This document discusses tuberculosis (TB) management in special situations. It provides WHO guidelines for TB treatment regimens based on category of TB, including doses and duration of treatment. It also summarizes TB treatment considerations for pregnancy, breastfeeding, infants, liver disease, renal disease, HIV co-infection, and other groups. Key recommendations include safe drugs to use in pregnancy, dose adjustments for liver and renal impairment, and extending TB treatment duration for certain high-risk patients.

1. By
Mahmoud E. Abou El-Magd
TB MANGEMENT IN
SPECIAL SITUATIONS
TB IN SPECIAL SITUATIONS 1

2. WHO ANTI-TB REGIMEN
DR.T.V.RAO MD 2
Category of TB Initial phase Continuation phase
1. New smear+ PTB
Severe smear- PTB
Severe extrapulmonary TB
Severe concomitant HIV
2m HRZE 4m HR
2. Previously Treated smear+ PTB
Relapse, Failure
Treatment after default
2m HRZES 1m HREZ 5m HRE
3. New case smear- PTB
Less severe extra-pulmonary TB
2m HREZ 4m HR

3. DOSE RANGE
DR.T.V.RAO MD 3
Drug Daily dose mg/kg 3 times weekly dose mg/kg
H 5 10
R 10 10
Z 25 35
E 15 30
S 15 15

4. DR.T.V.RAO MD 4

5. DR.T.V.RAO MD 5

6. PREGNANCY
DR.T.V.RAO MD 6
• Every woman of child bearing age should be asked if
she is pregnant prior to starting anti-TB treatment
• Successful outcome of pregnancy largely depends on
successful completion of anti-TB treatment
• Category I- drugs are safe in pregnancy
• Category II- Streptomycin should be avoided if possible
as it can cause ototoxicity of the foetus

7. DR.T.V.RAO MD 7
Hippocratic view
young woman with tuberculosis should become pregnant to improve her outcome!!

8. DR.T.V.RAO MD 8
 Tuberculosis during pregnancy -rarely an indication for a therapeutic abortion
But
 pregnant woman with MDRTB, should be offered abortion counseling medications
used are known to cause fetal abnormalities

9. DR.T.V.RAO MD 9
• no increase in congenital malformations or fetal damage when rifampicin, isoniazid and
ethambutol are used in combination
• pyrazinamide is also considered to be a safe drug in pregnancy

10. DR.T.V.RAO MD 10
• 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

11. BREASTFEEDING
DR.T.V.RAO MD 11
• Women on Category I and II Regimens should continue breastfeeding
• If mother has smear+ TB and baby does not have active TB, give baby INH, as
appropriate for weight, for 6 months followed by BCG vaccination

12. DR.T.V.RAO MD 12
appears to be safe when the mother is taking standard anti-tuberculous medication.
If the mother is taking isoniazid, pyridoxine supplementation should be given to the child
as a small amount of isoniazid is present in breast milk
Mother with open Tuberculosis
Breast feeding can be done with
INAH prophylaxis
mother can use a mask

13. INFANTS OF T.B. MOTHERS & BREAST FEEDING
DR.T.V.RAO MD 13
• 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

14. WOMEN ON O.C.P
DR.T.V.RAO MD 14
• Rifampicin: Hepatic enzyme inducer
• O.C.P may become ineffective
• Rifampicin babies
• Extra / alternative protection required
• Higher dosage

15. SCHEDULE FOR REINTRODUCTION OF ANTI-
TB DRUGS
DR.T.V.RAO MD 15
Day Drug and dose
1 INH 25 mg
2 INH 50 mg
3 INH 100 mg
4 INH 200 mg
5 INH 300 mg*
6 INH 300 mg + R 150 mg
7 INH 300 mg + R 300 mg
8 INH 300 mg + R 450 mg
9 INH 300 mg + R 600 mg*
10 INH 300 mg + R 600 mg + E 400 mg
11 INH 300 mg + R 600 mg + E 800 mg
12 INH 300 mg + R 600 mg + E 1200 mg*
13 INH 300 mg + R 600 mg + E 1200 mg + Z 500 mg
14 INH 300 mg + R 600 mg + E 1200 mg + Z 1000 mg
15 INH 300 mg + R 600 mg + E 1200 mg + Z 1500 mg
16 INH 300 mg + R 600 mg + E 1200 mg + Z 2000 mg*

