In vitro and in vivo antibacterial activities of L-084, a novel oral carbapenem, against causative organisms of respiratory tract infections.
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.
Miyazaki
S
S
Department of Microbiology, Toho University School of Medicine, Tokyo, Japan. shuichi@med.Toho-u.ac.jp
Hosoyama
T
T
Furuya
N
N
Ishii
Y
Y
Matsumoto
T
T
Ohno
A
A
Tateda
K
K
Yamaguchi
K
K
D000818:Animals; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics / Q000494:pharmacology; D019540:Area Under Curve; D015780:Carbapenems / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D006192:Haemophilus Infections / Q000188:drug therapy / Q000382:microbiology; D006193:Haemophilus influenzae / Q000187:drug effects; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D008813:Mice, Inbred ICR; D008826:Microbial Sensitivity Tests; D011355:Prodrugs / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D012141:Respiratory Tract Infections / Q000188:drug therapy / Q000382:microbiology*; D013290:Streptococcal Infections / Q000188:drug therapy / Q000382:microbiology; D013296:Streptococcus pneumoniae / Q000187:drug effects
D000900:Anti-Bacterial Agents; D015780:Carbapenems; D011355:Prodrugs; C120999:L 084