The document discusses guidelines for treating tuberculosis (TB) according to the National Tuberculosis Elimination Programme (NTEP) in India. It outlines the goals of TB treatment, general principles of combination drug therapy, and categories of drug-sensitive and drug-resistant TB. It provides details on recommended drug regimens for different types of TB cases, including mono drug-resistant TB, rifampin-resistant or multidrug-resistant TB, and management of associated adverse drug reactions. It also covers TB treatment in special populations and preventive therapy for latent TB infection.

1. Dr. Kiran G. Piparva,
Assistant professor, Pharmacology department
All India Institute of Medical Science (AIIMS), Rajkot
Date: 10/08/2022

2. Contents…
• Goal of treatment
• General principle of treatment
• Short course chemotherapy
• Treatment category of TB: DS/DR
• Variously regimens of TB
• TB- ADR –management
• TB management in special risk group..

3.  Aims:
 To kill the Dividing bacteria : to relieve symptoms (H)
 To kill the Persisting bacteria : as to avoid relapse and ensure total cure
(R)
 To prevent emergence of drug Resistance:
so to prevent treatment failure &
to ensure adequate response
Goal of antitubercular chemotherapy:

4. • Effectiveness of therapy depends on…..
• Type of infection :P/EP, New/ Pretreated, DS/DR
• Selection of effective drug combination
• Adequate dosing: Weight based
• Drug compliance
• Sufficient duration of treatment

5. Short course chemotherapy….
• 1995- WHO introduced- Short course regimen under DOT
programme
• 1997- Guideline framework – global TB control
• 2006- “Stop TB strategy” & awareness about “MDR TB” spread
• 2010- Revised patient category: New/ Previously treated/ DR-
TB
• 2012: TB declared notifiable disease in India
• 2016- Revised Latest guideline by RNTCP : emphasized on
extensive use of drug sensitivity testing/ liquid culture/ faster
genotyping for effective treatment.
• 2021: NTEP: National tuberculosis elimination programme

6. General principle of antitubercular chemotherapy:
1. Use Combination of 2-3 CIDAL drugs- always use to decreases resistant development.
- H/R- synergistic- cidal- Shorten Rx duration
- Z-woks at inflamed site –good sterilizing activity- further shorten
duration to 6 months.
- E- Prevent resistant & hasten sputum conversion
2. DOSE of 1st line ATD is standardized on weight basis
3. Single Daily dose recommended by Directly observed treatment (DOTs) – by WHO in 1995.
4. TWO PHASE Rx, initiation phase(IP), Continuation phase(CP)
5. Response will be fast in first few week on therapy .
HRZE

7. Radiological cure
Clinical cure
Bacteriological
cure
Adequacy of regimen – confirmed by sputum/smear conversion rates
AntiTB Regimen
Intensive phase
• With 4-6 drugs
• Fast symptomatic relief
• Bring sputum conversion
Continuation phase
• With 3-4 drug
• Bacteriological cure: Eliminate
remaining bacilli
• Relapse don’t occur

8. NTEP (2021) classified TB
Drug Sensitive ( DS-TB)
 Pt sensitive to all 1st line ATD-
 Mostly NEW pts OR
 Never taken ATD (or ,1month Rx)
DRUG RESISTANT (DR –TB)
Pt resistant to any 1st line or 2nd line
ATD

9. Drug Resistant TB
R/ R + H /
with or without other 1st line ATD
Resistant to 2nd line drugs
R only
RR-TB
R +H
MDR-TB
FQ
FQ+ injectable2nd
line drug
Pre XDR -TB XDR TB
H or any other
1st line but not R
Mono drug
resistant TB

10.  Drug-Sensitive(DS)TB: Sensitive to all 5 first line drugs – all new cases who have never
taken any drug or taken for less than 1 (one) month
 All oral Mono (H) /Poly drug resistant TB: Resistant to 1 (one) 1st line drug: H or any
other drugs but NOT to R
 Rifampicin Resistant (RR-TB): Resistant to R but NOT to H, with or without resistant to
other drugs – treated like MDR-TB
 Multidrug Resistant (MDR-TB): Resistant to both R and H with or without resistant to
any other drug]
 Pre- Extensive drug resistant TB (XDR-TB): MDR-TB with resistance to 1 drug from 2nd
line fluoroquinolone
 Extensive drug resistant TB (XDR-TB): MDR-TB with resistance to 1 fluoroquinolone
and 2nd line injectable drug

