Missed rifampicin and isoniazid resistance by commercial molecular assays

Authors

  • L Richards Division of Infectious Diseases, Department of Internal Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa https://orcid.org/0000-0003-1723-0382
  • F Ismail Centre for Tuberculosis, National Institute for Communicable Diseases, Division of the National Health Laboratory Service, Johannesburg, South Africa; Department of Medical Microbiology, School of Medicine, University of Pretoria, South Africa https://orcid.org/0000-0003-3070-9806
  • J Nel Division of Infectious Diseases, Department of Internal Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
  • S V Omar Centre for Tuberculosis, National Institute for Communicable Diseases, Division of the National Health Laboratory Services, Johannesburg, South Africa, Department of Medical Microbiology, University of Pretoria, Pretoria, South Africa and Department of Molecular Medicine, University of Witwatersrand, Johannesburg, South Africa; Department of Molecular Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa https://orcid.org/0000-0001-6983-1636

DOI:

https://doi.org/10.7196/SAMJ.2024.v114i17.1779

Keywords:

Multidrug resistant TB, TB diagnostics

Abstract

Drug-resistant tuberculosis (TB) has poor outcomes unless resistance is detected early, ideally by commercially available molecular tests. We present a case of occult multidrug-resistant TB where both rifampicin and isoniazid resistance were missed by molecular testing and were only identified by phenotypic testing.

Author Biographies

  • L Richards, Division of Infectious Diseases, Department of Internal Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa

    Consultant at Helen Joseph Hospital in the division of infectious diseases, department of internal medicine.

  • F Ismail, Centre for Tuberculosis, National Institute for Communicable Diseases, Division of the National Health Laboratory Service, Johannesburg, South Africa; Department of Medical Microbiology, School of Medicine, University of Pretoria, South Africa

    Farzana Ismail is the pathologist at the Centre for Tuberculosis at the National Institute for Communicable Diseases, and leads the WHO Supranational TB Reference laboratory section of the centre, while providing support to other National TB reference laboratories in the region. 

  • J Nel, Division of Infectious Diseases, Department of Internal Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa

    Consultant at Helen Joseph Hospital in the division of infectious diseases, department of internal medicine.

  • S V Omar, Centre for Tuberculosis, National Institute for Communicable Diseases, Division of the National Health Laboratory Services, Johannesburg, South Africa, Department of Medical Microbiology, University of Pretoria, Pretoria, South Africa and Department of Molecular Medicine, University of Witwatersrand, Johannesburg, South Africa; Department of Molecular Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa

    Shaheed Vally Omar is a medical Scientist with specialisation in Microbiology, focusing on Mycobacterium tuberculosis research since his post-graduate training. He currently leads the following scientific programmes in the Centre for Tuberculosis at the National Institute for Communicable Diseases in Johannesburg, South Africa; diagnostic evaluations for both active and latent disease state; drug resistance determination and surveillance; molecular epidemiology of drug resistance tuberculosis; and the application of novel technologies for these purposes. He further is the lead scientist of the National TB Reference Laboratory as well as the WHO TB Supranational Laboratory Network.

References

World Health Organization. Global tuberculosis report 2022. Geneva: WHO, 2022. https://www.who. int/teams/global-tuberculosis-programme/tb-reports/global-tuberculosis-report-2022 (accessed 22 March 2023).

Chen Y, Yuan Z, Shen X, Wu J, Wu Z, Xua B. Time to multidrug-resistant tuberculosis treatment initiation in association with treatment outcomes in Shanghai, China. Antimicrob Agents Chemother 2018;62(4):e02259-17 https://doi.org/10.1128/AAC.02259-17

Bernardo J. Diagnosis of pulmonary tuberculosis in adults. In: UpToDate, von Reyn CF (ed), UpToDate: Waltham, 2019 (accessed 15 July 2020).

Siu GK, Zhang Y, Lau TC, et al. Mutations outside the rifampicin resistance-determining region associated with rifampicin resistance in Mycobacterium tuberculosis. J Antimicrob Chemother 2011;66:730-733. https://doi.org/10.1093/jac/dkq519

Sekiguchi J, Miyoshi-Akiyama T, Augustynowicz-Kopec E, et al. Detection of multidrug resistance in Mycobacterium tuberculosis. J Clin Microbiol 2007;45:179-192. https://doi:10.1128/JCM.00750-06

World Health Organization. Using the Xpert MTB/RIF assay to detect pulmonary and extrapulmonary

tuberculosis and rifampicin resistance in adults and children: Expert group meeting report. Geneva:

WHO, 2013. https://apps.who.int/iris/handle/10665/112659 (accessed 22 March 2023).

