Origin and interstate spread of a New York City multidrug-resistant Mycobacterium tuberculosis clone family
Origin and interstate spread of a New York City multidrug-resistant Mycobacterium tuberculosis clone family
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DOI：
10.1001/jama.275.6.452
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发表时间：
1996-02-14
影响因子：
120.7
通讯作者：
Kreiswirth, BN
中科院分区：
文献类型：
--
作者：
Bifani, PJ;Plikaytis, BB;Kreiswirth, BN
客观。-确定来自纽约和其他地方的结核分枝杆菌分离株是否对四种或更多种主要抗菌药物具有耐药性，并在20世纪90年代引起广泛的疾病，代表新出现的克隆或不相关生物体的异质阵列。纽约市地区和美国选定地点。患者。-来自纽约1953名患者的结核分枝杆菌分离株和来自美国其他社区6名患者的多药耐药分离株。所有结核分枝杆菌菌株的方便样本（结核分枝杆菌分离株对利福平、链霉素、异烟肼和乙胺丁醇耐药，有时对乙硫异烟胺、卡那霉素、卷曲霉素或环丙沙星耐药）自1991年以来提交给公共卫生研究所结核病中心，并从美国各地提交给疾病控制和预防中心的样本，提交的样本代表了纽约市的结核分枝杆菌菌株。通过IS 6110和多态性富含CC的重复序列（PGRS）杂交模式、多重聚合酶链反应（PCR）分析和含有与利福平（rpoB）、异烟肼（katG和inhA位点）和链霉素（strA和rrs）抗性相关的突变的基因的自动DNA测序研究耐药结核分枝杆菌菌株的表征。从253例纽约市患者中回收了多重耐药结核分枝杆菌分离株，它们具有相同或密切相关的IS 6110和PGRS模式、多重PCR类型以及与利福平、异烟肼和链霉素耐药相关的基因突变。从佛罗里达和内华达州的患者、佐治亚州亚特兰大和弗拉的迈阿密的医护人员以及最近从纽约市搬到丹佛的科尔的个人中回收了具有这些相同分子特征的分离株，并在养老院环境中导致至少12人的疾病或皮肤试验转换。这些结果记录了一个密切相关的多药耐药结核分枝杆菌菌株家族后代的分子起源和传播，这些菌株最近有一个共同的祖先并经历了克隆扩增。这些生物体中的多药耐药表型是通过连续获得几个基因中的耐药突变而产生的，最有可能是由于抗生素选择随机发生的突变体与治疗不充分的感染。这些难以治疗的细菌在整个纽约市和至少另外四个美国城市的传播对世纪的结核病控制具有不利影响。
Objective.-To determine whether isolates of Mycobacterium tuberculosis from New York and elsewhere that are resistant to four or more primary antimicrobial agents and responsible for widespread disease in the 1990s represent a newly emerged clone or a heterogeneous array of unrelated organisms.Setting.-New York City area and selected locations in the United States.Patients.-M tuberculosis isolates from 1953 patients in New York and multidrug-resistant isolates from six patients from other US communities.Design.-Convenience sample of all M tuberculosis strains (M tuberculosis isolates resistant to rifampin, streptomycin, isoniazid, and ethambutol, and sometimes ethionamide, kanamycin, capreomycin, or ciprofloxacin) submitted to the Public Health Research Institute Tuberculosis Center since 1991 and samples submitted to the Centers for Disease Control and Prevention from throughout the United States, The samples submitted were representative of the New York City strains of M tuberculosis.Main Outcome Measure.-Characterization of resistant M tuberculosis strains studied by IS6110 and polymorphic CC-rich repetitive sequence (PGRS) hybridization patterns, multiplex polymerase chain reaction (PCR) analysis, and automated DNA sequencing of genes containing mutations associated with resistance to rifampin (rpoB), isoniazid (katG and inhA locus), and streptomycin (strA and rrs).Results.-Multidrug-resistant M tuberculosis isolates were recovered from 253 New York City patients and had the same or closely allied IS6110 and PGRS patterns, multiplex PCR type, and gene mutations associated with resistance to rifampin, isoniazid, and streptomycin. Isolates with these same molecular characteristics were recovered from patients in Florida and Nevada, health care workers in Atlanta, Ga, and Miami, Fla, and an individual who recently moved from New York City to Denver, Cole, and caused disease or skin test conversion in at least 12 people in a nursing home environment.Conclusions.-The results document the molecular origin and spread of progeny of a closely related family of multidrug-resistant M tuberculosis strains that have recently shared a common ancestor and undergone clonal expansion. The multidrug-resistant phenotype in these organisms arose by sequential acquisition of resistance-conferring mutations in several genes, most likely as a consequence of antibiotic selection of randomly occurring mutants in concert with inadequately treated infections. Dissemination of these difficult-to-treat bacteria throughout New York City and to at least four additional US cities has adverse implications for tuberculos control in the 21st century.