An Evaluation of False-positive Rifampicin Resistance on the Xpert MTB/RIF

Overview

Journal Mem Inst Oswaldo Cruz

Specialties Parasitology
Tropical Medicine

Date 2017 Nov 2

PMID 29091135

Citations 5

Authors

Yeliz Tanriverdi Cayci

Kemal Bilgin

Ahmet Yilmaz Coban

Asuman Birinci

Belma Durupinar

Affiliations

Soon will be listed here.

Abstract

Background: Mycobacterium tuberculosis (MTB) is one of the most significant causes of mortality and morbidity. Early diagnose is important especially in multiple drug resistant tuberculosis to avoid transmission. Traditional techniques requires at least one to three weeks for diagnosis of tuberculosis. Diagnostic delays with multiple drug resistant tuberculosis are associated with worse clinical outcomes and increased transmission The Xpert MTB/RIF assay is one of the new diagnostic device for the diagnosis of tuberculosis and rapid detection of rifampicin resistance.

Objective: We assessed the performance of Xpert MTB/RIF assay for detecting rifampicin resistance using phenotypic drug susceptibility tests as automated BD MGIT 960.

Methods: Total of 2136 specimens were included in the study. Xpert MTB/RIF testing was performed on samples, using version 4 cartridges, according to the manufacturer's recommendations. The MTBC culture and first-line phenotypic DST were performed in automated BD MGIT 960 (Becton & Dickinson, USA) according to the recommendations of the manufacturer. Agar proportion was used in the case of inconsistency for rifampicin resistance.

Findings: Thirty-four samples (19 respiratory and 15 nonrespiratory samples) were determined as positive for M. tuberculosis complex by Xpert MTB/RIF (Cepheid GeneXpert® System, USA). Xpert MTB/RIF assay detected 4/34 (11.7%) specimens as rifampicin resistant. One of the rifampicin resistant isolates was determined susceptible in MGIT 960 automated system. This isolate was also tested with agar proportion method and found susceptible to rifampicin.

Main Conclusion: The Xpert MTB/RIF assay can be used as first-line assay for the detection of M. tuberculosis. However, microbiologists must be aware of the limitations of the assay.

Citing Articles

Integrative utility of long read sequencing-based whole genome analysis and phenotypic assay on differentiating isoniazid-resistant signature of Mycobacterium tuberculosis.

Yu M, Hung C, Huang C, Wang C, Liang Y, Lin J J Biomed Sci. 2021; 28(1):86.

PMID: 34922550 PMC: 8684251. DOI: 10.1186/s12929-021-00783-x.

Challenges in the diagnosis of tuberculous meningitis.

Foppiano Palacios C, Saleeb P J Clin Tuberc Other Mycobact Dis. 2020; 20:100164.

PMID: 32462082 PMC: 7240715. DOI: 10.1016/j.jctube.2020.100164.

Xpert MTB/RIF assay for the diagnosis of rifampicin resistance in different regions: a meta-analysis.

Zong K, Luo C, Zhou H, Jiang Y, Li S BMC Microbiol. 2019; 19(1):177.

PMID: 31382894 PMC: 6683411. DOI: 10.1186/s12866-019-1516-5.

Xpert MTB/RIF and Xpert MTB/RIF Ultra for pulmonary tuberculosis and rifampicin resistance in adults.

Horne D, Kohli M, Zifodya J, Schiller I, Dendukuri N, Tollefson D Cochrane Database Syst Rev. 2019; 6:CD009593.

PMID: 31173647 PMC: 6555588. DOI: 10.1002/14651858.CD009593.pub4.

Molecular Detection of Mycobacterium tuberculosis from Stools in Young Children by Use of a Novel Centrifugation-Free Processing Method.

Walters E, Scott L, Nabeta P, Demers A, Reubenson G, Bosch C J Clin Microbiol. 2018; 56(9).

PMID: 29997199 PMC: 6113478. DOI: 10.1128/JCM.00781-18.

References

Theron G, Peter J, van Zyl-Smit R, Mishra H, Streicher E, Murray S . Evaluation of the Xpert MTB/RIF assay for the diagnosis of pulmonary tuberculosis in a high HIV prevalence setting. Am J Respir Crit Care Med. 2011; 184(1):132-40. DOI: 10.1164/rccm.201101-0056OC. View

Van Rie A, Warren R, Richardson M, Victor T, Gie R, Enarson D . Exogenous reinfection as a cause of recurrent tuberculosis after curative treatment. N Engl J Med. 1999; 341(16):1174-9. DOI: 10.1056/NEJM199910143411602. View

Huyen M, Kremer K, Lan N, Cobelens F, Buu T, Dung N . Mixed tuberculosis infections in rural South Vietnam. J Clin Microbiol. 2012; 50(5):1586-92. PMC: 3347091. DOI: 10.1128/JCM.00434-12. View

Blakemore R, Story E, Helb D, Kop J, Banada P, Owens M . Evaluation of the analytical performance of the Xpert MTB/RIF assay. J Clin Microbiol. 2010; 48(7):2495-501. PMC: 2897495. DOI: 10.1128/JCM.00128-10. View

