Open AccessIn Vitro and In Vivo Antibacterial Activities of L-084, a Novel Oral Carbapenem, against Causative Organisms of Respiratory Tract Infections
Author(s) -
Shunichi Miyazaki,
Takayuki Hosoyama,
Nobuhiko Furuya,
Yoshikazu Ishii,
Tetsuya Matsumoto,
Akira Ohno,
Kazuhiro Tateda,
Keizo Yamaguchi
Publication year - 2001
Publication title -
antimicrobial agents and chemotherapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.07
H-Index - 259
eISSN - 1070-6283
pISSN - 0066-4804
DOI - 10.1128/aac.45.1.203-207.2001
Subject(s) - microbiology and biotechnology , moraxella catarrhalis , streptococcus pneumoniae , haemophilus influenzae , ampicillin , imipenem , amoxicillin , in vivo , biology , levofloxacin , penicillin , klebsiella pneumoniae , antibacterial agent , respiratory tract infections , klebsiella pneumonia , antibiotics , staphylococcus aureus , escherichia coli , respiratory system , bacteria , antibiotic resistance , biochemistry , anatomy , gene , genetics
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 methicillin-susceptible 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 microg/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 microg/g of tissue, 6.18 h, and 31.0 microg. 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.