The biochemical basis of the antimicrobial action of sulfonamides and trimethoprim In vivo—I. : Action of sulfonamides and trimethoprim in blood and urine

Trimethoprim (2 μg/ml), sulfamethoxazole (5 μg/ml) and a combination of these compounds reduced the viable cell count of Escherichia coli in human blood and urine in a bactericidal manner. This bactericidal action can be prevented by thymidine or thymine, the effectiveness of thymidine being considerably greater than that of thymine. Growth kinetics in the presence of trimethoprim, thymidine or thymine differed strikingly. Concentrations of thymidine below 0.05 μg/ml were detectable by their growth promoting effect, which started without a lag. Considerably higher concentrations of thymine, however, did not initially prevent the onset of cell inactivation, but resulted in a higher level of survivors. It is concluded that the concentrations of thymidine and thymine in blood and urine are too low to prevent a bactericidal action of trimethoprim, sulfonamides or a combination of these whereas other compounds, such as amino acids and purines, which support the bactericidal action, are present in sufficient quantities.