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泰地唑胺活性与耐药性监测项目结果:2011年和2012年从美国和欧洲收集的革兰氏阳性病原体的体外敏感性

Results of the surveillance of Tedizolid activity and resistance program: in vitro susceptibility of gram-positive pathogens collected in 2011 and 2012 from the United States and Europe.

作者信息

Sahm Daniel F, Deane Jennifer, Bien Paul A, Locke Jeffrey B, Zuill Douglas E, Shaw Karen J, Bartizal Ken F

机构信息

Eurofins Global Central Laboratories, Chantilly, VA, 20151, USA.

Trius Therapeutics, a Subsidiary of Cubist, San Diego, CA, 92121, USA.

出版信息

Diagn Microbiol Infect Dis. 2015 Feb;81(2):112-8. doi: 10.1016/j.diagmicrobio.2014.08.011. Epub 2014 Aug 30.

DOI:10.1016/j.diagmicrobio.2014.08.011
PMID:25488274
Abstract

The in vitro activity and spectrum of tedizolid and comparators were analyzed against 6884 Gram-positive clinical isolates collected from multiple US and European sites as part of the Surveillance of Tedizolid Activity and Resistance Program in 2011 and 2012. Organisms included 4499 Staphylococcus aureus, 537 coagulase-negative staphylococci (CoNS), 873 enterococci, and 975 β-hemolytic streptococci. The MIC values that inhibited 90% of the isolates within each group (MIC90) were 0.25 μg/mL for Staphylococcus epidermidis and β-hemolytic streptococci and 0.5 μg/mL for S. aureus, other CoNS, and enterococci. Of 16 isolates with elevated tedizolid or linezolid MIC values (intermediate or resistant isolates), 10 had mutations in the genes encoding 23S rRNA (primarily G2576T), 5 had mutations in the genes encoding ribosomal proteins L3 or L4, and 5 carried the cfr multidrug resistance gene. Overall, tedizolid showed excellent activity against Gram-positive bacteria and was at least 4-fold more potent than linezolid against wild-type and linezolid-resistant isolates. Given the low overall frequency of isolates that would be resistant to tedizolid at the proposed break point of 0.5 μg/mL (0.19%) and potent activity against contemporary US and European isolates, tedizolid has the potential to serve as a valuable therapeutic option in the treatment of infections caused by Gram-positive pathogens.

摘要

作为2011年和2012年泰地唑胺活性与耐药性监测项目的一部分,分析了泰地唑胺及其对照药物对从美国和欧洲多个地点收集的6884株革兰氏阳性临床分离株的体外活性和抗菌谱。这些菌株包括4499株金黄色葡萄球菌、537株凝固酶阴性葡萄球菌(CoNS)、873株肠球菌和975株β溶血性链球菌。表皮葡萄球菌和β溶血性链球菌每组中抑制90%分离株的最低抑菌浓度(MIC90)为0.25μg/mL,金黄色葡萄球菌、其他CoNS和肠球菌的MIC90为0.5μg/mL。在16株泰地唑胺或利奈唑胺MIC值升高的分离株(中介或耐药分离株)中,10株编码23S rRNA的基因发生突变(主要是G2576T),5株编码核糖体蛋白L3或L4的基因发生突变,5株携带cfr多药耐药基因。总体而言,泰地唑胺对革兰氏阳性菌显示出优异的活性,对野生型和耐利奈唑胺的分离株的活性比利奈唑胺至少高4倍。鉴于在拟议的0.5μg/mL断点处对泰地唑胺耐药的分离株总体频率较低(0.19%),且对当代美国和欧洲分离株具有强效活性,泰地唑胺有潜力成为治疗革兰氏阳性病原体引起的感染的有价值的治疗选择。

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