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Performance of the G4 Xpert® MTB/RIF assay for the detection of Mycobacterium tuberculosis and rifampin resistance: a retrospective case-control study of analytical and clinical samples from high- and low-tuberculosis prevalence settings.
BMC Infect Dis. 2016 Dec 20; 16(1):764.BI

Abstract

BACKGROUND

The Xpert® MTB/RIF (Xpert) assay is a rapid PCR-based assay for the detection of Mycobacterium tuberculosis complex DNA (MTBc) and mutations associated with rifampin resistance (RIF). An updated version introduced in 2011, the G4 Xpert, included modifications to probe B and updated analytic software.

METHODS

An analytical study was performed to assess Xpert detection of mutations associated with rifampin resistance in rifampin-susceptible and -resistant isolates. A clinical study was performed in which specimens from US and non-US persons suspected of tuberculosis (TB) were tested to determine Xpert performance characteristics. All specimens underwent smear microscopy, mycobacterial culture, conventional drug-susceptibility testing and Xpert testing; DNA from isolates with discordant rifampin resistance results was sequenced.

RESULTS

Among 191 laboratory-prepared isolates in the analytical study, Xpert sensitivity for detection of rifampin resistance associated mutations was 97.7% and specificity was 90.8%, which increased to 99.0% after DNA sequencing analysis of the discordant samples. Of the 1,096 subjects in the four clinical studies, 49% were from the US. Overall, Xpert detected MTBc in 439 of 468 culture-positive specimens for a sensitivity of 93.8% (95% confidence interval [CI]: 91.2%-95.7%) and did not detect MTBc in 620 of 628 culture-negative specimens for a specificity of 98.7% (95% CI: 97.5%-99.4%). Sensitivity was 99.7% among smear-positive cases, and 76.1% among smear-negative cases. Non-determinate MTBc detection and false-positive RIF resistance results were low (1.2 and 0.9%, respectively).

CONCLUSIONS

The updated Xpert assay retained the high sensitivity and specificity of the previous assay versions and demonstrated low rates of non-determinate and RIF resistance false positive results.

Authors+Show Affiliations

Department of Medicine, New Jersey Medical School, Rutgers, The State University of New Jersey, 185 South Orange Avenue, MSB I-689, Newark, NJ, 07103, USA. Dharannj@njms.rutgers.edu.Department of Medicine, New Jersey Medical School, Rutgers, The State University of New Jersey, 185 South Orange Avenue, MSB I-689, Newark, NJ, 07103, USA. Current address: Sackler School of Graduate Biomedical Science - Tufts University, Boston, MA, USA.University of Massachusetts Medical School, Worcester, MA, USA.University of Massachusetts Medical School, Worcester, MA, USA.Orange County Health Care Agency, Santa Ana, CA, USA.Orange County Health Care Agency, Santa Ana, CA, USA.Wadsworth Center, New York State Department of Health, Albany, NY, USA.Wadsworth Center, New York State Department of Health, Albany, NY, USA.Florida Department of Health, Jacksonville, FL, USA.Florida Department of Health, Jacksonville, FL, USA.Clínica y Laboratorio de Tuberculosis, Hospital General Tijuana, Tijuana, Mexico.Foundation for Innovative New Diagnostics, Geneva, Switzerland.Foundation for Innovative New Diagnostics, Geneva, Switzerland.Cepheid, Sunnyvale, CA, USA.Department of Medicine, New Jersey Medical School, Rutgers, The State University of New Jersey, 185 South Orange Avenue, MSB I-689, Newark, NJ, 07103, USA. Allandda@njms.rutgers.edu.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

