Failure of First-Generation GeneXpert MTB/RIF to Detect Rifampicin Resistance in Cutaneous Tuberculosis: A Case Report

Kholoud Maafi; Zakaria Asbai; Karim Souly; Souad Aboudkhil

doi:10.63095/NBSEH.26.779811

Authors

Kholoud Maafi 1 Laboratory of Biotechnology, Agri-Food, Materials and Environment, Hassan II University of Casablanca (https://ror.org/001q4kn48); 2 Ibn Sina University Hospital in Rabat (https://ror.org/038zpvz53),Rabat, Morocco ; 3 Faculty of Medicine and Pharmacy of Rabat, Mohamed V University (https://ror.org/00r8w8f84), Rabat, Morocco
Zakaria Asbai Laboratory of Biotechnology, Agri-Food, Materials and Environment, Hassan II University of Casablanca (https://ror.org/001q4kn48)
Karim Souly 1 Ibn Sina University Hospital in Rabat (https://ror.org/038zpvz53),Rabat, Morocco ; 2 Faculty of Medicine and Pharmacy of Rabat, Mohamed V University (https://ror.org/00r8w8f84), Rabat, Morocco
Souad Aboudkhil Laboratory of Biotechnology, Agri-Food, Materials and Environment, Hassan II University of Casablanca (https://ror.org/001q4kn48)

DOI:

https://doi.org/10.63095/NBSEH.26.779811

Keywords:

Cutaneous tuberculosis, Rifampicin resistance, GeneXpert MTB/RIF Ultra

Abstract

Cutaneous tuberculosis is a rare form of extrapulmonary tuberculosis. The diagnosis remains challenging because of its clinical polymorphism and low bacillary load. We report the case of a 19-year-old Moroccan woman receiving methotrexate for recently diagnosed rheumatoid arthritis who developed cutaneous tuberculosis in the deltoid region. Initial GeneXpert MTB/RIF analysis detected Mycobacterium tuberculosis without identifying rifampicin resistance, leading to first-line anti-tuberculosis treatment. Despite excellent adherence and multidisciplinary follow-up, the lesion progressively worsened. Repeat molecular testing with GeneXpert MTB/RIF Ultra and GeneXpert MTB/XDR revealed rifampicin monoresistance, subsequently confirmed by phenotypic drug susceptibility testing. Adjustment of the treatment regimen according to the resistance profile resulted in rapid clinical improvement and progressive lesion regression. This case highlights the diagnostic limitations of the first-generation GeneXpert MTB/RIF assay in paucibacillary cutaneous tuberculosis and emphasizes the value of next-generation molecular techniques for the early detection of anti-tuberculosis drug resistance, particularly in immunocompromised patients.

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References

World Health Organization, 2024, Global tuberculosis report 2020. World Health Organization (October, 2024). https://www.who.int/teams/global-programme-on-tuberculosis-and-lung-health/tb-reports/global-tuberculosis-report-2024

Ministère de la Santé et de la Protection Sociale, 2025, Guide National de la lutte antituberculeuse au Maroc. Programme National de Lutte Antituberculeuse, Direction de l’Épidémiologie et de Lutte contre les Maladies. https://fr.scribd.com/document/939446213/Guide-du-PNLAT-2025-251008-095850

Hailu, S., Hurst, C., Cyphers, G., Thottunkal, S., Harley, D., Viney, K., Irwin, A., Dean, J., & Nourse, C., 2024, Prevalence of extra‐pulmonary tuberculosis in Africa: A systematic review and meta‐analysis. Tropical Medicine & International Health 29(4), 257‑265. https://doi.org/10.1111/tmi.13970

Ministry of Health and Social Protection of Morocco, 2026, The Ministry of Health and Social Protection strengthens screening and management efforts for all forms of tuberculosis on the occasion of World Tuberculosis Day 2026 [Translated from the original French]. Ministerial communiqué. (Rabat: Ministry of Health and Social Protection). https://www.sante.gov.ma/Pages/communiqués.aspx?communiqueID=485&

Jain R., Gupta G., Mitra D. K., & Randeep Guleria R., 2024, Diagnosis of extra pulmonary tuberculosis: An update on novel diagnostic approaches. Respiratory Medicine 225, 107601. doi: 10.1016/j.rmed.2024.107601

de Brito A. C., de Oliveira C. M., Unger D. A-A., & de Jesus Semblano Bittencour M., 2022, Cutaneous tuberculosis: epidemiological, clinical, diagnostic and therapeutic update. Anais Brasileiros de Dermatologia 97(2), 129-144. https://doi.org/10.1016/j.abd.2021.07.004

