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检测达托霉素对耐(linezolid)利奈唑胺阳性临床分离株的活性。

Daptomycin activity tested against linezolid-nonsusceptible gram-positive clinical isolates.

机构信息

JMI Laboratories, North Liberty, Iowa 52317, USA.

出版信息

Microb Drug Resist. 2009 Dec;15(4):245-9. doi: 10.1089/mdr.2009.0045.

DOI:10.1089/mdr.2009.0045
PMID:19857129
Abstract

Staphylococcus aureus, coagulase-negative staphylococci, and Enterococcus spp. represent the most frequently recovered organisms from bloodstream infections. As a treatment option, daptomycin has been recently approved for the treatment of S. aureus bacteremia and right-sided endocarditis. We evaluated the spectrum of activity and potency of daptomycin and other antibiotics against 142 linezolid-nonsusceptible clinical strains. The isolates were tested for susceptibility by reference broth microdilution methods utilizing physiologic free calcium ions levels (50 mg/L) when testing daptomycin. Staphylococcus spp. and Enterococcus spp. were selected and screened for 23S rRNA, L4 and L22 mutations, and the cfr gene. Daptomycin was potent against all linezolid-nonsusceptible staphylococci (minimal inhibitory concentrations MIC, 0.5 microg/ml) and enterococci (MIC(90), 1 microg/ml) isolates at the respective breakpoints of <or=1 microg/ml and <or=4 microg/ml. The majority of the isolates (84.5%) showed ribosomal target-site alterations, mainly G2576T, and five isolates (two S. aureus and three Staphylococcus epidermidis) had the mobile cfr element. In conclusion, daptomycin was the most active agent tested against this collection of gram-positive clinical organisms and ribosomal target mutations comprised the main resistance mechanism against linezolid.

摘要

金黄色葡萄球菌、凝固酶阴性葡萄球菌和肠球菌属代表了血流感染中最常分离到的病原体。达托霉素最近被批准用于治疗金黄色葡萄球菌菌血症和右侧心内膜炎,是一种治疗选择。我们评估了达托霉素和其他抗生素对 142 株利奈唑胺耐药临床分离株的活性和抗菌效力。采用参考肉汤微量稀释法检测分离株的药敏性,达托霉素检测时采用生理游离钙离子浓度(50mg/L)。选择金黄色葡萄球菌属和肠球菌属进行 23S rRNA、L4 和 L22 突变以及 cfr 基因检测。达托霉素对所有利奈唑胺耐药的葡萄球菌(MIC(90),0.5μg/ml)和肠球菌(MIC(90),1μg/ml)分离株均具有强大的抗菌活性,相应的折点分别为<或等于 1μg/ml 和<或等于 4μg/ml。大多数分离株(84.5%)显示核糖体靶位改变,主要为 G2576T,5 株分离株(2 株金黄色葡萄球菌和 3 株表皮葡萄球菌)具有可移动的 cfr 元件。总之,达托霉素是针对这组革兰阳性临床分离株最有效的药物,核糖体靶位突变是对利奈唑胺耐药的主要机制。

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