Vol.58 No.S-2 October 2010
In vitro and in vivo antibacterial activity of tosufloxacin tosilate hydrate against major causative bacteria of pneumonia and otitis media in pediatric patients
Research Laboratories, Toyama Chemical Co., Ltd., 2-4-1 Shimookui, Toyama, Japan
Abstract
We evaluated the in vitro and in vivo antibacterial activity of tosufloxacin(TFLX) against Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis, pediatric major pneumonia and otitis media pathogens. Results are as follows:
1. MIC90s of TFLX against pediatric clinical isolates of penicillin-susceptible S. pneumoniae(PSSP), penicillin-intermediate S. pneumoniae(PISP), and penicillin-resistant S. pneumoniae(PRSP) were 0.25 μg/mL each, which were 1/64 to 1/4 than those of levofloxacin(LVFX), ciprofloxacin, and norfloxacin, 1/64 to 1/2 than those of cefditoren, cefdinir, and cefcapene(CFPN), 1/8 to 4 times than that of clavulanic acid/amoxicillin, and <1/512 than that of azithromycin(AZM).
2. MIC90s of TFLX against pediatric clinical isolates of β-lactamase-negative ampicillin-susceptible(BLNAS) and β-lactamase-negative ampicillin-resistant H. influenzae(BLNAR) were 0.0078 μg/mL, which were 1/8 than or equal to those of other quinolones, 1/2,048 to 1/16 than those of β-lactams, and 1/256 than that of AZM.
3. MIC90 of TFLX against pediatric clinical isolates of M. catarrhalis was 0.0156 μg/mL, lowest among those of other quinolones and β-lactams.
4. TFLX showed bactericidal activity against PRSP and BLNAR at 1 and 2 times MIC or more, respectively.
5. The frequency of spontaneous mutant of S. pneumoniae and H. influenzae caused by TFLX were <9.3×10-10 and <8.4×10-10 at 4 to 16 times MIC, respectively, similar to LVFX.
6. The susceptibility of S. pneumoniae and H. influenzae to TFLX was decreased by 1/2 and equal after 7-time repeated subcultures at sub-MIC in the presence of TFLX, similar to that of LVFX.
7. Mutant prevention concentrations of TFLX against S. pneumoniae and H. influenzae were 0.4 and 0.07 μg/mL, respectively, similar to or lower than for LVFX.
8. Viable bacterial cells counts in lung in mice with pneumonia caused by PRSP in the TFLX-treated group was <4.22 Log10 of CFU/g, less than in LVFX, AZM, or CFPN-treated groups.
Key word
tosufloxacin, antimicrobial activity, animal model, child
Received
April 21, 2010
Accepted
August 23, 2010
Jpn. J. Chemother. 58 (S-2): 1-11, 2010