Qiu B., Wu Z., Tao B., Li Z., Song H., Dan Tian D., Wu J., Zhan M., & Jianming Wang Send J. W., 2022, Risk factors for types of recurrent tuberculosis (reactivation versus reinfection): A global systematic review and meta-analysis. International Journal of Infectious Diseases 116, 14–20. https://doi.org/10.1016/j.ijid.2021.12.344

World Health Organization, 2024, Manuel opérationnel de l’OMS sur la tuberculose. Module 3 : diagnostic - outils de diagnostic rapide pour le dépistage de la tuberculose. https://www.who.int/fr/publications/b/58221

Mexico, U. C. A. A., González, J. F. M., González, A. L. R., Del Estado de Puebla Puebla Mexico, U. P. A., Servín, M. M., De Guadalajara Zapopan Mexico, U. A., Ávila, P. I. N., De Guadalajara Zapopan Mexico, U. A., Almanza, A. M., & De México Celaya Mexico, U. L., 2025), Cutaneous Tuberculosis : A Comprehensive Review of Etiopathogenesis, Clinical Subtypes, Diagnostic Modalities, and Contemporary Therapeutic Approaches. International Journal of Medical Science and Clinical Research Studies 5(05). https://doi.org/10.47191/ijmscrs/v5-i05-06

Kaixuan Liu K., Zeng Z., MD; Lu W., Yang Y., Lin T., 2026, Tuberculosis-Related Outcomes in Dermatologic Patients, Receiving Systemic Therapy A Systematic Review and Meta-Analysis. JAMA Dermatology. www.doi.org/10.1001/jamadermatol.2026.2365

Jiang J., Yang J., Shi Y., Jin Y., Tang S., Zhang N., Lu Y., & Sun G., 2020, Head-to-head comparison of the diagnostic accuracy of Xpert MTB/RIF and Xpert MTB/RIF Ultra for tuberculosis: a meta-analysis. Infectious Infectious Diseases 52(11):763-775. https://doi.org/10.1080/23744235.2020.1788222

A. Kohli, M., Schiller, I., Dendukuri, N., Yao, M., Dheda, K., Denkinger, C. M., Schumacher, S. G., & Steingart, K. R., 2021, Xpert MTB/RIF Ultra and Xpert MTB/RIF assays for extrapulmonary tuberculosis and rifampicin resistance in adults. Cochrane Database of Systematic Reviews (1), CD012768. https://doi.org/10.1002/14651858.cd012768.pub3

Biadglegne, F., Tesfaye, W., Sack, U., & Rodloff, A. C., 2013, Tuberculous Lymphadenitis in Northern Ethiopia : In a Public Health and Microbiological Perspectives. PLoS ONE 8(12), e81918. https://doi.org/10.1371/journal.pone.0081918

Dhasmana, D. J., Ross, C., Bradley, C. J., Connell, D. W., George, P. M., Singanayagam, A., Jepson, A., Craig, C., Wright, C., Molyneaux, P. L., Wickremasinghe, M., Lalvani, A., Cooke, G. S., & Kon, O. M., 2014, Performance of Xpert MTB/RIF in the Diagnosis of Tuberculous Mediastinal Lymphadenopathy by Endobronchial Ultrasound. Annals of the American Thoracic Society 11(3), 392‑396. https://doi.org/10.1513/annalsats.201308-250oc

Bera, C., Michael, J. S., Burad, D., Shirly, S. B., Gibikote, S., Ramakrishna, B., Goel, A., & Eapen, C. E., 2015, Tissue XpertTM MTB/Rif assay is of limited use in diagnosing peritoneal tuberculosis in patients with exudative ascites. Indian Journal of Gastroenterology 34(5), 395‑398. https://doi.org/10.1007/s12664-015-0599-7

Al-Ateah S. M., Al-Dowaidi M. M, El-Khizzi N. A., 2012, Evaluation of direct detection of Mycobacterium tuberculosis complex in respiratory and non-respiratory clinical specimens using the Cepheid Gene Xpert(R) system. Saudi Medical Journal 33 (10):1100-5. https://pubmed.ncbi.nlm.nih.gov/23047207/

Hanif, S. N. M., Eldeen, H. S., Ahmad, S., & Mokaddas, E., 2011, GeneXpert® MTB/RIF for rapid detection of Mycobacterium tuberculosis in pulmonary and extra-pulmonary samples [Correspondence]. The International Journal of Tuberculosis and Lung Disease 15(9), 1274‑1275. https://doi.org/10.5588/ijtld.11.0394

