Pharm 101: Trimethoprim-Sulfamethoxazole

Class

Antifolate antibiotic

Pharmacodynamics
  • Synergistic combination of folate antagonists that blocks purine production and nucleic acid synthesis
  • Trimethoprim in combination with sulphonamides becomes bactericidal (synergistic effect), due to blockade of sequential steps in folate synthesis:
    • Sulphonamides inhibit dihydropteroate synthase, which catalyses PABA to DHFA (step before trimethoprim)
Pharmacokinetics
  • PO or IV administration
  • Formulated in 5:1 ratio of sulphamethoxazole:trimethoprim
  • Half-life 8 hours
  • Renal clearance:
    • 30-50% of sulphonamide and 50-60% of trimethoprim are excreted in urine within 24 hours
Antimicrobial activity
  • Most S aureus strains, MSSA and MRSA
  • Haemophilus, Moraxella catarrhalis, K pneumoniae
  • Clinical uses:
    • P jiroveci pneumonia
    • UTI, prostatitis
    • Bone and joint infections caused by S aureus
    • Uncomplicated skin and soft tissue infections
    • Some infections caused by susceptible strains of Shigella, Salmonella
Adverse effects
  • Similiar to trimethoprim, with additional adverse effects of sulphonamides:
    • GI upset
    • Fever, skin rashes, rarely Stevens-Johnson syndrome
    • Urinary tract disturbances: precipitates in urine
    • Haematological disturbances: haemolytic or aplastic anaemia, thrombocytopaenia
Further reading
References
Pharm 101 700

Pharmacology 101

Top 200 drugs

MBBS CCPU (RCE, Biliary, DVT, E-FAST, AAA) Rob is an Emergency Medicine Advanced Trainee based in Melbourne, Australia. He has special interests in medical education, ECG interpretation, and the use of diagnostic and procedural ultrasound in the undifferentiated and unwell patient.

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