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[秘鲁结核分枝杆菌分离株中异烟肼与乙硫异烟胺之间的交叉耐药性及其与C-15T突变的强关联]

[Cross-resistance between isoniazid and ethionamide and its strong association with mutation C-15T in Mycobacterium tuberculosis isolates from Peru].

作者信息

Sandoval Roxana, Monteghirfo Mario, Salazar Omar, Galarza Marco

机构信息

Servicio de Microbiología, Hospital Guillermo Almenara Irigoyen, Lima, Perú.

Departamento de Ciencias Dinámicas, Universidad Nacional Mayor de San Marcos, Lima, Perú.

出版信息

Rev Argent Microbiol. 2020 Jan-Mar;52(1):36-42. doi: 10.1016/j.ram.2019.03.005. Epub 2019 Jun 27.

Abstract

Several studies have shown cross-resistance between isoniazid and ethionamide, 2of the drugs used in the treatment of multidrug-resistant tuberculosis. The objective of this study was to determine the cross-resistance between both drugs in Mycobacterium tuberculosis isolates from a hospital with high incidence of tuberculosis in Lima, Peru. The frequency of mutations to isoniazid in the katG gene and the inhA promoter region was identified by the Genotype MTBDRplus v2.0 molecular test. The gold standard Agar Proportion method (APM) allowed todetect resistance to isoniazid and ethionamide. Of 107 isoniazid-resistant isolates (54 multidrug-resistant isolates identified by the Genotype MTBDRplus test, 45.8% (49/107) were also resistant to ethionamide by the APM. Mutations were found in the katG gene in 50.5% (54/107), in the promoter region inhA in 23.3% (25/107) and 14.0% (15/107) that share both mutations in the resistant isolates to INH. The absence of the wild type and mutation bands indicated that 12.1% (13/107) of the isolates were resistant to INH. The mutation C-15T in the inhA promoter region showed a strong association with resistance to ethionamide in 73.4% (36/49) of the isolates analyzed. The results of the present study suggest that the identification of mutations related to resistance to isoniazid, especially in the inhA promoter region, could be very useful to identify cross-resistance to ethionamide and improve the treatment of individuals suffering from this disease.

摘要

多项研究表明,异烟肼与乙硫异烟胺之间存在交叉耐药性,这两种药物用于治疗耐多药结核病。本研究的目的是确定秘鲁利马一家结核病高发医院的结核分枝杆菌分离株中这两种药物之间的交叉耐药性。通过Genotype MTBDRplus v2.0分子检测确定katG基因和inhA启动子区域对异烟肼的突变频率。金标准琼脂比例法(APM)可检测对异烟肼和乙硫异烟胺的耐药性。在107株对异烟肼耐药的分离株中(通过Genotype MTBDRplus检测鉴定出54株耐多药分离株),45.8%(49/107)通过APM也对乙硫异烟胺耐药。在50.5%(54/107)的分离株中发现katG基因突变,在23.3%(25/107)的分离株中发现inhA启动子区域突变,14.0%(15/107)的耐异烟肼分离株同时存在这两种突变。野生型和突变条带的缺失表明12.1%(13/107)的分离株对异烟肼耐药。inhA启动子区域的C-15T突变在73.4%(36/49)的分析分离株中与对乙硫异烟胺的耐药性密切相关。本研究结果表明,鉴定与异烟肼耐药相关的突变,尤其是inhA启动子区域的突变,对于鉴定对乙硫异烟胺的交叉耐药性以及改善该病患者的治疗可能非常有用。

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