該研究成果在線發(fā)表在《柳葉刀神經(jīng)醫(yī)學(xué)期刊》上,作者在文中提醒醫(yī)院應(yīng)該怎樣更好地照顧囊胞性纖維癥患者,同時(shí)提出當(dāng)前有關(guān)控制囊胞性纖維癥的措施和患者之間交差感染等關(guān)鍵問題.
在美國(guó)和歐洲,在囊泡性纖維癥患者當(dāng)中大約有3%-10%的病人正飽受耐藥性囊腫非典型分支桿菌的感染,就目前來(lái)說(shuō)這一數(shù)值仍有上升趨勢(shì).這一感染容易對(duì)人體的肺部產(chǎn)生損害,并且治療相當(dāng)之棘手.
劍橋大學(xué)的Andres Floto、桑格研究院的Julian Parkhill以及他們的同事們采用基因組序列和抗菌敏感性測(cè)試的方法,比較了受囊腫非典型分支桿菌感染的31名患者的基因組的遺傳相關(guān)性,當(dāng)然這些患者均被隔離.這組調(diào)查人群的對(duì)象是2007年至2011年因肺部感染而住進(jìn)劍橋派普沃斯醫(yī)院治療的患者.
研究者還采用了社會(huì)關(guān)系網(wǎng)分析的方法,以攜帶基因遺傳簇的患者和不攜帶基因遺傳簇的患者為研究對(duì)象,針對(duì)兩者交叉感染的幾率進(jìn)行了比較.又通過環(huán)境測(cè)試排除了潛在的感染源,比如支氣管窺鏡,、飲用水等.
研究發(fā)現(xiàn)攜帶兩類基因遺傳簇的患者,更容易受到感染.這是由于他們所感染的膿腫非典型分支桿菌亞種massiliense（從11個(gè)患者體內(nèi)獲得）在遺傳上有著高度的相似性或幾近相似.其DNA堿基對(duì)的差異性不足十對(duì).
“相對(duì)于其他患者,被單獨(dú)隔離的11個(gè)患者所表現(xiàn)出得關(guān)系更為密切,這使他們之間的感染進(jìn)一步加重”,Flto解釋說(shuō).而且,他補(bǔ)充道,“這組病人也有較高的機(jī)會(huì)被醫(yī)院內(nèi)部傳播的疾病所感染”.
研究組進(jìn)一步做了一系列實(shí)驗(yàn)來(lái)證實(shí)他們提出的交叉感染理論,他們提出膿腫非典型分支桿菌亞種massiliense可以在從一個(gè)病人感染另外一個(gè)病人的過程中產(chǎn)生突變,并可以將突變傳播,從幾個(gè)病人體內(nèi)（這些病人未長(zhǎng)期使用抗生素）分離出抗丁胺卡那霉素和克拉霉素的細(xì)菌也具有同樣的特性.
“全基因組測(cè)序的發(fā)展使我們清晰地認(rèn)識(shí)到患者之間可以相互傳播該病菌,在某一程度上能看到傳播的去向,這在以前是不可能完成的任務(wù)”.Parkhill說(shuō).
Floto補(bǔ)充說(shuō)：“盡管膿腫非典型分支桿菌亞種massiliense在患者體內(nèi)傳播的證據(jù)確鑿,其交叉感染的確切機(jī)理尚未建立.得益于當(dāng)前嚴(yán)格的控制感染的政策,我相信所有的該病菌的傳播都是通過間接的方式進(jìn)行的,例如通過污染物（頭發(fā),、衣物、床單等）或者通過氣溶膠（在肺功能測(cè)試時(shí)使用）產(chǎn)生過程中感染.（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.
