Vol.60 No.6 November 2012
Bactericidal activity and resistant selectivity evaluation of garenoxacin against Streptococcus pneumoniae in an in vitro pharmacokinetic model
1)Research Laboratories, Toyama Chemical Co. Ltd., 2-4-1 Shimookui, Toyama, Japan
2)Department of Microbiology and Infectious Diseases, Faculty of Medicine, Toho University School of Medicine
Abstract
We evaluated the bactericidal activity and resistance selectivity of garenoxacin mesilate hydrate (GRNX) against clinical isolates of levofloxacin(LVFX)-susceptible Streptococcus pneumoniae with no mutation or a mutation in ParC (Ser-79 to Phe) using an in vitro pharmacokinetic model simulating free serum concentrations for a standard clinical regimen [400 mg, q.d.], and compared its efficacy with that of LVFX (500 mg, q.d.).
GRNX showed excellent and rapid bactericidal activity against isolates of S. pneumoniae including the parC mutant, achieving a free AUC/MIC ratio above 246, without the emergence of resistant subpopulations.
The area above the killing curves (AAKC) of GRNX against 2 strains without mutation (S. pneumoniae D-5834 and D-5580) were >108 and >103 ΔLog10 CFU・h/mL. GRNX showed excellent bactericidal activity, without regrowth and emerging resistant subpopulations over 24 hr. The AAKCs of LVFX were >87.7 and >114 ΔLog10 CFU・h/mL. Although LVFX also showed a potent bactericidal activity, regrowth occurred over 24 hr.
The AAKCs of GRNX and LVFX against the parC mutant (S. pneumoniae D-5787) were >106 and 20.7 ΔLog10 CFU・h/mL, and the times to achieve 99.9% killing were 2.24 hr and 4.74 hr, respectively. GRNX showed excellent and rapid bactericidal activity, without regrowth and emerging resistant subpopulations over 24 hr. On the other hand, exposure to LVFX led to the outgrowth of resistant subpopulations which were 8-fold less susceptible to LVFX and had an additional amino acid substitution in GyrA (Ser-81 to Phe or Tyr).
In conclusion, our results suggest that GRNX is useful against S. pneumoniae infection in terms of rapid eradication and resistant prevention.
Key word
garenoxacin, in vitro, pharmacokinetic model, Streptococcus pneumoniae
Received
June 27, 2012
Accepted
September 12, 2012
Jpn. J. Chemother. 60 (6): 635-642, 2012
