Vol.58 No.6 November 2010
Bactericidal activity and resistant selectivity evaluation of pazufloxacin against Streptococcus pneumoniae in an in vitro pharmacokinetic model
Research Laboratories, Toyama Chemical Co. Ltd., 2-4-1 Shimookui, Toyama, Japan
Abstract
We evaluated the bactericidal activity and resistant selectivity of pazufloxacin(PZFX) 1,000 mg bis in die (b.i.d.), against Streptococcus pneumoniae by simulating the free serum concentration after PZFX drip infusion in an in vitro pharmacokinetic model compared to 500 mg b.i.d. Results are as follows:
1) In the in vitro pharmacokinetic model of PZFX 1,000 mg b.i.d., PZFX showed bactericidal activity against S. pneumoniae D-979, without regrowth occurring over 24 h. The area above the killing curves (AAKC) of PZFX 500 mg and 1,000 mg b.i.d. were 76.1 and >104 ΔLog CFU·h/mL, respectively. Bactericidal activity of PZFX 1,000 mg b.i.d. exceeded that of 500 mg b.i.d. The free AUC (fAUC)/MIC of 1,000 mg b.i.d was 35.3, which was 2.4-fold as high as that of 500 mg b.i.d.
2) Exposure of only PZFX 500 mg b.i.d. led to outgrowth of populations which were 2-fold less susceptible to PZFX but had no amino acid substitution in quinolone resistance-determining regions of GyrA, GyrB, ParC, and ParE, and no increased expression of reserpine-inhibited efflux pump. No PZFX-resistant population was detected in the 1,000 mg b.i.d. model.
Our results suggest that PZFX 1,000 mg b.i.d. is useful against S. pneumoniae infection in ensuring efficacy and resistant prevention.
Key word
pazufloxacin, in vitro, pharmacokinetic model, Streptococcus pneumoniae
Received
August 6, 2010
Accepted
September 13, 2010
Jpn. J. Chemother. 58 (6): 644-649, 2010
