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 c ompared the in vitro and in vivo antibacterial activities of L-036 with tho se of imipenem, faropenem, ceditoren-pivoxil, cefdinir, amoxicillin, and le vofloxacin. The MICs at which 90% of the isolates were inhibited of L-036 a gainst methicillin-susceptible staphylococci, Streptococcus pneumoniae incl uding penicillin-resistant organisms, Escherichia coli, Klebsiella pneumoni ae, Haemophilus influenzae including ampicillin-resistant organisms, Legion ella pneumophila, and Moraxella catarrhalis were equal to or less than 1 mu g/ml. In pharmacokinetics studies of L-084 in lungs of mice, the maximum co ncentration in serum, half-life, and area under the concentration-time curv e of this drug were 9.09 mug/g of tissue, 6.18 h, and 31.0 mug . h/ml, resp ectively. In murine respiratory infection models of penicillin-susceptible and -resistant S. pneumoniae and H. influenzae, the efficacies of L-084 wer e better than those of reference drugs. Our results indicate that the in vi tro high potency and good distribution in the lungs might be the underlying mechanisms of its efficacy in the murine model of pneumonia.