1. PROF. DR. ZAFAR HUSSAIN IQBAL
MBBS, DTCD, MRCP, FRCP
PROF. OF PULMONOLOGY
AIMC / JHL
Management of Tuberculosis
In Special Situations

2. 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

3. 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)

4. 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

5. 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

6. 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

7. 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

8. Women on O.C.P
 Rifampicin: Hepatic enzyme inducer
 O.C.P may become ineffective
 Rifampicin babies
 Extra / alternative protection required
 Higher dosage

9. 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

10. 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

11. 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

12. 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

13. 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

14. 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

15. Renal Impairment
Prothionamide : Safe, Billiary excretion
Thiacetazone, PAS, Cycloserine
 Should be avoided
 Partially excreted by kidneys

16. 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:600mg OD
<50 kg:450mg OD
>50 Kg:600mg OD
<50 kg:450mg OD
>50 Kg:600mg OD
PZA <50 kg: 1.5 G OD
>50 Kg: 2 G OD
25 – 30 mg/Kg
3 x/ week
<50 kg: 1.5 G OD
>50 Kg: 2 OD
Ethambutol 15 mg/Kg daily 15 – 25 mg/Kg
3x weekly, Max 2.5G
15 mg/Kg daily
Moxifloxacin 400mg daily Not suitable for
3 x weekly
400 mg daily

17. 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

18. 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

19. 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

20. 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

21. 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

22. 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
- STOPATT

23. 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

24. 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

25. 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

26. 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

27. THANK YOU