Synergistic Activity of Trimethoprim-Sulfamethoxazole on Gram-Negative Bacilli: Observations In Vitro and In Vivo

One hundred seventy-five strains of gram-negative bacillae of the Enterobacteriaceae which cause urinary tract infections were studied for MICs of sulfamethoxazole (SMZ) and trimethoprim (TMP). The synergistic effect of the TMP-SMZ was studied. An extrachromosomal location of genes responsible for resistance to sulfonamide and to TMP was sought. The synergistic effect of TMP-SMZ was observed in three groups of strains: sulfonamide- and TMP-sensitive strains, sulfonamide-resistant and TMP-sensitive strains, and sulfonamide-resistant, and low-level TMP-resistant strains. Strains belonging to the second and third group transferred their respective drug resistance to Escherichia coli KI2. A fourth group of strains was highly resistant to sulfonamide and TMP. It failed to transfer the resistance to TMP and to show a synergistic effect of TMP-SMZ. Results of treatment with TMP-SMZ in 135 episodes of urinary tract infections showed no difference between patients infected with sulfonamide-sensitive or sulfonamide-resistant strains.