T.B. Special Situations
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Transcript of T.B. Special Situations
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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
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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
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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)
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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
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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
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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
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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
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Women on O.C.P
Rifampicin: Hepatic enzyme inducer O.C.P may become ineffective Rifampicin babiesExtra / alternative protection required Higher dosage
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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
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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
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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
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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
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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
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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
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Renal Impairment
Prothionamide : Safe, Billiary excretion
Thiacetazone, PAS, Cycloserine Should be avoidedPartially excreted by kidneys
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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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THANK YOU