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Original Research: LUNG INFECTION |

Clinical Efficacy of Direct DNA Sequencing Analysis on Sputum Specimens for Early Detection of Drug-Resistant Mycobacterium tuberculosis in a Clinical Setting

Jeong-Hee Choi, MD, PhD; Kyung Wha Lee, PhD; Hye-Ryun Kang, MD, PhD; Yong Il Hwang, MD; SeungHun Jang, MD, PhD; Dong-Gyu Kim, MD; Cheol-Hong Kim, MD, PhD; In-Gyu Hyun, MD, PhD; Tae-Rim Shin, MD, PhD; Sang-Myeon Park, MD, PhD; Myung-Goo Lee, MD, PhD; Chang-Youl Lee, MD; Yong-Bum Park, MD; Ki-Suck Jung, MD, PhD
Author and Funding Information

From the Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine (Drs Choi, Kang, Hwang, Jang, D-G Kim, C-H Kim, Hyun, Shin, S-M Park, M-G Lee, C-Y Lee, Y-B Park, and Jung) Hallym University Medical Center; Lung Research Institute (Drs Choi, Kang, Hwang, Jang, D-G Kim, C-H Kim, Hyun, Shin, S-M Park, M-G Lee, C-Y Lee, Y-B Park, and Jung); and Hallym Institute for Genome Application (Dr K. W. Lee), Hallym University College of Medicine, Chuncheon, Gangwon-do, Korea.

Correspondence to: Ki-Suck Jung, MD, PhD, Professor, Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Hallym University Sacred Heart Hospital, 896 Pyeongan-dong, Dongan-gu, Anyang-si, Gyeonggi-do, 431-796 Korea; e-mail: pulmoks@hallym.or.kr


Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (www.chestjournal.org/site/misc/reprints.xhtml).


© 2010 American College of Chest Physicians


Chest. 2010;137(2):393-400. doi:10.1378/chest.09-0150
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Background:  Early detection of drug-resistant Mycobacterium tuberculosis is important for the control and prevention of disease transmission. However, conventional drug susceptibility tests for drug-resistant M tuberculosis take at least 3 to 8 weeks. Here, we report the clinical efficacy of direct DNA sequencing analysis for detecting drug-resistant TB on sputum specimens in a clinical setting.

Methods:  A total of 113 sputum specimens from 111 patients, who were suspected of having drug-resistant TB by clinicians, were used for DNA sequencing of katG, rpoB, embB, and pncA genes for isoniazid (INH), rifampin (RIF), ethambutol (EMB), and pyrazinamide (PZA) resistance, respectively, and the results were compared with drug susceptibility tests. The optimization of antituberculosis drugs according to the results of DNA sequencing and the treatment outcomes of the patients were also analyzed.

Results:  Turnaround time of the direct DNA sequencing analysis was 3.8 ± 1.8 days. We found mutations related to drug resistance in 30 clinical specimens for katG, 39 for rpoB, 13 for embB, and 24 for pncA. The sensitivity and specificity of the assay were 63.6% and 94.6% for INH, 96.2 and 93.9% for RIF, 69.2% and 97.5% for EMB, and 100% and 92.6% for PZA, respectively. Of the patients with RIF resistance, including multidrug-resistant TB by the assay, 92.5% of the patients with initial first-line antituberculosis drugs were changed to second-line antituberculosis drugs, and treatment was successful in 61.9% of these cases.

Conclusion:  Direct DNA sequencing analysis of clinical sputum specimens is a rapid and useful method for the detection and treatment of drug-resistant TB.


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