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Transcription:

2 CHEMOTHERAPY JAN. 1976

VOL. 24 NO. 1 CHEMOTHERAPY 3 Table 1 Antibacterial spectra of Cephacetrile, Cephalothin, Cephaloridine and Cefazolin

4 CHEMOTHERAPY JAN. 1976 Fig. 1 In vitro activity of Cephacetrile, Cephalothin, Cephaloridine and Cefazolin against clinically isolated bacterial strains

VOL 24 NO. 1 CHEMOTHERAPY 5 Table 2 Effect of inoculum size on antibacterial activity of Cephacetrile, Cephalothin, Cephaloridine and Cefazolin Viable cell counts of inoculum suspension Inoculum size : One loopful of bacterial suspension Medium : Trypticase soy agar

6 CHEMOTHERAPY JAN. 1976 Table 3 Effect of medium ph on antibacterial activity of Cephacetrile, Cephalothin, Cephaloridine and Cefazolin Fig. 2 Patterns of development of resistance of Staph. aureus 209 P to Cephacetrile, Cephalothin, Cephaloridine and Cefazolin Fig. 3 Patterns of development of resistance of E. coli NIHJ JC-1 to Cephacetrile, Cephalothin, Cephaloridine and Cefazolin

VOL. 24 NO. 1 CHEMOTHERAPY 7 Table 4 Effect of horse serum concentration in medium on antibacterial activity of Cephacetrile, Cephalothin, Cephaloridine and Cefazolin Table 5 Antibacterial activity of Cephacetrile on several agar medium

Table 6 Cross resistance among Cephacetrile, Cephalothin, Cephaloridine and Cefazolin Fig. 4 Bactericidal effect of Cephacetrile, Cephalothin, Cephaloridine and Cefazolin on Staph. aureus 209 P

Fig. 5 Bactericidal effect of Cephacetrile, Cephalothin, Cephaloridine and Cefazolin on E. coli NIHJ JC-1 Fig. 6 Bacteriolytic effect of Cephacetrile, Cephalothin, Cephaloridine and Cefazolin on Staph. aureus 209 P Fig. 7 Bacteriolytic effect of Cephacetrile, Cephalothin, Cephaloridine and Cefazolin on E. coli NIHJ JC-1

Table 7 Effect of ph on antibacterial activity of Cephacetrile at 100 Ž Inoculum size : One loopful of bacterial suspension (108/ml) Medium : Trypticase soy agar Table 8 Effect of ph on antibacterial activity of Cephacetrile at 37 Ž Table 9 Effect of ph on antibacterial activity of Cephacetrile at 4 Ž Inoculum size : One loopful of bacterial suspension (108/ml) Medium : Trypticase soy agar

Table 10 Protective effect of Cephacetrile, Cephalothin, Cephaloridine and Cefazolin on Staph. aureus 308 A-1 infection in CF1/H mice Note Five mice of each group were injected intraperitoneally with 0.5 ml of bacterial suspension in 5 % mucin. Cephalosporin was administered as a single dose immediately after challenge.

Table 11 Protective effect of Cephacetrile, Cephalothin, Cephaloridine and Cefazolin on Strept. pyogenes E-14 infection in CF1/H mice Note: Five mice of each group were injected intraperitoneally with 0. 5 ml of bacterial suspension in 5 % mucin. Cephalosporin was administered as a single dose immediately after challenge. Table 12 Protective effect of Cephacetrile, Cephalothin, Cephaloridine and Cefazolin on Strept. pneumoniae type I infection in CF1/H mice Note : Five mice of each group were injected intraperitoneally with 0. 5 ml of bacterial suspension in TSB. Cephalosporin was administered as twice doses 0 and 4 hours after challenge. Table 13 Protective effect of Cephacetrile, Cephalothin, Cephaloridine and Cefazolin on E. coli 0-111 infection in CF1/H mice Note : Five mice of each group were injected intraperitoneally with 0.5 ml of 5 % mucin which contained 1/10 volume of suspension of test organism. Cephalosporin was administered as a single dose immediately after challenge.

Table 14 Protective effect of Cephacetrile, Cephalothin, Cephaloridine and Cefazolin on Klebsiella pneumoniae infection in CF1/H mice Note : Five mice of each group were injected intraperitoneally with 0. 5 ml of bacterial suspension in 5% mucin. Cephalosporin was administered as a single dose inmmediately after challenge. Table 15 Protective effect of Cephacetrile, Cephalothin, Cephaloridine and Cefazolin on Proteus mirabilis IFO 3849 infection in CF1/H mice Note : Five mice of each group were injected intraperitoneally with 0.5 ml of bacterial suspension in 5 % mucin. Cephalosporin was administered as a single dose immediately after challenge.

