Question
Rationale of combining trimethoprim with sulfamethoxazole
Q8 1 marks Short Answers ★ ✓
Answer
Trimethoprim and sulfamethoxazole produce sequential blockade of bacterial folate synthesis at two different steps of the same pathway: sulfamethoxazole inhibits dihydropteroate synthase (blocking conversion of PABA to dihydrofolic acid), while trimethoprim inhibits dihydrofolate reductase (blocking conversion to tetrahydrofolic acid). This sequential, dual blockade produces a synergistic bactericidal effect greater than either drug alone, and also reduces the likelihood of resistance developing to either single agent.
1 Antimicrobials General Considerations
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