Cohen T, van Helden P, Wilson D, Colijn C, McLaughlin M, Abubakar I . Mixed-strain mycobacterium tuberculosis infections and the implications for tuberculosis treatment and control. Clin Microbiol Rev. 2012; 25(4):708-19. PMC: 3485752. DOI: 10.1128/CMR.00021-12. View

Mboowa G, Namaganda C, Ssengooba W . Rifampicin resistance mutations in the 81 bp RRDR of rpoB gene in Mycobacterium tuberculosis clinical isolates using Xpert® MTB/RIF in Kampala, Uganda: a retrospective study. BMC Infect Dis. 2014; 14:481. PMC: 4164707. DOI: 10.1186/1471-2334-14-481. View

Boehme C, Nabeta P, Hillemann D, Nicol M, Shenai S, Krapp F . Rapid molecular detection of tuberculosis and rifampin resistance. N Engl J Med. 2010; 363(11):1005-15. PMC: 2947799. DOI: 10.1056/NEJMoa0907847. View

Telenti A, Imboden P, Marchesi F, Lowrie D, Cole S, Colston M . Detection of rifampicin-resistance mutations in Mycobacterium tuberculosis. Lancet. 1993; 341(8846):647-50. DOI: 10.1016/0140-6736(93)90417-f. View

Glynn J, Yates M, Crampin A, Ngwira B, Mwaungulu F, Black G . DNA fingerprint changes in tuberculosis: reinfection, evolution, or laboratory error?. J Infect Dis. 2004; 190(6):1158-66. DOI: 10.1086/423144. View

10.

Ozyurt M . [Use of molecular techniques in the diagnosis of pulmonary and extrapulmonary tuberculosis]. Mikrobiyol Bul. 2012; 46(2):319-31. View

11.

Zumla A, Abubakar I, Raviglione M, Hoelscher M, Ditiu L, McHugh T . Drug-resistant tuberculosis--current dilemmas, unanswered questions, challenges, and priority needs. J Infect Dis. 2012; 205 Suppl 2:S228-40. DOI: 10.1093/infdis/jir858. View

12.

Van Rie A, Victor T, Richardson M, Johnson R, van der Spuy G, Murray E . Reinfection and mixed infection cause changing Mycobacterium tuberculosis drug-resistance patterns. Am J Respir Crit Care Med. 2005; 172(5):636-42. PMC: 2718533. DOI: 10.1164/rccm.200503-449OC. View

13.

Chakravorty S, Kothari H, Aladegbami B, Cho E, Lee J, Roh S . Rapid, high-throughput detection of rifampin resistance and heteroresistance in Mycobacterium tuberculosis by use of sloppy molecular beacon melting temperature coding. J Clin Microbiol. 2012; 50(7):2194-202. PMC: 3405605. DOI: 10.1128/JCM.00143-12. View

14.

Chang K, Lu W, Wang J, Zhang K, Jia S, Li F . Rapid and effective diagnosis of tuberculosis and rifampicin resistance with Xpert MTB/RIF assay: a meta-analysis. J Infect. 2012; 64(6):580-8. DOI: 10.1016/j.jinf.2012.02.012. View

15.

Steingart K, Schiller I, Horne D, Pai M, Boehme C, Dendukuri N . Xpert® MTB/RIF assay for pulmonary tuberculosis and rifampicin resistance in adults. Cochrane Database Syst Rev. 2014; (1):CD009593. PMC: 4470349. DOI: 10.1002/14651858.CD009593.pub3. View

16.

Van Rie A, Mellet K, John M, Scott L, Page-Shipp L, Dansey H . False-positive rifampicin resistance on Xpert® MTB/RIF: case report and clinical implications. Int J Tuberc Lung Dis. 2012; 16(2):206-8. PMC: 3680645. DOI: 10.5588/ijtld.11.0395. View

17.

Zetola N, Shin S, Tumedi K, Moeti K, Ncube R, Nicol M . Mixed Mycobacterium tuberculosis complex infections and false-negative results for rifampin resistance by GeneXpert MTB/RIF are associated with poor clinical outcomes. J Clin Microbiol. 2014; 52(7):2422-9. PMC: 4097703. DOI: 10.1128/JCM.02489-13. View

18.

Cohen T, Wilson D, Wallengren K, Samuel E, Murray M . Mixed-strain Mycobacterium tuberculosis infections among patients dying in a hospital in KwaZulu-Natal, South Africa. J Clin Microbiol. 2010; 49(1):385-8. PMC: 3020455. DOI: 10.1128/JCM.01378-10. View

19.

Falzon D, Jaramillo E, Schunemann H, Arentz M, Bauer M, Bayona J . WHO guidelines for the programmatic management of drug-resistant tuberculosis: 2011 update. Eur Respir J. 2011; 38(3):516-28. DOI: 10.1183/09031936.00073611. View

20.

Boehme C, Nicol M, Nabeta P, Michael J, Gotuzzo E, Tahirli R . Feasibility, diagnostic accuracy, and effectiveness of decentralised use of the Xpert MTB/RIF test for diagnosis of tuberculosis and multidrug resistance: a multicentre implementation study. Lancet. 2011; 377(9776):1495-505. PMC: 3085933. DOI: 10.1016/S0140-6736(11)60438-8. View