16. LIVER DISEASE
DR.T.V.RAO MD 16
• Three important issues complicate therapy:
• Hepatotoxicity of anti-TB drugs
• Acute liver disease with concurrent TB
• Chronic liver disease with concurrent TB

17. DR.T.V.RAO MD 17
• If possible, await resolution of acute hepatitis before starting TB treatment

18. ACUTE HEPATITIS
DR.T.V.RAO MD 18
• Consult TB expert
• Initial phase: SE for 3 months
• Continuation phase:
• RH for 6 months OR
• SE for 9 additional months
• Avoid Z, H, R and Eth (ethionamide) during acute hepatitis

19. ESTABLISHED CHRONIC LIVER
DR.T.V.RAO MD 19
• Preferred option
• Initial: 2 months RHES
• Continuation: 6 months RH
• Second option
• Initial: 2 months RES
• 10 months RE
• Third option
• Initial: 2 months HES
• Continuation: 10 months HE

20. HEPATOTOXICITY
DR.T.V.RAO MD 20
• Symptoms: Fever, malaise, right upper quadrant abdominal pain, nausea, vomiting, loss
of appetite
• Signs:
• ALT or AST more than 3x increased if symptoms of hepatitis are present, or more
than 5x increased without symptoms
• Bilirubin or alkaline phosphatase more than 2x increased
• Jaundice

21. TB DRUGS & HEPATOTOXICITY
DR.T.V.RAO MD 21
Hepatotoxic
• Pyrazinamide and isoniazid
are the most common causes
• Pyrazinamide causes the
most severe
• Rifampicin hepatotoxicity is
less common and less severe
• Ethionamide
NOT Hepatotoxic
• Ethambutol
• Streptomycin

22. DR.T.V.RAO MD 22
• Try to rule out other causes of acute liver disease
before attributing it to the TB treatment
• In hepatotoxicity, stop all TB drugs until the patient
improves
• In case of severe TB, consider using ―liver sparing
regimen‖ (Ethambutol, streptomycin, and Ciprofloxacin)
• Admit patients to the hospital if unable to maintain
hydration or if hepatic failure develops

23. ACUTE HEPATITIS:
DR.T.V.RAO MD 23
• Safest option in acute hepatitis not due to TB is to give streptomycin and ethambutol until
the hepatitis has resolved (for a maximum of 3 months) followed by a continuation phase
of INH and rifampicin for 6 months

24. REINTRODUCTION OF
DRUGS AFTER HEPATOXICITY
DR.T.V.RAO MD 24
• Continue EMB, streptomycin, +/- ciprofloxacin
• INH 300 mg daily x 4 days
• If no symptoms, add
• Rifampicin 600 mg daily x 4 days
• If no symptoms, 2 options:
• Do not try PZA
• Try PZA
• D/C streptomycin and ciprofloxacin when back on E, H, R

25. TREATMENT AFTER HEPATOTOXICITY (2)
DR.T.V.RAO MD 25
• Pyrazinamide toxicity
• 2 months RHES then 6 months RH
• Check sputum at 2, 5, and 7 months
• Pyrazinamide and isoniazid toxicity
• 2 months RES then 10 months RE
• Check sputum at 2, 5, 8, and 11 months
• Pyrazinamide and rifampicin toxicity
• 2 months HES then 10 months HE
• Check sputum at 2, 5, 8, and 11 months

26. ATT INDUCED HEPATITIS
DR.T.V.RAO MD 26
• 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

27. DR.T.V.RAO MD 27
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

28. RENAL DISEASE
DR.T.V.RAO MD 28
• Some patients with active TB will have renal disease due to either TB in the urinary tract
or another condition
• Adjust dose of ethambutol based on creatinine clearance if renal disease is suspected
• Avoid streptomycin unless specialist care is available
• Safest regimen: 2HRZ/4HR

