Trimethoprim and sulfamethoxazole act at different parts of the same pathway of synthesis of bacterial folate. Their long half-lives allow both to be given at 12-h intervals. Trimethoprim is active against most staphylococci, streptococci (not enterococci), Enterobacteriaceae, and Hemophilus species, but not Ps. aeruginosa or anaerobes. Trimethoprim can be used for urinary tract infection but in hospital-acquired infections susceptibility needs first to be demonstrated. Sulfamethoxazole adds little to trimethoprim for most infections, but trimethoprim-sulfamethoxazole is commonly used to treat Pneumocystis pneumonia in AIDS. Adverse effects are common at the high dose used (120 mg/kg/day intravenously in four divided doses) and are due mostly to the sulfonamide. Rash, nausea, vomiting, and diarrhea are common, and occasionally Stevens-Johnson syndrome occurs. Administration in pregnancy is contraindicated.
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