Vol.65 No.4 July 2017
In vitro and in vivo antibacterial activity of tosufloxacin against Mycoplasma pneumoniae from pediatric patients
1)Toyama Chemical Co., Ltd., 3-2-5 Nishishinjuku, Shinjuku-ku, Tokyo, Japan
2)Research Laboratories, Toyama Chemical Co., Ltd.
Abstract
We evaluated antibacterial activity, bactericidal activity and in vivo efficacy of tosufloxacin (TFLX) against Mycoplasma pneumoniae isolated from pediatric patients. Frequency of spontaneous mutation to TFLX resistance was also measured.
TFLX showed the lowest minimum inhibitory concentration (MIC)90 against clinical isolates of macrolide-resistant M. pneumoniae from pediatric patients. The MIC90 of TFLX against macrolide-resistant M. pneumoniae was 0.25 μg/mL, which was 1/2-, 1/2-, 1/8-, < 1/512-, < 1/512- and 1/256-fold compared with that of tetracycline, doxycycline, minocycline, clindamycin, clarithromycin (CAM) and azithromycin (AZM), respectively.
TFLX at 2 MIC and more decreased the viable count of macrolide-susceptible and -resistant M. pneumoniae by over 3 log CFU/mL from the initial inoculum in a time-kill assay. TFLX showed bactericidal activity against M. pneumoniae regardless of macrolide susceptibility.
The frequencies of spontaneous mutation to TFLX resistance in macrolide-susceptible and -resistant M. pneumoniae were < 1.5× 10-10 at ≥ 4 MIC and < 9.3× 10-10 at ≥ 4 MIC, respectively. The frequencies of spontaneous mutation to CAM and AZM were 7.6× 10-10-7.8× 10-9, generating resistant strains at all concentrations.
TFLX significantly reduced the viable bacterial count compared with the CAM and AZM groups (P< 0.001) in a murine pulmonary infection model caused by macrolide-resistant M. pneumoniae.
In conclusion, TFLX had strong antimicrobial and bactericidal activity. The frequency of spontaneous mutation to TFLX resistance was low. TFLX had stronger efficacy than CAM and AZM in a pulmonary infection model caused by macrolide-resistant M. pneumoniae.
Key word
Mycoplasma pneumoniae, tosufloxacin, antimicrobial activity
Received
January 19, 2017
Accepted
March 29, 2017
Jpn. J. Chemother. 65 (4): 577-584, 2017
