Management of tb in drug induce liver injury,cld,ckd,pregnancy and recent update about MDR TB.

1. Presented By
DR. Nur-A-Musabber
DEM student
Mymensingh Medical College

2. Prof. Dr. A.K.M. Fazlul Haque
Professor And Head
Department of Medicine
Mymensingh Medical college and hospital.

3.  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 declaredTB as global emergency 1993

4.  Total affected population in 2017 is 165 million
 Total cases notified 244 201
 Total new and relapse 242 639
 - % tested with rapid diagnostics at time of
diagnosis <1%
 - % with known HIV status 2%
 - % pulmonary 81%
 - % bacteriologically confirmed among pulmonary
74%

5.  Sputum smear examination
 Xray
 Tuberculin skin test(MT test)
 Culture ofTB bacilli
 Molecular test (Xpert)
 FNAC and Biopsy.

7.  Drug induced hepatitis
 AcuteViral heaptitis
 Chronic liver diseases
 Renal failure
 TB with HIV
 TB with DM
 Pregnancy
 Breast feeding woman

8.  Pyrazinamide are most hepatotoxic.
 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

9.  Ethnic and Racial variation :
 More common in India (11.5% risk) compared to
western countries (4.5% risk)
 Age : >50 years ,<35 years
 Pre-existing liver disease
 Extensive tuberculosis
 High alcohol consumption
 Malnutrition and hypo Albuminemia
 Other hepatotoxic drugs
 High dosage in relation to body weight

10.  Guidelines published by ATS/BTS/WHO/ERS/
IUATLD form the basis for management
 Serum transaminases, bilirubin,
ALP,creatinine and platelet count should be
obtained for all patients starting treatment
forTB

12.  Question 1:
 When to stop anti –TB drugs?
 Most authorities suggest ALT levels > 5 times
or >3 times in presence of symptoms i.e.
jaundice

13.  Ethambutol +
 Hepatosafe
flouroquinolone(Levofloxacin/Moxifloxacin/O
floxacin/Ciprofloxacin) + Aminoglycoside
(Streptomycin)
 Supportive management for hepatic
dysfunction

14.  ATS:When ALT levels are <2 times normal
(<80 IU/L)
 BTS/WHO : ALT within normal limits

15. ATS guideline
 Rifampicin in full dose
 Isoniazid in full dose after 3-7 days if LFT is
normal
 Monitor ALT 3-7 days after re-challenge
 PyrazinamideAfter 7 days if LFT remains
normal
 If DILI occurs stop the last offending drug

16. BTS guideline
 Isoniazid : Dose titration 2-3 days(50mg to
300mg/day) Daily monitoring of LFT
 Rifampicin : Dose titration 2-3 days (75mg to
600mg/day)Daily monitoring of LFT
 Pyrazinamide : Dose titration 2-3days(250mg
to 2000mg/day)Daily monitoring of LFT
 Stop offending drug

17.  Start all drugs in full dosage. Monitor LFT.
 Stop if DILI occurs again .Give Ethambutol
and Streptomycin
 Reintroduce one by one

19.  TB treatment should be deferred until the acute
hepatitis has resolved.
 If necessary to treat tb during acute hepatitis
,the combination of streptomycin and
ethambutol for three months is the safest
option.
 After resolving hepatitis ,patient can receive a
continuation phase of six month isoniazide and
rifampicin.
 If hepatitis not resolved, streptomycin and
ethambutol should be continued for a total 12
months.

20.  Patients with CLD should not receive
pyrazinamide.Isoniazide plus rifampicin plus
one or two non hepatotoxic drugs such as
streptomycin and ethambutol can be used for
total treatment duration of 8
months(2SHRE/6HR).

25.  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

26.  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
 withholdATT during this period

27.  WHO recommends that people withTB/HIV
complete theirTB therapy prior to
beginning ARV treatment unless there is
high risk of HIV disease progression and
death during the period ofTB treatment

28.  Insulin is the choice of drug.

29. • isonizid,rifampicin,pyrazinamide, ethambutol
: 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

30.  Mothers must continue anti tb drugs 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
• DoT.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

31.  Rifampicin: Hepatic enzyme inducer
 O.C.P may become ineffective
 Extra / alternative protection required

32. Definition
 MDR-TB caused by strains of
MycobacteriumTuberculosis resistant both
Rifampicin and Isoniazid with or without
resistance to other drugs.
 Single Isoniazid or Rifampicin resistance is
not MDR -TB
 MDRTB is a laboratory diagnosis, Not a
Clinical assumption

34.  WeakTB programs (DOTS)
 Low completion/cure rates
 Lack of treatment follow up and patient
support
 Unreliable drug supply
 Diagnostic delay
 Absent or inadequate infection control
measures
 Uncontrolled use of 2ndline drugs

35. ►INH
 Chromosomally mediated
 Loss of catalase/peroxidase

36.  Chromosomal mutation in the gene
encoding the bacterial RNA polymerase.
 Reduced binding to RNA polymerase

37.  Microscopy
 Culture
 Drug SusceptibilityTesting (DST)
 MolecularTesting
1. Automated real time PCR (Xpert MTB/RIF)
2. Line prob assays

38.  The Xpert MTB/RIF is a cartridge-based,
automated diagnostic test that can identify
Mycobacterium tuberculosis (MTB)DNA and
resistance to rifampicin (RIF)by nucleic acid
amplification technique(NAAT ).
 In December 2010, theWorld Health
Organization (WHO) endorsed the Xpert
MTB/RIF for use inTB endemic countries[2]
and declared it a major milestone for globalTB
diagnosis

43. 8 months (intensive phase)
Kanamycin,pyrazinamide,ofloxacin/levofloxa
cin,ethionamide,cycloserine
12 month(continuation phase)
Pyrazinamide,ofloxacin/levofloxacin,ethiono
mide,cycloserine.
Total duration is 20 months.

46. 4-6 months (intensive phase)
Kanamycin,moxifloxacin,prothionamide,
clofazimine,pyrazinamide,high dose
ethambutol.
5 month (continuation phase)
Moxifloxacin,clofazimine,pyrazinamide,
Ethambutol.
Total duration is 9-11 months.

47.  Baseline Follow up
 Sputum Smear microscopyWeekly until Smear
negative ( 2 sample one week apart)Then
monthly
 culture Monthly-intensive phase
 Quarterly- continuation phase
 DST Any culture positive at or beyond 4 months
 RFT Monthly-intensive phase
 LFT 3 Monthly Who are at risk
 (alcoholics,HBV,HCV)
 TSH 6 Monthly if getting PAS,ETO,PTO

48.  Baseline Follow up
 CD4 6 Monthly
 CBC As required
 Audiometry Monthly-intensive phase
 Weight Monthly
 CXR 6 Monthly

49. THANKYOU