In vitro and in vivo bacteriological studies on the combination of sulfamethoxazole (SMX) and trimethoprim (TMP) revealed the following results :
1. Antimicrobial activities of SMX and TMP, alone and in combination, were investigated employing the broth dilution method and a checkerboard technic. Activities of the combination of SMX and TMP were markedly enhanced by potentiation against strains of Staphylococcus aureus and Escherichia coli originally sensitive to SMX alone. The growth of Staphylococci highly resistant to SMX alone was also inhibited by SMX-TMP combination through potentiation, however, the degree of potentiation by the combination was not too impressive in Escherichia coli strains highly resistant to SMX alone.
2. Evaluation of the changes of minimal inhibitory concentrations (MICs) of the combination of SMX and TMP in various combination ratios indicated that MICs of the combination mixed in ratios of 1. : 1 to 20 : 1 (SMX : TMP) were enhanced by potentiation or synergism in strains of Staphylococcus aureus and Escherichia coli originally sensitive to SMX. MICs of SMX-TMP combination in a ratio of 1 : 1 against strains highly resistant to SMX were identical with those of TMP alone but MICs of the combination tended toward increase as the ratio of SMX increased.
3. MICs of SMX and TMP alone and 20 : 1 combination were investigated in a number of grampositive and negative laboratory strains according to the method as recommended by an expert group of the Japan Society of Chemotherapy. MICs of the combination were found to be more significantly potentiated than that of SMX alone in all strains but for Pseudomonas. These MICs were comparable to those of currently available antibiotics.
4. Potentiation of the antimicrobial activities by SMX-TMP combination was clearly demonstrated also in a test of 50 strains of Staphylococcus aureus and 37 strains of Escherichia coli isolated from clinical materials. Activities against strains highly resistant to sulfonamide were significantly improved by potentiation.
5. Studies of the influence of SMX-TMP combination on growth curves of Staphylococci revealed that potentiation by the combination was evident in staphylococcal strains sensitive to SMX alone. But the degree of potentiatiation was to a lesser extent in SMX-resistant strains.
6.In vivo studies on experimented infection of mice with Staphylococcus aureus and Escherichia coli confirmed potentiation of activities by SMX-TMP combination in strains both sensitive and resistant to SMX alone. The doses of combination required to treat mice infected with sulfonamide resistant Staphylococcus aureus and Escherichia coli were more than those required to treat animals with sulfonamide sensitive bacterial infection. The survival of mice experimentally infected with Salmonella was also improved by the combination of SMX and TMP.
