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Activities of newer fluoroquinolones against ciprofloxacin resistant Streptococcus pneumoniae
被引:35
作者:
Coyle, EA
Kaatz, GW
Rybak, MJ
机构:
[1] Detroit Receiving Hosp & Univ Hlth Ctr, Dept Pharm Serv, Antiinfect Rec Lab, Detroit, MI 48201 USA
[2] Wayne State Univ, Coll Pharm & Allied Hlth Profess, Detroit, MI 48202 USA
[3] Wayne State Univ, Sch Med, Dept Internal Med, Div Infect Dis, Detroit, MI 48201 USA
[4] Dept Vet Affairs Med Ctr, Detroit, MI USA
关键词:
D O I:
10.1128/AAC.45.6.1654-1659.2001
中图分类号:
Q93 [微生物学];
学科分类号:
071005 ;
100705 ;
摘要:
The incidence of ciprofloxacin resistance in Streptococcus pneumoniae is Low but steadily increasing, which raises concerns regarding the clinical impact of potential cross-resistance with newer fluoroquinolones. To investigate this problem, we utilized an in vitro pharmacodynamic model and compared the activities of gatifloxacin, grepafloxacin, Levofloxacin, moxifloxacin, and trovafloxacin to that of ciprofloxacin against two laboratory-derived, ciprofloxacin-resistant derivatives of S. pneumoniae (strains R919 and R921), Ciprofloxacin resistance in these strains involved the activity of a multidrug efflux pump and possibly, for R919, a mutation resulting in an amino acid substitution in GyrA, Gatifloxacin, grepafloxacin, levafloxacin, moxifloxacin, and trovafloxacin achieved 99.9% killing of both R919 and R921 in less than or equal to 28 h. With respect to levofloxacin, significant regrowth of both mutants was observed at 48 h (P < 0.05), For gatifloxacin, grepafloxacin, moxifloxacin, and trovafloxacin, regrowth aas minimal at 48 h, with each maintaining 99.9% killing against both mutants. No killing of either R919 or R921 was observed with exposure to ciprofloxacin, During model experiments, resistance to gatifloxacin, grepafloxacin, moxifloxacin, and trovafloxacin did not develop but the MICs of ciprofloxacin and levofloxacin increased 1 to 2 dilutions for both R919 and R921. Although specific area under the concentration-time curve from 0 to 24 h (AUC(0-24))/MIC and maximum concentration of drug in serum (C-max)/MIC ratios have not been defined far the fluoroquinolones with respect to gram-positive organisms, our study revealed that significant regrowth and/or resistance was associated with AUC(0-24)/MIC ratios of less than or equal to 31.7 and C-max/MIC ratios of less than or equal to3.1. It is evident that the newer fluoroquinolones tested possess improved activity against S, pneumoniae, including strains for which ciprofloxacin MICs were elevated.
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页码:1654 / 1659
页数:6
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