trimethoprim

Trimethoprim is a synthetic antimicrobial agent used to treat a range of bacterial infections. It works by inhibiting bacterial dihydrofolate reductase, blocking the synthesis of tetrahydrofolic acid, which is necessary for DNA and remote RNA production. When used alone it is generally bacteriostatic; when combined with a sulfonamide such as sulfamethoxazole, it provides synergistic bactericidal activity by blocking two steps in the same folate pathway.

Trimethoprim is available both as a single-drug preparation and in fixed-dose combinations with sulfamethoxazole (commonly 80/400 mg or 160/800 mg per tablet). It is used to treat or prevent infections caused by susceptible organisms, including urinary tract infections, acute otitis media, and bronchitis. It is also employed for Pneumocystis jirovecii pneumonia prophylaxis and treatment in immunocompromised patients, and for certain diarrheal illnesses caused by susceptible pathogens.

Pharmacokinetically, trimethoprim is well absorbed orally, with peak plasma levels occurring within a few hours. It is variably protein-bound and has a half-life of about 8–11 hours in adults. It is primarily excreted by the kidneys, and dose adjustments are often required in renal impairment.

Safety and cautions: common adverse effects include nausea, vomiting, and rash. Serious hypersensitivity reactions can occur, as can hematologic toxicity with prolonged use or folate deficiency. Hyperkalemia and photosensitivity have been reported. The drug can interact with anticoagulants, methotrexate, and other medications, and it carries risks in pregnancy and in newborns, including potential kernicterus; use during late pregnancy and in neonates is generally avoided. Resistance can arise via dihydrofolate reductase variants.