[Therapeutic efficacy of levofloxacin against a model of replicable Legionella pneumophila lung infection in DBA/2 mice].
The in vitro and in vivo antibacterial activities of levofloxacin (LVFX), a quinolone antibacterial, against clinically isolated Legionella pneumophila were investigated in comparison with those of existing antimicrobial agents approved for legionnaires disease. The minimum inhibitory concentrations (MICs) of the agents against 42 strains of L. pneumophila isolated in Japan were determined using agar dilution methods with buffered starch yeast extract agar. MIC90 of LVFX was 0.03 microg/ml and this activity was similar to ciprofloxacin and pazufloxacin, and higher than telithromycin and minocycline. Therapeutic efficacy of LVFX was studied against a pneumonia model induced by intranasal of L. pneumophila strain suzuki serogoup 1 in DBA/2 mice. Therapeutic doses in mice were selected that would closely match human exposure profile, area under the concentration-time curve (AUC) for a human oral dose of LVFX at 500 mg once a day. LVFX decreased significantly the bacterial burden in the lungs from the next day of commencing treatment. These results, including in vitro antibacterial activity against clinical isolates and therapeutic efficacy of a humanized dosing regimen, provide good evidence to support the use of LVFX at 500 mg once a day for treating patient with legionnaires disease.
Kashimoto
Yoshinori
Y
Daiichi Sankyo Co. Ltd., Biological Research Laboratories IV.
Kurosaka
Yuichi
Y
Karibe
Yukie
Y
Uoyama
Saori
S
Fujikawa
Katsuko
K
Namba
Kenji
K
Otani
Tsuyoshi
T
Yamaguchi
Keizo
K
D000284:Administration, Oral; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000494:pharmacology; D004195:Disease Models, Animal; D024881:Drug Resistance, Bacterial; D005260:Female; D016952:Legionella pneumophila / Q000187:drug effects / Q000254:growth & development* / Q000302:isolation & purification; D007877:Legionnaires' Disease / Q000188:drug therapy* / Q000382:microbiology*; D064704:Levofloxacin; D051379:Mice; D008811:Mice, Inbred DBA; D008826:Microbial Sensitivity Tests; D015242:Ofloxacin / Q000008:administration & dosage* / Q000494:pharmacology; D016896:Treatment Outcome
D000900:Anti-Bacterial Agents; D064704:Levofloxacin; D015242:Ofloxacin