Resistance to Linezolid Is Mediated by the cfr Gene in the First Report of an Outbreak of Linezolid-Resistant Staphylococcus aureus
Resistance to Linezolid Is Mediated by the cfr Gene in the First Report of an Outbreak of Linezolid-Resistant Staphylococcus aureus
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DOI：
10.1086/650574
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发表时间：
2010-03-15
影响因子：
11.8
通讯作者：
Sanchez-Garcia, Miguel
中科院分区：
文献类型：
--
作者：
Morales, Gracia;Picazo, Juan J.;Sanchez-Garcia, Miguel
背景。从2008年4月到6月，我们在重症监护室发现了12名患者和其他病房的3名患者感染耐甲氧西林金黄色葡萄球菌，该金黄色葡萄球菌也对利奈唑胺耐药。我们研究了23S核糖体RNA (rRNA) V结构域的耐药点突变或cfr基因的存在与此次暴发有关的机制。研究菌株是在重症监护病房和其他病房获得的。根据临床和实验室标准协会的指南，使用自动方法、E-test或稀释穆勒-辛顿琼脂测定最低抑制浓度。采用脉冲场凝胶电泳对菌株进行基因分型，并对其进行测序，以确定23S rRNA中是否存在点突变。采用特异性聚合酶链反应检测cfr基因的存在。利奈唑胺最低抑菌浓度为16 ~ 32 mg/L，对替加环素、万古霉素和达托霉素均敏感。脉冲场凝胶电泳序列分型结果显示，每位患者仅携带1株耐利奈唑胺、耐甲氧西林金黄色葡萄球菌。所有分离株均证实存在cfr基因。此外，23S rRNA结构域V的测序结果显示，迄今为止报道的最常见的利奈唑胺耐药机制突变G2576T未在所有菌株中检测到。我们报告cfr基因的存在，其潜在的耐药机制涉及耐利奈唑胺金黄色葡萄球菌的临床爆发。
Background. From April through June 2008, we identified 12 patients in the intensive care unit and 3 patients on other wards infected with methicillin-resistant Staphylococcus aureus that was also resistant to linezolid. We investigated the mechanism of resistance-point mutations in domain V of 23S ribosomal RNA ( rRNA) or presence of the cfr gene-involved in the outbreak.Methods. Strains for the study were obtained in the intensive care unit and other wards. Minimal inhibitory concentrations were determined using automated methods, the E-test, or dilution in Mueller-Hinton agar in accordance with Clinical and Laboratory Standards Institute guidelines. Strains were genotyped using pulsed-field gel electrophoresis and were sequenced to determine the presence of point mutations in 23S rRNA. The presence of the cfr gene was determined by specific polymerase chain reaction.Results. The minimal inhibitory concentrations of linezolid ranged from 16 mg/L to 32 mg/L, and all the strains were susceptible to tigecycline, vancomycin, and daptomycin. Typing of strains sequentially isolated by pulsed-field gel electrophoresis showed that each patient carried only 1 clonal type of linezolid-resistant, methicillin-resistant S. aureus as detected by sequential isolations. The presence of the cfr gene was confirmed in all the isolates. Furthermore, sequencing of domain V of 23S rRNA showed that the most common mechanism of linezolid resistance reported to date, mutation G2576T, was not detected in any of the strains analyzed.Conclusions. We report the presence of the cfr gene underlying the resistance mechanism involved in a clinical outbreak of linezolid-resistant S. aureus.