The document discusses recent advances in the treatment of tuberculosis (TB) and multi-drug resistant TB (MDR-TB) in India. It outlines the standard first-line and MDR-TB treatment regimens used in the country, including the introduction of a shorter 9-11 month regimen for MDR-TB. It also discusses the use of newer drugs like bedaquiline and delamanid to treat more resistant forms of TB. Additionally, it covers improvements to infection control practices in healthcare facilities to help eliminate TB transmission.

1. Treatment advances in
management of TB and MDR TB
2019
Dr Praveen GS
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2. Paediatric
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7. Regime for drug sensitive TB in India
• Daily treatment
• 2 HREZ + 4HRE for new patient (continuation phase includes
Ethambutol)
• Weight Band wise drug dosage
• 4 weight bands for adults & 6 weight bands for children
• FDC
• Comprehensive approach (including ADR Monitoring, improved
recording reporting, ICT enabled treatment adherence)

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10. Evolution continues
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12. Treatment of Drug Sensitive TB
Type of TB Case Treatment regimen in IP Treatment regimen in CP
New/ Previously
Treated
(2) HRZE (4) HRE
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13. No separate regimen for Previously treated
cases
• All previously treated cases also need to be initiated on standard first
line regimen (2 HRZE+4 HRE)
• CB NAAT at baseline to rule out Rifampicin resistance.
• FL-LPA to be offered to all Previously treated patients at baseline itself
to know INH susceptibility status.
• No need to wait for the FL-LPA results to start on First line regimen.
• Cases without specimens can be directly initiated on First-line regime
(need to be followed up clinically/ radiologically to identify any non-
response).
• Honorarium for treatment supporters same as New patient.
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14. Regimens for Treatment for TB
# Conventional MDR TB Regimen (24 m) for pregnant women or for EP TB patients those who are not eligible for shorter regimen.
*Offer molecular testing and treatment for H mono/poly resistance to TB patients prioritized by risk as per the available lab capacity
**LC DST (Mfx 2.0, Km, Cm, Lzd) will be done only for patients with any resistance on baseline SL-LPA. DST to Z, Cfz, Bdq & Dlm would be considered for policy in future,
whenever available, standardized & WHO endorsed.
$ States to advance in phased manner as per PMDT Scale up plan for universal DST based on lab capacity and policy on use of diagnostics
All diagnosed TB patientsPresumptive TB
Key/Vulnerable populations
• Paediatric age group
• People living with HIV
• EPTB sites
• Smear negative/NA with X-ray
suggestive of TB
• Non responders to
treatment
• DR-TB contacts
• Previously treated TB
• TB-HIV co-infection
• New TB cases $
CBNAAT
RR TB RS TB
FL-LPA*SL - LPA**
Shorter MDR TB
Regimen (9-11 m)#
First line
treatment
FQ and SLI Sensitive FQ and/or SLI Resistance H Sensitive
Newer Drugs & DST
guided treatment
Continue same regimen
(shorter MDR or H
mono/poly regimen)
In case of addl resistance, failing regimen, drug intolerance, return after
interruption (>1 m) or emergence of any exclusion criteria
H mono/poly
resistant TB
regimen
H Resistant
Continue First line
treatment
For discordance on LPA for RR-TB
– repeat CBNAAT at LPA lab
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15. Standard regimen for initiating treatment of H mono-poly DR-TB
at district DR-TB centre based on FL-LPA
H mono/poly DR-TB (R susceptible H
resistant TB & DST of SEZ not known)
6 months of
Levofloxacin, Rifampicin, Ethambutol, Pyrazinamide
• No separate Intensive phase and continuation phase
• Base line SL LPA to be offered for all patients with H resistance. No need to wait for
the results of SL LPA to initiate treatment. If additional resistance to FQ found- replace
Lfx with High dose Moxifloxacin.
• Follow up smear to be done monthly from the end of third month. Culture at the end
of 3rd month and at end of treatment, then at 12,18,24 months flowing treatment.
• Treatment duration may be extended up to 9 months based on smear, culture and
clinical progress.
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16. Shorter MDR-TB Regimen for Rif Resistance
• Treatment duration: 9-11 months
• Indicated for pulmonary & extra pulmonary case
(plural effusion and lymph nodes) RR-TB or MDR-TB
patients regardless of patient age or HIV status
• Exclusion criteria:
• Second-line drug resistance (FQ and/or SLI drugs)
• Pregnancy
• Extra pulmonary case (other than plural effusion and lymph
nodes)
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17. Standard regimen for initiating treatment of MDR/RR-TB at district DR-
TB centre based on CBNAAT or FL-LPA
Resistance Pattern
Regimen
Class
Intensive
Phase
Continuation
Phase
Shorter MDR-TB Regimen
R resistant + H
sensitive/ unknown
Or MDR -TB
Shorter
MDR-TB
Regimen
(4-6) Mfxh
Km* Eto Cfz Z
Hh E
(5) Mfxh Cfz Z E
Regimen for MDR/RR-TB
R resistant + H
sensitive/ unknown
Or MDR -TB
Conventiona
l MDR-TB
Regimen
(6-9) Lfx Km
Eto Cs Z E
(18) Lfx Eto Cs E
*If the intensive phase is prolonged, the injectable agent is only given
three times a week in the extended intensive phase.29-04-2019 ITS TIME TO END TB 17

