Post on 31-Dec-2015
description
Management of Tuberculosis (TB) and
Multidrug-Resistant TB (MDR TB)
Monica Avendano, MD, FRCPCAssociate Professor of Medicine
University of TorontoMedical Director, TB Service
West Park Healthcare Centre, Toronto
Tuberculosis is a Social Disease with a Medical
Aspect.
Sir William Osler in 1902(1849-1919)
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.
Worldwide Trends & the Burden of TB Disease
The worldwide burden is still growing.
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
Risk Factorswhich Perpetuate Worldwide TB
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)
1,600 Cases in 2009TB Rate - 4.7/100.00065% of cases in Foreign Born persons-
Rate 14/100.00021% in First Nation People- Rate 28/100.000Rate in Nunavut 174/100.00075% of cases are in large urban centres in
Ontario, BC and QuebecSocially marginalized groups
Rate in Atlantic Region 1/100.000
Management of TB
• Medical Management Diagnosis Treatment Follow-up
• Psychosocial Management Stigma Multicultural issues Financial implications Impact on family life
Management of TB
DiagnosisSuspect 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 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
Goals1. Sterilize the lesion2. Avoid development of resistance
Clinical Principles1. Treat with multiple drugs2. Adequate dosages3. Sufficient duration4. Expert monitoring
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): resistantto Isoniazid and Rifampin
Extensively Drug-resistant (XDR TB): MDR TBwith additional resistance to a quinolone and an injectable
Anti-TB DrugsGroup 1
- Isoniazid, Rifampin, Pyrazinamide,EthambutolGroup 2
- Amikacin, Kanamycin, CapreomycinGroup 3
- F-QuinolonesGroup 4
- Ethionamide, Cycloserine. PAS,Prothionamide Group 5
- Clofazimine,Imipenem, Thioacetazone, Clavulin, Macrolides, Linezolid
Duration of TB Treatment
Drugs Duration
INH/RMP/PZA + EMB x 2 months INH/RMP x 4 months
6 months
INH/RMP + EMB9 months
No INH or No RMP 18 – 24 months
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 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 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• 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
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(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(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(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 (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 MoxifloxacinDecember 15, 2009: Isoniazid and B6 addedStools with mucus and blood Totally unable to walk and sit downDecember 21, 2009: MDR TB with additional
resistance to Ethambutol, Ethionamide, Streptomycin and Rifabutin
December 22, 2009: Transferred to WPHCC
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 ClofazimineBacteriologic conversion May 2010 Resolution of abscesses
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 ManagementTreatment 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
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
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
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
Tuberculosis anywhere is Tuberculosis everywhere