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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.
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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.
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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.
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Rusen ID, Chiang CY, 2018. Building the evidence base for shortened MDR-TB treatment regimens. Int J Tuberc Lung Dis 22: 1–2.
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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.
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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.
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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: 1472–1477.
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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.
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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.
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Potentially High Number of Ineffective Drugs with the Standard Shorter Course Regimen for Multidrug-Resistant Tuberculosis Treatment in Haiti
Kathleen F. Walsh
Kathleen F. Walsh
Center for Global Health, Weill Cornell Medicine, New York, New York;
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Ariadne Souroutzidis
Ariadne Souroutzidis
Analysis Group, Boston, Massachusetts;
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Stalz Charles Vilbrun
Stalz Charles Vilbrun
The Haitian Group for the Study of Kaposi’s Sarcoma and Opportunistic Infections (GHESKIO), Port-au-Prince, Haiti;
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Miranda Peeples
Miranda Peeples
Analysis Group, Boston, Massachusetts;
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Guy Joissaint
Guy Joissaint
The Haitian Group for the Study of Kaposi’s Sarcoma and Opportunistic Infections (GHESKIO), Port-au-Prince, Haiti;
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Sobieskye Delva
Sobieskye Delva
The Haitian Group for the Study of Kaposi’s Sarcoma and Opportunistic Infections (GHESKIO), Port-au-Prince, Haiti;
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Pamphile Widmann
Pamphile Widmann
The Haitian Group for the Study of Kaposi’s Sarcoma and Opportunistic Infections (GHESKIO), Port-au-Prince, Haiti;
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Gertrude Royal
Gertrude Royal
The Haitian Group for the Study of Kaposi’s Sarcoma and Opportunistic Infections (GHESKIO), Port-au-Prince, Haiti;
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Jake Pry
Jake Pry
Division of Biostatistics, Department of Public Health Sciences, University of California, Davis, California;
Centre for Infectious Diseases Research (CIDRZ), Lusaka, Zambia;
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Centre for Infectious Diseases Research (CIDRZ), Lusaka, Zambia;
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Heejung Bang
Heejung Bang
Centre for Infectious Diseases Research (CIDRZ), Lusaka, Zambia;
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Jean W. Pape
Jean W. Pape
The Haitian Group for the Study of Kaposi’s Sarcoma and Opportunistic Infections (GHESKIO), Port-au-Prince, Haiti;
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Serena P. Koenig
Serena P. Koenig
Division of Global Health Equity, Harvard Medical School, Brigham and Women’s Hospital, Boston, Massachusetts
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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.
Author Notes
Financial support: Supported by the Fogarty International Center (grant #R25TW009337; 5D43TW010062-04).
Authors’ addresses: Kathleen F. Walsh, Cornell University Joan and Sanford I Weill Medical College, Center for Global Health, New York, NY, E-mail: kfw2001@med.cornell.edu. Ariadne Souroutzidis and Miranda Peeples, Biostatistics, Analysis Group, Boston, MA, E-mails: asouroutzidis@mgail.com and miranda.peeples@analysisgroup.com. Stalz Charles Vilbrun, Guy Joissaint, Sobieskye Delva, Pamphile Widmann, Gertrude Royal, and Jean W. Pape, Medicine, The Haitian Group for the Study of Kaposi’s Sarcoma and Opportunistic Infections (GHESKIO), Port-au-Prince, Haiti, E-mails: stalzsog@gmail.com, joissaintguy@yahoo.fr, sobdel@gmail.com, pamphile.widmann@yahoo.fr, tatideroyal@gmail.com, and hbang@ucdavis.edu. Jake Pry, Division Biostatistics, University of California, Davis, CA, and Center for Infectious Disease Research Zambia (CIDRZ), Biostatistics, Lusaka, Zambia, E-mail: jmpry@ucdavis.edu. Heejung Bang, Division of Biostatistics, University of California, Davis, CA, E-mail: hbang@ucdavis.edu. Serena P. Koenig, Division of Global Health Equity, Brigham and Women’s Hospital, Boston, MA, E-mail: skoenig@bwh.harvard.edu.
ProCite
RefWorks
Reference Manager
BibTeX
Zotero
EndNote
-
1.
WHO, 2017. Global Tuberculosis Report 2017. Geneva, Switzerland: World Health Organization.
-
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.
-
3.
WHO, 2018. Rapid Communication: Key Changes to Treatment of Multidrug- and Rifampicin-Resistant Tuberculosis (MDR/RR-TB). Geneva, Switzerland: World Health Organization.
-
4.
WHO, 2016. WHO Treatment Guidelines for Drug-Resistant Tuberculosis 2016 Update. Geneva, Switzerland: World Health Organization.
-
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: 684–692.
-
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: 1188–1194.
-
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: 517–524.
-
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.
-
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.
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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.
-
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.
-
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.
-
13.
Rivera VR et al. 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: 1140–1146.
-
14.
WHO, 2008. Guidelines for the Programmatic Management of Drug-Resistant Tuberculosis Emergency Update 2008. Geneva, Switzerland: World Health Organization.
-
15.
WHO, 2011. Guidelines for the Programmatic Management of Drug-Resistant Tuberculosis 2011 Update. Geneva, Switzerland: World Health Organization.
-
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: 715–721.
-
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.
-
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.
-
19.
Rusen ID, Chiang CY, 2018. Building the evidence base for shortened MDR-TB treatment regimens. Int J Tuberc Lung Dis 22: 1–2.
-
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.
-
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.
-
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: 1472–1477.
-
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.
-
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.
-
25.
Breen RA et al. 2006. Adverse events and treatment interruption in tuberculosis patients with and without HIV co-infection. Thorax 61: 791–794.
-
26.
Ahmad Khan F et al. 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.
-
27.
Trebucq A et al. 2018. Treatment outcome with a short multidrug-resistant tuberculosis regimen in nine African countries. Int J Tuberc Lung Dis 22: 17–25.
-
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.
-
29.
Ngabonziza JCS et al. 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.
-
30.
Bastos ML et al. 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: 1364–1374.
-
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: 300–301.
-
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: 1670–1674.
-
33.
Kontos F et al. 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: 331–333.
-
34.
Kamal SM et al. 2015. Anti-tuberculosis drug resistance in Bangladesh: reflections from the first nationwide survey. Int J Tuberc Lung Dis 19: 151–156.
-
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: 465–472.
-
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: 139–145.
-
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.
-
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: 946–951.
-
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.
-
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: 529–534.
-
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.
-
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.
-
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.
-
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: 71–75.
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45.
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