1921
Volume 100, Issue 2
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645

Abstract

Abstract.

Multidrug-resistant tuberculosis (MDR-TB) outcomes are poor partly because of the long treatment duration; the World Health Organization conditionally recommends a shorter course regimen to potentially improve treatment outcomes. Here, we describe the drug susceptibility patterns of a cohort of MDR-TB patients in Haiti and determine the number of likely effective drugs if they were treated with the recommended shorter course regimen. We retrospectively examined drug susceptibility patterns of adults initiating MDR-TB treatment between 2008 and 2015 at the Haitian Group for the Study of Kaposi’s Sarcoma and Opportunistic Infections in Port-au-Prince, Haiti. First- and second-line drug susceptibility testing (DST) was analyzed and used to determine the number of presumed effective drugs. Of the 239 patients analyzed, 226 (95%), 183 (77%), 135 (57%), and 38 (16%) isolates were resistant to high-dose isoniazid, ethambutol, pyrazinamide, and ethionamide, respectively. Eight patients (3%) had resistance to either a fluoroquinolone or a second-line injectable and none had extensively resistant TB. Of the 239 patients, 132 (55%) would have fewer than five likely effective drugs in the intensive phase of the recommended shorter course regimen and 121 (51%) would have two or fewer likely effective drugs in the continuation phase. Because of the high rates of resistance to first-line TB medications, about 50% of MDR-TB patients would be left with only two effective drugs in the continuation phase of the recommended shorter course regimen, raising concerns about the effectiveness of this regimen in Haiti and the importance of using DST to guide treatment.