National Department of Health, South Africa. National tuberculosis management guidelines. Pretoria: NDoH, 2014. https://www.knowledgehub.org.za/elibrary/national-tuberculosis-management-guidelines

(accessed 22 March 2023).

Schluger NW. Epidemiology and molecular mechanisms of drug-resistant tuberculosis. In: UpToDate,

von Reyn CF (ed). UpToDate: Waltham, 2019 (accessed 15 July 2020).

NationalDepartmentofHealth,SouthAfrica.Managementofrifampicinresistanttuberculosis:Aclinical

reference guide. Pretoria: NDoH, 2019. https://www.health.gov.za/wp-content/uploads/2020/11/

management-of-rifampicin-resistant-tb-booklet-0220-v11.pdf (accessed 22 March 2023).

World Health Organization. Treatment of tuberculosis guidelines, fourth edition. Geneva: WHO,

https://apps.who.int/iris/handle/10665/44165 (accessed 22 March 2023).

Solari L, Santos-Lazaro D, Puyen ZM. Mutations in Mycobacterium tuberculosis isolates with discordant results for drug-susceptibility testing in Peru. Int J Microbiol 2020;2020:1-5. https://doi.

org/10.1155/2020/8253546

Kang JY, Hur J, Kim S, et al. Clinical implications of discrepant results between genotypic MTBDRplus and phenotypic Löwenstein-Jensen method for isoniazid or rifampicin drug susceptibility tests in tuberculosis patients. J Thorac Dis 2019;11(2):400-409. https://doi.org/10.21037/jtd.2019.01.58

Yakrus MA, Driscoll J, Lentz AJ, et al. Concordance between molecular and phenotypic testing of Mycobacterium tuberculosis complex isolates for resistance to rifampin and isoniazid in the United States. J Clin Microbiol 2014;52(6):1932-1937. http://doi: 10.1128/JCM.00417-14

Karumbi J, Garner P, Cochrane Infectious Diseases Group. Directly observed therapy for treating tuberculosis. Cochrane Database Syst Rev 2015;2015(5):CD003343. https://doi.org/10.1002/14651858. CD003343.pub4

World Health Organization. Catalogue of mutations in Mycobacterium tuberculosis complex and their association with drug resistance. Geneva: WHO, 2021. https://www.who.int/publications/i/ item/9789240028173 (accessed 22 March 2023).

Jagielski T, Bakuła Z, Brzostek A, et al. Characterisation of mutations conferring resistance to rifampin in Mycobacterium tuberculosis clinical strains. Antimicrob Agents Chemother 2018;62(10):e01093-18. https://doi.org/10.1128/AAC.01093-18

CawsM,DuyPM,ThoDQ,LanNT,HoaDV,FarrarJ.Mutationsprevalentamongrifampin-andisoniazid- resistant Mycobacterium tuberculosis isolates from a hospital in Vietnam. J Clin Microbiol 2006;44(7):2333- 2337. https://doi.org/10.1128/JCM.00330-06

Wua X, Gaoa R, Shenc X, et al. Use of whole-genome sequencing to predict Mycobacterium tuberculosis drug resistance in Shanghai, China. Int J Infect Dis 2020;90:48-53. https://doi. org/10.1016/j.ijid.2020.04.039

Ismail NA, Mvusi L, Nanoo A, et al. Prevalence of drug-resistant tuberculosis and imputed burden in South Africa: A national and sub-national cross-sectional survey. Lancet Infect Dis 2018;18(7):779- 787. https://doi:10.1016/S1473-3099(18)30222-6

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Published

2024-07-01

Issue

SAMJ Vol. 114 No. 7

Section

In Practice

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Copyright (c) 2024 L Richards, F Ismail, J Nel, S V Omar

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How to Cite

1.
Richards L, Ismail F, Nel J, Omar SV. Missed rifampicin and isoniazid resistance by commercial molecular assays. S Afr Med J [Internet]. 2024 Jul. 1 [cited 2025 Apr. 22];114(7):e1779. Available from: https://samajournals.co.za/index.php/samj/article/view/1779

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