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基因型MTBDRplus检测与异烟肼耐药结核病抗菌药物敏感性试验结果差异分析。

Analysis of discrepant results between the Genotype MTBDRplus assay and an antimicrobial drug susceptibility test for isoniazid-resistant tuberculosis.

作者信息

Jo Kyung-Wook, Yeo Yoomi, Sung Heungsup, Kim Mi-Na, Shim Tae Sun

机构信息

Division of Pulmonary and Critical Care Medicine, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea.

Department of Internal Medicine, Chunggu Sungshim Hospital, South Korea.

出版信息

Respir Med. 2017 Jan;122:12-17. doi: 10.1016/j.rmed.2016.11.016. Epub 2016 Nov 22.

Abstract

BACKGROUND

We investigated discrepant results determined using the GenotypeMTBDRplus assay and a conventional antimicrobial drug susceptibility test (ADST) for isoniazid (INH) resistance using sequencing analysis and analyzed the clinical course of patients with discrepant results.

METHODS

Among 1373 MTBDRplus assays performed at our tertiary referral center in South Korea between August 2009 and December 2015, the results for 46 (3.4%) differed from those for ADST. KatG and inhA gene sequencing analysis results were available for 23 patients. ADSTs were carried out using the absolute concentration method with Löwenstein-Jensen media.

RESULTS

Results from 11 patients indicated INH susceptibility by MTBDRplus assay and INH resistance by ADST. For 5 of these patients, sequencing revealed no evidence of mutations, whereas specific mutations were detected in the remaining 6 patients. These should have been detected using the MTBDRplus assay. The other 12 patients had isolates with the opposite discrepancy, that is INH resistance by MTBDRplus assay but INH susceptibility by ADST. For 7 of these cases, sequencing results were consistent with those of the MTBDRplus assay. However, sequencing analysis did not explain the discrepancies in the remaining 5 patients. All 23 patients with discrepant results received individualized treatment regimens determined by the attending physician according to their test results and susceptibility to other drugs, such as rifampin. Good outcomes were reported for the majority.

CONCLUSION

Discrepancies between test results for INH resistance on the MTBDRplus assay and ADST appear to be infrequent. Gene sequencing analysis is useful for identifying the cause of the discrepancy.

摘要

背景

我们使用测序分析研究了采用GenotypeMTBDRplus检测法和传统抗微生物药物敏感性试验(ADST)检测异烟肼(INH)耐药性时出现的结果差异,并分析了结果存在差异的患者的临床病程。

方法

2009年8月至2015年12月期间,在韩国我们的三级转诊中心进行的1373次MTBDRplus检测中,46次(3.4%)的结果与ADST结果不同。23例患者可获得KatG和inhA基因测序分析结果。ADST采用罗氏培养基绝对浓度法进行。

结果

11例患者的结果显示,MTBDRplus检测法表明对INH敏感,而ADST显示对INH耐药。其中5例患者的测序未发现突变证据,而其余6例患者检测到特定突变。这些突变本应通过MTBDRplus检测法检测到。另外12例患者的分离株结果相反,即MTBDRplus检测法显示对INH耐药,但ADST显示对INH敏感。其中7例的测序结果与MTBDRplus检测法一致。然而,测序分析无法解释其余5例患者的差异。所有23例结果存在差异的患者均接受了主治医师根据其检测结果及对利福平等其他药物的敏感性确定的个体化治疗方案。大多数患者报告预后良好。

结论

MTBDRplus检测法和ADST检测INH耐药性的结果差异似乎不常见。基因测序分析有助于确定差异的原因。

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