Friedrich S.O., Von Groote-Bidlingmaier F., & Diacon A. H., 2011, Xpert MTB/RIF assay for diagnosis of pleural tuberculosis. Journal of Clinical Microbiology 49(12):4341-2. https://doi.org/10.1128/jcm.05454-11

Gu Y., Wang G., Dong W., Li Y., Ma Y., Shang Y., Qin S., & Huang H., 2015, Xpert MTB/RIF and GenoType MTBDRplus assays for the rapid diagnosis of bone and joint tuberculosis. International Journal of Infectious Diseases 36, 27-30. https://doi.org/10.1016/j.ijid.2015.05.014

Nhu N. T., Heemskerk D., Thu do D.A., Chau T. T., Mai N.T., Nghia H. D., Loc P. P., Ha T. M., Merson L., Thinh T. V., Day J., Chau N. V., Wolbers M., Farrar J., & Caws M., 2014, Evaluation of GeneXpert MTB/RIF for diagnosis of tuberculous meningitis. Journal of Clinical Microbiology 52(1):226-33. www.doi.org/10.1128/JCM.01834-13

Meldau, R., Peter, J., Theron, G., Calligaro, G., Allwood, B., Symons, G., Khalfey, H., Ntombenhle, G., Govender, U., Binder, A., Van Zyl-Smit, R., Dheda, K., 2014, Comparison of same day diagnostic tools including Gene Xpert and unstimulated IFN-γ for the evaluation of pleural tuberculosis : a prospective cohort study. BMC Pulmonary Medicine 14(1), 58. https://doi.org/10.1186/1471-2466-14-58

Wang G., Wang S., Yang X., Sun Q., Jiang G., Huang M., Huo F., Ma Y., Chen X., Huang H., 2020, Accuracy of Xpert MTB/RIF Ultra for the diagnosis of pleural TB in a multicenter cohort study. Chest 157(2), 268-275. https://pubmed.ncbi.nlm.nih.gov/31437432/

Rufai, S. B., Singh, A., Kumar, P., Singh, J., & Singh, S., 2015, Performance of Xpert MTB/RIF Assay in Diagnosis of Pleural Tuberculosis by Use of Pleural Fluid Samples. Journal of Clinical Microbiology 53(11), 3636‑3638. https://doi.org/10.1128/jcm.02182-15

Peter JG, Zijenah LS, Chanda D, Clowes P, Lesosky M, Gina P, Mehta N., Calligaro G., Lombard C. J., Kadzirange G., Bandason T., Chansa A., Liusha N., Mangu C., Mtafya B., Msila H., Rachow A., Hoelscher M., Mwaba P., Theron G., Keertan Dheda K., 2016, Effect on mortality of point-of-care, urine-based lipoarabinomannan testing to guide tuberculosis treatment initiation in HIV-positive hospital inpatients: a pragmatic, parallel-group, multicountry, open-label, randomised controlled trial. Lancet 387(10024):1187-97. https://pubmed.ncbi.nlm.nih.gov/26970721/

Rufai, S. B., Singh, A., Singh, J., Kumar, P., Sankar, M. M., Singh, S., Nigam, K., Sharma, D., Gupta, A. K., &Rawat, V. S., 2017, Diagnostic usefulness of Xpert MTB/RIF assay for detection of tuberculous meningitis using cerebrospinal fluid. Journal of Infection 75(2), 125‑131. https://doi.org/10.1016/j.jinf.2017.04.010

Vadwai V., Boehme C., Nabeta P., Shetty A., Alland D., & Rodrigues C., 2011, Xpert MTB/RIF: a new pillar in diagnosis of extrapulmonary tuberculosis? Journal of Clinical Microbiology 49(7), 2540-5. https://pubmed.ncbi.nlm.nih.gov/21593262/

Nataraj G., Kanade S., Mehta P., 2016, Xpert((R)) MTB/RIF for improved case detection of extra-pulmonary TB in a tertiary care setting in urban India. International Journal of Tuberculosis and Lung Disease 20(7), 890-894. https://www.researchgate.net/publication/303892896_XpertW_MTBRIF_for_improved_case_detection_of_extra-pulmonary_TB_in_a_tertiary_care_setting_in_urban_India

Sharma S. K., Kohli M., Chaubey J., Yadav R. N., Sharma R., Singh B. K., Sreenivas V., Sharma A., Bhatia R., Jain D., Seenu V., Dhar A., & Soneja M., 2014, Evaluation of Xpert MTB/RIF assay performance in diagnosing extrapulmonary tuberculosis among adults in a tertiary care centre in India. European Respiratory Journal 44(4):1090-3. https://pubmed.ncbi.nlm.nih.gov/25063241/

