Sulfamethoxazole-Trimethoprim 合剤の基礎的検討
1973 年 21 巻 2 号 p. 317-323
詳細
1973 年 21 巻 2 号 p. 317-323
1. Antibacterial activities of sulfamethoxazole (SMX) and trimethoprim (TMP) alone and in combination, were investigated against 7 bacterial strains including Staphylococcus aureus, Escherichia coli and Shigella employing MUELLER-HINTON medium.
In vitro activities against tested organisms were not significantly influenced whether lysed horse blood was added or not to the medium, when the size of inoculum was adjusted to 103-104/cm2.
2. Minimum inhibitory concentrations (MIC) of SMX and TMP, alone and in combination (mixture ratio 19 : 1) were determined on 63 bacterial strains by the agar plate dilution method.
1) MIC of TMP was found to be lower than that of SMX in 55 strains.
2) MIC of SMX-TMP combination was lower than that obtained by either one of the single agents in the following strains tested, all of 4 Salmonella strains, all of 5 Proteus-providence strains, 1 Cloaca strain, 1 Citrobacter strain, 2 Serratia strains, 8 of 26 Staphylococcus aureus strains and 4 of 8 Pseudomonas strains.
3) MIC of the combination was identical with or higher than the lower MIC of the two single agents in 18 of 26 strains of Staphylococcus aureus (including 7 SMX resistant strains), all of 7 Escherichia coli, 4 Klebsiella and 5 Shigella strains; and 4 of 8 Pseudomonas strains.
4) FIC index calculated on the results mentioned above indicated the synergism in 62 of all 63 tested strains.
3. Rapidly growing acid-fast bacillus, M. fortuittum 238, was selected as a test organism for the bioassay of SMX in body fluids. This Mycobacterium was primarily resistant to TMP and sensitive to SMX. The technique developed enabled bioassay of SMX in concentrations exceeding 3. 12 mcg/ml using the agar diffusion method.
4. Plasma and urine concentrations of SMX and TMP were determined in 3 volunteers after a single oral administration of 800 mg SMX and 160 mg TMP. SMX levels were determined chemically by BRATTON-MARSHALL method and biologically by the cup diffusion method as described above. TMP concentrations were bioassayed using the technique reported by REEVES and CHILDE.