11. Various TB Drug regimens:
1. Drug sensitive TB
2. Drug resistant TB –
a. Monodrug/ polydrug resistant TB,
b. RR-TB,
c. MDR TB
d. Pre XDR TB
e. XDR TB
3. Rx of TB in pregnancy and breastfeeding women
4. Mx of ADR of antitubercular drug
5. Rx of TB in AIDS patients
5. Chemoprophylaxis (latent TB infection )
6. Role of corticosteroids
7. RX of MAC infection

12. 1. Regimen for New case/ Previously treated Drug Sensitive case:
In severe extrapulmonary TB: Rx is extended by 3 – 6 months in both above cases (N/PT)

13. • WHO recommended standardized
• Daily dose of all 1st line ATD are available as
FDC with advantage of ……
-Ensuring that patients takes all the
drugs : risk of bacilli being to only 1 or
2 ATDs is eliminated
- So resistant is not fostered
• So Separate FDC for first line for (IP) and
(CP) provided by NTEP
• No of tab FDC should be taken as per dose
shown in beside table.

14. *A=Adult FDC (HRZE = 75/150/400/275; HRE = 75/150/275)
FDC(4) FDC(3)

15. Mono drug resistant TB: M. TB is resistant to Any 1st line drug except Rifampin:
Drug regimen according to NTEP-2021:
IP (6) and CP (9): Drug regimen remain same only duration is different:
Total 4 drugs: 3 drugs (1stline: R+ 2 Sensitive drugs) + 1 drug from 2nd line FQ(Lfx) = 4
drugs =6 months: Lfx+R+Z+E
Resistant to H IP(Duration of Rx - 6
months)
CP(Duration of Rx- 9
months)
H/ any other 1st line
drug
Lfx +R+Z+E Lfx+R+Z+E
1. All oral H or Mono drug (1st line drugs) resistant TB regimen:

16. Drug dose for Mono DR TB
• If Lfx cannot be used Replace with Mfxh
• Mfxh /Z Lzd Cfz + Cs
• Mfxh +Z add 2 /3 drugs (Lzd,Cfz and Cs)
• R resistance Switch to MDR TB treatment
Treatment duration : (6 or 9 months) Lfx R E Z

17.  Treatment algorithm for H Mono/ Poly drug resistant TB :
(LPA-line probe assay, LCDST: Liquid Culture Drug Sensitivity test)

18. 2. Management of RR TB/ MDR TB
• Half million NEW CASES of Rifampicin resistance TB
(RR-TB) occurred in 2019,globally.
• Estimated number of RR-TB/MDR cases in India is
1,24,000 (9.1/lakh population).
• Rx of MDR – is difficult to manage because…
- More rapid course of disease with worse
outcome
- Require Complex multiple 2nd line drug
regiments
- For longer duration
- More toxic ADRs
- More expensive

19. Rifampicin Resistant: RR TB/ MDR TB
Rifampicin Resistant Rifampicin Sensitive
1st line- LPA
2nd line- LPA
LC- DST to Z, Bdq, Cfz, Mfx, Lzd, Dlm
H Resistant (any 1 Kat/ Inh A gene)
+FQ Sensitive
a. Shot Oral Bdq regimen
H Resistant (Both Kat/ Inh A gene)
+FQ Resistant
b. Longer Oral MDR/XDR regimen
c. Longer oral M/XDR as per replacement
Not responding cases
RR MDR/ XDR (if Inj-R)

20. How to select drug regimen for MDR/RR TB: Grouping of drugs

21. Chronology of selection of drug
from group c :
Delamaind
Amikacin
Pyrazinamide
Ethionamide
PAS
Ethambutol
Meropenem
Imipenem

22. • Duration and no.of drugs :IP Phase(7 drugs)+CP Phase: (4)
• Include drugs from Group A to Group C in hierarchical order:
• Group A: All 3:Levofloxacin(OrMoxi)+Bedaquiline+Linezolid
(LLB)
• Group B: 1or 2: Cycloserine (OR Terizidone)+ Clofazimine: CC:
• Group C: Remaining 1st line (Z, PAS, Eto, Pto),
Meropenem/Imipenem, Amikacin/ streptomycin: Selection based on
DST results and previous anti TB drug used individually
Drug selection (7)
Group A: LLB ❸
Group B: CC ❶/❷
Group C: 1st line (Z,PAS,
Eto, Pto)+ meropenem,
Ak ❷
Drug regimen for RR-TB/MDR-TB

