L-084 (a prodrug of LJC 11,036 [L-036]) is a new oral carbapenem.Here we compared the in vitro and in vivo antibacterial activities of L-036 with those of imipenem, faropenem, ceditoren-pivoxil, cefdinir, amoxicillin, and levofloxacin. The MICs at which 90% of the isolates were inhibited of L-036 against methicillinsusceptible staphylococci, Streptococcus pneumoniae including penicillin-resistant organisms, Escherichia coli, Klebsiella pneumoniae, Haemophilus influenzae including ampicillin-resistant organisms, Legionella pneumophila, and Moraxella catarrhalis were equal to or less than 1 g/ml. In pharmacokinetics studies of L-084 in lungs of mice, the maximum concentration in serum, half-life, and area under the concentration-time curve of this drug were 9.09 g/g of tissue, 6.18 h, and 31.0 g ⅐ h/ml, respectively. In murine respiratory infection models of penicillin-susceptible and -resistant S. pneumoniae and H. influenzae, the efficacies of L-084 were better than those of reference drugs. Our results indicate that the in vitro high potency and good distribution in the lungs might be the underlying mechanisms of its efficacy in the murine model of pneumonia.Carbapenems such as imipenem, meropenem, and panipenem, which are commercially available parenteral drugs, have broad-spectrum activity against both gram-positive and gram-negative bacteria. To date, there are many types of oral antimicrobial agents such as ␤-lactams, fluoroquinolones, and penems with broad antibacterial activities. Recently, there has been an increase in the incidence of community-acquired respiratory tract infections caused by penicillin-resistant Streptococcus pneumoniae, penicillinase-producing Haemophilus influenzae, and ␤-lactamase-nonproducing ampicillin-resistant H. influenzae (3,13,18). In addition, the incidence of infections caused by fluoroquinolone-resistant organisms also seems to have increased (1,5,14). These conditions highlight the need for novel antimicrobial agents active against these problematic pathogens. At present, various oral carbapenems such as GV118819X, CS-834, DZ-2640, and CL191,121 remain under development (12, 15, 16, 19, 20).hept-2-ene-2-carboxylate, is a novel oral carbapenem synthesized at the Medical Research Laboratories, Lederle (Japan), Ltd., Saitama, Japan. In the study described here, we evaluated the in vitro antibacterial properties of LJC 11,036 (L-036) and the in vivo activities of L-084 (a prodrug of L-036) by using models of murine bronchopneumonia caused by H. influenzae and pneumonia caused by S. pneumoniae. We also compared the potency of this drug with those of faropenem, imipenem, levofloxacin, cefditoren-pivoxil (a prodrug of cefditoren), cefdinir, and amoxicillin. MATERIALS AND METHODSAntimicrobial agents. The following antimicrobial agents, used in this study, were obtained from the indicated sources: L-036 and L-084, Wyeth Lederle Japan, Tokyo, Japan; faropenem, Suntory, Tokyo, Japan; imipenem, Banyu Pharmaceutical Co., Tokyo, Japan; levofloxacin, Daiichi Pharmaceutical Co., Tokyo, J...

A new alginate lyase‐producing micro‐organism, designated as Bacillus sp. strain ATB‐1015, was effectively isolated from soil samples pretreated for 3 months with a substrate of the enzyme, sodium alginate. Alginate lyase activity was assayed by the degrading activity of biofilm on Teflon sheet discs, which was formed by a mucoid strain of Pseudomonas aeruginosa PAM3 selected from clinical isolates. The extracellular alginate lyase was precipitated with ammonium sulphate from the culture broth, and purified by gel filtration and anion exchange chromatography. The molecular weight of the lyase was estimated to be 41 kDa by SDS polyacrylamide gel electrophoresis and Sephacryl S‐200 HR column chromatography. The optimum pH and temperature for the enzyme activity were around 7·5 and 37 °C, respectively, and the Km value was 0·17% with the substrate, sodium alginate. The lyase activity was completely inhibited by treatment with 1 mmol l−1 of EDTA and the decreased activity was almost completely recovered by the addition of 2 mmol l−1 of CaCl2. The activity was not affected by treatment with the protein denaturants, 0·01 mol l−1 of SDS or 1 mmol l−1 of urea. The lyase had substrate specificity for both the poly‐guluronate and poly‐mannuronate units in the alginate molecule.

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