CHEMOTHERAPY JUNE 1987 Table1 Media used *BHIB, brain heart infusion broth (Difco); /3 -NAD, S -nicotinamidoadeninedinucleotide (Sigma Chemical Co.);

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VOL.35 S-2 CHEMOTHERAPY Fig.1 Chemical structure of carumonam

CHEMOTHERAPY JUNE 1987 Table1 Media used *BHIB, brain heart infusion broth (Difco); /3 -NAD, S -nicotinamidoadeninedinucleotide (Sigma Chemical Co.); STB, sensitivity test broth (Nissui); BHIA, brain heart infusion agar (Difco); STA, sensitivity test agar (Nissui)

CHEMOTHERAPY Table 2 Antibacterial activity of CRMN against standard strains of bacteria * By the agar dilution method ( Inoculum size: 106 cells/ml)

CHEMOTHERAPY JUNE 1987 Fig. 2 Antibacterial activity of CRMN against S. aureus Fig. 3 Antibacterial activity of CRMN against E. coli

VOL. 35 S-2 CHEMOTHERAPY Fig. 4 Antibacterial activity of CRMN against C. freundii Fig. 5 Antibacterial activity of CRMN against K. pneumoniae

CHEMOTHERAPY JUNE 1987 Fig. 6 Antibacterial activity of CRMN against S. marcescens Fig. 7 Antibacterial activity of CRMN against P. vulgaris

VOL. 35 S-2 CHEMOTHERAPY Fig. 8 Antibacterial activity of CRMN against P. mirabilis Fig. 9 Antibacterial activity of CRMN against P. aeruginosa

CHEMOTHERAPY JUNE 1987 Table 3-1 Comparative MICs of CRMN and other antibiotics tested against clinical isolates

VOL. 35 S-2 CHEMOTHERAPY Table 3-2 Comparative MICs of CRMN and other antibiotics tested against clinical isolates * MICso and MIC90 values were represented as the concentration at which more than 50% and 90% of the isolates were inhibited, respectively. Inoculum size ; 1 loopful of bacterial suspension (1 x 106cells/m1) Enterobacter cloacae Citrobacter freundii

CHEMOTHERAPY JUNE 1987 Fig. 10 Antibacterial activity of CRMN against H. influenzae

VOL. 35 S-2 CHEMOTHERAPY Table 4 Bactericidal activity of CRMN against standard strains MBC: Minimal bactericidal concentration (pg/m1) MIC: Minimal inhibitory concentration (pg/m1)

CHEMOTHERAPY JUNE 1987 P. aeruginosa, X. maltophilia Table 5 Antibacterial activity of CRMN against,9-lactamase producing organisms * Inoculum size: 1 loopful of bacterial suspension (106 cells/ml).

VOL. 35 S-2 CHEMOTHERAPY Fig. 11 Bactericidal activity of CRMN and AZT against E. coli GN5482 CRMN AZT Fig. 12 Bactericidal activity of CRMN and AZT against E. coli K-12 C600 CRMN AZT Fig. 13 Bactericidal activity of CRMN and AZT against P. vulgaris GN7919 CRMN AZT

CHEMOTHERAPY JUNE 1987 Fig. 14 Bactericidal activity of CRMN and AZT against P. vulgaris OX-19 CRMN AZT Table 6 Ĉ-lactamase stability of CRMN against PCase, CSase and CXase * Cephaloridine=100 ** Substrate=Cephaloridine

VOL.35 S-2 CHEMOTHERAPY Table 7 Stability of CRMN against swine renal dehydropeptidase *Not detected

CHEMOTHERAPY JUNE 1987 1) IMADA, A.; K. KITANO, K. KINTAKA, M. MUROI & M. ASAI : Sulfazecin and isosulfazecin, novel filactam antibiotics of bacterial origin. Nature 289: 590-591, 1981 2) KISHIMOTO, S.; M. SENDAI, S. HASHIGUCHT, M. TOMIMOTO, Y. SATOH, T. MATSUO, M. KONDO & M. OCHIAI: Synthesis of sulfazecin-type 2- azetidinones with a carbon substituent at the 4- position. J. Antibiotics 36 : 1421-1424, 1981 6) WALEY, S. G.: A spectrophotometric assay of beta-lactamase action on penicillins. Biochem. J. 139: 780-789, 1974 7) LOWRY, O.H.; N.J. ROSEBROUGH, A. L. FARR & R. J. RANDALL: Protein measurements with the Folin phenol reagents. J. Biol. Chem. 192: 265 275, 1951 8) LITCHFIELD, J.T. & F. WILCOXON : A simple method of evaluating dose-effect experiments. J. Pharmacol. 92 : 99-113, 1948 IN VITRO AND IN VIVO ANTIBACTERIAL ACTIVITY OF CARUMONAM KUNIO INOUE, TAMIKO NAKANE, KOUJI MATSUDA, MATSUHISA INOUE* and Susumu MITSUHASHI Episome Institute, Seta, Gunma *Laboratory of Drug Resistance in Bacterial, Gunma University School of Medicine, Maebashi, Gunma The in vitro and in vivo antibacterial activity of carumonam (CRMN) against both Gram-positive and Gram-negative clinical isolates was studied in comparison with that of aztreonam and cefotaxime. CRMN showed potent antibacterial activity against Gram-negative bacteria, particularly strains of Enterobacteriaceae. It also inhibited strains of Pseudomonas at low concentrations, but showed less activity against Gram-positive bacteria. It was highly resistant to hydrolysis by both chromosomal and plasmid-mediated P-lactamases. On the other hand, the 50 % effective dose (ED50) in experimental murine mice infections was 0.098 mg/kg against Escherichia coli ML4707, 2.64 mg/kg against Serratia marcescens GN7577 and 0.43 mg/kg against Klebsiella pneumoniae GN6445.

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