该研究成果在线发表在《柳叶刀神经医学期刊》上,作者在文中提醒医院应该怎样更好地照顾囊胞性纤维症患者,同时提出当前有关控制囊胞性纤维症的措施和患者之间交差感染等关键问题.
在美国和欧洲,在囊泡性纤维症患者当中大约有3%-10%的病人正饱受耐药性囊肿非典型分支杆菌的感染,就目前来说这一数值仍有上升趋势.这一感染容易对人体的肺部产生损害,并且治疗相当之棘手.
剑桥大学的Andres Floto、桑格研究院的Julian Parkhill以及他们的同事们采用基因组序列和抗菌敏感性测试的方法,比较了受囊肿非典型分支杆菌感染的31名患者的基因组的遗传相关性,当然这些患者均被隔离.这组调查人群的对象是2007年至2011年因肺部感染而住进剑桥派普沃斯医院治疗的患者.
研究者还采用了社会关系网分析的方法,以携带基因遗传簇的患者和不携带基因遗传簇的患者为研究对象,针对两者交叉感染的几率进行了比较.又通过环境测试排除了潜在的感染源,比如支气管窥镜、饮用水等.
研究发现携带两类基因遗传簇的患者,更容易受到感染.这是由于他们所感染的脓肿非典型分支杆菌亚种massiliense（从11个患者体内获得）在遗传上有着高度的相似性或几近相似.其DNA碱基对的差异性不足十对.
“相对于其他患者,被单独隔离的11个患者所表现出得关系更为密切,这使他们之间的感染进一步加重”,Flto解释说.而且,他补充道,“这组病人也有较高的机会被医院内部传播的疾病所感染”.
研究组进一步做了一系列实验来证实他们提出的交叉感染理论,他们提出脓肿非典型分支杆菌亚种massiliense可以在从一个病人感染另外一个病人的过程中产生突变,并可以将突变传播,从几个病人体内（这些病人未长期使用抗生素）分离出抗丁胺卡那霉素和克拉霉素的细菌也具有同样的特性.
“全基因组测序的发展使我们清晰地认识到患者之间可以相互传播该病菌,在某一程度上能看到传播的去向,这在以前是不可能完成的任务”.Parkhill说.
Floto补充说：“尽管脓肿非典型分支杆菌亚种massiliense在患者体内传播的证据确凿,其交叉感染的确切机理尚未建立.得益于当前严格的控制感染的政策,我相信所有的该病菌的传播都是通过间接的方式进行的,例如通过污染物（头发、衣物、床单等）或者通过气溶胶（在肺功能测试时使用）产生过程中感染.（生物谷Bioon.com）
DOI:10.1016/S0140-6736(13)60632-7
PMC:
PMID:
Whole-genome sequencing to identify transmission of Mycobacterium abscessus between patients with cystic fibrosis: a retrospective cohort study
Josephine M Bryant BSc a ?, Dorothy M Grogono MRCP b ?, Daniel Greaves MRCP d, Juliet Foweraker FRCPath b, Iain Roddick BSc f, Thomas Inns MSc g h, Mark Reacher FFPH f, Charles S Haworth FRCP b, Martin D Curran PhD e, Simon R Harris PhD a, Prof Sharon J Peacock FRCP d, Prof Julian Parkhill PhD a , Dr R Andres Floto FRCP b c d
Background
Increasing numbers of individuals with cystic fibrosis are becoming infected with the multidrug-resistant non-tuberculous mycobacterium (NTM) Mycobacterium abscessus, which causes progressive lung damage and is extremely challenging to treat. How this organism is acquired is not currently known, but there is growing concern that person-to-person transmission could occur. We aimed to define the mechanisms of acquisition of M abscessus in individuals with cystic fibrosis.
Method
Whole genome sequencing and antimicrobial susceptibility testing were done on 168 consecutive isolates of M abscessus from 31 patients attending an adult cystic fibrosis centre in the UK between 2007 and 2011. In parallel, we undertook detailed environmental testing for NTM and defined potential opportunities for transmission between patients both in and out of hospital using epidemiological data and social network analysis.
Findings
Phylogenetic analysis revealed two clustered outbreaks of near-identical isolates of the M abscessus subspecies massiliense (from 11 patients), differing by less than ten base pairs. This variation represents less diversity than that seen within isolates from a single individual, strongly indicating between-patient transmission. All patients within these clusters had numerous opportunities for within-hospital transmission from other individuals, while comprehensive environmental sampling, initiated during the outbreak, failed to detect any potential point source of NTM infection. The clusters of M abscessus subspecies massiliense showed evidence of transmission of mutations acquired during infection of an individual to other patients. Thus, isolates with constitutive resistance to amikacin and clarithromycin were isolated from several individuals never previously exposed to long-term macrolides or aminoglycosides, further indicating cross-infection.
Interpretation
Whole genome sequencing has revealed frequent transmission of multidrug resistant NTM between patients with cystic fibrosis despite conventional cross-infection measures. Although the exact transmission route is yet to be established, our epidemiological analysis suggests that it could be indirect.
