cotrimoxazole

Cotrimoxazole, also known as co‑trimoxazole or trimethoprim‑sulfamethoxazole, is a fixed‑ratio combination antimicrobial agent composed of trimethoprim and sulfamethoxazole. Both components are sulfamethoxazole, a sulfonamide, and trimethoprim, a synthetic dihydrofolate analogue. The two drugs inhibit sequential enzymes in bacterial folate synthesis, producing a synergistic bacteriostatic effect.

Trimethoprim inhibits bacterial dihydrofolate reductase, whereas sulfamethoxazole blocks dihydropteroate synthase. This dual blockade prevents synthesis of thymidylate and purines, essential for DNA replication, leading to growth arrest of susceptible bacteria.

The combination is indicated for urinary tract infections, community‑acquired pneumonia, acute otitis media, Shigella‑ and certain Escherichia coli‑associated diarrhoea, and prophylaxis of Pneumocystis jirovecii pneumonia in immunocompromised patients. It is also used for other infections such as skin and soft‑tissue infections, meningitis, and peritonitis when appropriate.

Cotrimoxazole is available as oral tablets, powder for suspension, intravenous solution and single‑dose sachets. Typical adult dosing for infections ranges from 1–1.25 g of the combination twice daily, with adjustments for renal function and clinical severity.

Common adverse reactions include gastrointestinal upset, skin rash, and photosensitivity. Serious but less frequent events are Stevens‑Johnson syndrome, severe cutaneous adverse reactions, and aplastic anaemia, especially in individuals with sulfonamide hypersensitivity.

The drug is contraindicated in patients with sulfonamide allergy, severe hepatic or renal impairment, or during pregnancy after the first trimester, except in lifesaving situations. Concomitant use with warfarin may increase bleeding risk, and interactions with other drugs may elevate serum concentrations.

Trimethoprim is rapidly absorbed and has a half‑life of approximately eight hours; sulfamethoxazole has a half‑life of about ten hours. Both agents are distributed widely in body fluids. Cotrimoxazole was first introduced in the 1960s and continues to be one of the most widely used combination antibiotics worldwide.