In-vitro activity of atovaquone, sulphamethoxazole and dapsone alone and combined with inhibitors of dihydrofolate reductase and macrolides against Pneumocystis carinii

Abstract

The anti-Pneumocystis carinii activity of atovaquone, dapsone and sulphamethoxazole alone and combined with dihydrofolate reductase (DHFR) inhibitors and macrolides was investigated against five clinical isolates of P. carinii. The susceptibility tests were performed by inoculation of the organisms on to cell monolayer and parasite count after 72 h incubation at 37 degrees C. Culture plates were added to Dulbecco's modified Eagle's medium containing serial dilutions of atovaquone, dapsone and sulphamethoxazole alone or in combination with diaveridine, pyrimethamine, trimethoprim, azithromycin, clarithromycin and roxithromycin. Atovaquone, dapsone and sulphamethoxazole were found to be effective at levels well below the concentrations that could be achieved clinically, while DHFR inhibitors were shown to combine effectively with dapsone and sulphamethoxazole. No synergy could be demonstrated between atovaquone and DHFR inhibitors or macrolides. A mild synergic effect was noted when macrolides were combined with dapsone and sulphamethoxazole. Pyrimethamine (0.5 mg/L) combined with dapsone and trimethoprim (0.5 mg/L) combined with sulphamethoxazole exerted the strongest inhibitory effect.