Trimethoprim

Trimethoprim selectively inhibits bacterial dihydrofolate reductase (DHFR), blocking the reduction of dihydrofolate to tetrahydrofolate — an essential cofactor for thymidylate, purine, and amino acid synthesis. Its selectivity for bacterial over mammalian DHFR is approximately 50,000-fold, based on structural differences between the bacterial and human enzymes. When combined with sulfamethoxazole (which blocks the preceding step in folate synthesis), the dual sequential blockade produces synergistic bactericidal activity.

Adult

160 mg (trimethoprim component) / 800 mg (sulfamethoxazole component) twice daily (for SIBO, 10-day course).

Pediatric

4–5 mg/kg of trimethoprim component per dose twice daily (in combination with sulfamethoxazole for SIBO, 10-day course).

Renal adjustment

Usual initial dose, then half normal dose if eGFR 20–50 mL/minute/1.73 m2; 100 mg every 24 hours if eGFR less than 20 mL/minute/1.73 m2

Hepatic adjustment

Manufacturer advises caution; maximum 400 mg daily in hepatic failure (risk of decreased elimination)

Max dose

400 mg daily (in hepatic failure)

• pregnancy (theoretical teratogenic risk)