Trimethoprim-sulfamethoxazole

• Brand names: Bactrim, Septrin, co-trimoxazole
• Route: Oral (intravenous available)

The two drugs block consecutive steps in bacterial folate synthesis: sulfamethoxazole inhibits dihydropteroate synthase and trimethoprim inhibits dihydrofolate reductase.

Blocking the pathway twice starves the organism of the folate it needs to make DNA, and the combination is bactericidal even though each component alone is bacteriostatic.

Human cells take up preformed folate from the diet and are far less affected, which gives the combination its selectivity.

• Adult skin and soft-tissue infection: one or two double-strength tablets (160/800 mg trimethoprim/sulfamethoxazole) twice daily for 7–14 days.
• Larger patients and deeper infections are often given the two-tablet dose; children are dosed at 8–12 mg/kg/day of the trimethoprim component, divided twice daily.
• The dose is reduced in kidney impairment and the drug is generally avoided when creatinine clearance is below 15 mL/min.
• Drinking plenty of fluid reduces the small risk of crystal formation in the urine.

Doses listed are typical adult regimens quoted for reference. The actual dose, route and duration are decided by a clinician for the individual patient.

Sulfonamides were the first broadly effective antibacterials, developed from the dye Prontosil by Gerhard Domagk at Bayer in the 1930s.

Trimethoprim was synthesised by George Hitchings and Gertrude Elion at Burroughs Wellcome in the 1950s during work on antifolates that also produced anticancer drugs.

The fixed combination was introduced in 1968 and became a global staple because of its low cost, oral dosing and long shelf life.

• Rash and photosensitivity; rarely Stevens-Johnson syndrome or toxic epidermal necrolysis.
• Raised potassium and raised creatinine, particularly in older patients and those on ACE inhibitors or ARBs.
• Nausea, low blood counts, and folate-related anaemia on long courses.
• Should be avoided in late pregnancy, in newborns, and in people with a sulfonamide allergy or G6PD deficiency.

• Treatment and prevention of Pneumocystis jirovecii pneumonia in people with HIV or on immunosuppression.
• Urinary tract infection, travellers' diarrhoea, listeriosis, nocardiosis and toxoplasmosis prophylaxis.