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Trimethoprim-sulfamethoxazole: An overview

D Byron May, PharmD, BCPS
Section Editor
David C Hooper, MD
Deputy Editor
Jennifer Mitty, MD, MPH


Trimethoprim-sulfamethoxazole (TMP-SMX), also known as co-trimoxazole, is a combination of two antimicrobial agents that act synergistically against a wide variety of bacteria. Although other combinations of sulfonamides are available with trimethoprim, TMP-SMX is by far the most widely used.

This topic will review basic issues related to the clinical use of trimethoprim-sulfamethoxazole. The multiple clinical settings in which this combination may be used are discussed separately in the appropriate topic reviews.


The two components, TMP and SMX, work sequentially to inhibit enzyme systems involved in the bacterial synthesis of tetrahydrofolic acid (THF) [1,2].

SMX is a structural analog of para-aminobenzoic acid (PABA) and competes with PABA to inhibit the synthesis of dihydrofolic acid, an intermediate step in the formation of THF [1,3]. SMX binds to dihydropteroate synthetase which catalyses this reaction [3].

TMP binds to bacterial dihydrofolate reductase (in preference to human dihydrofolate reductase), also preventing the formation of THF [4].

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Literature review current through: Nov 2017. | This topic last updated: Dec 13, 2016.
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