27993132

Citation

Dharan, Nila J., et al. "Performance of the G4 Xpert® MTB/RIF Assay for the Detection of Mycobacterium Tuberculosis and Rifampin Resistance: a Retrospective Case-control Study of Analytical and Clinical Samples From High- and Low-tuberculosis Prevalence Settings." BMC Infectious Diseases, vol. 16, no. 1, 2016, p. 764.
Dharan NJ, Blakemore R, Sloutsky A, et al. Performance of the G4 Xpert® MTB/RIF assay for the detection of Mycobacterium tuberculosis and rifampin resistance: a retrospective case-control study of analytical and clinical samples from high- and low-tuberculosis prevalence settings. BMC Infect Dis. 2016;16(1):764.
Dharan, N. J., Blakemore, R., Sloutsky, A., Kaur, D., Alexander, R. C., Ghajar, M., Musser, K. A., Escuyer, V. E., Rowlinson, M. C., Crowe, S., Laniado-Laborin, R., Valli, E., Nabeta, P., Johnson, P., & Alland, D. (2016). Performance of the G4 Xpert® MTB/RIF assay for the detection of Mycobacterium tuberculosis and rifampin resistance: a retrospective case-control study of analytical and clinical samples from high- and low-tuberculosis prevalence settings. BMC Infectious Diseases, 16(1), 764.
Dharan NJ, et al. Performance of the G4 Xpert® MTB/RIF Assay for the Detection of Mycobacterium Tuberculosis and Rifampin Resistance: a Retrospective Case-control Study of Analytical and Clinical Samples From High- and Low-tuberculosis Prevalence Settings. BMC Infect Dis. 2016 Dec 20;16(1):764. PubMed PMID: 27993132.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Performance of the G4 Xpert® MTB/RIF assay for the detection of Mycobacterium tuberculosis and rifampin resistance: a retrospective case-control study of analytical and clinical samples from high- and low-tuberculosis prevalence settings. AU - Dharan,Nila J, AU - Blakemore,Robert, AU - Sloutsky,Alex, AU - Kaur,Devinder, AU - Alexander,Richard C, AU - Ghajar,Minoo, AU - Musser,Kimberlee A, AU - Escuyer,Vincent E, AU - Rowlinson,Marie-Claire, AU - Crowe,Susanne, AU - Laniado-Laborin,Rafael, AU - Valli,Eloise, AU - Nabeta,Pamela, AU - Johnson,Pamela, AU - Alland,David, Y1 - 2016/12/20/ PY - 2016/07/18/received PY - 2016/11/15/accepted PY - 2016/12/21/entrez PY - 2016/12/21/pubmed PY - 2017/6/3/medline KW - Diagnostics KW - G4 KW - GeneXpert KW - Tuberculosis KW - Xpert SP - 764 EP - 764 JF - BMC infectious diseases JO - BMC Infect Dis VL - 16 IS - 1 N2 - BACKGROUND: The Xpert® MTB/RIF (Xpert) assay is a rapid PCR-based assay for the detection of Mycobacterium tuberculosis complex DNA (MTBc) and mutations associated with rifampin resistance (RIF). An updated version introduced in 2011, the G4 Xpert, included modifications to probe B and updated analytic software. METHODS: An analytical study was performed to assess Xpert detection of mutations associated with rifampin resistance in rifampin-susceptible and -resistant isolates. A clinical study was performed in which specimens from US and non-US persons suspected of tuberculosis (TB) were tested to determine Xpert performance characteristics. All specimens underwent smear microscopy, mycobacterial culture, conventional drug-susceptibility testing and Xpert testing; DNA from isolates with discordant rifampin resistance results was sequenced. RESULTS: Among 191 laboratory-prepared isolates in the analytical study, Xpert sensitivity for detection of rifampin resistance associated mutations was 97.7% and specificity was 90.8%, which increased to 99.0% after DNA sequencing analysis of the discordant samples. Of the 1,096 subjects in the four clinical studies, 49% were from the US. Overall, Xpert detected MTBc in 439 of 468 culture-positive specimens for a sensitivity of 93.8% (95% confidence interval [CI]: 91.2%-95.7%) and did not detect MTBc in 620 of 628 culture-negative specimens for a specificity of 98.7% (95% CI: 97.5%-99.4%). Sensitivity was 99.7% among smear-positive cases, and 76.1% among smear-negative cases. Non-determinate MTBc detection and false-positive RIF resistance results were low (1.2 and 0.9%, respectively). CONCLUSIONS: The updated Xpert assay retained the high sensitivity and specificity of the previous assay versions and demonstrated low rates of non-determinate and RIF resistance false positive results. SN - 1471-2334 UR - https://www.unboundmedicine.com/medline/citation/27993132/Performance_of_the_G4_Xpert®_MTB/RIF_assay_for_the_detection_of_Mycobacterium_tuberculosis_and_rifampin_resistance:_a_retrospective_case_control_study_of_analytical_and_clinical_samples_from_high__and_low_tuberculosis_prevalence_settings_ L2 - https://bmcinfectdis.biomedcentral.com/articles/10.1186/s12879-016-2039-4 DB - PRIME DP - Unbound Medicine ER -