23. a. Shorter Oral Bedaquiline containing RR TB/MDR regimen
Continuation phase: CP
(5 months)
2nd line: Levofloxacin (Lfx)
Clofazimine (CFZ)
1st line : Pyrazinamide (Z)
Ethambutol (E)
Intensive phase: IP
(4-6months)
Bedaquiline (Bdq) +
2nd line drugs: Levofloxacin (Lfx)
Clofazimine (CFZ)+
1st drug: Pyrazinamide (Z)
Ethambutol (E)
High dose Isoniazid (Hh)
Ethionamide (Eto)
IP: (4-6) Bdq+ (4) (Lfx +CFZ+Z+E+ Hh+ Eto) = 7 drugs for 4-6months ( B-L-CfHEEZ)
CP: (Lfx +CFZ+E+Z) = 4 drugs for 5months ( L-CEZ)

24. Dosage: of Shorter oral Bedaquiline-containing MDR/RR-TB/XDR TB
regimen drugs for adults

25. Exclusion for short term oral regimen…
• Children below 5 years of age
• Pregnancy, lactating mother
• Drug intolerance/ allergy
• Extensive Bilateral TB/ Cavitation
• Extrapulmonary (miliary TB, TB meningitidis)

26. Shorter alternative Injectable containing MDR/RR TB regimen
Intensive phase(4 months)
2nd line: Amikacin(Ak)
High dose Moxifloxacin (MFx)
Clofazimine (CFZ)
1st line: Pyrazinamide (Z)
Ethambutol (E)
High dose Isoniazid (Hh)
Ethionamide (Eto)
Continuation phase(5 months)
2nd line: High dose Moxifloxacin (Mfx)
Clofazimine(CFZ)
1st line: Pyrazinamide (z)
Ethambutol (E)

27. For injectable treatments: Prerequisite
 Not to be used when: RR/MDR TB/ FQ resistant
 Injectable (aminoglycoside) is added
 Lfx- replaced by Mfx.
 Duration: max -11months
 Pyridoxin (10mg/kg) to be given along with high dose of INH
 Baseline : Audiometry and repeated at every 2 months
 S. Creatinine: Baseline and every 1month after starting treatment

28. Cont…

29. - Regimen selection: All group A (3) +all group B (2) : BLLCC
- Duration: 18-20 months treatment- No separate IP or CP.
- Dose of Lzd will be tapered to 300 mg after the initial 6-8 months
of treatment.
- Pyridoxin prophylaxis
Regimen: B+2L+2C:
Bedaquiline, Levofloxacin, Linezolid, Clofazimine, Cycloserine
Bdq+LzLfx CfzCy
b. Longer oral MDR / XDR-TB regimen
c. Pre XDR- XDR : Rx same for 20 months

30. • National Tuberculosis Elimination Programme - NTEP Regimens

31. BPaL regimen:
- Bedaquiline, Pretomanid and Linezolid regimen
- Under operational research condition
- Does not apply to routine programmatic use.
- BPaL showed 90% favorable outcomes among XDR (89%), MDR with
FQ resistance, treatment intolerant /non responders (92%)
- MDR-TB patients with resistant to FQ, who have either no previous
exposure to Bedaquiline and linezolid.

32. BPL regimen
Pretomanid
200 mg OD
orally-26 Wk
Bedaquiline
400 mg OD for initial
2 weeks then
200 mg 3 times/ Wk
orally- 24 weeks
Linezolid
1200 mg OD
orally- 24 weeks

33. Common ADR of 1st line TB drugs
SIDE EFFECTS OF ATD Drug(s) responsible Management of ADR
Minor No need of discontinuation of drug
Anorexia, nausea, abdominal
pain
Rifampicin Start drug with meal, symptomatic Mx
Orange/ red coloured urine Rifampicin No need of any treatment
Burning sensation in feet Isoniazid Start T. Pyridoxin
Joint pain Pyrazinamide Symptomatic , NSAIDs
Major
Deafness (no wax on otoscopy) Streptomycin STOP drug permanently - wait for
resolution of symptoms-
reconstruction of new regimen
Dizziness (vertigo, nystagmus) Streptomycin
Visual impairment/ loss Ethambutol
Generalized purpura Isoniazid, Rifampicin, Pyrazinamide STOP drug permanently - wait for
resolution of symptoms-
reintroduction of drugs at a time with
small dose and increases 3 days
Skin itching/ rash Streptomycin, Rifampicin, Isoniazid
Jaundice (other causes excluded) TO BE CONTINUE…. P.T.O.

