Trimethoprim and co-trimoxazole

There have been few comparisons of the efficacy of trimethoprim and co-trimoxazole. In uncomplicated urinary tract, bronchopulmonary, and ear infections, no advantage of co-trimoxazole over trimethoprim has been documented (7,8). However, in complicated urinary tract infections most studies have shown better results with co-trimoxazole than with trimethoprim alone (9). Despite the widespread use of co-trimoxazole for about 35 years, bacterial resistance has not emerged as a major problem (10,11). 

Severe adverse drug reactions with trimethoprim and co-trimoxazole are rare (12-14). This also applies to children (15). The adverse effects of co-trimoxazole correspond to those expected from a sulfonamide (16). In HIV-infected patients, adverse effects of co-trimox-azole are more frequent and more severe (17-19). Hematological disturbances due to co-trimoxazole include mild anemia, leukopenia, and thrombocytopenia, which may be due to folic acid antagonism. Serious metabolic disturbances that are associated with trimethoprim include hyperkalemia and metabolic acidosis. Trimethoprim can cause hypersensitivity reactions. However, with co-trimoxazole, the sulfonamide is generally believed to be more allergenic (12). Generalized skin reactions predominate. Other effects, such as anaphylactic shock, are extremely rare (20-22). Carcinogenicity due to trimethoprim or co-trimoxazole has not been reported. 

Aseptic meningitis and meningoencephalitis occur with trimethoprim and co-trimoxazole (29-39). The pathogenetic mechanism is still uncertain. 

The skin rashes due to trimethoprim and co-trimoxazole are mostly maculopapular and are related to the duration of treatment (125). They occur with a frequency of 1.3-5.9% (94,126-128). 

Most interactions of trimethoprim and co-trimoxazole with other drugs are due to fohc acid antagonism. This may be more pronounced with co-trimoxazole than with either drug alone. Such interactions have previously been suspected with anticonvulsants, such as barbiturates, phe-nytoin, and primidone, which themselves produce folic acid deficiency and megaloblastic anemia (88). In order to circumvent the risk of folate deficiency, folic acid or folinic acid can be given. There is some concern that folate replacement may antagonize the desired antimicrobial effect, particularly in some protozoal parasites, but this concern has been debated (89). 

Martin AJ, Lacey RW. A blind comparison of the efficacy and incidence of unwanted effects of trimethoprim and co-trimoxazole in the treatment of acute infection of the urinary tract in general practice. Br J Clin Pract 1983 37(3) 105-11. 

Thompson JF, Chalmers DH, Hunnisett AG, Wood RF, Morris PJ. Nephrotoxicity of trimethoprim-and co-trimoxazole in renal allograft recipients treated with cyclosporine. Transplantation 1983 36 204-206. 

SULFONAMIDES, TRIMETHOPRIM, AND CO-TRIMOXAZOLE fSED-15, 3216, 3510 SEDA-31, 442 SEDA-32, 477 SEDA-33, 528 ... 

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