TRIMETHOPRIM

'Trimethoprim' (INN) (IPA: ) is a bacteriostatic antibiotic mainly used in the prophylaxis and treatment of urinary tract infections. It belongs to the class of chemotherapeutic agents known as dihydrofolate reductase inhibitors. Trimethoprim was formerly marketed by GlaxoWellcome under trade names including 'Proloprim', 'Monotrim' and 'Triprim'; but these trade names have been licensed to various generic pharmaceutical manufacturers. In clinical use it is often abbreviated 'TRI' or 'TMP'; its common laboratory abbreviation is 'W'.

Contents

Mechanism of action

Co-trimoxazole

Clinical indications

Footnotes

External links

Mechanism of action

Trimethoprim acts by interfering with the action of bacterial dihydrofolate reductase, inhibiting synthesis of tetrahydrofolic acid. Tetrahydrofolic acid is an essential precursor in the ''de novo'' synthesis of the DNA nucleotide thymidylate. 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 bases necessary for DNA replication.

Co-trimoxazole

Trimethoprim was commonly used in combination with sulfamethoxazole, a sulfonamide antibiotic, which inhibits an earlier step in the folate synthesis pathway (see diagram above). This combination, also known as 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.

Footnotes

1. Reassessment of the rationale for the combinations of sulphonamides with diaminopyrimidines, Brumfitt W, Hamilton-Miller JM, , , J Chemother, 1993
2. Limitations of and indications for the use of co-trimoxazole, Brumfitt W, Hamilton-Miller JM, , , J Chemother, 1994
3. Resistance among Escherichia coli to sulphonamides and other antimicrobials now little used in man, Bean DC, Livermore DM, Papa I, Hall LM, , , J Antimicrob Chemother, 2005
4. Increasing prevalence of antimicrobial resistance among isolates of Streptococcus pneumoniae from the PROTEKT surveillance study, and compatative in vitro activity of the ketolide, telithromycin, Felmingham D, Reinert RR, Hirakata Y, Rodloff A, , , J Antimicrob Chemother, 2002
5. A disseminated multidrug-resistant clonal group of uropathogenic Escherichia coli in pyelonephritis, Johnson JR, Manges AR, O'Bryan TT, Riley LW, , , Lancet, 2002
6. Antibiotic failure in the treatment of urinary tract infections in young women, Lawrenson RA, Logie JW, , , J Antimicrob Chemother, 2001 - suggest some small advantage in UTIs
7. Co-trimoxazole use restricted, , , , Drug Ther Bull, 1995

External links

★ Nucleic acid inhibitors (PDF file).