PPT on ATT in special situations

1. Tuberculosis in special
situations
Dr. Rahul K. Gupta
MD(Medicine) DM (Pulmonary Critical care & Sleep Medicine)
Assistant Professor Respiratory Medicine
HIMS Dehradun

2. Content
ATT in
ATT
induced
hepatitis
/hepatiti
s from
other
cause
and CLD
ATT in
CKD and
patient
on RRT
ATT in
geriatric
patients
ATT in
cancer
patients
ATT and
contrace
ption
ATT in
pregnant
female
ATT in
psychiatr
ic
conditio
ns

3. Abbreviations
• H- Isoniazid
• R- Rifampicin
• P- Pyrazinamide
• E- Ethambutol

4. ATT induced hepatitis
• Symptoms and sign of hepatitis with AST /ALT above 3 time of ULN
• Serum Bilirubin 2 time of ULN
• AST/ALT 5 time of ULN

5. ATT in ATT induced hepatitis
● Stop all drugs and wait till enzyme < 2X of ULN
● Streptomycin/levofloxacin/ethambutol can be started in severe cases
● Start least hepatotoxic drug at a time when enzymes return < 2X of ULN
● In prolonged or severe cases Pyrazinamide may be permanently discontinued
● In above cases HRE treatment eventually extended to 9 months.

6. Reintroduction of ATT after drug induced hepatitis
AST/ALT<2 time
of ULN
• Start R with
E
Recheck
AST/ALT after
3–7 days
If normal
AST/ALT
• Add H, with
subsequent
rechecking of
liver enzymes
If symptoms
reoccur or liver
enzymes
increase
With hold last
added drug &
replace with
others. Duration-
counted when
full dose started
Monitoring may
required for
ALT and AST
weekly basis
initially,
fortnightly after
second month.

7. Chronic liver disease
● Isoniazid, Rifampicin or Pyrazinamide may cause hepatotoxicity.
● Rifampicin may cause cholestasis
● Ethambutol and Fluoroquinolones considered safe in CLD
● Where possible, H or R (both bactericidal and sterilizing ) should be included.
● In advanced CLD, coagulation factors should be carefully monitored

8. CHILD TURCOTTE PUGH SCORE
-
1 point 2 point 3 point
Ascites None mild mod/sev.
Albumin >3.5 2.8-3.5 <2.8
Bilirubin <2 2-3 >3
HE no i-ii iii-iv
PT <1.7 1.7-2.3 >2.3
Class Score
A 5-6
B 7-9
C 10-15

9. CPT score Drugs to use Remark
CTP ≤7 2 potentially hepatotoxic HR continuation phase prolonged to 7 months, after a
2-month intensive HRE
CTP 8–10 One hepatotoxic drug,
preferably R
R and E with a fluoroquinolone/injectable or
cycloserine for 12 to 18 months
CTP ≥11 Little/Not hepatotoxic
drug
EMB with FQ, cycloserine/ injectable for 18 to 24
months (similar to an MDR-TB regimen)
Some experts avoid aminoglycosides in patients with severe, unstable liver disease due to
concerns about renal insufficiency or bleeding from the site of injected medication due to
thrombocytopenia and/or coagulopathy.

10. ATT in pre existing liver disease
ALT level > 3 ULN before
treatment
Pre existing liver disease
9HRE
2SHRE/ 7HR
6-9 RZE
Containing two
hepatotoxic drugs
2SHE/10 HE
Containing one
hepatotoxic drug
18-24 SLE
Containing no
hepatotoxic drugs

11. DR-TB and liver disease
● Pyrazinamide, ethionamide and PAS are potentially hepatotoxic
● Levofloxacin rarely cause hepatitis
● Most second line ATT can be use safely in mild liver disease
● Other cause of hepatitis should be rule out

12. Outcome
Effectiveness
Side effect
Best
regime
Not
aggressive
for liver

13. TB & CKD

14. Burden
● Higher prevalence of TB in CKD as compared to general population
● Patients on dialysis have a 10 to 12fold higher risk of TB
● Incidence of TB in RRT patients has range nearly 5%–10% in India.

15. CKD and RRT
acquired
immunodeficienc
y state
Decreased IL2
production by act T -
helper cells
Diminished
Leucocytes
chemotaxis
Concomitant
immunosuppressive
therapy
Pathogenesis

16. Diagnosis of TB in CKD
● Difficult to diagnose because of multiple factors
● Tuberculin skin test is often negative
● Atypical radiological findings due to immuno-compromised status
● May develop pleural effusion due to heart failure, uraemic pleuritis or
hypoproteinemia
● Diagnostic value of ADA in pleural fluid is unreliable

17. Principles of management
● Principles of anti TB treatment during dialysis and following RRT remain similar
● Depends upon the pharmacology of drugs in the setting of CKD and during MHD
● Interaction with immunosuppressive drugs used
● Clearance of drugs by the kidneys
● Removal of some antituberculosis agents via haemodialysis

18. Treatment of Tuberculosis in Patients on Dialysis
● Monitoring of creatinine in 1-2 weeks
● Adequate hydration
● Dose adjustments in adults with creatinine clearance below 30 mL/minute is necessary
● Dose interval modifications where appropriate and after dialysis
● H and R are eliminated by biliary excretion, so no change in dosing is necessary
● Significant renal excretion of E and metabolites of Z

19. Dose adjustments in adults with creatinine clearance below
30 mL/minute in DS-TB
Drugs Dose
adjustment
Dose
Rifampicin No 10mg/kg (max. 600mg) per day or thrice per week
Isoniazid No 5mg/kg (max. 300mg) per day or15mg/kg (max 900 mg)
thrice per week
Ethambutol Yes 15-25mg/kg thrice per week
Pyrazinamide Yes 25-35mg/kg thrice weekly
Streptomycin yes 12-15mg/kg thrice per week

