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