14 40

Cited 0 times in

Evaluation of a Rapid Molecular Drug-Susceptibility Test for Tuberculosis

 Yingda L Xie  ;  Soumitesh Chakravorty  ;  Derek T Armstrong  ;  Sandra L Hall  ;  Laura E Via  ;  Taeksun Song  ;  Xing Yuan  ;  Xiaoying Mo  ;  Hong Zhu  ;  Peng Xu  ;  Qian Gao  ;  Myungsun Lee  ;  Jongseok Lee  ;  Laura E Smith  ;  Ray Y Chen  ;  Joon Sung Joh  ;  YoungSoo Cho  ;  Xin Liu  ;  Xianglin Ruan  ;  Lili Liang  ;  Nila Dharan  ;  Sang-Nae Cho  ;  Clifton E Barry 3rd  ;  Jerrold J Ellner  ;  Susan E Dorman  ;  David Alland 
 NEW ENGLAND JOURNAL OF MEDICINE, Vol.377(11) : 1043-1054, 2017-09 
Journal Title
Issue Date
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Aminoglycosides / pharmacology ; Antitubercular Agents / pharmacology* ; Antitubercular Agents / therapeutic use ; China ; DNA, Bacterial / analysis* ; Drug Resistance, Multiple, Bacterial / genetics* ; Female ; Fluoroquinolones / pharmacology ; Humans ; Isoniazid / pharmacology ; Male ; Microbial Sensitivity Tests / methods* ; Middle Aged ; Mutation* ; Mycobacterium tuberculosis / drug effects* ; Mycobacterium tuberculosis / genetics ; Mycobacterium tuberculosis / isolation & purification ; Point-of-Care Systems* ; Prospective Studies ; Republic of Korea ; Sensitivity and Specificity ; Sequence Analysis, DNA* ; Sputum / microbiology ; Tuberculosis, Multidrug-Resistant / drug therapy ; Young Adult
Background: Fluoroquinolones and second-line injectable drugs are the backbone of treatment regimens for multidrug-resistant tuberculosis, and resistance to these drugs defines extensively drug-resistant tuberculosis. We assessed the accuracy of an automated, cartridge-based molecular assay for the detection, directly from sputum specimens, of Mycobacterium tuberculosis with resistance to fluoroquinolones, aminoglycosides, and isoniazid.

Methods: We conducted a prospective diagnostic accuracy study to compare the investigational assay against phenotypic drug-susceptibility testing and DNA sequencing among adults in China and South Korea who had symptoms of tuberculosis. The Xpert MTB/RIF assay and sputum culture were performed. M. tuberculosis isolates underwent phenotypic drug-susceptibility testing and DNA sequencing of the genes katG, gyrA, gyrB, and rrs and of the eis and inhA promoter regions.

Results: Among the 308 participants who were culture-positive for M. tuberculosis, when phenotypic drug-susceptibility testing was used as the reference standard, the sensitivities of the investigational assay for detecting resistance were 83.3% for isoniazid (95% confidence interval [CI], 77.1 to 88.5), 88.4% for ofloxacin (95% CI, 80.2 to 94.1), 87.6% for moxifloxacin at a critical concentration of 0.5 μg per milliliter (95% CI, 79.0 to 93.7), 96.2% for moxifloxacin at a critical concentration of 2.0 μg per milliliter (95% CI, 87.0 to 99.5), 71.4% for kanamycin (95% CI, 56.7 to 83.4), and 70.7% for amikacin (95% CI, 54.5 to 83.9). The specificity of the assay for the detection of phenotypic resistance was 94.3% or greater for all drugs except moxifloxacin at a critical concentration of 2.0 μg per milliliter (specificity, 84.0% [95% CI, 78.9 to 88.3]). When DNA sequencing was used as the reference standard, the sensitivities of the investigational assay for detecting mutations associated with resistance were 98.1% for isoniazid (95% CI, 94.4 to 99.6), 95.8% for fluoroquinolones (95% CI, 89.6 to 98.8), 92.7% for kanamycin (95% CI, 80.1 to 98.5), and 96.8% for amikacin (95% CI, 83.3 to 99.9), and the specificity for all drugs was 99.6% (95% CI, 97.9 to 100) or greater.

Conclusions: This investigational assay accurately detected M. tuberculosis mutations associated with resistance to isoniazid, fluoroquinolones, and aminoglycosides and holds promise as a rapid point-of-care test to guide therapeutic decisions for patients with tuberculosis. (Funded by the National Institute of Allergy and Infectious Diseases, National Institutes of Health, and the Ministry of Science and Technology of China; ClinicalTrials.gov number, NCT02251327 .).
Files in This Item:
T992017236.pdf Download
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Microbiology (미생물학교실) > 1. Journal Papers
Yonsei Authors
Cho, Sang Nae(조상래)
사서에게 알리기


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.