20. Second line ATT
which require no
dose adjustment
in CKD
Rifapentine
Rifabutin
Ethionamide
Prothinamide
PAS
Moxifloxacin
Clofazimine
Linezolid
Bedaquiline
Management
of Drug
resistant
tuberculosis
in CKD

21. Drug Dose in DR-TB
Cycloserine 500mg per dose thrice per week
Imipenem/cilastin 500mg/8hrly (Ccr-20-40) , 500mg/12hrly (Ccr-<20)
Meropenem 750mg/12hrly (Ccr-20-40) , 500mg/12hrly (Ccr-<20)
Capreomycin 15mg/kg thrice weekly
Kanamycin 15mg/kg thrice weekly
Amikacin 15mg/kg thrice weekly
Levofloxacin 750-1000mg/dose thrice weekly
Dose adjustments in adults with creat. clearance below 30 mL/min

22. Treatment of Tuberculosis in Recipients of Renal
Transplantation
● Dosage modification done during MHD is no longer required
● Corticosteroids should be use 1.5 times the baseline dosage.
● Possibility of hepatotoxicity by Azathioprine to be
differentiated from ATT.
● Rifampicin reduce blood tacrolimus by increase in its hepatic
metabolism so blood levels should be monitored.

23. Malignancy and Tuberculosis
● Abnormal immune system in cancer may cause infection or
reactivation.
● Association between cancer immunotherapy, such as immune
checkpoint inhibitors (ICBs) and TB infection increasingly
reported
● Anti-cancer and antituberculosis treatments can be use safely
and effectively.

24. Older
patients
and anti
tubercular
treatment
Geriatric patients and Anti
TB drugs
Comorbidities
Adverse
reactions
Frailty
Polypharmacy
Cognitive
impairment/
dementia
Drug-induced
hepatotoxicity
Optic
neuritis

25. TB in patients with seizure disorder
● H and R may interfere with many of the antiseizure medications.
● High dose H also carries a high risk of seizure
● H should be avoided in patients with active seizure disorders.

26. DR- TB in seizure disorder
● TB itself cause seizure, but if seizure develop after treatment its likely
due to drugs
● Cycloserine and Fluoroquinolone can have interaction with anti-
epileptics
● Cycloserine, fluoroquinolone and Ethionamide can be associated with
seizures.
● Prior evaluation required- weather control on medication or uncontrol

27. ● Uncontrol seizure require prior control before starting DR-TB treatment.
● Cycloserine should be avoided in uncontrolled seizure.
● If no drug appropriate Cycloserine can be use while adjusting anti-
seizure drug.

28. TB in patients with seizure disorder
Pyridoxin prophylaxis
○ Protect against the neurological adverse effects of isoniazid or cycloserine
○ Used in patients with seizure disorders
○ 10 to 25 mg/day for H
○ 25 mg pyridoxine / 250 of cycloserine daily
○ 1–2 mg/kg/day for paediatric patients at risk for neurological sequel.

29. TB and Contraceptive pills usage
● Efficacy of oral contraceptive pills may be decreased.
○ Rifampicin is a potent inducer of hepatic enzymes
○ Due to vomiting
○ Drug interactions with second line anti-TB drugs
● Use of an oral contraceptive pill containing a higher dose of estrogen
● Use of another form of contraception

30. Drug sensitive TB and Pregnancy
● Women in child bearing age should ask about current or plan pregnancy
● All first line drugs are safe except streptomycin
● Should continue breast feeding
● Take all measure to prevent transmission of TB
● After ruling out TB in infants, should receive IPT
● Mother receiving H, infant should get Pyridoxin 5mg/day

31. Drug TB in pregnancy
● Women in childbearing age should be counsel about use of appropriate
contraception
● Women in childbearing age should be tested for pregnancy in pre treatment
evaluation
● If gestational age <20 week should be advised for MTP
● If patient not willing for MTP or gestational age >20 week risk to mother and
foetus should explain
● In first trimester Kanamycin and Ethionamide should not be use and add PAS
● After first trimester omit Kanamycin only, should be replace with PAS

32. Duration of pregnancy
Explain about disease/risk to
foetus and drugs side effect
<= 20 weeks
Advise MTP
MTP
Start and continue
treatment
Unwilling for MTP
<= 12weeks – omit Kanamycin &
Ethionamide add PAS
> 12 weeks – omit Kanamycin only;
add PAS
Replace PAS with Kanamycin after
delivery and continue till end of IP
>20 weeks
Illegible for MTP
Start modified regime
Omit Kanamycin ;add
PAS till delivery
Replace PAS with
Kanamycin after delivery
and continue till end of
IP
Drug
resistant
Tuberculosis
in pregnancy
(Source NTEP training
module)

33. DR TB in patients with Psychosis
● Evaluation carried out by psychiatrist before starting treatment
● Careful monitoring of developing psychosis on treatment
● Fluoroquinolones, cycloserine and ethionamide may associated with
psychosis.
● Pyridoxin prophylaxis may be useful
● Cycloserine may also associated with severe depression and suicidal
tendency.
● Use of cycloserine is not absolute contraindication in psychiatric
patients, close monitoring is require.

34. DR TB in
patients
with
Psychosis
DR TB Patient with
psychosis/suicidal
ideation/dangers
Start antipsychotic
treatment if not
improve after
stopping cycloserine
Temporary withhold
Cycloserine, individual
/group counselling
Restart cycloserine when
symptoms resolve and
close monitoring
Rule out other
cause
Socioeconomic
Hypothyroidism
Alcohol
Other substance
Depression

35. Source and further reading
WHO Operational handbook on tuberculosis,module
NTEP training modules

36. THANK YOU