ALTERED TRIMETHOPRIM-SULFAMETHOXAZOLE RATIOS FOR PROPHYLAXIS AND TREATMENT OF TOXOPLASMA-GONDII AND PNEUMOCYSTIS-CARINII DUAL INFECTIONS INRAT MODEL

Trimethoprim-sulfamethoxazole (TMP-SMX) is the first-line drug for pro phylaxis and treatment of Pneumocystis carinii pneumonia (PCP) and for prophylaxis of toxoplasmosis in HIV-infected patients. Evidence indic ating intolerance related to the dose of SMX led us to examine the eff icacy of altered TMP-SMX ratios in a corticosteroid-treated rat model, Infections were assessed by counting P. carinii cysts in lung and by titration of Toxoplasma gondii burdens in tissue culture. For prophyla xis, the reference regimen of 20 mg/kg TMP plus 100 mg/kg SMX was effe ctive. Reduced doses of SMX (5 and 20 mg/kg) effective against PCP wer e effective against toxoplasmosis, provided the TMP dose was increased to 100 mg/kg. For curative treatment, the reversed ratio of 100 mg/kg TMP plus 20 mg/kg SMX was not effective. These results may provide a basis for altering the TMP-SMX ratios in setting of prophylaxis for bo th infections, especially in HIV-infected patients who often poorly to lerate sulfonamides.