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  • Title: Trimethoprim: mechanisms of action, antimicrobial activity, bacterial resistance, pharmacokinetics, adverse reactions, and therapeutic indications.
    Author: Gleckman R, Blagg N, Joubert DW.
    Journal: Pharmacotherapy; 1981; 1(1):14-20. PubMed ID: 6985448.
    Abstract:
    Trimethoprim has recently been marketed as a single-entity product for the treatment of initial episodes of uncomplicated symptomatic urinary tract infections; it was previously available only in combination with sulfamethoxazole. Trimethoprim exerts antimicrobial activity by blocking the reduction of dihydrofolate to tetrahydrofolate, the active form of folic acid, by susceptible organisms. It has inhibitory activity for most gram-positive aerobic cocci and some gram-negative aerobic bacilli. Resistance to trimethoprim may be either intrinsic or acquired. Acquired resistance most commonly stems from a chromosomal mutation that results in the production of a dihydrofolate reductase enzyme which is less vulnerable to trimethoprim inhibition. Gastrointestinal intolerance and skin eruptions are the most common untoward reactions resulting from the administration of trimethoprim. Trimethoprim constitutes very effective therapy for women with acute symptomatic urinary tract infections caused by E. coli, and the compound compares favorably with alternative standard agents, such as ampicillin and cephalexin. The safety of trimethoprim in the pregnant woman has not been established. Since indiscriminate use of trimethoprim could foster the emergence of trimethoprim resistance, thereby negating the value of both trimethoprim and trimethoprim-sulfamethoxazole, trimethoprim should only be prescribed for well defined indications. Trimethoprim is currently being investigated as definitive therapy for a wide range of infections, including bacterial exacerbations of chronic bronchitis, bacterial pneumonia, and typhoid fever. Initial reports are encouraging.
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