Risk factors for treatment failure in multidrug resistant tuberculosis in Tunisia: An analytic study


Fatma Tritar
Soumaya Ben Saad
Mariem Ferchichi
Amani Ben Mansour
Azza Slim
Othmen Naffati
Hedia Bellali
Leila Slim
Hafaoua Daghfous



The emergence of multidrug resistant tuberculosis (MDR-TB) is a threat to global public health. The aim of our study was to determine risk factors for treatment failure in MDR-TB.


Retrospective study conducted between January 2000 and March 2019 including patients with MDR-TB. Characteristics of patients with therapeutic failure were compared to cured ones. Logistic regression analysis was used to identify risk factors for treatment failure.


Our study included 140 patients aged of 42±13 years (18-80).  Fifty-seven percent of patients had treatment success and 12% had treatment failure. In multivariate logistic regression analysis, treatment failure was associated with age over 45 years (OR=1.05; 95%CI, 1.024-7.736;p=0.014), primary education level and illiteracy (OR=5.022; 95%CI, 1.316-19.161;p=0,018), history of incarceration (OR=3.291; 95%CI, 1.291-21.083;p=0.016), undernutrition (OR=4.544; 95%CI, 2.304-54.231;p=0,027), extensive TB (OR=6.406; 95%CI, 1.761-23.922; p=0.038), initial high grade positive smears (OR=1.210; 95%CI, 1.187-32.657; p=0.045), positive smear culture at 90 days of treatment (OR=6.871, 95%CI, 3.824-23.541; p=0.003), poor adherence (OR=6.110; 95%CI, 2.740-12.450; p=0.021) and occurrence of psychiatric adverse events (OR=3.644 95%CI, 2.560- 27.268; p=0.041).


Therapeutic education, nutritional and psychological support and close follow-up are strongly recommended to optimize the prognosis of MDR-TB.


mycobacterium tuberculosis, susceptibility test, second-line drug, Prognosis, epidemiology, Tunisia, North Africa



  1. World Health Organization. Global tuberculosis report. Geneva: WHO; 2020.
  2. F Tritar, H Daghfous, S Ben Saad, L Slim- Saadi. Prise en charge de la tuberculose multirésistante. Rev Pneum Clin 2015,71:130-9.
  3. International union against tuberculosis and respiratory diseases. Practical guide of management of resistant tuberculosis. 2018. https://www.tbonline.info/media/uploads/documents/theunion_dr-tb-guide.pdf
  4. Ben Saad-Baouab S, Hantous S, Daghfous H, Ben Miled K, Tritar F. Apport de l’imagerie dans la prise en charge de la tuberculose multirésistante. Tun Med. 2019;97:445-54.
  5. Grey D. Étude rétrospective simulant l’impact d’une évolution des recommandations de la Haute Autorité de santé (HAS) vers les critères proposés par la Global Leadership Initiative on Malnutrition (GLIM) sur la prévalence de la dénutrition dans un hôpital public français. Nutr Clin Metab. 2019;33(3):205–11.
  6. Djuretic T, Herbert J, Drobniewski F, Yates M, Smith EG, Magee JG, et al. Antibiotic resistant tuberculosis in the United Kingdom: 1993-1999. Thorax. 2002;57(6):477–82.
  7. Faustini A, Hall AJ, Perucci CA. Risk factors for multidrug resistant tuberculosis in Europe: a systematic review. Thorax. 2006;61(3):158–63.
  8. Porco TC, Oh P, Flood JM. Antituberculosis drug resistance acquired during treatment: an analysis of cases reported in California, 1994-2006. Clin Infect Dis. 2013;56(6):761–9.
  9. Horo K, Aka Danguy E, Kouassi Boko A, N’gom AS, Gode CV, Ahui Brou JM, et al. Multi-drug resistance of tuberculosis: 81 patients monitored in an ivory coast pneumology unit. Rev Pneumol Clin. 2011;67(1):82–8.
  10. Helbling P, Altpeter E, Raeber PA, Pfyffer GE, Zellweger JP. Surveillance of antituberculosis drug resistance in Switzerland 1995-1997: the central link. Eur Respir J. 2000;16(2):200-2.
  11. Suárez PG, Floyd K, Portocarrero J, Alarcón E, Rapiti E, Ramos G, et al. Feasibility and cost-effectiveness of standardised second-line drug treatment for chronic tuberculosis patients: a national cohort study in Peru. Lancet. 2002;359(9322):1980-9.
  12. Nathanson E, Gupta R, Huamani P, Leimane V, Pasechnikov AD, Tupasi TE, et al. Adverse events in the treatment of multidrug-resistant tuberculosis: results from the DOTS-Plus initiative. Int J Tuberc Lung Dis. 2004;8(11):1382-4.
  13. Iseman MD. Treatment of multidrug-resistant tuberculosis. N Engl J Med. 1993;329(11):784-91.
  14. Törün T, Tahaoğlu K, Ozmen I, Sevim T, Ataç G, Kir A, et al. The role of surgery and fluoroquinolones in the treatment of multidrug-resistant tuberculosis. Int J Tuberc Lung Dis. 2007;11(9):979-85.
  15. Mordant P, Henry B, Morel S, Robert J, Veziris N, Le Dû D, et al. Adjuvant surgical resection for multidrug-resistant tuberculosis: a review. Rev Mal Respir 2014;31(4):511–24.
  16. World Health Organization. WHO consolidated guidelines on tuberculosis: drug-resistant tuberculosis treatment. Geneva: WHO; 2020.
  17. Aguilera XP, Gonzalez C, Najera De Ferrari M, Hirmas M, Delgado I, Olea A, et al. Tuberculosis in prisoners and their contacts in Chile: estimating incidence and latent infection. Int J Tuberc Lung Dis. 2016;20(1):63-70.
  18. Anderson C, Story A, Brown T, Drobniewski F, Abubakar I. Tuberculosis in UK prisoners: a challenge for control. J Epidemiol Community Health. 2010;64(4):373-6.
  19. Salindri AD, Kipiani M, Kempker RR, Gandhi NR, Darchia L, Tukvadze N, et al. Diabetes reduces the rate of sputum culture conversion in patients with newly diagnosed multidrug-resistant tuberculosis. Open Forum Infect Dis. 2016;3(3):126.
  20. Singhal A, Jie L, Kumar P, Hong GS, Leow MS, Paleja B, et al. Metformin as adjunct antituberculosis therapy. Sci Transl Med. 2014;6(263):263-9.
  21. Nunn AJ, Phillips PJ, Meredith SK, Chiang CY, Conradie F, Dalai D, et al. A Trial of a shorter regimen for rifampin-resistant tuberculosis. N Engl J Med. 2019;380(13):1201-13.
  22. Boehme CC, Nabeta P, Hillemann D, Nicol MP, Shenai S, Krapp F, et al. Rapid molecular detection of tuberculosis and rifampin resistance. N Engl J Med. 2010;363(11):1005-15.
  23. Degner NR, Wang JY, Golub JE, Karakousis PC. Metformin use reverses the increased mortality associated with diabetes mellitus during tuberculosis treatment.Clin Infect Dis. 2018;66(2):198-205.
  24. Das SK, Das A, Gangopadhyay A, Sinha AK. Primary disseminated extrapulmonary multidrug resistant tuberculosis. Indian J Med Microbiol. 2012;30(3):364-6.