Trimethoprim

Trimethoprim (generic pharmaceutical manufacturers. In clinical use it is often abbreviated TRI or TMP; its common laboratory abbreviation is W.

Mechanism of action

  Trimethoprim acts by interfering with the action of bacterial dihydrofolate reductase, inhibiting synthesis of thymidine. Bacteria are unable to take up folic acid from the environment (i.e. the infection host) and are thus dependent on their own de novo synthesis. Inhibition of the enzyme starves the bacteria of nucleotides necessary for DNA replication.

Co-trimoxazole

Trimethoprim was commonly used in combination with co-trimoxazole, TMP-sulfa, or TMP-SMX, results in an in vitro synergistic antibacterial effect by inhibiting successive steps in folate synthesis, this claimed benefit was not seen in general clinical use.^{[1] [2]} Its use has been declining due to reports of sulfamethoxazole bone marrow toxicity, resistance and lack greater efficacy in treating common urine and chest infections,^[3][4][5][6] and side effects of antibacterial sulfonamides. As a consequence, the use of co-trimoxazole was restricted in 1995.^[7]

Clinical indications

Trimethoprim, used as monotherapy, is indicated for the prophylaxis and treatment of urinary tract infections (cystitis). Co-trimoxazole, with its greater efficacy against a limited number of bacteria, remains indicated for some infections; for example, it is used as prophylaxis in patients at risk for Pneumocystis jirovecii pneumonia (e.g. AIDS patients and those with some hematological malignancies) and as therapy in Whipple's disease.