29. DR.T.V.RAO MD 29
• 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

30. GRADES OF RENAL IMPAIRMENT IN CKD
DR.T.V.RAO MD 30
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

31. DR.T.V.RAO MD 31
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

32. DR.T.V.RAO MD 32
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

33. DR.T.V.RAO MD 33
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

34. DR.T.V.RAO MD 34
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

35. DR.T.V.RAO MD 35
Prothionamide : Safe, Billiary excretion
Thiacetazone, PAS, Cycloserine
• Should be avoided
• Partially excreted by kidneys

36. DOSE CHART OF ATT IN CKD BTS
GUIDELINES 2010
DR.T.V.RAO MD 36
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

37. CHEMOPROPHYLAXIS IN CKD
DR.T.V.RAO MD 37
• 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

38. ATT IN HEMODIALYSIS
DR.T.V.RAO MD 38
• 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

39. ATT IN RENAL TRANSPLANT
DR.T.V.RAO MD 39
• 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

40. ANTITUBERCULOSIS DRUGS
DR.T.V.RAO MD 40
• First-Line Drugs
• Isoniazid
• Rifampin
• Pyrazinamide
• Ethambutol
• Rifabutin*
• Rifapentine
• Second-Line Drugs
Streptomycin
Cycloserine
p-Aminosalicylic acid
Ethionamide
Amikacin or kanamycin*
Capreomycin
Levofloxacin*
Moxifloxacin*
Gatifloxacin*

41. DR.T.V.RAO MD 41
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

42. WHY EXTEND CONTINUATION-PHASE
TREATMENT FOR 3 MONTHS?
DR.T.V.RAO MD 42
• Cavitary disease and positive sputum culture at 2 months associated with increased
relapse in clinical trials
• Extended continuation phase decreased relapses in silicotuberculosis (from 20% to 3%)

43. WHEN TO EXTEND CONTINUATION-PHASE
TREATMENT FOR 3 MONTHS?
DR.T.V.RAO MD 43
• Cavitary pulmonary disease and positive sputum cultures at completion of initial phase
• Initial phase excluded PZA
• Once-weekly INH and rifapentine started in continuation phase and sputum specimen
collected at the end of initial phase is culture positive
• HIV-infected with positive 2-month sputum culture

44. ALGORICONTINUATION-PHASE TREATMENT FOR
CULTURE-POSITIVE THM TO GUIDE DURATION OF TB
PATIENTS
DR.T.V.RAO MD 44
High clinical suspicion for active TB
Place patient on initial-phase regimen:
INH, RIF, EMB, PZA for 2 months
Is
specimen collected at
end of initial phase (2
months) culture
positive?
YESNO
Give continuation-phase
treatment of INH/RIF daily or
twice weekly for 4 months

45. DR.T.V.RAO MD 45
Was
there
cavitation on
initial CXR?
Give continuation-phase
treatment of INH/RIF daily or
twice weekly for 7 months
Is the
patient HIV
positive?
NO
YES
YES
Give continuation- phase
treatment of INH/RIF daily
or twice weekly for
4 months
Give continuation- phase
treatment of INH/RIF
daily for
7 months
NO

46. Algorithm to Guide Treatment of
Culture-Negative TB
High clinical suspicion for active TB despite negative
smears based on:
• Abnormal chest x-ray
• Clinical symptoms
• No other diagnosis
• Positive tuberculin skin test
Patient placed on initial phase regimen:
INH, RIF, EMB, PZA for 2 months

47. Algorithm to Guide Treatment of
Culture-Negative TB (Continued)
Give continuation- phase
treatment
of INH/RIF daily
or twice weekly for
2 months
NO YES
Was
there
symptomatic
or chest x-ray
improvement after
2 months of
treatment?
NO YES
Is
initial culture
positive?
Continue
treatment for culture-
positive TB
• Discontinue treatment
• Patient presumed to have
LTBI
• Treatment completed

