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National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention
Neha Shah, MD MPH Field Medical Officer
Centers for Disease Control and Prevention California Department of Public Health NTCA April 2017
Division of Tuberculosis Elimination
Acknowledgments
• Chuck Daley • Faiz Khan • Pennan Barry • US MDR Treatment Guidelines Workgroup • California MDR Service
Have you used the short course therapy?
Are you excited to use it?
Current approach to MDR TB treatment
WHO Treatment of MDR-TB Duration of Therapy
Intensive phase of at least 8 months’ duration (conditional recommendation, very low quality of evidence)
Total treatment duration of at least 20 months is recommended in patients without any previous MDR-TB treatment (conditional recommendation, very low quality of evidence)
WHO 2011 Update
Global MDR TB Treatment Outcomes, 2007-2012
50%
WHO, Global Tuberculosis Report 2015
What is the short course regimen?
Short Course Standardized Regimen for MDR-TB Van Deun, et al. Am J Respir Crit Care Med 2010;182:684-692
Completion – 5.3% Death – 5.3% Cure – 82.5% Default – 5.8% Success – 87.8% Failure – 0.5% Relapse – 0.5%
4(+)KCGEHZP/5 GEZC
C = clofazimine, E = ethambutol, G = gat ifloxacin, H = isoniazid, K = kanamycin, O = ofloxacin, P = prothionamide, Z = pyrazinamide
Short(er) Course Regimen for MDR-TB
Isoniazid*
Gatifloxacin*
Pyrazinamide Ethambutol
0 1 2 3 4 5 6 7 8 9+ months
Clofazimine Prothionamide
Kanamycin
Initial Phase (7 drugs) Continuation Phase (4 drugs)
*High dose Injectable given 7 days/week
WHO Guideline Drug Doses
http://www.who.int/tb/areas-of-work/drug-resistant-tb/treatment/FAQshorter_MDR_regimen.pdf December 2016
Treatment Variation in duration
Country Init ial Phase Continuat ion Phase
Total Durat ion
Min Max
Bangladesh 4 6 5 9 – 11
Cameroon 4 6 8 12 - 14
Niger 4 6 8 12 - 14
Swaziland 4 8 5 9 - 13
Uzbekistan 4 6 5 9 – 11
Multiple 4 6 5 9 – 11
Treatment Variation in medication dosing
Fluroquinolones – 2 studies used 800mg Gatifloxacin = high dose – 2 studies used 400mg Moxifloxaxin
Prothionamide – 4 studies used is throughout and 2 only in intensive phase
High dose INH – Highest dose was 600mg – 1 study used usual dose
Eligibility Criteria
Choosing the MDR-TB Regimen
Laboratory Testing
Ethambutol and pyrazinamide growth-based testing unreliable
Isoniazid testing at low- and high-dose levels not always available internationally
WHO recommendation: do not take into account these tests
Eligibility For Short-course Regimen for MDR-TB in Europe
Cohort
Drug Resistance in MDR-TB (%)
Eligible for Short-Course Regimen
N SLID FQ Pto/Eto E Z N %
Austria 80 41 25 48 64 63 8 10 France 114 30 32 71 65 59 7 6 Germany 70 23 27 57 80 73 6 9 Portugal 200 51 48 83 52 75 9 5 TBnet* 148 28 21 47 54 62 18 12 Total 612 37 33 64 60 67 48 8
*16 countries in Europe Lange C, et al. AJRCCM 2016;194:1029
Can we use this in the US?
For Discussion
Should we use DST data for EMB, PZA, low- and high-level INH to determine eligibility?
Would you substitute a medication if there is resistance? – What if there is intolerance to a medication?
Would you give both ethionamide and high-dose INH if one is resistant?
What is the correct dose for quinolones? Would you give injectable medication 7 days/week