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References

  1. WHO, 2017. Global Tuberculosis Report 2017. Geneva, Switzerland: World Health Organization. [Google Scholar]
  2. Falzon D, Schunemann HJ, Harausz E, Gonzalez-Angulo L, Lienhardt C, Jaramillo E, Weyer K, , 2017. World Health Organization treatment guidelines for drug-resistant tuberculosis, 2016 update. Eur Respir J 49: 1602308. [Google Scholar]
  3. WHO, 2018. Rapid Communication: Key Changes to Treatment of Multidrug- and Rifampicin-Resistant Tuberculosis (MDR/RR-TB). Geneva, Switzerland: World Health Organization. [Google Scholar]
  4. WHO, 2016. WHO Treatment Guidelines for Drug-Resistant Tuberculosis 2016 Update. Geneva, Switzerland: World Health Organization. [Google Scholar]
  5. Van Deun A, Maug AK, Salim MA, Das PK, Sarker MR, Daru P, Rieder HL, , 2010. Short, highly effective, and inexpensive standardized treatment of multidrug-resistant tuberculosis. Am J Respir Crit Care Med 182: 684692. [Google Scholar]
  6. Piubello A, Harouna SH, Souleymane MB, Boukary I, Morou S, Daouda M, Hanki Y, Van Deun A, , 2014. High cure rate with standardised short-course multidrug-resistant tuberculosis treatment in Niger: no relapses. Int J Tuberc Lung Dis 18: 11881194. [Google Scholar]
  7. Kuaban C, Noeske J, Rieder HL, Ait-Khaled N, Abena Foe JL, Trebucq A, , 2015. High effectiveness of a 12-month regimen for MDR-TB patients in Cameroon. Int J Tuberc Lung Dis 19: 517524. [Google Scholar]
  8. Nunn AJ, Rusen ID, Van Deun A, Torrea G, Phillips PP, Chiang CY, Squire SB, Madan J, Meredith SK, , 2014. Evaluation of a standardized treatment regimen of anti-tuberculosis drugs for patients with multi-drug-resistant tuberculosis (STREAM): study protocol for a randomized controlled trial. Trials 15: 353. [Google Scholar]
  9. The UNION, 2017. STREAM Clinical Trial Results Provide Vital Insight into Nine-Month Treatment Regimen for Multidrug-Resistant Tuberculosis. Available at: http://guadalajara.worldlunghealth.org/media/conference-news/updates/stream-clinical-trial-results-provide-vital-insight-into-nine-month-treatment-regimen-for-multidrug-resistant-tuberculosis. Accessed June 1, 2018. [Google Scholar]
  10. Partners in Health, 2017. Joint Statement on STREAM Stage One MDR-TB Clinical Trial results. Available at: https://www.pih.org/article/stream-stage-one-results?utm_source=twitter&utm_medium=organicsocial&utm_content=stream1&utm_campaign=general&source=organictwitter_general. Accessed June 1, 2018. [Google Scholar]
  11. WHO, 2018. Position Statement on the Continued Use of the Shorter MDR-TB Regimen Following an Expedited Review of the STREAM Stage 1 Preliminary Results. Geneva, Switzerland: World Health Organization. [Google Scholar]
  12. WHO, 2015. Haiti Tuberculosis Profile. Available at: https://extranet.who.int/sree/Reports?op=Replet&name=%2FWHO_HQ_Reports%2FG2%2FPROD%2FEXT%2FTBCountryProfile&ISO2=HT&LAN=EN&outtype=html. Accessed May 16, 2017. [Google Scholar]
  13. Rivera VR, 2017. Diagnostic yield of active case finding for tuberculosis and HIV at the household level in slums in Haiti. Int J Tuberc Lung Dis 21: 11401146. [Google Scholar]
  14. WHO, 2008. Guidelines for the Programmatic Management of Drug-Resistant Tuberculosis Emergency Update 2008. Geneva, Switzerland: World Health Organization. [Google Scholar]
  15. WHO, 2011. Guidelines for the Programmatic Management of Drug-Resistant Tuberculosis 2011 Update. Geneva, Switzerland: World Health Organization. [Google Scholar]
  16. Charles M, Vilbrun SC, Koenig SP, Hashiguchi LM, Mabou MM, Ocheretina O, Pape JW, , 2014. Treatment outcomes for patients with multidrug-resistant tuberculosis in post-earthquake Port-au-Prince, Haiti. Am J Trop Med Hyg 91: 715721. [Google Scholar]
  17. Vilbrun SC, Walsh K, Joseph J, Delva S, Jeantine O, Joissaint G, Koenig SP, Pape JW, High Retention in a Community-Based MDR-TB Program in Haiti; , 2016. Abstract book, 47th World Conference on Lung Health of the International Union Against Tuberculosis and Lung Disease (the Union). Liverpool, United Kingdom: The International Journal of Tuberculosis and Lung Disease. [Google Scholar]
  18. Mukadi JCY, , 2017. STREAM Trial (Evaluation of a Standardised Treatment Regimen of Anti-Tuberculosis Drugs for Patients with Multidrug-Resistant Tuberculosis): Preliminary Stage 1 Results. The 48th UNION World Conference on Lung Health, Guadalajara, Mexico, October 11–14, 2017. [Google Scholar]
  19. Rusen ID, Chiang CY, , 2018. Building the evidence base for shortened MDR-TB treatment regimens. Int J Tuberc Lung Dis 22: 12. [Google Scholar]
  20. Hoa NB, Nhung NV, Khanh PH, Hai NV, Quyen BT, , 2015. Adverse events in the treatment of MDR-TB patients within and outside the NTP in Pham Ngoc Thach hospital, Ho Chi Minh City, Vietnam. BMC Res Notes 8: 809. [Google Scholar]
  21. Seung KJ, Omatayo DB, Keshavjee S, Furin JJ, Farmer PE, Satti H, , 2009. Early outcomes of MDR-TB treatment in a high HIV-prevalence setting in southern Africa. PLoS One 4: e7186. [Google Scholar]
  22. Yee D, Valiquette C, Pelletier M, Parisien I, Rocher I, Menzies D, , 2003. Incidence of serious side effects from first-line antituberculosis drugs among patients treated for active tuberculosis. Am J Respir Crit Care Med 167: 14721477. [Google Scholar]
  23. Schnippel K, Berhanu RH, Black A, Firnhaber C, Maitisa N, Evans D, Sinanovic E, , 2016. Severe adverse events during second-line tuberculosis treatment in the context of high HIV co-infection in South Africa: a retrospective cohort study. BMC Infect Dis 16: 593. [Google Scholar]
