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赤道几内亚五个地区抗结核药物耐药性研究:发生率、危险因素、基因突变基因分型及分子流行病学

Study of resistance to anti-tuberculosis drugs in five districts of Equatorial Guinea: rates, risk factors, genotyping of gene mutations and molecular epidemiology.

作者信息

Tudó G, González J, Obama R, Rodríguez J M, Franco J R, Espasa M, Simarro P R, Escaramís G, Ascaso C, García A, Jiménez de Anta M T

机构信息

Hospital Clinic de Barcelona, Servei de Microbiologia, Barcelona, Spain.

出版信息

Int J Tuberc Lung Dis. 2004 Jan;8(1):15-22.

Abstract

SETTING

Five districts in Equatorial Guinea, March 1999 to February 2001.

OBJECTIVES

To determine tuberculosis drug resistance among new and previously treated cases, the risk factors associated with resistance, and the mutations associated with isoniazid and rifampicin (katG, inhA and rpoB genes) resistance, and to genotype resistant strains.

RESULTS

A positive culture identified as Mycobacterium tuberculosis complex was obtained in 240/499 patients. Susceptibility testing was performed in 236 strains. The overall resistance rate in new cases was 16.9% compared to 41.6% in previously treated cases. Isoniazid resistance was the most frequent (respectively 12.5% and 16.6%) in the two groups, while multidrug resistance was observed in 1.7% and 25% of new and previously treated cases, respectively. Female sex was statistically associated with resistance in new cases. Of 41 isoniazid-resistant strains, 33 (80.5%) had mutations in the inhA gene; none had mutations in the katG gene and eight had no mutations in either gene. All strains had low-level isoniazid resistance. Of eight strains resistant to rifampicin, six had mutations in the rpoB gene. Genotyping defined seven clusters.

CONCLUSIONS

Moderate resistance was found in new cases. Low-level isoniazid resistance predominated among mutations in the inhA gene, with a high percentage of clustering in resistant strains.

摘要

背景

1999年3月至2001年2月,赤道几内亚的五个地区。

目的

确定新发病例和既往治疗病例中的结核病耐药情况、与耐药相关的危险因素以及与异烟肼和利福平(katG、inhA和rpoB基因)耐药相关的突变,并对耐药菌株进行基因分型。

结果

499例患者中,240例培养结果为结核分枝杆菌复合群阳性。对236株菌株进行了药敏试验。新发病例的总体耐药率为16.9%,而既往治疗病例为41.6%。异烟肼耐药在两组中最为常见(分别为12.5%和16.6%),而新发病例和既往治疗病例中耐多药率分别为1.7%和25%。女性在新发病例中与耐药具有统计学关联。在41株异烟肼耐药菌株中,33株(80.5%)inhA基因发生突变;katG基因无突变,8株两个基因均无突变。所有菌株均为低水平异烟肼耐药。在8株利福平耐药菌株中,6株rpoB基因发生突变。基因分型确定了7个聚类。

结论

新发病例中发现中度耐药。inhA基因突变中低水平异烟肼耐药占主导,耐药菌株中聚类比例较高。

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