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