Quantification of the Antibacterial Action of Trimethoprim Alone and in Combination with Sulfonamides by Bacterial Growth Kinetics

The dependence of growth rates of Escherichia coli on sulfonamides or trimethoprim (TMP) has been established. The new steady state is obtained shortly after addition of TMP, whereas a lag phase of about five generations is observed for sulfonamides. The inhibitory effect of TMP is about five times larger than the effect of sulfamethoxazole (SMZ) as evaluated from the plot of 1/ko–kapp vs. 1/C. The inhibitory effect of sulfonamides as well as that of TMP is reversible if the drug containing culture is diluted. Whereas sulfonamide is only bacteriostatic, TMP can cause bacterial death if a certain threshold of concentration (≧ 1 µм) is passed; a decrease in number of bacteria is observed. Combinations of TMP and sulfonamide at concentrations where both drugs act merely bacteriostatically lead to effects considerably greater than would be expected from simple additivity. It is justifiable to say that the combination of sulfonamide and TMP has a synergistic effect.