超级细菌的暴发困扰着英国剑桥市新生儿特殊护理病房的医护人员。在基因测序的帮助下，去年以来持续数月的困境终于结束了。刊登在近期出版的《柳叶刀—传染病》上的一份研究报告称，科学家首次测序了病原体基因，以便积极控制进行中的超级细菌暴发。
英国剑桥大学的临床微生物学家Sharon Peacock及其同事被卷入了这场超级细菌暴发的困境中。当时，几天内，当地的罗西医院婴儿24小时特别监护室中的三个婴儿的耐甲氧西林金黄色葡萄球菌（MRSA）测试相继呈阳性。
从这三个婴儿身上分离出的细菌对一类抗生素表现出耐药性，研究人员表示，这指向一个公共细菌源。病房被彻底地清扫干净，医护人员希望超级细菌噩梦能够就此结束。
不过，出于科学家的好奇心，Peacock研究小组继续调查了这三个病例是否与之前的半年里罗西医院出现的一系列MRSA感染有联系。
实验室测试结果显示，那时至少还有另外8名儿童感染了相似耐药性的MRSA菌株。但是，有数周没有出现感染病例，这又显示超级细菌的感染并不是简单地从该病房的婴儿传染到婴儿。
为了将一连串事件串联起来，Peacock研究小组开始对取自该医院的这种MRSA菌株以及收集自其他医院的成年患者的相似的菌株的基因进行测序。基因组测序结果显示，婴儿病房的菌株与其他疑似病例的菌株相吻合。
不过，罗西医院的细菌暴发并没有结束。该病房杀菌数天后，又有一个婴儿的MRSA检测结果呈阳性。
不断的MRSA传染，让Peacock和罗西医院流行病学家们如临大敌。确定暴发菌株基因序列后，他们开始从婴儿病房的154个工作人员中寻找暴发的菌株。其中一人的相关检测结果呈阳性，尽管还没有出现任何症状。
“我们将会将这个人隔离出感染链，以便有效地预防持续暴发。” Peacock说。
进一步的监查还在这些成年人之中发现了另外的传染病，这些人还包括从自己孩子身上接触过MRSA的父母。一共有14个患者——6个婴儿和8个成人——出现严重感染，亟须治疗。最后一个确诊案例发生在大暴发一年之后，病人是一位父亲，他从配偶那里接触了MRSA。值得庆幸的是，没有人死亡。
这里，基因测序提供了明晰的线索，这是其他方法难以做到的，该论文的合作者、英国维康信托基金会桑格研究所微生物学家Julian Parkhill表示。
基因测序能够揭示细菌暴发过程中发生的一系列小规模的基因突变，帮助流行病学家编写一个进化树，并追踪暴发的源头。进化分析显示，这名受感染的雇员很可能是从该病房的一个患病婴儿那里感染了MRSA。
doi:10.1016/S1473-3099(12)70268-2
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PMID:
Whole-genome sequencing for analysis of an outbreak of meticillin-resistant Staphylococcus aureus: a descriptive study
Simon R Harris PhD, Edward JP Cartwright MBBS, M Estée T?r?k FRCP, Matthew TG Holden PhD, Nicholas M Brown MD, Amanda L Ogilvy-Stuart FRCP, Matthew J Ellington DPhil, Michael A Quail PhD, Stephen D Bentley PhD, Prof Julian Parkhill PhD, Prof Sharon J Peacock FRCP
Background
The emergence of meticillin-resistant Staphylococcus aureus (MRSA) that can persist in the community and replace existing hospital-adapted lineages of MRSA means that it is necessary to understand transmission dynamics in terms of hospitals and the community as one entity. We assessed the use of whole-genome sequencing to enhance detection of MRSA transmission between these settings.
Methods
We studied a putative MRSA outbreak on a special care baby unit (SCBU) at a National Health Service Foundation Trust in Cambridge, UK. We used whole-genome sequencing to validate and expand findings from an infection-control team who assessed the outbreak through conventional analysis of epidemiological data and antibiogram profiles. We sequenced isolates from all colonised patients in the SCBU, and sequenced MRSA isolates from patients in the hospital or community with the same antibiotic susceptibility profile as the outbreak strain.
Findings
The hospital infection-control team identified 12 infants colonised with MRSA in a 6 month period in 2011, who were suspected of being linked, but a persistent outbreak could not be confirmed with conventional methods. With whole-genome sequencing, we identified 26 related cases of MRSA carriage, and showed transmission occurred within the SCBU, between mothers on a postnatal ward, and in the community. The outbreak MRSA type was a new sequence type (ST) 2371, which is closely related to ST22, but contains genes encoding Panton-Valentine leucocidin. Whole-genome sequencing data were used to propose and confirm that MRSA carriage by a staff member had allowed the outbreak to persist during periods without known infection on the SCBU and after a deep clean.
Interpretation
Whole-genome sequencing holds great promise for rapid, accurate, and comprehensive identification of bacterial transmission pathways in hospital and community settings, with concomitant reductions in infections, morbidity, and costs.
Funding
UK Clinical Research Collaboration Translational Infection Research Initiative, Wellcome Trust, Health Protection Agency, and the National Institute for Health Research Cambridge Biomedical Research Centre.
