N-Formimidoyl thienamycin (MK0787) was active against beta-lactamase-producing strains and was an effective inhibitor of beta-lactamases extracted and purified from these strains except for plasmid-mediated penicillinase type IV.

The cephalosporin ~-lactamase (cephalosporinase) was purified from a strain of Proteus morganii which showed resistance to cephalosporins.The optimal pH was about 8.5, and the optimal temperature was 40°C. The isoelectric point was 8.7 and the molecular weight was estimated to be about 41,000 from sodium dodecyl sulfate-acrylamide gel electrophoresis. The enzyme activity was inhibited by cloxacillin, ampicillin, carbenicillin, cefuroxime, cefotaxime, ceftizoxime (FK749), cefinenoxime (SCE-1365), cefoxitin, cefinetazole, YM09330 and moxalactam (6059-S), but not by clavulanic acid or CP-45899. The $-lactamase also hydrolyzed cephaloridine, cefazolin, cephalothin, cephalexin, cefotiam, cefamandole and benzylpenicillin. These results suggest the possibility that the properties of Q-lactamases may be characterized by measuring the kinetic parameters of the enzyme toward newly-introduced 9-lactam antibiotics and s-lactamase inhibitors.Since ABRAHAM and CHAINl) reported the production of (3-lactamase by Escherichia coli, the enzyme has been considered to have a significant role in the resistance of organisms to 14-lactam antibiotics.2,I) On the one hand, ~-lactamases from various bacteria have been classified with their substrate specificities, physical and biochemical properties and reactions with antisera.3) Recently, many 13-lactam antibiotics have developed throughout the world. In our laboratory, we had a chance to investigate more broad substrate specificities by using newly-introduced drugs against 14 distinct 14-lactamases. In the present work, an attempt has been made to study some of the properties of cephalosporinase produced by a strain of Proteus morganii GN5407. The identification of this enzyme and its distinction from other cephalosporinases were obtained by conventional methods with the addition of new substrates. Materials and MethodsBacterial Strains P. morganii strains were isolated from clinical sources and (3-lactam-resistant strains in which plasmids mediating penicillinase production were not detected were selected for this study. MediaHeart infusion (HI) agar was a product of Eiken Chemical Co., Ltd. Medium-B and peptone water were used for liquid cultures. Medium-B consisted of 2 g of yeast extract, 10 g of polypeptone, 7 g of Na2HPO, • 12H2O, 2 g of KH2PO4i 1.2 g of glucose and 0.4 g of MgSO4.7H2O in 1,000 ml of distilled water. Peptone water consisted of 10 g of polypeptone, 5 g of NaCI and 1,000 ml of distilled water. Drug Resistance Drug resistance was determined by using two-fold dilutions in HI agar with an inoculum of 104 organisms. The level of resistance was expressed as the minimum inhibitory concentration (MIC) of each drug. The MIC values were scored after 18 hours of incubation at 37°C.

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The in vitro antibacterial activities of YM-13115, a new parenteral cephalosporin, were compared with those of ceftazidime, cefoperazone, and cefsulodin. The compound was highly active against the common members of the Enterobacteriaceae and 2 to 256 times more active than cefoperazone. YM-13115 shown in Fig. 1. Matsui et al. (8) examined the pharmacokinetics of YM-13115 in animals and showed that this compound gives rise to high and persistent plasma levels in monkeys. In this paper we report a comparison of the in vitro activities of YM-13115 with those of ceftazidime (17), cefoperazone (6), and cefsulodin (16) against various grampositive cocci, members of the Enterobacteriaceae, Pseudomonas aeruginosa, and Haemophilus influenzae. In addition, we report on the bactericidal activity of YM-13115 and its susceptibility to P-lactamases.MATERIALS AND METHODS Antibiotics. YM-13115 and ceftazidime were synthesized for this study in the Central Research Laboratories of Yamanouchi Pharmaceutical Co., Ltd. Cefoperazone and ampicillin (both from Toyama Chemical Co., Ltd., Toyama, Japan), cefsulodin (Takeda Chemical Industries, Osaka, Japan), cephaloridine (Shionogi Pharmaceutical Co., Ltd., Osaka, Japan), and potassium benzylpenicillin (Meiji Seika Kaisha, Ltd., Tokyo, Japan) were obtained commercially.

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