Altered trimethoprim-sulfamethoxazole ratios for prophylaxis and treatment of Toxoplasma gondii and Pneumocystis carinii dual infections in rat model.

Abstract

Trimethoprim-sulfamethoxazole (TMP-SMX) is the first-line drug for prophylaxis and treatment of Pneumocystis carinii pneumonia (PCP) and for prophylaxis of toxoplasmosis in HIV-infected patients. Evidence indicating intolerance related to the dose of SMX led us to examine the efficacy 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 prophylaxis, the reference regimen of 20 mg/kg TMP plus 100 mg/kg SMX was effective. Reduced doses of SMX (5 and 20 mg/kg) effective against PCP were 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 both infections, especially in HIV infected patients who often poorly tolerate sulfonamides.