IN-VITRO ACTIVITY OF ATOVAQUONE, SULFAMETHOXAZOLE AND DAPSONE ALONE AND COMBINED WITH INHIBITORS OF DIHYDROFOLATE-REDUCTASE AND MACROLIDES AGAINST PNEUMOCYSTIS-CARINII

The anti-Pneumocystis carinii activity of atovaquone, dapsone end sulp hamethoxazole alone and combined with dihydrofolate reductase (DHFR) i nhibitors and macrolides was investigated against five clinical isolat es of P. carinii. The susceptibility tests were performed by inoculati on 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 m odified Eagle's medium containing serial dilutions of atovaquone, daps one and sulphamethoxazole alone or in combination with diaveridine, py rimethamine, trimethoprim, azithromycin, clarithromycin and roxithromy cin. Atovaquone, dapsone and sulphamethoxazole were found to be effect ive at levels well below the concentrations that could be achieved cli nically, while DHFR inhibitors were shown to combine effectively with dapsone and sulphamethoxazole. No synergy could be demonstrated betwee n atovaquone and DHFR inhibitors or macrolides. A mild synergic effect was noted when macrolides were combined with dapsone and sulphamethox azole. Pyrimethamine (0.5 mg/L) combined with dapsone and trimethoprim (0.5 mg/L) combined with sulphamethoxazole exerted the strongest inhi bitory effect.