Clonal Emergence of Invasive Multidrug-Resistant Staphylococcus epidermidis Deconvoluted via a Combination of Whole-Genome Sequencing and Microbiome Analyses
Clonal Emergence of Invasive Multidrug-Resistant Staphylococcus epidermidis Deconvoluted via a Combination of Whole-Genome Sequencing and Microbiome Analyses
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DOI：
10.1093/cid/ciy089
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发表时间：
2018-08-01
影响因子：
11.8
通讯作者：
Shelburne, Samuel A.
中科院分区：
文献类型：
--
作者：
Li, Xiqi;Arias, Cesar A.;Shelburne, Samuel A.
背景资料。致病菌是一种典型的人类共生细菌，但也会导致疾病，它们对抗菌素的耐药性有很大贡献。表皮葡萄球菌是一种典型的致病菌，因为它是一种普遍存在的人类共生菌，但也是医疗保健相关菌血症的主要原因。我们试图确定最近对利奈唑胺耐药的侵袭性表皮葡萄球菌分离株增加的病因。对2013至2016年间在德克萨斯州休斯敦MD Anderson癌症中心收集的176株表皮葡萄球菌进行了全基因组测序(WGS)。分子关系通过互补的系统基因组学方法进行评估。通过逆转录定量聚合酶链式反应检测粪便标本中利奈唑胺耐药决定基因CFR的丰度。176株细菌中39株对利奈唑胺耐药(22%)。在39株耐利奈唑胺的表皮葡萄球菌感染中，有31株是由一种对多种抗菌药耐药的特定克隆引起的，该克隆在白血病患者中传播，并在49kb的质粒(本文称为pMB151a)上携带CFR。Cfr基因周围6kb的pMB151a与从中国家畜相关葡萄球菌中分离到的含有cfr基因的质粒几乎100%相同。对白血病患者的一系列粪便样本的分析显示，在使用利奈唑胺后，肠道菌群呈进行性葡萄球菌占优势，CFR丰度增加。利奈唑胺的使用加上L所做的多药耐药传播的结合，推动了侵袭性、耐利奈唑胺的表皮葡萄球菌的扩张。我们的结果支持这样一种观点，即抗生素管理和感染控制措施的结合可能有助于控制多重耐药病原体的传播。
Background. Pathobionts, bacteria that are typically human commensals but can cause disease, contribute significantly to anti-microbial resistance. Staphylococcus epidermidis is a prototypical pathobiont as it is a ubiquitous human commensal but also a leading cause of healthcare-associated bacteremia. We sought to determine the etiology of a recent increase in invasive S. epidermidis isolates resistant to linezolid.Methods. Whole-genome sequencing (WGS) was performed on 176 S. epidermidis bloodstream isolates collected at the MD Anderson Cancer Center in Houston, Texas, between 2013 and 2016. Molecular relationships were assessed via complementary phylogenomic approaches. Abundance of the linezolid resistance determinant cfr was determined in stool samples via reverse-transcription quantitative polymerase chain reaction.Results. Thirty-nine of the 176 strains were linezolid resistant (22%). Thirty-one of the 39 linezolid-resistant S. epidermidis infections were caused by a particular clone resistant to multiple antimicrobials that spread among leukemia patients and carried cfr on a 49-kb plasmid (herein called pMB151a). The 6 kb of pMB151a surrounding the cfr gene was nearly 100% identical to a cfr-containing plasmid isolated from livestock-associated staphylococci in China. Analysis of serial stool samples from leukemia patients revealed progressive staphylococcal domination of the intestinal microflora and an increase in cfr abundance following linezolid use.Conclusions. The combination of linezolid use plus transmission of a multidrug-resist an l done drove expansion of invasive, linezolid-resistant S. epidermidis. Our results lend support to the notion that a combination of antibiotic stewardship plus infection control measures may help to control the spread of a multidrug-resistant pathobiont.