Antimicrobial effects of trimethoprim and sulphadiazine in infected urine and blood.

Sulphadiazine and trimethoprim in a wide range of concentrations were added to urine from patients with untreated urinary-tract infections. At therapeutic concentrations, the antibacterial activity of trimethoprim was not increased by the addition of sulphadiazine. Exposure of Escherichia coli to trimethoprim in urine was not associated with an increase in resistance to that agent. It was also not possible to select, in vitro, stable resistance to trimethoprim in sensitive cultures of E. coli. At therapeutic levels in blood, trimethoprim and sulphadiazine singly produced mainly a bactericidal action on pathogens responsible for urinary-tract infections. Sulphadiazine occasionally enhanced the effect of trimethoprim at subtherapeutic levels. These findings support the need for further evaluation of trimethoprim alone, rather than its use as a combination with a sulphonamide.