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Class Explorer · Anti-infectives

Sulfonamide antibacterials

Sequential blockade of folate synthesis: sulfamethoxazole blocks dihydropteroate synthase, trimethoprim blocks dihydrofolate reductase. Bacteria make folate, we eat it, which is the selectivity.

Members

Also in this class: Trimethoprim alone. Full pages arrive as the library grows.

Compare the members

Trimethoprim-sulfamethoxazole
Role
UTI, PJP, MRSA skin
Chief hazard
Hyperkalemia and rash

Shared across the class

Indications
Urinary tract infection · Pneumocystis pneumonia, treatment and prophylaxis · Community MRSA skin infection · Some Nocardia and Stenotrophomonas
Adverse effects
Rash, including Stevens-Johnson syndrome · Hyperkalemia · Rise in creatinine without a true fall in GFR · Bone-marrow suppression · Photosensitivity
Contraindications
Sulfonamide hypersensitivity · Third trimester of pregnancy · Severe hepatic or renal impairment
Monitoring
Potassium, particularly with RAAS blockade · Creatinine, remembering that trimethoprim blocks tubular secretion and raises it without harming the kidney · CBC on prolonged courses · INR in warfarin patients, where the interaction is one of the strongest in practice

What makes each agent different

  • The combination is synergistic and bactericidal where either agent alone is bacteriostatic, which is why it is almost never used as a single agent.

The creatinine rise on trimethoprim is a measurement artefact of blocked tubular secretion. Distinguishing it from true AKI saves needless investigation, and the clue is that urea and electrolytes are otherwise unchanged.

Trimethoprim behaves like amiloride at the collecting duct, which is why the hyperkalemia is real and dangerous alongside an ACE inhibitor or spironolactone.

Last reviewed 2026-08-16 · Goodman & Gilman's The Pharmacological Basis of Therapeutics, 14th ed.