1. Management of Tuberculosis (TB) and Multidrug-Resistant TB (MDR TB)
Monica Avendano, MD, FRCPC
Associate Professor of Medicine
University of Toronto
Medical Director, TB Service
West Park Healthcare Centre, Toronto

2. Tuberculosis is a Social Disease with a Medical Aspect.
Sir William Osler in 1902
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3. Worldwide Trends & the Burden of TB Disease
TB is still one of the leading causes of death in low-income and middle-income countries.
TB remains a threat to public health in industrialized countries.
The worldwide burden is still growing.

4. Risk Factors which Perpetuate Worldwide TB
Ongoing Exposure to TB
Increasing Poverty:
-Lack of or poor housing
-Poor nutrition
-Over crowding
-No access or erratic access to healthcare
Wars and Natural Disasters
Mass Migrations usually from poor resources settings to industrialized settings

5. Tuberculosis in the World
Incidence: 9.5 million new cases/year
Prevalence: 14 million cases
95% of cases in resource poor settings
1.1 millions co-infection TB/ HIV (12% HIV Positive have TB)
1.7 millions deaths/year
98% deaths in poor resource countries
WHO 2010

6. Tuberculosis in Canada (Demographically and Geographically Focused)
1,600 Cases in 2009
TB Rate /
65% of cases in Foreign Born persons Rate 14/
21% in First Nation People- Rate 28/
Rate in Nunavut 174/
75% of cases are in large urban centres in Ontario, BC and Quebec
Socially marginalized groups
Rate in Atlantic Region 1/

7. Management of TB Medical Management Diagnosis Treatment Follow-up
Psychosocial Management
Stigma
Multicultural issues
Financial implications
Impact on family life

8. Management of TB Diagnosis Suspect TB/Think TB
Clinical (presenting symptoms, duration of symptoms, previous TB)
Diagnostic Imaging
(X-Rays, CT Scans, MRI’s)
Bacteriology (smears, cultures)
Pathology of biopsy specimens
Epidemiological Factors

9. Management of TB Obtain adequate clinical specimen
Drug susceptibility in first isolate
At least 3 bactericidal drugs
Adequate duration of treatment: beyond the time of sputum conversion and amelioration of symptoms
Adequate follow-up: prescribing the drugs is just the beginning
Attention to psychosocial factors

10. Treatment of TB Goals Sterilize the lesion
Avoid development of resistance
Clinical Principles
Treat with multiple drugs
Adequate dosages
Sufficient duration
Expert monitoring

11. Drug Susceptibility in TB
Fully susceptible to all first line drugs
Mono-Resistant: resistant to a single first
line drug (Most frequently to Isoniazid)
Poly-Resistant: resistant to 2 or more first line drugs but not to Isoniazid and Rifampin
Multidrug-Resistant (MDR TB): resistant
to Isoniazid and Rifampin
Extensively Drug-resistant (XDR TB): MDR TB
with additional resistance to a quinolone and an injectable

12. Anti-TB Drugs Group 1 - Isoniazid, Rifampin, Pyrazinamide,Ethambutol
- Amikacin, Kanamycin, Capreomycin
Group 3
- F-Quinolones
Group 4
- Ethionamide, Cycloserine. PAS,Prothionamide
Group 5
- Clofazimine,Imipenem, Thioacetazone, Clavulin,
Macrolides, Linezolid

13. Duration of TB Treatment
Drugs
Duration
INH/RMP/PZA + EMB x 2 months INH/RMP x 4 months
6 months
INH/RMP + EMB
9 months
No INH or No RMP
18 – 24 months

14. Poly-Resistant TB Case Study
KL, 44 year old female, born in Congo. Lived in Russia for 3 months looking after sister in a TB ward
Arrived in Canada as a refuge claimant 3 years prior to her diagnosis of TB
No previous history of TB
Gave a 1 year history of right sided chest pain and cough
3 weeks of fever, chills, malaise and weight loss
Seen by community physician who diagnosed pneumonia Biaxin x 7 days; Levofloxacin x 7 days
Not better
Stopped working as a PSW in a seniors home
Went to an ER
Abnormal CXR: bilateral UL’s cavities
Referred to the WPHC’s TB Clinic

15. Poly-resistant TB Case Study
Admitted with presumptive diagnosis of TB
Induced Sputum: AFB+, AMTD +
Treatment with the 4 drugs from Group 1
Culture grew in 4 weeks
M. TB resistant to Isoniazid, Ethambutol,
Pyrazinamide,Streptomycin, Ofloxacin and Ethionamide POLY- RESISTANT TB

16. Poly-resistant TB Case Study
Treatment modified :
Rifampin iv, Amikacin iv, Imipenem iv, Clarithromycin, PAS and Clofazimine
PAS discontinued due to increased TSH
Bacteriologic conversion after 5 months of treatment
Treated for 2 years after bacteriologic conversion
Completed treatment January 2011
Last seen March Remains well, CXR and CT Scan show scarring

17. MDR TB > 450,000 cases identified every year
150,000 deaths/year from a disease that could and should be curable
MDR TB is MAN MADE
-Mismanagement of Fully susceptibleTB or INH
resistant TB
-Poor quality of drugs
-Drugs shortages erratic supply
- Patients not taking drugs correctly
XDR TB results from failure to properly manage MDR TB

