Co-trimoxazole combines trimethoprim and sulfamethoxazole, producing sequential blockade of bacterial folate synthesis: sulfamethoxazole inhibits dihydropteroate synthase (blocking conversion of PABA to dihydrofolic acid), while trimethoprim inhibits dihydrofolate reductase (blocking conversion to tetrahydrofolic acid). This dual, sequential block at two steps of the same pathway produces a synergistic bactericidal effect.
