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
(1849-1919)

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
 IncreasingPoverty:
-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 - 4.7/100.000
 65% of cases in Foreign Born persons-
Rate 14/100.000
 21% in First Nation People- Rate 28/100.000
 Rate in Nunavut 174/100.000
 75% of cases are in large urban centres in
Ontario, BC and Quebec
 Socially marginalized groups
 Rate in Atlantic Region 1/100.000

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
1. Sterilize the lesion
2. Avoid development of resistance
Clinical Principles
1. Treat with multiple drugs
2. Adequate dosages
3. Sufficient duration
4. 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
 Group 2
- 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 6 months
months
9 months
INH/RMP + EMB
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 2011. 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 2011. 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
Tuberculosis
everywhere