INFECTION: TRIMETHOPRIM

Question 1

TRIMETHOPRIM: INDICATIONS

Answer 1

• Trimethoprim is a first choice for uncomplicated urinary tract infections (UTI).
• Co-trimoxazole (trimethoprim combined with sulfamethoxazole) is used for treatment and prevention of pneumocystis pneumonia in people with immunosuppression, e.g. due to HIV infection

Question 2

TRIMETHOPRIM: MOA

Answer 2

• Bacteria are unable to use external sources of folate, so need to make their own for essential functions including DNA synthesis.
• Trimethoprim inhibits bacterial folate synthesis, slowing bacterial growth (bacteriostatic)
• It has a broad spectrum of action against Gram-positive and Gram-negative bacteria, particularly enterobacteria, e.g. Escherichia coli.

Question 3

TRIMETHOPRIM: ADVERSE EFFECTS

Answer 3

• Gi upset
• Skin rash
• Severe hypersensitivity inc. anaphylaxis, drug fever and erythm multiforme
• Impair haematopoesis causing haematological disorders such as megaloblastic anaemia, leucopenia and thrombocytopenia
• Can cause hyperkalaemia and elevation of plasma creatinine levels

Question 4

TRIMETHOPRIM: WARNINGS

Answer 4

• 1st trimester of pregnancy
• Folate deficiency
• Renal impairment
• Neonates, the elderly and those with HIV infection are susceptible to adverse side effects

Question 5

TRIMETHOPRIM: INTERACTIONS

Answer 5

• Use with potassium-elevating drugs (e.g. aldosterone antagonists, ACE inhibitors, angiotensin receptor blockers) predisposes to hyperkalaemia
• Use with other folate antagonists (e.g. methotrexate) and drugs that increase folate metabolism (e.g. phenytoin) increases the risk of adverse haematological effects
• Trimethoprim can enhance the anticoagulant effect of warfarin by killing normal gut flora that synthesise vitamin K.