Molecular epidemiology of quinolone resistance and comparative in vitro activities of new quinolones against European Staphylococcus aureus isolates.
Molecular epidemiology of quinolone resistance and comparative in vitro activities of new quinolones against European Staphylococcus aureus isolates.
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喹诺酮耐药性的分子流行病学以及新型喹诺酮类药物对欧洲金黄色葡萄球菌分离株的体外活性比较。
DOI：
10.1111/j.1574-695x.1999.tb01400.x
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发表时间：
1999
影响因子：
--
通讯作者：
D. Milatovic
中科院分区：
文献类型：
--
作者：
F. Schmitz;F. Schmitz;A. Fluit;S. Brisse;J. Verhoef;K. Köhrer;D. Milatovic
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新的氟喹诺酮类药物(FQ)可能被用作金黄色葡萄球菌感染的替代治疗选择。我们的目标是：(1)确定来自23所欧洲大学医院的434株甲氧西林敏感金黄色葡萄球菌和457株甲氧西林耐药金黄色葡萄球菌中7种FQS的体外活性；(2)表征所有环丙沙星耐药金黄色葡萄球菌(n=433)中grlA和gyrA基因突变的发生率；(3)确定耐环丙沙星金黄色葡萄球菌中喹诺酮类药物外排的菌株比例。
方法
(1)采用微量稀释法测定不同FQS的体外活性。(2)对扩增出的DNA进行测序。(3)测定环丙沙星在利血平存在和不存在时的最低抑菌浓度(MIC)。
结果
(1)无论菌株对甲氧西林的耐药性如何，西塔沙星和克林沙星的体外活性最好。(2)所有环丙沙星耐药株均存在GrlA突变，即Ser-80-->；Phe或Tyr或Glu-84-->；Lys或Ala-116-->；Glu或Pro，或Ser-80-->；Phe和Glu-84->；Val的组合。GrlA的这些变化与Gyra的变化相结合，即Ser-84-->；Leu或Lys或Glu-88-->；Lys或Val。(3)利血平可降低约30%临床分离株的环丙沙星MIC值。
结论
(1)目前欧洲对氟喹诺酮耐药突变的概述表明，在临床分离株中，只有有限数量的grlA和gyrA经典突变导致了耐药性。(2)约30%的环丙沙星耐药金黄色葡萄球菌与外排泵有关。(3)西塔沙星和克林沙星是两种很有前景的新型FQs，具有良好的抗葡萄球菌活性。新的FQS可能与外排泵抑制剂联合使用，可能在治疗金黄色葡萄球菌感染方面发挥作用。
UNLABELLED
New fluoroquinolones (FQ) may possibly be used as alternative therapeutic options for Staphylococcus aureus infections. Our objectives were: (1) to define the in vitro activities of seven FQs in a collection of 434 methicillin-susceptible and 457 methicillin-resistant S. aureus from 23 European university hospitals; (2) to characterise the prevalence of mutations in the grlA and gyrA genes in all ciprofloxacin-resistant (n=433) isolates of S. aureus; (3) to determine the percentage of ciprofloxacin-resistant S. aureus strains with measurable quinolone efflux.
METHODS
(1) The in vitro activities of different FQs were determined by microdilution tests. (2) PCR-amplified DNA was sequenced. (3) Ciprofloxacin minimum inhibitory concentrations (MIC) were determined in the presence and absence of reserpine, which inhibits efflux pumps.
RESULTS
(1) Irrespective of the methicillin resistance of the isolates, sitafloxacin and clinafloxacin showed the best in vitro activities. (2) All ciprofloxacin-resistant isolates exhibited GrlA alterations, namely Ser-80-->Phe or Tyr or Glu-84-->Lys or Ala-116-->Glu or Pro or a combination of Ser-80-->Phe and Glu-84-->Val. These alterations in GrlA were combined with alterations in GyrA, namely Ser-84-->Leu or Lys or Glu-88-->Lys or Val. (3) Reserpine reduced ciprofloxacin MIC values in ca. 30% of the clinical isolates tested.
CONCLUSIONS
(1) This current European overview of mutations involved in FQ resistance demonstrates that only a limited number of classical mutations in grlA and gyrA contributed to resistance in clinical isolates. (2) An efflux pump is involved in ca. 30% of ciprofloxacin-resistant S. aureus isolates. (3) Sitafloxacin and clinafloxacin are two very promising new FQs with good anti-staphylococcal activity. New FQs, perhaps in combination with efflux pump inhibitors, might play a role in the treatment of S. aureus infections.