T.B. Special Situations

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T.B. Special Situations

  1. 1. PROF. DR. ZAFAR HUSSAIN IQBAL MBBS, DTCD, MRCP, FRCP PROF. OF PULMONOLOGY AIMC / JHL Management of Tuberculosis In Special Situations
  2. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 15. Renal Impairment Prothionamide : Safe, Billiary excretion Thiacetazone, PAS, Cycloserine  Should be avoided  Partially excreted by kidneys
  16. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 27. THANK YOU

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