About management of tb

1. Management of TB
July 2023
Govt. Villupuram Medical College

2. Common signs and symptoms of TB
Common signs and symptoms of TB include cough for more than two
weeks, fever, significant weight loss, loss of appetite, hemoptysis (blood in
sputum) and any abnormality in chest radiograph.
Cough for
more than
two weeks
Fever (evening
rise)
Weight
loss
Blood in
sputum

3. 4 symptom complex
for TB screening among PLHIV
Adult
Current cough
Fever
Weight loss
Night Sweats
Children
Current cough
Fever
Poor weight gain
Contact with TB case
Getahun H et al. Development of a standardized screening rule for tuberculosis in people living with
HIV in resource constrained settings: individual participant data meta-analysis of observational
studies. PLoS Medicine, 2011, 8(1): e1000391. doi:10.1371/journal.pmed.1000391.
Meta analysis over 8000 patients, the NPV 97.7% (95% CI 97.4–98.0)
3

4. Diagnosis of TB
Sputum
Microscopy
Rapid Molecular
Test
CBNAAT
TrueNAT
Line Probe
Essay
Culture &
Sensitivity
X-ray/ CT
Histopathology-
Biopsy/ FNAC
Diagnostic tools
Microbiological Clinical

5. Classification based on Treatment
• DS-TB : Drug Sensitive TB
• DR-TB: Drug Resistant TB
[All TB where it is not possible to confirm DR are
cosidered as DS-TB]

6. GeneXpert

7. Truenat

8. UDST – Universal Drug Susceptibility
Testing
• All samples are subjected to CBNAAT-MTB
(GeneXpert)
• CBNAAT-MTB detects
- MTB DNA and
- Rifampicin resistance (mutations of the rpoB gene)

9. Line Probe Assay (LPA )
FL-LPA Detects R & H Resistance
SL-LPA Detects SLI & FQ Resistance
™
FL-LPA: First Line LPA
SL-LPA: Second Line LPA
R: Rifampicin
H: Isoniazid
SLI: Second Line Injectables – Sm,Am,Km
FQ: Fluoroquinolones

10. C-DST
• SOLID CULTURE :
– Lowenstein Jensen Medium
• LIQUID CULTURE:
– MGIT (Mycobacteria growth indicator tube)

11. Classification based on Treatment
• DS-TB : Drug Sensitive TB
• DR-TB: Drug Resistant TB
[All TB where it is not possible to confirm DR are
considered as DS-TB]

12. Anti TB-Drugs

13. First Line Drugs (HRZE)
• Isoniazid (INH) – H
• Rifampicin – R
• Pyrazinamide – Z
• Ethambutol – E
• Streptomycin - S

14. * Reference: WHO Consolidated Guidelines for TB module 4: Treatment of DR-TB 2020
Groups & steps Medicine Abbreviation
Group A
Include all three
medicines
Levofloxacin or
Moxifloxacin
Lfx
Mfx
Bedaquiline Bdq
Linezolid Lzd
Group B
Add one or both
medicines
Clofazimine Cfz
Cycloserine (or)
Terizidone
Cs
Trd
Group C
Add to complete
the regimen and
when medicines
from Group A and
B cannot be used
Ethambutol E
Delamanid Dlm
Pyrazinamide Z
Imipenem-cilastatin or
Meropenem
Ipm-Cln
Mpm
Amikacin
(OR Streptomycin)
Am
(S)
Ethionamide or
Prothionamide
Eto
Pto
p-aminosalicylic acid PAS
Drugs not included in Groups
A–C
• Kanamycin and Capreomycin:
o Associated with poorer outcomes
o No longer recommended for use in
MDR-TB regimens.
• Gatifloxacin
o Non availability of quality-assured
preparations due to concern about
dysglycaemias.
• Thioacetazone
o Not available in a quality-assured
formulation.
• Clavulanic acid
o Only a companion agent to the
carbapenems (Imp-Cln and Mpm)
o Not to be counted as an effective
TB agent
14
Grouping* of anti-TB drugs for treatment
of DR-TB

15. DS-TB Treatment

16. Dosage
DRUG ADULT DAILY DOSE PEADIATRIC DAILY DOSE
H 5 mg/kg 10 mg/kg
R 10 mg /kg 15 mg/kg
Z 25 mg/kg 35 mg/kg
E 15 mg/kg 20 mg/kg
S 15 mg/kg 20mg/kg

17. Theoretical basis of ATT
• A : Rapidly multiplying
bacteria
• B: Slowly multiplying
bacteria
• C: Capable of sporadic
bursts of metabolism,
multiplication. [Potential
source for relapses]
• ?D: Dormant non-
replicating bacilli.
[Potential source for
relapses]

18. Pharmacology - HRZE
Drug MoA Distribution Metabolism Excretion Renal Disease –
Dose
Adjustment
Pregnancy Resistance
– Gene
Mutation
H Inhibits synthesis of
mycolic acids
All Body
fluids
Liver –
Acetylation
Slow or Fast
Urine Not needed
(Slow acetylators
may accumulate)
Safe Kat G
InH A
R Inhibits DNA
dependent RNA
Polymerase
All Body
fluids and All
Organs
Liver -
CYP450
Enzyme
inducer
Urine – 30%
Feces – 65%
Not Needed Safe rpoB
Z Inhibits synthesis of
mycolic acids
All Body
fluids
Liver Urine Needed Safe
E Inhibits RNA
synthesis
BBB - Poor ¾ - Absorbed
½ -
Metabolized
in Liver
Urine Needed Safe