18. Treatment….
Newer anti-TB drugs- Bdq, Dlm.
•Bedaquiline
- Diarylquinoline, targets mycobacterial ATP synthase
- Strong bactericidal, sterilizing activities
- High volume of distribution, extensive tissue distribution, highly bound to
plasma proteins
- Hepatically metabolized, extended half-life
- Improves the time to culture conversion in MDR-TB patients
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19. Bedaquiline…
- Indications
• MDR/RR-TB patients with resistance to any/all FQ or any/all SLI
• XDR-TB patients
• Mixed pattern resistant TB patients
• Treatment failures of MDR-TB + FQ/SLI resistance or XDR-TB &
MDR-TB patients with extensive pulmonary lesions, advanced disease
& others at higher baseline risk for poor outcome
- Regulatory approval…
In March 2016, RNTCP introduced BDQ through conditional access
program at 6 DR-TBCs. The preparation for expansion of access to Bdq
to all states initiated in 201729-04-2019 ITS TIME TO END TB 20

20. Bedaquiline…
- Inclusion criteria
• Adults >18yrs having pulmonary MDR-TB
• Non pregnant females/females not on hormonal birth control methods.
Should be willing to continue practicing birth control methods/ post
menopausal for 2 yrs
• Controlled stable arrhythmia
- Exclusion criteria
• Uncontrolled cardiac arrhythmias that requires medication
• QT/QTc interval marked prolongation(>450ms)/ h/o additional risk factors
for Torsades de pointes
• Evidence of chorioretinitis, optic neuritis/ uveitis at screening which
precludes long term Lzd therapy
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21. Bedaquiline…
- Following lab abnormalities
Creatinine >1.5 times ULN
Hemoglobin <6.5gm/dl
Platelet count <49,999/mm3
ANC ≤749/mm3
AST >2.5 times ULN
ALT >2.5 times ULN
Total Bilirubin >1.6 times ULN
Lipase >1.5 times ULN or with no signs/symptoms of pancreatitis
Note: ↓K+, ↓Mg2+,↓Ca2+ should be corrected before BDQ use.
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22. Bedaquiline..
• Dosage
Bdq 400 mg OD – 2 weeks + OBR
200mg 3 times/week – 3rd-22nd week +OBR
From 25th week to end of treatment- continue other 2nd line drugs
Concomitant use of Mfx and Cfz are avoided.
• Drug interactions
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23. Bedaquiline…
•Special toxicities due to Bdq
- AST/ALT elevation, Amylase/Lipase elevation, Musculoskeletal
abnormalities- myonecrosis, Gastrointestinal disorders
- Cardiac rhythm disturbances QT interval monitoring
ECG should be obtained before initiation of treatment, daily for first 2
weeks, then every 2 weeks for 3 months and then monthly.
ECG weekly if other QT prolonging drugs are included in the regimen
Normal value- QTc interval <440ms
>450 ms  R/o other causes
>480 ms (or increase of >60 from baseline)  Repeat ECG,
Check Serum K, Mg, Ca- correct it, withhold Bdq till then.
if 480 -500 ms, patient stable, electrolytes-N  Repeat ECG weekly
>500ms, confirmed by repeat ECG discontinue Bdq.29-04-2019 ITS TIME TO END TB 24

24. DELAMANID
• Nitroimidazole
• Mech of action : block the
synthesis of mycolic acid.

25. Eligibility for Delamanid/ Bedaquiline
Bedaquiline or Delamanid is indicated in MDR-TB patients not
eligible for the newly WHO-recommended shorter regimen.
These may include:
• MDR/RR-TB patients with resistance to any/all Fluoroquinolones
OR to any/all Second Line Injectables
• XDR-TB patients
• Mixed pattern resistant TB patients
• Treatment failures of MDR-TB + FQ/SLI resistance OR XDR-TB
• MDR/RR-TB patients with extensive pulmonary lesions, advanced
disease and others deemed at higher baseline risk for poor
outcomes
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26. Decision for initiating Regimen
First Line Regimen
1.MDR/RR-TB
1. Shorter MDR-TB Regimen
2. Conventional MDR- TB Regimen
2.H Mono/Poly Drug-Resistant TB
3.MDR/RR-TB with additional resistance to any/all FQ or SLI
4.XDR-TB
5.Mixed pattern resistant TB
1. with H mono + FQ/SLI/Lzd resistance
2. with MDR/RR-TB + FQ/SLI ± Lzd resistance
3. Other patients who need careful regimen designing
4. Non tuberculous mycobacterium (NTM)
At the
DDR-TB
Center
At the
NDR-TB
Center
At PHC/CHC
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27. AIC kit to be given to all patients AIC in hospitals/health facilities
Air borne Infection Control
• All health facilities/hospitals to
undergo facility risk assessment
for air borne infection control
• Hospital Infection Control
committee to train/periodically
assess and correct risks for air
borne infection transmission
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28. Government revises schedule H1
• All pharmacies to
maintain schedule
H1 register
• All sales of anti-TB
drugs to be recorded
• Name of patient,
name of prescribing
doctor, drugs
dispensed to be
recorded
• ACS (Health) has
written to DG(K) to
enforce this rule
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29. Other changes
• No IP extension
• INDEX TB
• NTM treatment
• Palliative care
• STEPS[JEET]
• System for TB Elimination in Private Sector
• Joint Effort for Elimination of TB
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