48. DETERMINING DRUG COMPLETION (1)
• Completion primarily defined by number of ingested doses within specified time frame
• Examples
1) 6-month daily regimen (7 days/wk) = at least 182 doses of INH
and RIF, and 56 doses of PZA
2) 6-month daily regimen (5 days/wk) =
at least 130 doses

49. DETERMINING DRUG COMPLETION (2)
• Specified doses must be administered
1) Within 3 months for initial phase
2) Within 6 months for 4-month continuation phase
$ Consider therapy interrupted if target doses not met within specified time period

50. TREATMENT INTERRUPTIONS IN THE INITIAL
PHASE
YES
Start over
from the
beginning
Is the
treatment
completed
within 3
months?
Start over
from the
beginning
Continue
treatment to
complete total
doses
warranted
NO
NO YES
How long is the interruption?
Is it < 14
days?

51. CONTINUATION PHASE TREATMENT
INTERRUPTIONS
-Additional treatment
may not be necessary if sputum
was AFB smear negative at
baseline
-If sputum smear was positive,
continue treatment to complete
planned total number of doses
warranted
NO YESIs it
<80%?
Is the
duration of interruption
<3 months?
Start initial phase 4-
drug regimen from
beginning
What is the total percentage of doses completed?
NO YES
Continue treatment; if not
completed in
6 months, start
initial phase 4-drug
regimen from beginning

52. DRUG INTERACTIONS
• Relatively few drug interactions substantially change concentrations of antituberculosis drugs
• Antituberculosis drugs sometimes change concentrations of other drugs
-Rifamycins can decrease serum concentrations of many drugs, (e.g., most of the HIV-1
protease inhibitors), to subtherapeutic levels
-Isoniazid increases concentrations of some drugs (e.g., phenytoin) to toxic levels

53. DR.T.V.RAO MD 53

54. DR.T.V.RAO MD 54

55. DR.T.V.RAO MD 55

58. MANAGEMENT OF ANTITUBERCULOSIS INDUCE
HEPATITIS
Of the first-line anti-TB drugs, isoniazid, pyrazinamide and rifampicin can all
cause liver damage
The management of hepatitis induced by TB treatment depends on:
— whether the patient is in the intensive or continuation phase of TB treatment;
— the severity of the liver disease;
— the severity of the TB

59. All drugs should be stopped
If the patient is severely ill with TB and it is considered unsafe to
stop TB treatment, a non-hepatotoxic regimen consisting of
streptomycin, ethambutol and a fuoroquinolone should be started.
If TB treatment has been stopped, it is necessary to wait for liver
function tests to revert to normal and clinical symptoms (nausea,
abdominal pain) to resolve before
reintroducing the anti-TB drugs.

60. Once drug-induced hepatitis has resolved, the drugs are
reintroduced one at a time. If symptoms recur or liver function tests
become abnormal as the drugs are reintro-duced, the last drug
added should be stopped.
Some advise starting with rifampicin because it is less likely than
isoniazid or pyrazinamide to cause hepatotoxicity and is the most
efective agent After 3–7 days, isoniazid may be reintroduced.
In patients who have experienced jaundice but tolerate the
reintroduction of rifampicin and isoniazid, it is advisable to avoid
pyrazinamide.

61. ALTERNATIVE REGIMEN
If rifampicin cannot be used………………………2SHE/10HE)
regimen without rifampicin is 2 months of isoniazid, ethambutol and
streptomycin followed by 10 months of isoniazid and ethambutol.
If isoniazid cannot be used………………………........(6-9RZE)
6–9 months of rifampicin, pyrazinamide and ethambutol
If pyrazinamide cannot be used…………………..(2HRE/7HR)
before the patient has completed the intensive phase, the total duration of
isoniazid and rifampicin therapy may be extended to 9 months
If neither isoniazid nor rifampicin can be used….8-24 EOS)
the non-hepatotoxic regimen consisting of streptomycin, ethambutol and a
fuoroquinolone should be continued for a total of 18–24 months.

62. DR.T.V.RAO MD 62