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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. Tuberculosis is a Social Disease with a Medical Aspect.

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management of tuberculosis tb and multidrug resistant tb mdr tb

Management of Tuberculosis (TB) andMultidrug-Resistant TB (MDR TB)

Monica Avendano, MD, FRCPC

Associate Professor of Medicine

University of Toronto

Medical Director, TB Service

West Park Healthcare Centre, Toronto

worldwide trends the burden of tb disease
Worldwide Trends & the Burden of TB Disease
  • TB is still one of theleading causes ofdeathin low-income and middle-income countries.
  • TB remains athreat to public health in industrialized countries.
  • The worldwide burden is still growing.
risk factors which perpetuate worldwide tb
Risk Factorswhich 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
tuberculosis in the world
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

tuberculosis in canada demographically and geographically focused
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
management of tb
Management of TB
  • Medical Management




  • Psychosocial Management


Multicultural issues

Financial implications

Impact on family life

management of tb diagnosis suspect tb think tb
Management of TBDiagnosisSuspect 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
management of tb1
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
treatment of tb
Treatment of TB


  • Sterilize the lesion
  • Avoid development of resistance

Clinical Principles

  • Treat with multiple drugs
  • Adequate dosages
  • Sufficient duration
  • Expert monitoring
drug susceptibility in tb
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

anti tb drugs
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

poly resistant tb case study
Poly-Resistant TBCase 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
poly resistant tb case study1
Poly-resistant TBCase 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

poly resistant tb case study2
Poly-resistant TBCase 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
mdr tb
  • > 450,000 cases identified every year
  • 150,000 deaths/year from a disease that could and should be curable

-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
mdr tb case study 1
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

mdr tb case study 11
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

mdr tb case study 12
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
mdr tb case study 13
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.

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
mdr tb case study 21
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
mdr tb case 2
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


  • Bacteriologic conversion May 2010
  • Resolution of abscesses
mdr tb case 21
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
mdr tb management
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
management of mdr tb
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
mdr tb in ontario
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

mdr tb control
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