and atovaquone and dapsone were simply additive, Lovastatin, which inhibi ts 3-hydroxy-methylglutaryl coenzyme A reductase, was inactive whether it was used alone or in combination with other agents, None of the sy nergistic drug combinations was as effective as trimethoprim-sulfameth oxazole. We conclude that the rat model can be used to test combinatio ns of anti-P. carinii agents for synergistic activity by well-establis hed statistical techniques, While some combinations of clinically used antimicrobial drugs have enhanced anti-P. carinii activity, further s tudies are needed before clinical trials can be contemplated.