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 (UWA) CCPU (RCE, Biliary, DVT, E-FAST, AAA) Emergency Medicine Advanced Trainee in Melbourne, Australia. Special interests in diagnostic and procedural ultrasound, medical education, and ECG interpretation. Editor-in-chief of the LITFL ECG Library. Twitter: @rob_buttner

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