Management of Tuberculosis

In Special Situations

P R O F. D R . Z A FA R H U S S A I N I Q B A L
M B B S , D T C D , M R C P, F R C P
P R O F. O F P U L M O N O L O G Y
AIMC / JHL
 Tuberculosis - Global

 TB is shadow of poverty
 1/3rd of the world population infected (1.7 billion)
 10% gets the disease
 10 million new cases each year
 4 million deaths each year
 Crash of Boeing 747 each hour every day
 1 untreated pt. infects 10-15 persons per year
 WHO declared TB as global emergency 1993
 Tuberculosis - Pakistan

 Ranks 8th amongst 22 high burden countries

 Incidence 181 /100,000
 Est. no of new TB cases 297,108
 New sputum smear +ve 81 /100,000
 Prevalence 329 /100,000
 Mortality 40 /100,000
 New MDR Tb cases 3.2 %

(WHO Global TB Report Published in 2009 – Data of 2007)

 Tuberculosis - Diagnosis

Pulmonary TB
 Direct sputum smear microscopy - Gold Standard
 CXR – unreliable, helpful in smear negative cases
 Tuberculin testing – limited value in clinical work
 ESR – no diagnostic value
 Serological tests
 PCR
Extra-Pulmonary TB
 Tissue smear for AFB and AFB culture
 Histology
 Clinical setting
 Tuberculosis – Treatment

New case
 Smear positive pulmonary TB
 Smear negative pulmonary TB
 Extra-pulmonary TB

Initial intensive phase – 2 RHEZ

Continuation phase – 6 RH or 6 HE

Re-treatment
 Relapses
 Treatment failure
 Defaulter

Initial phase – 2 RHEZ + S, 1 RHEZ

Continuation phase – 5 RHE
 Pregnancy

• H, R, PZA, E : Safe, No evidence of teratogenecity or

congenital malformations
• Add Pyridoxine with INH to avoid small risk of CNS damage
in infants
• Rifampicin : High dose teratogenic in animals
• Streptomycin : Ototoxic, may cause deafness in babies,
Contraindicated
• Capreomycin, Kenamycin, Viomycin
• Ethionamide & Prothionamide : Teratogenic
Infants of T.B. mothers & Breast Feeding

• Mothers must continue A.T.T during feeding

• Child should not be separated
• Mother should cover her mouth during cough particularly if
smear +ve
• INH prophylaxis : 5 mg/Kg 2 months
• Do T.T - if –ve, stop INH, give BCG
- if +ve, continue INH 4 months, then BCG
• Do not give BCG while on INH
• INH resistant BCG
• Rifampicin + INH – 3 months
 Women on O.C.P

 Rifampicin: Hepatic enzyme inducer

 O.C.P may become ineffective
 Rifampicin babies
 Extra / alternative protection required
 Higher dosage
 Renal Impairment - CKD

 Acquired Immunodeficiency state - High risk of T.B.

 50% Tuberculin -ve
 Common in Asian and African origin in UK
 Three categories
 CKD
 Dialysis

 Transplant

General principle - Standard chemotherapy, standard duration,

Dose interval modification
Creatinine clearance is a better indicator than serum creatinine
 Grades Of Renal Impairment In CKD

Stage 1 CKD : Normal CC with structural abnormality

Stage 2 CKD : CC 60 – 90ml/ min

Stage 3 CKD : CC 30 – 60ml/min

Stage 4 CKD : CC 15 – 30ml/min

Stage 5 CKD : CC < 15ml/min with or without dialysis

 Renal Impairment

Rifampicin:
 Safe , Active metabolite excreted in bile.
 Inactive metabolite (10%) excreted in urine
 Use normal dose in all stages

INH
 Safe, Metabolized in liver .
 Add pyridoxine to avoid P.N.
 Use normal dose in all stages
 Renal Impairment

Pyrazinamide
 Metabolized in liver
 Delayed elimination of drug & metabolites in CKD 4 & 5
 Needs dose interval adjustment
CKD 1-3 < 50kg : 1.5g daily
> 50Kg : 2 g daily
CKD 4-5 25-30 mg/Kg 3 x / week
 Renal Impairment

Ethambutol

 Nephrotoxic , Renal excretion - 80% unchanged

 Ocular toxicity – dose dependent
 Serum monitoring required – should be <1.0ug/ml
CKD 1-3 15mg/kg daily
CKD 4-5 15-25mg/Kg 3 x week
Max 2.5 g
 Renal Impairment

