Co-trimoxazole (Trimethoprim + Sulfamethoxazole)

How it works

The two components block sequential steps of bacterial folate synthesis — sulfamethoxazole inhibits dihydropteroate synthase and trimethoprim inhibits dihydrofolate reductase — giving a synergistic, often bactericidal effect on susceptible organisms.

Prescribing in practice

• It can cause life-threatening skin reactions (Stevens-Johnson syndrome and toxic epidermal necrolysis), bone-marrow suppression and folate-related blood disorders, and haemolysis in G6PD deficiency — stop immediately for any rash or unexplained cytopenia.
• It commonly raises serum potassium and can produce a reversible rise in creatinine; avoid or use with great caution alongside methotrexate and other folate antagonists or marrow-suppressing or potassium-raising drugs.
• Avoid in pregnancy (folate antagonism), ensure adequate hydration, and reserve broader use to where sensitivities or guidance support it under local antimicrobial guidance.

Monitoring

Monitor full blood count and U&E (including potassium and renal function) with prolonged or higher-dose treatment, and review promptly if a rash, sore throat, bruising or unexplained illness develops.

Counselling the patient

• Take it with plenty of fluid and complete the course.
• Stop and seek urgent advice at once if you develop a rash, mouth ulcers, blistering, sore throat, fever or unusual bruising or bleeding.
• Tell your clinician about other medicines, especially methotrexate.

Evidence & guidelines

First-line for Pneumocystis jirovecii pneumonia treatment and prophylaxis in UK and HIV-association guidance; other uses follow culture sensitivities and local antimicrobial guidance.