Li, Y., Pang, Y., Zhang, T., Xian, X., Wang, X., Yang, J., Wang, R., Chen, M., & Chen, W., 2017, Rapid diagnosis of extrapulmonary tuberculosis with Xpert Mycobacterium tuberculosis/rifampicin assay. Journal of Medical Microbiology 66(7), 910‑914. https://doi.org/10.1099/jmm.0.000522

Du, J., Huang, Z., Luo, Q., Xiong, G., Xu, X., Li, W., Liu, X., & Li, J., 2015, Rapid diagnosis of pleural tuberculosis by Xpert MTB/RIF assay using pleural biopsy and pleural fluid specimens. Journal of Research in Medical Sciences 20(1):26–31. https://pmc.ncbi.nlm.nih.gov/articles/PMC4354061/

Ligthelm, L. J., Nicol, M. P., Hoek, K. G. P., Jacobson, R., Van Helden, P. D., Marais, B. J., Warren, R. M., & Wright, C. A., 2011, Xpert MTB/RIF for Rapid Diagnosis of Tuberculous Lymphadenitis from Fine-Needle-Aspiration Biopsy Specimens. Journal of Clinical Microbiology 49(11), 3967‑3970. https://doi.org/10.1128/jcm.01310-11

Wang, G., Wang, S., Jiang, G., Yang, X., Huang, M., Huo, F., Ma, Y., Dai, G., Li, W., Chen, X., & Huang, H., 2019, Xpert MTB/RIF Ultra improved the diagnosis of paucibacillary tuberculosis: A prospective cohort study. Journal of Infection 78(4), 311‑316. https://doi.org/10.1016/j.jinf.2019.02.010

Sun, Q., Wang, S., Dong, W., Jiang, G., Huo, F., Ma, Y., Huang, H., & Wang, G., 2019, Diagnostic value of Xpert MTB/RIF Ultra for osteoarticular tuberculosis. Journal of Infection 79(2), 153‑158. https://doi.org/10.1016/j.jinf.2019.06.006

Wu, X., Tan, G., Gao, R., Yao, L., Bi, D., Guo, Y., Yu, F., & Fan, L., 2019, Assessment of the Xpert MTB/RIF Ultra assay on rapid diagnosis of extrapulmonary tuberculosis. International Journal of Infectious Diseases 81, 91‑96. https://doi.org/10.1016/j.ijid.2019.01.050

Wang, G., Wang, S., Yang, X., Sun, Q., Jiang, G., Huang, M., Huo, F., Ma, Y., Chen, X., & Huang, H., 2020, Accuracy of Xpert MTB/RIF Ultra for the diagnosis of pleural TB in a multicenter cohort study. Chest 157(2), 268-275. https://pubmed.ncbi.nlm.nih.gov/31437432/

Dorman, S. E., Schumacher, S. G., Alland, D., Nabeta, P., Armstrong, D. T., King, B., Hall, S. L., Chakravorty, S., Cirillo, D. M., Tukvadze, N., Bablishvili, N., Stevens, W., Scott, L., Rodrigues, C., Kazi, M. I., Joloba, M., Nakiyingi, L., Nicol, M. P., Ghebrekhristos, Y., Anyango, I., Murithi, W., Dietze, R., Peres, R. L., Skrahina, A., Auchynka, V., Chopra, K. K., Hanif, M., Liu, X., Yuan, X., Boehme, C. C., Ellner, J. J., & Denkinger, C. M., 2018, Xpert MTB/RIF Ultra for detection of Mycobacterium tuberculosis and rifampicin resistance: a prospective multicentre diagnostic accuracy study. The Lancet Infectious Diseases 18(1), 76-84. www.doi.org/10.1016/S1473-3099(17)30691-6

Suh, E., Jung, S., Lee, J., Jhun, B. W., Kim, T. Y., Huh, H. J., & Lee, N. Y., 2025, Prospective Comparative Evaluation of the Xpert MTB/RIF and Xpert MTB/RIF Ultra Assays for Detecting Mycobacterium tuberculosis and Rifampin Resistance in High-resource, Intermediate-burden Settings. Annals of Laboratory Medicine 45(6), 583‑590. https://doi.org/10.3343/alm.2025.0101

Van Rie, A., Whitfield, M. G., De Vos, E., Scott, L., Da Silva, P., Hayes, C., Heupink, T. H., Sirgel, F. A., Stevens, W., & Warren, R. M., 2019, Discordances between molecular assays for rifampicin resistance in Mycobacterium tuberculosis: frequency, mechanisms and clinical impact. Journal of Antimicrobial Chemotherapy 75(5), 1123‑1129. https://doi.org/10.1093/jac/dkz564