Amino glycosides – Streptomycin

• Nephrotoxic, renal excretion- 80% unchanged
• Reduced clearance in elderly
• Needs dose interval adjustment in all stages
• 12-15mg/Kg - 2 or 3 time/week
• Monitor serum levels, ensure trough levels (at 24hrs) of < 2
ugm/ml
• New recomandations - avoid Aminoglycosides
• Use Moxiflocacin - 400mg daily CKD 1-3
 Renal Impairment

Prothionamide : Safe, Billiary excretion

Thiacetazone, PAS, Cycloserine

 Should be avoided
 Partially excreted by kidneys
 Dose chart of ATT in CKD
BTS Guidelines 2010
DRUG Stage 1- 3 CKD Stage 4 - 5 CKD Transplant
INH 300mg daily 300mg daily 300mg daily

Rifampicin <50 kg:450mg OD <50 kg:450mg OD <50 kg:450mg OD

>50 Kg:600mg OD >50 Kg:600mg OD >50 Kg:600mg OD

PZA <50 kg: 1.5 G OD 25 – 30 mg/Kg <50 kg: 1.5 G OD

>50 Kg: 2 G OD 3 x/ week >50 Kg: 2 OD

Ethambutol 15 mg/Kg daily 15 – 25 mg/Kg 15 mg/Kg daily

3x weekly, Max 2.5G

Moxifloxacin 400mg daily Not suitable for 400 mg daily

3 x weekly
 Chemoprophylaxis in CKD

 INH 6 months
 RH 3 months
R 4-6months
 RZ 2 months

 Protective efficiency 60 -65 % with 6H

50 % with 3 RH
 Long term use of INH not recommended
 ATT in Hemodialysis

 Immediately after HD – To avoid premature removal

 4- 6 hrs before HD – To reduce toxicity
 R & H – Standard daily dose
 PZA – Standard dose – 3 x weekly
 Ethambutol - Standard dose – 3 x weekly
 Avoid Streptomycin
 ATT in Renal Transplant

 Standard dosage and duration of HRZE

 May need modification until normal renal function
 Ethambutol can be replaced with Moxifloxacin

 Rifampicin Hepatic enzyme inducer – risk of graft rejection

Dose adjustment for Ciclosoprin ,Tacrolimus
Mycofenolate
Double the dose of steroids
 ATT Induced Hepatitis

• Usually present early but may present any time

• More with fixed drug combination than with split regimen

• Mild / transient derangement in LFTs is normal (15 – 20 %)

• TYPES – Hepatocellular , Cholestatic , Mixed

• Check viral serology (B,C) in all patients who develop hepatitis

while on ATT
 ATT Induced Hepatitis
RISK FACTOR

• Age >35 years

• Female sex
• Oriental race (EAST ASIAN)
• Pre-existing liver disease
• Extensive tuberculosis
• High alcohol consumption
• Malnutrition and hypo Albuminemia
• Other hepatotoxic drugs
• Slow Acetylator status
• High dosage in relation to body weight
 Management
Recommendation Of Joint TB Committee Of BTS

• ↑ ALT/AST (< Twice normal)

- Continue ATT
- Check after 2 weeks

• ↑ ALT/AST (>Twice normal)

- Continue ATT
- Check LFTs weekly for 2 weeks
- Then every 2 weeks until normal

• ↑ ALT/AST (>Thrice normal) + Symptoms

- Anorexia, Nausea, Vomiting, Abdominal Pain , Jaundice
- STOP ATT
 Recommendation Of Joint TB Committee Of BTS

AST/ALT (>5 time normal) OR ↑ Bilirubin

Even If Patient Asymptomatic
Stop ATT

If patient is smear –ve / Clinically stable

- Wait until LFTs are normal
- No need for alternate drugs

If patient is smear +ve / Clinically unstable

- Start Ethambutol, Streptomycin and one of the reserve drugs until LFT‘s
are normal
- Continue safe drugs until LFTs are normal
 Recommendation Of Joint TB Committee

When LFT’s are normal

• Reintroduce ATT to detect offending drugs

• Start with least hepatotoxic one by one
INH > RIF > PZA
If no reaction
• Continue ATT
• Stop alternate drugs

If reaction has developed

• Stop offending drug
• Continue remaining drugs
• Ensure adequate regimen and duration
 HIV - Infected or AIDS

 Standard regimen – usually good response

 Drug reactions more common
 Thiacetazone should be avoided
 Prolonged treatment
 Patients on Anti-retroviral therapy- high risk of
interaction with Rifampicin
withhold ATT during this period
 SILICOSIS

 More prone to develop P.T.B

 Difficult to treat - Impaired macrophages function
Poor penetration of drug in P.M.F
 Hong Kong study – rock islands of Granite 40% suffer
from P.T.B
 High relapse rate – 22 to 33% : 2 & 5 years
 Slower sputum conversion
 Standard regimen, longer duration
THANK YOU