The evolution of drug resistance in Mycobacterium tuberculosis:: From a mono-rifampin-resistant cluster into increasingly multidrug-resistant variants in an HIV-seropositive population

The evolution of drug resistance in Mycobacterium tuberculosis:: From a mono-rifampin-resistant cluster into increasingly multidrug-resistant variants in an HIV-seropositive population
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DOI:
10.1086/588822
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发表时间:
2008-07-01
影响因子:
6.4
通讯作者:
Kreiswirth, Barry N.
Kreiswirth, Barry N.
中科院分区:
医学2区
文献类型:
--
作者:
Bifani, Pablo;Mathema, Barun;Kreiswirth, Barry N.

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我们描述了单利福平耐药 (RIF(R)) 结核分枝杆菌菌株簇(命名为 AU-RIF(R))的基因型和表型特征以及额外耐药性的获得。检查了药物敏感性、决定耐药性的区域序列以及基本临床数据。在 29 个分离株中鉴定出 rpoB 中罕见的密码子重复 (514(TTC)),赋予高水平的 RIFR(最低抑制浓度 > 256 μg/mL)。 AU-RIF(R) 菌株对异烟肼产生了继发耐药性,并对 6 种不同抗生素产生了 7 种耐药性组合。感染 AU-RIFR 菌株的患者主要是免疫功能低下的。这些数据表明,宿主因素(例如 HIV 状态)可能允许单 RIF(R) 菌株传播并促进额外耐药性的积累。
We describe the genotypic and phenotypic characteristics of a mono-rifampin-resistant (RIF(R)) Mycobacterium tuberculosis strain cluster (designated AU-RIF(R)) and the acquisition of additional drug resistance. Drug susceptibility, sequences of regions that determine drug resistance, and basic clinical data were examined. A rare codon duplication (514(TTC)) in rpoB conferring high levels of RIFR (minimum inhibitory concentration of > 256 mu g/mL) in 29 isolates was identified. AU-RIF(R) strains developed secondary resistance to isoniazid and 7 resistance combinations to 6 different antibiotics. Patients infected with AU-RIFR strains were primarily immunocompromised. These data suggest that host factors, such as HIV status, may allow dissemination of mono-RIF(R) strains and facilitate the accumulation of additional drug resistance.