In vitro activity of pazufloxacin, tosufloxacin and other quinolones against Legionella species.
OBJECTIVE
The activities of pazufloxacin and tosufloxacin against Legionella spp. were evaluated in vitro and compared with those of other quinolones, macrolides and azithromycin.


METHODS
The conventional MICs were determined by the microbroth dilution method. Intracellular activities of drugs were evaluated by a cfu count. The minimal extracellular concentration inhibiting intracellular growth of bacteria (MIEC) was determined by a colorimetric cytopathic assay.


RESULTS
MICs of pazuloxacin and tosufloxacin at which 90% (MIC90) of isolates are inhibited in 76 different Legionella spp. strains (38 ATCC strains and 38 clinical isolates) were 0.032 and 0.016 mg/L, whereas the MIC90s of levofloxacin, ciprofloxacin, garenoxacin, erythromycin, clarithromycin and azithromycin were 0.032, 0.032, 0.032, 2.0, 0.125 and 2.0 mg/L, respectively. Pazufloxacin and tosufloxacin at 4x MIC inhibited intracellular growth of Legionella pneumophila SG1 (80-045 strain), as did other quinolones, clarithromycin and azithromycin, whereas erythromycin at 4x MIC did not. MIECs of pazufloxacin, tosufloxacin, levofloxacin, ciprofloxacin and garenoxacin for the strain were 0.063, 0.004, 0.016, 0.032 and 0.008 mg/L respectively, which were superior to those of macrolides and azithromycin. Pazufloxacin showed potent activity against three additional clinical isolates of L. pneumophila SG1, one clinical isolate each of L. pneumophila SG3 and SG5, as well as Legionella micdadei, Legionella dumoffii and Legionella longbeachae SG1.


CONCLUSIONS
Pazufloxacin and tosufloxacin, as well as other quinolones, were more potent than macrolides and an azalide. Present data warrant further study on the efficacy of these drugs in the treatment of Legionella infections.
Higa
Futoshi
F
First Department of Internal Medicine, Graduate School of Medicine, University of the Ryukyus, Okinawa 903-0215, Japan. fhiga@med.u-ryukyu.ac.jp
Akamine
Morikazu
M
Haranaga
Shusaku
S
Tohyama
Masato
M
Shinzato
Takashi
T
Tateyama
Masao
M
Koide
Michio
M
Saito
Atsushi
A
Fujita
Jiro
J
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D017963:Azithromycin / Q000494:pharmacology; D002460:Cell Line; D015169:Colony Count, Microbial; D024841:Fluoroquinolones / Q000494:pharmacology; D007875:Legionella / Q000187:drug effects*; D018942:Macrolides / Q000494:pharmacology; D008264:Macrophages / Q000382:microbiology; D051379:Mice; D008826:Microbial Sensitivity Tests; D009287:Naphthyridines / Q000494:pharmacology; D010078:Oxazines / Q000494:pharmacology; D015363:Quinolones / Q000494:pharmacology*
D000900:Anti-Bacterial Agents; D024841:Fluoroquinolones; D018942:Macrolides; D009287:Naphthyridines; D010078:Oxazines; D015363:Quinolones; C078052:pazufloxacin; D017963:Azithromycin; C055185:tosufloxacin