66. Accuracy of a highly multiplexed, ten-color, point-of-care assay for rapid Mycobacterium tuberculosis drug susceptibility testing: A prospective, multicenter study
Session: Oral Abstract Session: Advances in Epidemiology and Diagnosis of Mycobacterial Diseases
Thursday, October 27, 2016: 8:30 AM
Room: 275-277
Background: Drug-resistant tuberculosis (TB) is a growing threat but available drug susceptibility testing (DST) methods require substantial laboratory infrastructure and time. The investigational XDR assay is a point-of-care test that detects resistance mutations to 1st and 2nd line TB drugs without the need for a biosafety laboratory or extensive training; time to result is 2 hours. We conducted a prospective study to determine the accuracy of the XDR assay to detect resistance to isoniazid (INH), ofloxacin (OFL), moxifloxacin (MXF), kanamycin (KAN), and amikacin (AMK), using both phenotypic and molecular reference standards

Methods: The study was conducted in China and Republic of Korea, enrolling adults with pulmonary TB symptoms and suspected or documented resistance to 1st or 2nd line drugs. Sputa were tested directly using the XDR cartridge with a 10-color GeneXpert instrument (Cepheid, Sunnyvale, CA). Sputum samples also underwent NALC-NaOH processing, then liquid (MGIT) and solid (LJ) culture; M.tb isolates underwent MGIT phenotypic DST and Sanger DNA sequencing of katG, gyrA, gyrB, rrs genes and eis and inhA promoter regions.

Results: 322/405 (80%) enrollees had M.tbisolated in culture; 306/322 (95%) had results for all tests and were included in the primary analysis. Compared to sequencing, the assay's sensitivities for detection of resistance mutations were INH 97.5% (95% CI 95.2, 97.5), MXF/OFL 94.0% (89.7, 95.6), KAN 92.9% (84.3, 95.1), and AMK 96.7% (81.5, 99.8); specificities were >99% for all targets. Compared to phenotypic DST, the assay's sensitivities were INH 83.5% (80.9, 84.0), MXF 87.8% (81.3, 92.4), OFL 88.5% (82.9, 92.2), KAN 71.4% (61.5, 76.8), and AMK 70.7% (60.8, 73.0); specificity after discrepant resolution by sequencing was 99.6% for KAN and 100% for all other drugs.

Conclusion: The XDR assay met diagnostic accuracy target product profiles proposed by the WHO for a rapid DST when using sequencing as a reference standard. Other beneficial attributes include rapid time to result and ease of use.

*Yingda Xie, MD1, *Soumitesh Chakravorty, Ph.D2, Derek Armstrong, M.H.S.3, Sandra Armakovitch, MPH4, Laura Via, Ph.D1, Taeksun Song, Ph.D5, Hong Zhu, MD6, Peng Xu, Ph.D7, Qian Gao, Ph.D7, Myungsun Lee, MD8, Jong Seok Lee, Ph.D9, Ray Chen, MD1, Clifton Barry III, Ph.D1, Jerrold Ellner, MD, FIDSA10, Susan Dorman, MD3 and David Alland, MD2, (1)Tuberculosis Research Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, (2)Center for Emerging and Re-Emerging Pathogens, Rutgers New Jersey Medical School, Newark, NJ, (3)Johns Hopkins University, Baltimore, MD, (4)Boston Medical Center, Boston, MA, (5)University of Cape Town, Cape Town, South Africa, (6)Henan Provincial Chest Hospital, Sino-US TB Research Collaboration, Zhengzhou, China, (7)Biomedical Sciences and Medical Microbiology, Fudan University, Shanghai, China, (8)International TB Research Center, Seoul, Korea, The Republic of, (9)International Tuberculosis Research Center, Masan, Korea, The Republic of, (10)Medicine/Infectious Diseases, Boston Medical Center, Boston, MA

Disclosures:

Xie, None

Chakravorty, None

D. Armstrong, None

S. Armakovitch, None

L. Via, None

T. Song, None

H. Zhu, None

P. Xu, None

Q. Gao, None

M. Lee, None

J. S. Lee, None

R. Chen, None

C. Barry III, None

J. Ellner, None

S. Dorman, None

D. Alland, None

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