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

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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