CASE REPORT
Phthisiology
doi: 10.25005/2074-0581-2026-28-3-879-886
IMPACT OF GENOME SEQUENCING IN THE TREATMENT OF TOTALLY DRUG-RESISTANT TUBERCULOSIS: A CASE REPORT

B.P. PIRMAKHMADZODA1,2,, Z.KH. TILLOEVA1,3

1Department of Phthisiopulmonology, Avicenna Tajik State Medical University, Dushanbe, Republic of Tajikistan
2City Center for Tuberculosis Control, Dushanbe, Republic of Tajikistan
3Department of Epidemiology, Hygiene and Environmental Protection with a Course in Microbiology and Virology, Institute of Postgraduate Education in Healthcare of the Republic of Tajikistan, Dushanbe, Republic of Tajikistan

Totally drug-resistant tuberculosis (TDR-TB) is an extremely severe clinical phenotype characterized by resistance to all first-line and virtually all second-line anti-TB agents. Advances in whole-genome sequencing (WGS) offer critical opportunities to map comprehensive resistance profiles and rapidly optimize individualized therapeutic regimens.

This case report describes the successful management of a patient with TDR-TB. The initial presentation was diagnosed as infiltrative pulmonary tuberculosis in the destruction (lysis) phase, confirmed via GeneXpert MTB/Rif. The baseline diagnostic workup followed national clinical guidelines. It included chest radiography, GeneXpert testing, complete blood counts, screening for HIV, HBsAg, and anti-HCV antibodies, and routine urinalysis and stool examinations. Second-line anti-TB therapy was initiated in an inpatient setting and transitioned to outpatient care; however, the patient experienced multiple episodes of non-adherence and loss to follow-up.

Subsequent drug susceptibility testing and whole-genome sequencing identified Mycobacterium tuberculosis complex (Beijing lineage) with resistance to rifampin, ethambutol, pyrazinamide, levofloxacin, moxifloxacin, linezolid, streptomycin, and ethionamide. Notably, susceptibility to bedaquiline, clofazimine, delamanid, amikacin, capreomycin, and pretomanid was preserved. The therapeutic regimen was adjusted dynamically based on these genomic insights, ultimately resulting in a favorable definitive outcome (treatment outcome: "cured").

This case underscores the clinical utility of genomic sequencing in managing highly resistant tuberculosis, emphasizing its pivotal role in designing effective, individualized treatment regimens within resource-limited settings.

Keywords: Tuberculosis, total drug resistance, genomic sequencing, individualized treatment, case report.

Download file:

References
  1. Bobokhojaev OI, Sirodzhidinova UYu, Nurov RM, Pirmakhmadzoda BP, Abdurakhimov AA, Saydaliev SM, i dr. Zakonomernosti epidemicheskogo protsessa i effektivnost' lecheniya bol'nykh tuberkulyozom s raznymi spektrami lekarstvennoy ustoychivosti v Respublike Tadzhikistan [Epidemic patterns and effectiveness of treatment of tuberculosis patients with different drug resistance profiles in the Republic of Tajikistan]. Tuberkulyoz i bolezni lyogkih. 2023;101(2):73-9. https://doi.org/10.58838/2075-1230-2023-101-2-73-79
  2. Goletti D, Meintjes G, Andrade BB, Zumla A, Shan Lee S. Insights from the 2024 WHO Global Tuberculosis Report – More comprehensive action, innovation, and investments required for achieving WHO End TB goals. Int J Infect Dis. 2025;150:107325. https://doi.org/10.1016/j.ijid.2024.107325
  3. Tilloeva ZKh, Mirzoev AS. Tuberkulyoz s mnozhestvennoy lekarstvennoy ustoychivost′yu v period pandemii COVID-19 v g. Dushanbe [Multi-drug-resistant tuberculosis in COVID-19 pandemic period, Dushanbe]. Zdravookhranenie Tadzhikistana. 2023;2:105-12. https://doi.org/10.52888/0514-2515-2023-357- 2-105-112.
  4. Tilloeva ZKh, Mirzoev AS. Rezul′taty lecheniya bol′nykh tuberkulyozom s mnozhestvennoy lekarstvennoy ustoychivost′yu sredi klyuchevykh grupp naseleniya v period pandemii COVID-19 v g. Dushanbe, Tadzhikistan [Results of treatment of patients with multiple drug resistant tuberculosis among key populations during the covid-19 pandemic in Dushanbe, Tajikistan]. Tuberkulyoz i bolezni lyogkikh. 2024;102(3):24-33. https://doi.org/10.58838/2075-1230- 2024-102-3-24-33
  5. Bobokhojaev OI. Experience in optimizing the accessibility of services for tuberculosis in the Republic of Tajikistan. J Community Med Health Solut. 2022;3:64-8.
  6. Mphothulo N, Hlangu S, Furin J, Moshabela M, Loveday M. Navigating DR-TB treatment care: A qualitative exploration of barriers and facilitators to retention in care among people with history of early disengagement from drug-resistant tuberculosis treatment in Johannesburg, South Africa. BMC Health Serv Res. 2025;25(1):122. https://doi.org/10.1186/s12913-025-12265-z
  7. Zhang G, Zhang H. Zhang Y, Hu X, Tang M, Gao Q. Targeted next-generation sequencing technology showed great potential in identifying spinal tuberculosis and predicting the drug resistance. J Infect. 2023;87(6):e110-2. https://doi. org/10.1016/j.jinf.2023.10.018
  8. Riley DS, Barber MS, Kienle GS, Aronson JK, von Schoen-Angerer T, Tugwell P, et al. CARE guidelines for case reports: Explanation and elaboration document. J Clin Epidemiol. 2017; 89:218-35. https://doi.org/10.1016/j.jclinepi.2017.04.026
  9. Poling MI, Dufresne CR. Strategies for improving case reports involving patients with rare diseases. Cureus. 2025;17(2):e79864. https://doi.org/10.7759/ cureus.79864
  10. Seid G, Alemu A, Diriba G, Zerihun B, Tadesse G, Mariam SH, et al. Drug resistance profile of Mycobacterium tuberculosis complex isolated from pulmonary tuberculosis patients and their household contacts in central Ethiopia. BMC Infect Dis. 2025;25(1):806. https://doi.org/10.1186/s12879-025-11220-x
  11. Meundi AD, Richardus JH. "I consulted so many doctors": The journey of tuberculosis patients in Bengaluru, India, from first symptoms to diagnosis. BMC Health Serv Res. 2025;25(1):397. https://doi.org/10.1186/s12913-025-12547-6
  12. Giovenco D, Shah NS, Ansorge K, Operario D, Gandhi NR. New drugs are not enough: Addressing social determinants as a critical component of drug-resistant TB care. IJTLD Open. 2025;2(4):183-6. https://doi.org/10.5588/ijtldopen.25.0075
  13. Tilloeva Z, Aghabekyan S, Davtyan K, Goncharova O, Kabirov O, Pirmahmadzoda B, et al. Tuberculosis in key populations in Tajikistan – A snapshot in 2017. J Infect Dev Ctries. 2020;14(11.1):94S-100S. https://doi.org/10.3855/jidc.11952
  14. Schwab TC, Perrig L, Göller PC, Guebely De la Hoz FF, Lahousse AP, Minder B, al. Targeted next-generation sequencing to diagnose drug-resistant tuberculosis: A systematic review and meta-analysis. Lancet Infect Dis. 2024;24(10):1162-76. https://doi.org/10.1016/S1473-3099(24)00263-9