19. Adverse Events
Drug Adverse Events
H Peripheral Neuropathy
Hepatotoxicity
Seizures
R Hepatotoxicity
Orange-Red Body Secretions
Cutaneous Syndrome – Flushing +/- Pruritis +/- Rashes, faces&Scalp with eyes
watering
Abdominal Syndrome –Pain, Nausea, Vomiting, Diarrhea
Flu like syndrome – Fever, Chills, Malaise, Head ache, Body ache
Rare – Acute hemolytic anemia, Thrombocytopenia, Nephritis
Z Arthralgia
Severe Hepatotoxicity
E Retrobulbar Neuritis

20. FDC
• Fixed Dose Combinations vs Single drug
• FDC
– Difficult to find ADR Causing Drug
– Bioavailability may vary
– Easy for Patient ( May not skip any individual drug)

21. NTEP Regimen
2 months IP: HRZE + 4 months CP: HRE
4FDC 3FDC

22. Recommended duration of Therapy
Pulmonary TB 6 months [2 IP + 6 CP]
LN TB 6 months [2 IP + 6 CP]
Abdominal TB 6 months [2 IP + 6 CP]
TB PLEF 6 months [2 IP + 6 CP]
Pericardial TB 6 months [2 IP + 6 CP]
CNS TB 12 months [2 IP + 10 CP]
Ocular TB 9 - 12 months [2 IP + 7 - 10 CP]
Bone TB 12 months [2 IP + 10 CP]
Renal/ENT/Genital TB 6 months [2 IP + 6 CP]
Miliary TB Depends on involved Organs

23. Steroids in TB
• CNS TB
• Pericardial TB
• Adrenal TB
• Ocular TB
• Miliary TB – CNS, Heart, Adrenal, Eye, ARDS
• Endobronchial TB
• IRIS
• Relative Indication:
– Mediastinal LN Compressing Major Vessels

24. Dose
PREDNISOLONE :
1mg/kg/day (~ 60 mg) : First 2 weeks,
Then taper
10mg/week next 6 weeks

25. CNS TB - Steroids
• Dexamethasone
– 0.4 mg/kg/day : 1st week
– 0.3 mg/kg/day : 2nd week
– 0.2 mg/kg/day : 3rd week
– 0.1 mg/kg/day : 4th week
– 4mg/day : 5th week
– 3mg/day : 6th week
– 2 mg/day : 7th week
– 1 mg/day: 8th week
» OR >>
• Prednisolone
– 1mg/kg/day : First 2 weeks, Then taper 10mg/week next 6 weeks

26. Pericardial TB - Steroids
• Prednisolone
– 1 mg/kg/day * 4 weeks
– 0.5 mg/kg/day * 4 weeks
– 0.25 mg/kg/day * 2 weeks
– 0.125 mg/kg/day * 1 weeks

27. Dose adjustment of anti-TB drugs in
presence of renal impairment
eCrCl (Cockcroft and Gault formula)
• Men: IBW (kg) X (140 – age) / 72 X Serum Creatinine (mg/dl)
• Women: 0.85 X IBW (kg) X (140 – Age) / 72 X Serum creatinine (mg/dl)

28. Dose adjustment of anti-TB drugs in
presence of renal impairment
Drug Dose if eCrCl < 30 ml/min [or] on HD
(If on HD drug should be given after HD)
H No adjustment
R No adjustment
Z 25 mg/kg /dose thrice in a week (Not Daily)
[or]
Half the dose daily
E 15 mg/kg /dose thrice in a week (Not Daily)
[or]
Half the dose daily

29. Drug-induced liver injury

30. Copyrights apply

31. ATT induced hepatitis
• Clinical symptoms:
– Abdominal pain, Vomiting, Unexplained fatigue, Jaundice,
Altered sensorium
STOP ATT:
If Liver enzymes (AST,ALT) > 3 times of Baseline with
above symptoms
[or]
Liver enzymes (AST,ALT) > 5 times of Baseline without
above symptoms

32. REINTRODUCTION OF ATT HEPATOXIC
DRUGS
• Reintroduce only if ALT and AST < 2 ULN & Normal bilirubin
• Start one drug at time: helps identify the culprit
– Rifampicin may be introduced at 10 mg/kg dose
– After one week add Isoniazid 5 mg/kg if LFT normal
– After one week add pyrazinamide 25 mg/kg if LFT is normal
• If ATT hepatitis severe (liver failure, coagulopathy or
altered sensorium): Pyrazinamide reintroduction may be
avoided
• Duration of ATT: count only when full ATT is started

33. Chronic Liver Disease
Child-Turcotte-Pugh score Score

34. ATT SELECTION FOR UNDERLYING
LIVER DISEASE
CTP Regimen
Score 1-6 9 months HRE
OR
2 months HRE + 7 months of HR
Score 7-10 One hepatotoxic drug regimen can be used:
2 months H/R + E & SLI
Followed by
10 months H/R + E
Score 11-15 No hepatotoxic drug:
18 to 24 months using a combination of E, FQ, Cs & SLI
Acute hepatitis Avoid hepatotoxic drugs:
ATT with non-hepatotoxic drugs if urgent ATT required

35. Skin Reaction to ATT
• Mild Rash:
– Treat with Antihistamines & Continue ATT
• Moderate to Severe Rash:
– STOP ATT
– If Severe Use Oral Prenisolone
– Then Reintroduce one drug by one

36. Reintroduction