PROF. DR. ZAFAR HUSSAIN IQBALM B B S , D T C D , M R C P, F R C PP R O F. O F P U L M O N O L O G Y
A I M C / J H L
Management of TuberculosisIn Special Situations
Tuberculosis - Global
TB is shadow of poverty1/3rd of the world population infected (1.7 billion)10% gets the disease10 million new cases each year4 million deaths each yearCrash of Boeing 747 each hour every day1 untreated pt. infects 10-15 persons per yearWHO declared TB as global emergency 1993
Tuberculosis - Pakistan
Ranks 8th amongst 22 high burden countries Incidence 181 /100,000Est. no of new TB cases 297,108 New sputum smear +ve 81 /100,000Prevalence 329 /100,000Mortality 40 /100,000New MDR Tb cases 3.2 %
(WHO Global TB Report Published in 2009 – Data of 2007)
Tuberculosis - Diagnosis
Pulmonary TBDirect sputum smear microscopy - Gold StandardCXR – unreliable, helpful in smear negative casesTuberculin testing – limited value in clinical workESR – no diagnostic valueSerological tests PCR
Extra-Pulmonary TBTissue smear for AFB and AFB cultureHistologyClinical setting
Tuberculosis – Treatment
New case Smear positive pulmonary TBSmear negative pulmonary TBExtra-pulmonary TB
Initial intensive phase – 2 RHEZContinuation phase – 6 RH or 6 HE
Re-treatmentRelapsesTreatment failureDefaulter
Initial phase – 2 RHEZ + S, 1 RHEZContinuation 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 babiesExtra / alternative protection required Higher dosage
Renal Impairment - CKD
Acquired Immunodeficiency state - High risk of T.B.50% Tuberculin -veCommon in Asian and African origin in UKThree 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 urineUse 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 & 5Needs 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 dependentSerum 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 avoidedPartially excreted by kidneys
Dose chart of ATT in CKDBTS 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/Kg3 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
Chemoprophylaxis in CKD
INH 6 monthsRH 3 monthsR 4-6monthsRZ 2 months
Protective efficiency 60 -65 % with 6H
50 % with 3 RHLong term use of INH not recommended
ATT in Hemodialysis
Immediately after HD – To avoid premature removal4- 6 hrs before HD – To reduce toxicityR & H – Standard daily dosePZA – Standard dose – 3 x weeklyEthambutol - Standard dose – 3 x weeklyAvoid Streptomycin
ATT in Renal Transplant
Standard dosage and duration of HRZEMay need modification until normal renal functionEthambutol 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 oneINH > 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.BDifficult to treat - Impaired macrophages function
Poor penetration of drug in P.M.FHong Kong study – rock islands of Granite 40% suffer
from P.T.BHigh relapse rate – 22 to 33% : 2 & 5 yearsSlower sputum conversion Standard regimen, longer duration
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