Properties of cephalosporinase from Proteus morganii.

clinical isolates to R-3746 was determined by the agar dilution method. Ninety percent or more of pathogens such as Staphylococcus aureus, streptococci, Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, indole-positive and indole-negative Proteus spp., Providencia rettgeri, and Haemophilus influenzae were inhibited at concentrations ranging from .0.01 to 1.56 ,ug/ml. Furthermore, at a concentration of 3.13 ,ug/ml, 50% or more of Staphylococcus epidermidis, Morganella morganii, Citrobacterfreundii, and Serratia marcescens strains were also inhibited. Pseudomonas aeruginosa and Xanthomonas maltophilia were resistant to R-3746.The activity of R-3746 was scarcely influenced by several growth conditions. R-3746 was highly resistant to hydrolysis by Il-lactamases derived from various species of bacteria. Killing-curve studies demonstrated bactericidal activity of R-3746 at concentrations above the MIC. R-3746 showed high affinity for penicillinbinding proteins 1, 3, and 4 of Staphylococcus aureus and 1A, 1l$s, and 3 of Escherichia coli. Systemic infections in mice caused by various pathogens, including j3-lactamase-producing strains, responded well to therapy with oral doses of CS-807.Various oral cephem antibiotics having relatively broad antibacterial spectra have been developed and used worldwide (2, 3,15,18,19,34 Fig. 1.The present report deals with the in vitro antibacterial activity of R-3746 together with the therapeutic effect of CS-807 on systemic infections in mice compared with cefaclor, amoxicillin, cefixime, and T-2588 (T-2525).* Corresponding author. MATERIALS AND METHODSChemicals. CS-807 and R-3746 were prepared by Sankyo Co., Ltd., Tokyo, Japan. The other antibiotics were gifts: penicillin G, amoxicillin, and methicillin from Banyu Pharmaceutical Co., Ltd., Tokyo, Japan; cephaloridine from Nihon Glaxo Co., Ltd., Tokyo, Japan; cefaclor from Shionogi & Co., Ltd., Osaka, Japan; cefixime from Fujisawa Pharmaceutical Co., Ltd., Osaka, Japan; and T-2588 and T-2525 from Toyama Chemical Co., Ltd., Tokyo, Japan. All antibiotics were prepared daily with distilled water to the desired concentrations. '4C-labeled penicillin G (potassium 6-phenyl [1-_4C]

Section: Discussionmentioning

confidence: 99%

In vitro and in vivo antibacterial activities of CS-807, a new oral cephalosporin

Utsui¹,

Inoue²,

Mitsuhashi³

1987

“…The compound also showed a high stability to penicillinase (PCase) types II (2) and III (oxacillin-hydrolyzing PCase; 17) and type IV (carbenicillin-hydrolyzing PCase; 14). However, E-0702 was partially hydrolyzed by PCase type I (TEM-type PCase; 3), P. morganii cephalosporinase (16), and the cefuroxime-hydrolyzing 1-lactamases (9) produced by P. vulgaris (5), Pseudomonas cepacia (4), and Bacteroides fragilis (13). The stability of E-0702 to 1-lactamase was almost the same as that of CFP.…”

Section: Methodsmentioning

confidence: 99%

In vitro antibacterial activity of E-0702, a new semisynthetic cephalosporin

Katsu¹,

Kitoh²,

Inoue³

et al. 1982

E-0702 is an antipseudomonal cephalosporin derivative which has a broad spectrum of antibacterial activity against clinical isolates of gram-positive and gram-negative bacteria. Its in vitro antibacterial activities were less than those of cefoperazone and cefotaxime against Staphylococcus aureus and Staphylococcus epidermidis, but were significantly high against gram-negative bacteria including the Pseudomonas group. It was most characteristic that E-0702 showed high antibacterial activity against Pseudomonas aeruginosa. E-0702 was relatively stable to inactivation by plasmid-mediated penicillinases and cephalosporinases produced by gram-negative bacteria.Many new cephalosporins with a broad antibacterial spectrum have been developed in the past few years. Several of these antibiotics have been in clinical use for the treatment of a wide range of bacterial infections. E-0702, (6R, 7R)-3- (Fig. 1), is a new antipseudomonal cephalosporin derivative with a broad antibacterial spectrum, developed by Eisai Co., Ltd., Tokyo, Japan. The current report summarizes the results of studies of the in vitro antibacterial activity and P-lactamase stability of this new cephalosporin with clinical isolates stocked in this laboratory. MATERIALS AND METHODSAntibiotics. E-0702 was synthesized in the research laboratories of Eisai Co. As comparative compounds, cefoperazone (CFP) and cefotaxime (CTX) were supplied by Toyama Chemical Co., Japan, and Hoechst Japan Ltd., Japan, respectively. Cephaloridine, cefazolin, and penicillin G (PCG) were obtained commercially.Organisms. The strains of gram-positive and gramnegative bacteria used in this study were isolated from clinical materials in Japan between 1979 and 1981 and have been maintained since isolation in the Laboratory of Drug Resistance in Bacteria, Gunma University, Japan.Media. Sensitivity test (ST) agar, ST broth (Nissui Seiyaku Co., Japan), and nutrient agar containing bromothymol blue and lactose were used. For the dilution of cell suspensions, buffered saline containing 0.01% gelatin (1)

“…Nucleotide sequences corresponding to several enzymes from Morganella, both chromosomally and plasmid encoded, have been reported and deposited in databases (3,4,11,31). Reported pIs for these enzymes usually range between 7.2 and 7.6, although other pIs were also reported (3,31,36,38). The plasmid-encoded DHA-1 and DHA-2 ␤-lactamases, apparently derived from the Morganella AmpC enzyme and reported in several countries around the world, are always inducible, like their chromosome-encoded counterparts (2,12,19,37,39).…”

mentioning

confidence: 98%

Biochemical and Molecular Characterization of Three New Variants of AmpC β-Lactamases from Morganella morganii

Power

Galleni

Ayala

et al. 2006

Morganella morganii produces an inducible, chromosomally encoded AmpC ␤-lactamase. We describe in this study three new variants of AmpC within this species with apparent pIs of 6.6 (M19 from M. morganii strain PP19), 7.4 (M29 from M. morganii strain PP29), and 7.8 (M37 from M. morganii strain PP37). After gene sequencing, deduced amino acid sequences displayed one to six substitutions when compared to the available Morganella AmpC sequences. An AmpR-encoding gene was also found upstream of ampC, including the LysR regulators' helix-turn-helix DNA-binding domain and the putative T-N 11 -A-protected region in the ampR-ampC intercistronic sequence. All three AmpC variants were purified from in vitro-generated derepressed mutants and showed overall similar kinetic parameters. None of the observed amino acid changes, occurring at the surface of the protein, appear to have a major influence in their catalytic properties. Morganella AmpCs exhibit the highest catalytic efficiencies (k cat /K m ) on classical penicillins, cefoxitin, narrow-spectrum cephalosporins, and cefotaxime. Cefotaxime was more effectively hydrolyzed than other oxyimino-cephalosporins, whereas cefepime was 3 log-fold less efficiently hydrolyzed than other cephalosporins such as cephalothin. Several differences with other AmpC ␤-lactamases were found. Ampicillin was more efficiently hydrolyzed than benzylpenicillin. High k cat /K m values were observed for oxacillin and piperacillin, which are usually poor substrates for AmpC. A fairly efficient hydrolysis of imipenem was detected as well. Aztreonam, carbenicillin, and tazobactam were effective transient inactivators of these variants.