💊 Trimethoprim and Co-trimoxazole

Trimethoprim is a folate antagonist antibiotic. Co-trimoxazole is a combination antibiotic comprising trimethoprim and sulfamethoxazole, a sulfonamide antibiotic.

Trimethoprim inhibits bacterial dihydrofolate reductase, blocking the synthesis of tetrahydrofolic acid. Sulfamethoxazole inhibits dihydropteroate synthase. Together, in co-trimoxazole, they provide sequential blockade of bacterial folic acid synthesis, leading to synergistic bactericidal activity.

Trimethoprim is primarily used for uncomplicated urinary tract infections (UTIs) in the UK. Co-trimoxazole has a broader spectrum and is indicated for Pneumocystis jirovecii pneumonia (PJP) prophylaxis and treatment, Nocardiosis, and some severe UTIs or respiratory infections where resistance patterns allow.

Both are contraindicated in hypersensitivity to trimethoprim or sulfonamides. Co-trimoxazole is contraindicated in severe hepatic or renal impairment, and in infants under 6 weeks. Caution is advised in patients with folate deficiency or severe blood disorders.

Common adverse effects include gastrointestinal upset, skin rashes (including Stevens-Johnson syndrome with co-trimoxazole), and hyperkalaemia (due to trimethoprim's effect on renal potassium excretion). Myelosuppression (anaemia, neutropenia) is a serious but less common effect, especially with co-trimoxazole.

For short courses, monitoring is usually not required. For prolonged therapy, particularly with co-trimoxazole, or in patients at risk, monitor full blood count (for myelosuppression) and renal function (urea and electrolytes, especially potassium) regularly.

Always check for sulfonamide allergy before prescribing co-trimoxazole. Counsel patients about the risk of hyperkalaemia and to report any muscle weakness or palpitations. Advise patients to maintain adequate hydration to prevent crystalluria, especially with co-trimoxazole.

Trimethoprim is a common first-line for uncomplicated UTIs. Co-trimoxazole is crucial for PJP prophylaxis/treatment in immunocompromised patients. Remember the risk of hyperkalaemia with trimethoprim and the potential for severe skin reactions with sulfonamides.

SBAs often test the use of trimethoprim for UTIs and co-trimoxazole for PJP. Questions may also focus on the adverse effect of hyperkalaemia, especially in elderly patients or those on ACE inhibitors, or the risk of severe skin reactions.