18. MDR TB Case Study (1) LW,19 year old male, born in China
Arrived in Canada as a landed immigrant
In China
Pulmonary TB treated for 2 years with frequent changes in his medications (Rifampin,Isoniazid, Ethambutol , Ofloxacin and Amikacin)
Because of persistent disease Treatment Failure, admitted to hospital (3 months)
Left Upper Lobectomy.
Came to Canada 2 months after discharge from the Chinese hospital

19. MDR TB Case Study(1) In Canada
Attended school in Toronto (grade 9), from November until June the following year
Chest X-Ray in March (for surveillance purposes) reported abnormal. Not investigated
Presented in July with productive cough, weight loss, night sweats and fatigue of 3 months duration
Referred by community physician to the TB Clinic at WPHC. Abnormal Chest Radiography
Admitted to WPHC from the clinic with presumptive diagnosis of MDR TB

20. MDR TB Case Study(1) On admission Cachectic, febrile, cough +++
Sputum Smears 4+, AMTD +
Initial Treatment : Moxifloxacin iv, Amikacin iv, Clofazimine, Cycloserine and PAS
Culture positive in 3 weeks
MDR TB with additional resistance to Ethambutol and Rifabutin

21. MDR TB Case Study(1) Slow response to the treatment
At West Park for 7 months
Regular follow-ups in clinic after discharge
Completed 32 months of treatment in January 2011 (24 months after bacteriologic conversion)
Follow-up every 3 months for the first year after treatment completion: CXR, bacteriologic update (induced sputum) and Chest CT Scan if CXR shows even minimal changes
Last clinic visit April Remains well.

22. MDR TB CASE STUDY (2)
22 years old man, Tibetan born, lived in India for 10 years, came to Canada January 2008 as a refugee claimant
No previous history of TB
Smoker, ETHOL drinker, “party boy”
September 2009:
Malaise, poor appetite, anal pain radiated to left lumbosacral area and left gluteus
Unable to walk, febrile, not responding to “Tibetan medicines”
November 15, 2009 , went to ER.
Admitted to acute care Hospital
Diagnosed: Sacral Osteomyelitis
Pus aspirated, grew anaerobes and Gram negative organisms. Treated with IV Moxifloxacin and Flagyl

23. MDR TB Case Study (2) In Acute Care:
Chest X-Ray abnormal. Sputum AFB +++
CT Scan of Chest  Posterior Segment RUL infiltrate
Bronchoscopy  Smear +
December 1st,2009, Started anti-TB Treatment:
Oral Rifampin, Ethambutol and Moxifloxacin
December 15, 2009: Isoniazid and B6 added
Stools with mucus and blood
Totally unable to walk and sit down
December 21, 2009: MDR TB with additional resistance to Ethambutol, Ethionamide, Streptomycin and Rifabutin
December 22, 2009: Transferred to WPHCC

24. MDR TB Case (2) On Admission to WPHC:
Febrile, cachectic, large right thigh abscess (sacral abscess drained through the rectum and down through the abdominal muscles sheet)
Stools grew TB
Initial Phase of Treatment (6 months):
IV Amikacin, Moxifloxacin and Imipenem, plus oral Pyrazinamide (x 3 months),Clofazimine,Cycloserine, Linezolid, and B6
Continuation Phase of Treatment:
Oral Moxifloxacin, Cycloserine, Clavulin B6, and
Clofazimine
Bacteriologic conversion May 2010
Resolution of abscesses

25. MDR TB Case (2) Discharged July 30, 2010 after 7 months in hospital
Follow up every 3 months for 1 year after discharge
December 2010, significant improvement, able to ambulate with a walker, gaining weight
Last seen in Clinic April 11, 2011
- Weight gain 23 ½ kilos
-Able to walk without a gait aid
-Chest x-ray clear
Plan is to continue treatment until May 2012

26. MDR TB Management
Treatment should be individualized and based on drug susceptibility studies
Patient to receive all the drugs to which the infecting M.TB is susceptible. When available drugs need to be given iv
If there is past history of TB and drugs previously received are known, give at least 3 drugs (bactericidal) never used before
If drug susceptibility still unknown give at least 3 bactericidal drugs, but no Rifampin or Isoniazid
Treatment for 2 years following bacteriologic conversion
DOT mandatory
Well structured and strict follow-up
Surgery in selected cases

27. Management of MDR TB Prolonged Hospitalization
Significant psycho-social issues
Requires increased number of drugs
Poor tolerance to the drugs
Increased drug- associated toxicity
Long term Follow-Up is necessary
Increased health care costs

28. MDR TB in Ontario
Affects mainly foreign born individuals in Canada for less than 5 years
Significant number of patients have previous history of TB
People from countries with high burden of TB and Drug Resistant TB will continue to migrate to Canada

29. MDR TB Control
Extraordinary measures are needed in countries with the highest rates of TB and MDR TB: rapid detection, access to drugs and steady drugs supply and effective and expert care.
The only reasonable approach is strengthening TB Control worldwide to prevent MDR TB and XDR TB

30. Tuberculosis
anywhere is
everywhere