27
PROF. DR. ZAFAR HUSSAIN IQBAL MBBS, DTCD, MRCP, FRCP PROF. OF PULMONOLOGY AIMC / JHL Management of Tuberculosis In Special Situations

T.B. Special Situations

Embed Size (px)

Citation preview

Page 1: T.B. Special Situations

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

Page 2: T.B. 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

Page 3: T.B. Special Situations

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)

Page 4: T.B. Special Situations

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

Page 5: T.B. Special Situations

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

Page 6: T.B. Special Situations

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

Page 7: T.B. Special Situations

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

Page 8: T.B. Special Situations

Women on O.C.P

Rifampicin: Hepatic enzyme inducer O.C.P may become ineffective Rifampicin babiesExtra / alternative protection required Higher dosage

Page 9: T.B. Special Situations

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

Page 10: T.B. Special Situations

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

Page 11: T.B. Special Situations

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

Page 12: T.B. Special Situations

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

Page 13: T.B. Special Situations

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

Page 14: T.B. Special Situations

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

Page 15: T.B. Special Situations

Renal Impairment

Prothionamide : Safe, Billiary excretion

Thiacetazone, PAS, Cycloserine Should be avoidedPartially excreted by kidneys

Page 16: T.B. Special Situations

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

Page 17: T.B. Special Situations

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

Page 18: T.B. Special Situations

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

Page 19: T.B. Special Situations

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

Page 20: T.B. Special Situations

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

Page 21: T.B. Special Situations

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

Page 22: T.B. Special Situations

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

Page 23: T.B. Special Situations

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

Page 24: T.B. Special Situations

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

Page 25: T.B. Special Situations

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

Page 26: T.B. Special Situations

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

Page 27: T.B. Special Situations

THANK YOU