  24. Yimer G, Gry M, Amogne W, Makonnen E, Habtewold A, Petros Z, Aderaye G, Schuppe-Koistinen I, Lindquist L, Aklillu E, , 2014. Evaluation of patterns of liver toxicity in patients on antiretroviral and anti-tuberculosis drugs: a prospective four arm observational study in ethiopian patients. PLoS One 9: e94271. [Google Scholar]
  25. Breen RA, 2006. Adverse events and treatment interruption in tuberculosis patients with and without HIV co-infection. Thorax 61: 791794. [Google Scholar]
  26. Ahmad Khan F, 2017. Effectiveness and safety of standardised shorter regimens for multidrug-resistant tuberculosis: individual patient data and aggregate data meta-analyses. Eur Respir J 50: 1602308. [Google Scholar]
  27. Trebucq A, 2018. Treatment outcome with a short multidrug-resistant tuberculosis regimen in nine African countries. Int J Tuberc Lung Dis 22: 1725. [Google Scholar]
  28. Whitfield MG, Soeters HM, Warren RM, York T, Sampson SL, Streicher EM, van Helden PD, van Rie A, , 2015. A global perspective on pyrazinamide resistance: systematic review and meta-analysis. PLoS One 10: e0133869. [Google Scholar]
  29. Ngabonziza JCS, 2017. Half of rifampicin-resistant Mycobacterium tuberculosis complex isolated from tuberculosis patients in sub-saharan Africa have concomitant resistance to pyrazinamide. PLoS One 12: e0187211. [Google Scholar]
  30. Bastos ML, Collaborative Group for Meta-analysis of Individual Patient Data in M-T , 2014. Treatment outcomes of patients with multidrug-resistant and extensively drug-resistant tuberculosis according to drug susceptibility testing to first- and second-line drugs: an individual patient data meta-analysis. Clin Infect Dis 59: 13641374. [Google Scholar]
  31. Chedore P, Bertucci L, Wolfe J, Sharma M, Jamieson F, , 2010. Potential for erroneous results indicating resistance when using the Bactec MGIT 960 system for testing susceptibility of Mycobacterium tuberculosis to pyrazinamide. J Clin Microbiol 48: 300301. [Google Scholar]
  32. Pfyffer GE, Palicova F, Rusch-Gerdes S, , 2002. Testing of susceptibility of Mycobacterium tuberculosis to pyrazinamide with the nonradiometric BACTEC MGIT 960 system. J Clin Microbiol 40: 16701674. [Google Scholar]
  33. Kontos F, 2003. Multicenter evaluation of the fully automated Bactec MGIT 960 system for susceptibility testing of Mycobacterium tuberculosis to pyrazinamide: comparison with the radiometric Bactec 460TB system. J Microbiol Methods 55: 331333. [Google Scholar]
  34. Kamal SM, 2015. Anti-tuberculosis drug resistance in Bangladesh: reflections from the first nationwide survey. Int J Tuberc Lung Dis 19: 151156. [Google Scholar]
  35. Vasquez-Campos L, Asencios-Solis L, Leo-Hurtado E, Quispe-Torres N, Salazar-Lindo E, Bayona J, Becerra MC, , 2004. Drug resistance trends among previously treated tuberculosis patients in a national registry in Peru, 1994–2001. Int J Tuberc Lung Dis 8: 465472. [Google Scholar]
  36. Katiyar SK, Bihari S, Prakash S, Mamtani M, Kulkarni H, , 2008. A randomised controlled trial of high-dose isoniazid adjuvant therapy for multidrug-resistant tuberculosis. Int J Tuberc Lung Dis 12: 139145. [Google Scholar]
  37. Niehaus AJ, Mlisana K, Gandhi NR, Mathema B, Brust JC, , 2015. High prevalence of inhA promoter mutations among patients with drug-resistant tuberculosis in KwaZulu-Natal, South Africa. PLoS One 10: e0135003. [Google Scholar]
  38. Abate D, Tedla Y, Meressa D, Ameni G, , 2014. Isoniazid and rifampicin resistance mutations and their effect on second-line anti-tuberculosis treatment. Int J Tuberc Lung Dis 18: 946951. [Google Scholar]
  39. Hu Y, Hoffner S, Jiang W, Wang W, Xu B, , 2010. Extensive transmission of isoniazid resistant M. tuberculosis and its association with increased multidrug-resistant TB in two rural counties of eastern China: a molecular epidemiological study. BMC Infect Dis 10: 43. [Google Scholar]
  40. Rahim Z, Nakajima C, Raqib R, Zaman K, Endtz HP, van der Zanden AG, Suzuki Y, , 2012. Molecular mechanism of rifampicin and isoniazid resistance in Mycobacterium tuberculosis from Bangladesh. Tuberculosis (Edinb) 92: 529534. [Google Scholar]
  41. Ssinabulya I, Nabunnya Y, Kiggundu B, Musoke C, Mungoma M, Kayima J, , 2016. Hypertension control and care at Mulago Hospital ambulatory clinic, Kampala-Uganda. BMC Res Notes 9: 487. [Google Scholar]
  42. Global Alliance for TB Drug Development, 2015. A Phase 3 Study Assessing the Safety and Efficacy of Bedaquiline Plus PA-824 Plus Linezolid in Subjects with Drug Resistant Pulmonary Tuberculosis. Available at: https://clinicaltrials.gov/show/NCT02333799. Accessed October 10, 2018. [Google Scholar]
  43. Dheda K, University of Cape Town; , 2015. An Open-label RCT to Evaluate a New Treatment Regimen for Patients with Multi-Drug Resistant Tuberculosis. Available at: https://clinicaltrials.gov/show/NCT02454205. Accessed October 10, 2018. [Google Scholar]
  44. Zhang Z, Li T, Qu G, Pang Y, Zhao Y, , 2015. In vitro synergistic activity of clofazimine and other antituberculous drugs against multidrug-resistant Mycobacterium tuberculosis isolates. Int J Antimicrob Agents 45: 7175. [Google Scholar]
  45. Ramon-Garcia S, Gonzalez Del Rio R, Villarejo AS, Sweet GD, Cunningham F, Barros D, Ballell L, Mendoza-Losana A, Ferrer-Bazaga S, Thompson CJ, , 2016. Repurposing clinically approved cephalosporins for tuberculosis therapy. Sci Rep 6: 34293. [Google Scholar]
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  • Received : 11 Jun 2018
  • Accepted : 26 Oct 2018
  • Published online : 26 Dec 2018

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