COMBINATIONS OF SULFONAMIDES WITH DIAMINOPYRIMIDINES - HOW, WHEN AND WHY

Co-trimoxazole is still widely used for indications where trimethoprim alone is equally effective. The pharmacological rationale of the comb ination of trimethoprim and sulphamethoxazole involves synergistic act ion of the two drugs. This is true only from a laboratory point of vie w; several considerations have led to the conclusion that the synergis m between the two components is of only in vivo marginal importance in determining the clinical efficacy of co-trimoxazole. This is due to a greater tissue affinity of trimethoprim compared to that of sulphamet hoxazole and, therefore, to the different tissue concentration ratios obtained in vitro and in vivo. Another claim sustaining the combinatio n is the prevention of developing resistance to trimethoprim; however, there is no substantial clinical evidence to support this claim. It d oes seem likely that trimethoprim has protected against the emergence of the sulphonamide resistance. This slight benefit is outweighed by t he disadvantages of the combination, mainly consisting of the occurren ce of adverse events due to the sulphonamide moiety. Consequently, the incidence and severity of the adverse events seen with co-trimoxazole should be reduced by using trimethoprim alone. There are only a few c ases where co-trimoxazole is better than trimethoprim: toxoplasmosis, brucellosis, nocardiosis, chancroid and pneumonia due to Pneumocystis carinii. For the other and many common infections, scientific rational e, economic and clinical reasons dictate that trimethoprim is superior to co-trimoxazole.