Pharmacodynamic activity of fluoroquinolones against ciprofloxacin-resistant Streptococcus pneumoniae

被引:31
作者
Zhanel, GG
Roberts, D
Waltky, A
Laing, N
Nichol, K
Smith, H
Noreddin, A
Bellyou, T
Hoban, DJ
机构
[1] Univ Manitoba, Fac Med, Dept Med Microbiol, Winnipeg, MB, Canada
[2] Univ Manitoba, Fac Pharm, Dept Med Microbiol, Winnipeg, MB R3T 2N2, Canada
[3] Hlth Sci Ctr, Dept Clin Microbiol, Winnipeg, MB, Canada
[4] Hlth Sci Ctr, Dept Med, Winnipeg, MB, Canada
关键词
D O I
10.1093/jac/dkf022
中图分类号
R51 [传染病];
学科分类号
100401 ;
摘要
The susceptibility and pharmacodynamic activity of ciprofloxacin and new fluoroquinolones were studied against low-level (MIC 4 mg/L) and high-level (MIC 16 mg/L) ciprofloxacin-resistant Streptococcus pneumoniae. An in vitro pharmacodynamic model simulating free fluoroquinolone (protein unbound) serum concentrations, using Cp-max and AUC(0-24) achieved (in healthy volunteers) after standard oral doses that are used for community-acquired respiratory infections, was used to compare bacterial killing by five fluoroquinolones against six ciprofloxacin-resistant S. pneumoniae isolates (four different resistance mutant phenotypes: ParC, efflux, ParC with efflux, and ParC and GyrA) obtained from an ongoing Canadian respiratory organism surveillance study. The potency (MIC only) of fluoroquinolones was gemifloxacin > moxifloxacin > gatifloxacin > levofloxacin > ciprofloxacin. Ciprofloxacin (free AUC(0-24)/MIC 0.9-3.5) produced no reduction of growth at 6, 24 or 48 h compared with the initial inoculum in all six strains. Levofloxacin (free AUC(0-24)/MIC 18-35) was bactericidal (greater than or equal to3 log(10) killing) at 6, 24 and 48 h for the ParC as well as the efflux mutants, but only bactericidal at 24 h for the ParC with efflux strain. Levofloxacin (free AUC(0-24)/MIC 4.4) demonstrated no reduction of growth relative to the initial inoculum against the ParC and GyrA mutants. Gatifloxacin and moxifloxacin (free AUC(0-24)/MIC 48 and 60, respectively) were bactericidal at 6, 24 and 48 h against the ParC, efflux, and ParC with efflux mutants, but demonstrated little to no growth reduction (free AUC(0-24)/MIC 6 and 7.5, respectively) in ParC and GyrA mutants. Gemifloxacin (free AUC(0-24)/MIC 67-133) was bactericidal (greater than or equal to3 log(10) killing) at 6, 24 and 48 h in all low-level ciprofloxacin-resistant S. pneumoniae mutants. Against two of the ParC and GyrA mutants, gemifloxacin (free AUC(0-24)/MIC 32) was bactericidal at 6, 24 and 48 h but against one ParC and GyrA mutant (free AUC(0-24)/MIC 16) gemifloxacin demonstrated reduced activity with initial killing at 24 h but with subsequent regrowth. These data indicate that ciprofloxacin produces no inhibition of growth of low- or high-level ciprofloxacin-resistant S. pneumoniae, whereas gatifloxacin, levofloxacin and moxifloxacin (moxifloxacin>gatifloxacin>levofloxacin) were bactericidal for low-level resistant strains but produced little or no inhibition of high-level resistant strains. Gemifloxacin at simulated free AUC(0-24)/MIC greater than or equal to32, was bactericidal against low- and high-level resistant strains. When simulated free AUC(0-24)/ MIC was <16, gemifloxacin allowed regrowth of high-level ciprofloxacin-resistant strains.
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页码:807 / 812
页数:6
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