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

• Buttner R. Pharm 101: Trimethoprim

References

• Katzung BG. Basic and Clinical Pharmacology. 14e. 2018: 834-837