Authors' information:

Pirmakhmadzoda Bobodzhon Pirmakhmad,
Director of the City Center for Tuberculosis Control; Assistant Professor, Department of Phthisiopulmonology, Avicenna Tajik State Medical University
ORCID ID: 0009-0009-8844-3052
E-mail: sharipovbobojon07@gmail.com

Tilloeva Zulfiya Khaybulloevna,
Candidate of Medical Sciences, Assistant Professor, Department of Phthisiopulmonology, Avicenna Tajik State Medical University; Assistant Professor, Department of Epidemiology, Hygiene and Environmental Protection with a Course in Microbiology and Virology, Institute of Postgraduate Education in Healthcare of the Republic of Tajikistan
Researcher ID: AEN-4626-2022
Scopus ID: 57220065383
ORCID ID: 0000-0002-7668-1688
SPIN: 9259-9917
E-mail: ztilloeva@gmail.com

Information about support in the form of grants, equipment, medications

This work was conducted as part of the research project "Multidrug-resistant tuberculosis: diagnostic methods and treatment effectiveness in the Republic of Tajikistan" at the Avicenna Tajik State Medical University (State Registration Number: 0117 TJ 00805). The authors did not receive financial support from manufacturers of medicines and medical equipment

Conflicts of interest: No conflict

Address for correspondence:

Tilloeva Zulfiya Khaybulloevna
Candidate of Medical Sciences, Assistant Professor, Department of Phthisiopulmonology, Avicenna Tajik State Medical University; Assistant Professor, Department of Epidemiology, Hygiene and Environmental Protection with a Course in Microbiology and Virology, Institute of Postgraduate Education in Healthcare of the Republic of Tajikistan

734026, Republic of Tajikistan, Dushanbe, Sino str., 29-31

Tel.: +992 (934) 477353

E-mail: ztilloeva@gmail.com


This work is licensed under a Creative Commons Attribution 4.0 International License.

Materials on the topic:
  1. CHARACTERISTICS OF PLEURAL ADHESIONS, OPERATIVE TIME, AND BLOOD LOSS IN PATIENTS OPERATED ON FOR PULMONARY TUBERCULOSIS
  2. ARTIFICIAL PNEUMOPERITONEUM IN DESTRUCTIVE PULMONARY TUBERCULOSIS AS AN ADJUNCT TO PULMONARY SURGERY
  3. RATIONALE FOR THE EFFECTIVE APPLICATION OF THE EXPERIENCE OF ANTI-TUBERCULOSIS CARE SETTINGS DURING THE COVID-19 PANDEMIC
  4. EFFECTIVENESS OF MAGNETIC RESONANCE IMAGING IN THE DIAGNOSIS OF TUBERCULOSIS IN HIV-INFECTED CHILDREN: A CASE REPORT

◄ Back to the list