Key Words: Klebsiella pneumoniae, CEP-AIS, MIC, "MBC", MIC of drugs in combination
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1 Key Words: Klebsiella pneumoniae, CEP-AIS, MIC, "MBC", MIC of drugs in combination
2 Fig. 1. The following three kinds of overnight broth cultures of 10 strains of Kl. pneumoniae were inoculated on the agar plates containing two-fold dilutions of CET: a) undiluted culture; b) 100 fold diluted culture; c) 10,000 fold diluted culture. After an over night incubation at 37 Ž, the MIC was determined Then, CET inactivating substance was added to each of surfaces of the plate where test bacteria had previously been inoculated. After an overnight incubation at 37 Ž, the "MBC" was measured. Antibacterial Activity of CET against pneumoniae with Different Sizes of Inocula Fig. 2. Two-dimensional, two-fold dilution procedure of GM and CET was carried out by the agar plate method, and the effects of the combined use of the antibiotics were examined. Antibacterial Activity of CET Used in Combin with GM against Kl. pneumoniae
3 Fig. 3. Two-dimensional, two-fold dilution procedure of GM and CET was carried out by the agar plate method, and the effects of combined use of the antibiotics were examined. The MIC of CET which was used in combination with a certain concentration of GM. and the MIC of GM which was used in combination with a certain concentration of CET were examined. In the chess-board, the number of the strains of bacteria which were inhibited by the combination of corresponding concentrations of both antibiotics was cumulatively shown. Combined Effect of Cephalothin and Gentamicin against Kt. pneumoniae
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6 Cephalothin and Carbenicillin, Amer. J. Med. Sci., 266: 13-21, ) Edwards, P. R. and Ewing, W. H.: Identifica- of Enterobacteriaceae, 3rd Ed., Burgess tion Publishing Company, Minneapolis, Minnesota, ) Wallance, J. F., Atlas, E., Bear, D. M., Brown, N. K., Clark, H. and Turck, M.: Evaluation of an Indanyl Ester of Carbenicillin, Antimicrob. Ag. Chemother., , ) Neu, H. C. and Winshell, E. B.: Relation of 1) Garrod, L. P., Lambert, H. P. and O'Grady, F.: Antibiotic and Chemotherapy, 4th Ed., Churchill Livingstone, Edinburgh and London, ) Derrington, A. W.: Combinations of Antibiotics, Med. J. Aust., 2: , ) Klastersky, J., Henri, A. and Vandenborre, L.: Antimicrobial Activity of Tobramycin and Gentamicin Used in Combination with Activity and Cellular Location to Resistance of Enterobacter to Penicillins and Cephalosporins, Antimicrob. Ag. Chemother., , ) Holt, R. J. and Stewart, G. T.: Production of Amidase and f3-lactamase by Bacteria, 36: , In Vitro Study on Effects of Combined Use of Antibiotics GOta MASUDA, Susumu TOMIOKA Department of Internal Medicine, School of Medicine, Keio University The following in vitro studies were carried out using 23 strains of Klebsiella pneumoniae isolated from clinical materials in recent years: 1) The MIC of Cephalothin (CET) against Kl. pneumoniae was determined by the agar dilution method. Then, the amount of 0.002ml of CET-inactivating substance, which is supposed to consist mainly of Cephalosporinase with the ability to inactivate 250,000Ag of CET/ml was added to each of surfaces of the plate which had previously been inoculated with test bacteria. After an overnighti ncubation at 37 Ž, the minimal concentration of CET at which no colony appeared was judged as "MBC". As a result, it was found that the values of MIC and "MBC" were markedly affected by the number of inoculated bacteria. In the group with the undiluted culture of bacteria, the MIC was ƒêg/ml in most of the strains and "MBC" was 400 ƒêg/ml or more in almost all of the strains; on the other hand, in the group with 10,000 fold dilutions, MIC and "MBC" showed almost the same values, from 3.13 to 6.25ƒÊg/ ml in most of the strains. 2) The effects of the combined use of Gentamicin (GM) and CET were examined using agar plate inoculated with the undiluted culture of bacteria by the two-dimensional, two-fold dilution procedure. The combined use of GM and CET did not show such a significant difference between MIC and "MBC" as seen in the single use of CET. 3) The effects of the combined use of GM and CET on 20 strains of K 1.pneumoniae were examined by the agar dilution method. By the two-dimensional, two-fold dilution procedure of these drugs, the MIC of CET which was used in combination with a certain concentration of GM and the
7 MIC of GM which was used in combination with a certain concentration of CET were examined. Then, the number of bacteria having these MICs was counted and shown in the chess-board. Our survey on the number of bacteria, which growth was inhibited by the various combinations of GM and CET, clearly demonstrated that the in vitro antibacterial effects of GM and CET upon K1. pneumoniae were synergistic. In addition, it was confirmed that the concentrations of both antibiotics needed to inhibit the growth of almost all of the strains correspond to the blood concentrations which are obtained by usual doses of these antibiotics.
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