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VOL.32 S-9 CHEMOTHERAPY Table 1 Minimum inhibitory concentrations of AC-1370, CPZ and CAZ Table 2 Efficacy of AC-1370 and CPZ against systemic infections in mice *Inoculum size: 106 cells/ml * 95% confidence limits

CHEMOTHERAPY DEC. 1984 Table 3 Effects of administration schedule on therapeutic efficacies of AC-1370 and CPZ against systemic infection with P. aeruginosa 15 846 Treatment was started two hours after infection and administered one, twp and four times with a one hour interval between doses. Fig. 1 Therapeutic efficacy of AC-1370,and CPZ on number of bacteria in the peritoneal cavity of rmice infected with P. aeruginosa 15846

VOL.32 S-9 CHEMOTHERAPY Fig. 2 Serum and peritoneal exudate levels of AC-1370 and CPZ after s.c. injection to mice infected with E. coli 444 Fig. 3 Protective effect on experimental urinary tract infection with E. coli KC-14 in mice 48hr after inoculation (2. 5x105 cells/bladder) Fig. 4 Protective effect on experimental urinary tract infection with K. pneumoniae KC-1 in mice 48hr after inoculation (3. 0x104 cells/bladder) Fig. 5 Effect of AC-1370, CPZ and CAZ admini stration on number of bacteria in the kidney of mice infected with P. aeruginosa E-2 by the transurethral inoculation (7. 0x103 cells/bladder)

CHEMOTHERAPY DEC. 1984 Fig. 8 Protective effects of AC-1370, CPZ and CAZ on experimental respiratory tract infection with K. pneumoniae DT-S in mice Fig. 6 Kidney levels of AC-1370, CPZ and CAZ after s.c. injection to mice infected with E. coli KC-14 Days after infection Fig. 7 Therapeutic efficacy of AC-1370 and reference compounds on number of bacteria in the lung of mice infected with K. pneumoniae DT-S

VOL.32 S-9 CHEMOTHERAPY Fig. 9 Lung levels of AC-1370, CPZ and CAZ after s.c. injection to mice infected with K. pneumoniae DT-S Table 4 Efficacy of AC-1370 and CPZ against experimental infection with E. coli 444 in neutropenic mice DDY male mice were given cyclophosphamide intraperitoneally in a dose of 150 mg/kg. Three days later, they were challenged i.p. with E. coli 444. The mean neutrophil count at this time was reduced from 5,700 to 430/mm3. * 95% confidence limits

CHEMOTHERAPY DEC. 1984 Fig. 10 The migration and phagocytosis by neutrophils Changes in number of PMN in peritoneal cavity Phagocytosis of P. aeruginosa 15846 by PMN in peritoneal cavity

VOL.32 S-9 CHEMOTHERAPY 2) OHNISHI, H.; H. KOSUZUME, H. INABA, M. OKURA, H. Mocmzum, Y. SUZUKI & R. FUJII: Effects of AC -1370, a new semisynthetic cephalosporin, on phagocyte functions. Antimicrob. Agents Chemother. 23 (6): 874-880, 1983 4) Cefoperazone (T-1551, CPZ) ait t ti-: Chemotherapy 28 (6): 1-974, 1980 5) Ceftazidime (CAZ, SN401)t4E-: Chemotherapy 31 (3): 1-1050, 1983 7) LITCHFIELD, J. T. & F. WILCOXON: A simplified method of evaluating dose-effect experiments. J. Pharmacol. Exp. Ther. 96: 99 `113, 1949 THE EFFECT OF AC-1370 IN EXPERIMENTAL INFECTIONS IN MICE YOSHIKI OBANA, HIROYUKI HASHIZUME, YUMIKO FUJINOBU, TAKESHI NISHINO and TERUO TANINO Department of Microbiology, Kyoto Pharmaceutical University The therapeutic efficacies of AC-1370, a new cephem, were compared with those of cefoperazone (CPZ) and ceftazidime (CAZ) in experimental infections in mice, in an attempt to find out the activation on host defense mechanisms. Against experimental intraperitoneal infections caused by P. aeruginosa, the efficacy of AC-1370 was equivalent or superior to that of CPZ. The MICs of AC-1370 against the test strains, however, were inferior to those of CPZ. Against experimental urinary tract infections, the efficacy of AC-1370 was superior to that of CPZ and inferior to that of CAZ. Serum and organ levels of AC-1370 in infected mice were more durable than those of CPZ and CAZ. The relationship between AC-1370 and neutrophils was investigated. As a result of the therapeutic efficacy of AC-1370 on experimental infection in compromised mice, the efficacy of AC-1370 was more dependent on the neutrophils than that of CPZ. As to the migration and phagocytosis by neutrophils in drugtreated mice, AC-1370 activated the function of neutrophils.

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