trimethoprimsulfamethoxazole

Trimethoprim-sulfamethoxazole (TMP-SMX), also known as cotrimoxazole, is a fixed-dose combination antibiotic that pairs trimethoprim with sulfamethoxazole. The two agents act synergistically to block bacterial folate synthesis, producing a bactericidal effect.

Mechanism of action: Sulfamethoxazole inhibits dihydropteroate synthase, an early step in folate production, while trimethoprim inhibits dihydrofolate reductase, a later step. The sequential blockade reduces availability of tetrahydrofolate needed for DNA synthesis, enhancing antibacterial potency.

Indications and use: TMP-SMX treats a range of infections including uncomplicated urinary tract infections, lower and upper respiratory tract infections, sinusitis, otitis media, and traveler's diarrhea due to susceptible organisms. It is a preferred option for Pneumocystis jirovecii pneumonia prophylaxis and treatment in immunocompromised patients, such as those with HIV/AIDS. It can also be used for certain skin and soft tissue infections caused by community-associated MRSA, depending on local guidelines and susceptibility.

Administration and dosing: TMP-SMX is available in oral and intravenous forms and is supplied as fixed-dose combinations. Dosing varies with infection, patient weight, age, and kidney function; regimens are chosen by clinicians and may require adjustments for renal impairment.

Safety, adverse effects, and interactions: Common adverse effects include nausea, vomiting, and rash. Serious reactions such as Stevens-Johnson syndrome, hypersensitivity, and hematologic abnormalities can occur. Hyperkalemia and drug interactions (notably with warfarin, methotrexate, and certain anticonvulsants) are considerations. It is contraindicated in sulfa allergies, in infants under two months, and with certain pregnancy-related concerns; use in pregnancy and breastfeeding requires careful risk–benefit assessment. Resistance can limit effectiveness in some settings.