6) BARBEN, M. & P. M. WATERWORTH : Penicillinase-resistant penicillins and cephalosporins. Brit. Med. J. 2: 344 `349, 1964 7) MUGGLETON, P. W.; C. H. O'CALLAGHAN & W. K. STEVENS : Laboratory evaluation of a new antibiotic-cephaloridine (cephanon). Brit. Med. J. 2 : 1234 `1237, 1964 8) STEWART, G. T. & R. J. HOLT : Laboratory and clinical results with cephaloridine. Lancet, II: 1305-4309, 1964 9) KARIYONE, K.; H. HARADA, M. KURITA & T. TAKANO : Cefazolin, a new semisynthetic cephalosporin antibiotic. I. Synthesis and chemical properties of cephazolin. J. Antibiotics 23: 131 `136, 1970 10) NISHIDA, M.; T. MATSUBARA, T. MURAKAWA, Y. MINE & Y. YOKOTA : Cefazolin, a new 1) CHAUVETTE, R. R.; E. H. FLYNN, B. G. JACK- SON, E. R. LAVAGNINO, R. B. MORIN, R. A. MUELLER, R. P. PIOCK, R. W. ROESKE, C. W. RYAN, J. L. SPENCER & E. VAN HEYNINGEN : Chemistry of cephalosporin antibiotics. II. Preparation of a new class of antibiotics and the relation of structure to activity. J. Am. Chem. Soc. 84 : 3401 `3402, 1962 2) BONIECE, W. B.; W. E. WICK, D. H. HOLMES & C. E, REDMAN : In vitro and in vivo laboratory evaluation of cephalothin, a new broad spectrum antibiotic. J. Bact. 84 : 1292-1296, 1962 3) Godzeski, C. W.; G. Brier & D. E. PAVEY : Cephalothin, a new cephalosporin with a broad antibacterial spectrum. Appl, Microbiol. 11 : 122 `127, 1963 4) CHANG, T. W. & L. Weinstein : In vitro biological activity of cephalothin. J. Bact. 85: 1022 `1027, 1963 semisynthetic cephalosporin antibiotic. II. In vitro and in vivo antimicrobial activity. J. Antibiotics 23 : 137 `148, 1970 11) SILVERBLATT, F,; W. O. HARRISON & M. TURCK : Nephrotoxicity of cefazolin antibiotics in experimental animals. J. Infect. Dis. 128 : S 367 `S 372, 1973 12) KNUSEL, F.; E. A. KONOPKA, J. GELZER & A. ROSSELET : Antimicrobial studies in viaro with CIBA 36, 278-Ba, a new cephalosporin derivative. Antimicr. Agents & Chemoth. -1970 : 140 `449, 1971 13) KRADOLFER, F.; W. SACKMANN, O. Zak, H. BRUNNER, R. HESS, E. A. KONOPKA & J. GELZER : CIBA 36, 278-Ba : Chemotherapy and toxicology in laboratory animals. Antimicr. Agents & Chemoth. -1970:150 `455, 1971 14) REED, L. J. & H. MUENCH, : A simple method of estimating fifty per cent endopoints. Am. J. Hyg. 27 : 493, 1938

ANTIBACTERIAL ACTIVITY OF CEPHACETRILE KANJI TSUCHIYA, TAKESHI NISHI and TOKIKO OISHI Central Research Division, Takeda Chemical Industries, Ltd., Osaka, Japan SACHIKO GOTO and YASUKO KANEKO Department of Microbiology, Toho University of Medicine, Tokyo, Japan Cephacetrile (CEC) shows in vitro antibacterial activity against gram-positive and gram-negative bacteria as well as Cephalothin(CET), Cephaloridine (CER) and Cefazolin (CEZ). CEC exhibits stronger activity against clinical isolates of Proteus mirabilis than that of other cephalosporins. Several antibacterial features of CEC such as the influence of inoculum size, medium ph, effect of addition of horse serum, development of resistance, cross resistance, and bactericidal and bacteriolytic activity were shown to be almost identical to those of other cephalosporins. The antibacterial activity of CEC was stable in solution at ph levels of 2 to 9, especially at ph 4. The in vivo protective activity of CEC was slightly weak than that of CEZ in mice infected intraperitoneally with certain strains of the gram-positive species, and CEC has similar activity with CET in mice infected with certain strains of the gram-negative species.

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