34. Hepatotoxicity by ATD
 Most common ADR -
 first 2 months of Rx
 Common in preexisting condition-
alcoholics, malnourished, chronic
liver disease, age > than 35years.
 Fever, anorexia , lose of appetite,
abdominal pain, jaundice - LFT
 Most common culprit drug :
H > Z> R
If mild reaction :
STOP drug – resolution of reaction -
subsequently discontinued drug are restarted one
at a time - Rfirst – 7days-H
If TB us severe: Nonhepatotoxic regimen:
S+E+1FQ should be started – subsequently
reintroduced older drug one at a time.
If hepatitis recurs : stop last added drug permanently
If R/H tolerated – don’ t start Z- prolong HR -9months
If R Culprit- HES -2months –HE 10 months
If H is culprit – REZ – 9 months

35. ADR Drug associated with Management
QT prolongation: Bedaquiline ECG monitoring
Bone marrow suppression, Optic
neuritis
Linezolid CBC, Ophthalmological check up- Stop drug
Seizure, Depression- Psychiatric
symptoms, suicidal tendency
Cycloserine, H,
Etionamide
Neurological examination, Depression-
Psychiatric evaluation- Stop drug
Discolouration of skin and
secretion-
Clofazimine No need to withdrawal of drug Counselling
Gynecomastia, Hypothyrodism Ethionamide Counselling – reversible on withdrawal of
drug
ADR of 2nd line/ Newer antiTB drugs

36. Management of MDR-TB in pregnancy

37. Target population (Drug sensitive TB) Prophylacxis
HIV patient 6 (H) weight bases dose OD – 6months
Infant <12 months in close contact with
active TB
3 (HR) – weight based dose weekly- 3 months
Household contact < 5 years 3 (HR) – weight based dose weekly- 3 months
Household contact > 5 years,
immunocompromised person, silicosis,
patient on dialysis , transplantation
3 (HR), 6(H)
Drug resistant TB
H Resistant ( R sensitive) contact 4 (R) Rifampicin: >10 mg/kg/day (age>10yrs) <10 years
age: 15mg/kg : 6months
R resistant (FQ sensitive) contact 6 (Lfx): Levofloxacin Age >14yrs , BW: 45 : 750mg
Age < 15 years (range approx. 15–20 mg/kg/day): – 4
months
Chemoprophylaxis for contacts of TB

38. Role of corticosteroid in TB management
Corticosteroid should not be used in tuberculosis patients. However in certain TB it is
recommended under adequate chemotherapeutic coverage :
Indication of steroid:
• Seriously ill patients (military TB or severe pulmonary TB)
• When hypersensitivity reaction to antitubercular drugs
• In Meningeal/ Renal/Pericardial/ Pleural TB – to reduces exudation – prevent
organization and stricture
• In AIDS patients with severer manifestation of tuberculosis
• CONTRAINDICATION: intestinal TB: silent perforation
Prednisolone: 20-40 mg twice daily for 4-6 a week than tapering of steroid 5mg every week

39. TB in AIDS patients
HIV-TB is a serious problem……
• Why treatment of TB in HIV is difficult?????
- Higher incidence of extrapulmonary TB, More severe, more lethal, more
infectious
- Drug drug interaction
- Difficult to diagnose, sputum smear negative
- Atypical radiological presentation
- More ADR of ATD occurs in HIV patients
- Risk of recurrence of TB is also high
• Irrespective of CD 4 count: Start ART
• Anti TB treatment (First) – within 2 week – ART
• Start DR- TB Rx with 2nd line anti TB drug
ART ATD

41. What is new in 2021 guideline ?
• Prevent- Detect- Treat- Built strategies
• Proper Pre treatment counselling for DR-TB
• Streptomycin as 2nd line TB drug
• DST guided regimen
• No separate intensive or continuation phase for M/XDR TB treatment
• BPaL regimen in research mode
• Strict counselling for MTP in pregnant mother with DR-TB
• Transition to digital recording, reporting and monitoring system
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