MANAGEMENT OF TB: Two phase chemotherapy, General plan, Management of Drug Sensitive Tuberculosis - new and previously treated cases , All oral H mono/poly DR TB regimen, MDR/RR TB - Shorter MDR TB regimen , Management of XDR TB

General plan

All presumptive patients undergo diagnostic workup (sputum smear, CBNAAT)
In case of microbiologically confirmed TB or clinically diagnosed TB,
Pretreatment counselling (about the disease and treatment)
Pretreatment evaluation
- detailed history, weight, height, CBC, LFT, RFT, Chest X Ray,Pregnancy test in DS TB
- above investigations + previous ATT history, HIV testing, Audiogram, TSH levels, ECG, etc. in DR TB
3. Treatment according to the sensitivity status
4. Follow up

Management of Drug Sensitive Tuberculosis - new and previously treated cases

Intensive phase : 2 HRZE
Continuation phase : 4 HRE

In CNS TB, Skeletal TB, Disseminated TB - CP extended to 6 months

In TB pericarditis and meningeal TB - Steroids as adjuvant

Streptomycin is administered only in TB meningitis or to replace any first line due to ADR

All oral H mono/poly DR TB regimen

(6) Lfx R E Z
Extended to 9 months in :
Extensive disease
Uncontrolled comorbidities
Extrapulmonary TB
Sputum smear positivity at the end of 4th month
Extended to one year in :
CNS, Skeletal and miliary TB
Sputum positive at the end of 5th month - treatment failure

MDR/RR TB - Shorter MDR TB regimen

□ Intensive phase : (4-6) Mfxh Km/Am Eto Cfz Z Hh E
After 4 months :
* In case sputum smear remains positive ⇨ LPA, Culture DST
If no additional resistance ⇨ intensive phase extended maximum upto 6 months ( injectable are given three times a week in the extended IP)
If additional resistance ⇨ regimen is altered accordingly
*In case sputum smear becomes negative ⇨ Continuation phase
□ Continuation phase : (5) Mfxh Cfz Z E
sputum positive at the end of 6th month - treatment failure

MDR/RR TB - All oral longer MDR TB regimen

(18-20) Bdq(6) Lfx Lzd Cfz Cs
At the end of 6th month,
If culture becomes negative, Linezolid dose is tapered from 600 mg to 300 mg
If culture remains positive, Linezolid 600 mg dose is extended for one more month (maximum upto 8 months only)

Culture positive after 8 months - treatment failure

Bedaquiline and Delamanid would be given only for 6 months (24 weeks)
Inclusion criteria :
⊙ Patients with MDR/RR TB : > 6 years for Delomanid and ≥ 18 years for Bedaquiline
⊙ Females who are non pregnant, not on hormonal birth control methods
⊙ Patients with controlled stable arrythmia
Exclusion criteria :
⊙ Pregnant and lactating mother
⊙ Uncontrolled cardiac arrhythmia

Bedaquiline :
Week 0-2 : 400 mg daily + other drugs
Week 3-24 : 200 mg thrice a week + other drugs
Week 25 to end of treatment : no Bedaquiline - other second line drugs only
Delamanid :
> 12 years : 100 mg BD for 24 weeks + other drugs
6 to 11 years : 50 mg BD for 24 weeks + other drugs

Management of XDR TB

All oral longer MDR TB Regimen is given for 20 months

(20) Bdq(6) Lfx Lzd Cfz Cs

1. Management of Tuberculosis Angelin.A

2. Two phase chemotherapy Intensive phase : ⊙ short, aggressive ⊙three or more drugs combined to rapidly kill as many bacilli as possible ⊙brings about sputum conversion Continuation phase ⊙eliminates the remaining dormant or persisting bacilli

3. Directly Observed Treatment, Short Course (DOTS) chemotherapy In Intensive phase, ⊙patient swallows the drug in the presence of health worker or trained volunteer In Continuation phase, ⊙ medicines for one week issued in a multiblister combipack ⊙ first dose swallowed in the presence of health worker or trained volunteer ⊙ empty multiblister combipack to be returned next week

4. General plan All presumptive patients undergo diagnostic workup (sputum smear, CBNAAT) In case of microbiologically confirmed TB or clinically diagnosed TB, Pretreatment counselling (about the disease and treatment) Pretreatment evaluation - detailed history, weight, height, CBC, LFT, RFT, Chest X Ray,Pregnancy test in DS TB - above investigations + previous ATT history, HIV testing, Audiogram, TSH levels, ECG, etc. in DR TB 3. Treatment according to the sensitivity status 4. Follow up

5. Management of Drug Sensitive Tuberculosis - new and previously treated cases Intensive phase : 2 HRZE Continuation phase : 4 HRE In CNS TB, Skeletal TB, Disseminated TB - CP extended to 6 month s In TB pericarditis and meningeal TB - Steroids as adjuvant Streptomycin is administered only in TB meningitis or to replace any first line due to ADR

6. Drug dosages for first line anti - TB drugs DRUGS ADULTS (mg/kg daily) CHILDREN(mg/kg daily) Isoniazid (H) 10 5 Rifampicin (R) 15 10 Pyrazinamide (Z) 35 25 Ethambutol (E) 20 15 Streptomycin (S) 20 15

7. Daily dose schedule as per weight bands of FDCs of FDCs Weight category (kg) IP H RZE (75/150/400/275) CP HRE (75/150/275) 25 - 34 2 2 35 - 49 3 3 50 - 64 4 4 65 - 75 5 5 ≥ 75 6 6 Number of tablets

8. Management of Drug Resistant Tuberculosis Classification of drug resistance in TB: Mono resistance - resistance to one first line anti TB drug only Polydrug resistance - resistance to more than one first line anti TB drug ( but not isoniazid and rifampicin simultaneously) Multi Drug Resistance ( MDR ) - resistance to at least both isoniazid and rifampicin Extensive Drug Resistance ( XDR ) - MDR + resistance to any fluoroquinolone + resistance to one of three second line injectable Rifampicin Resistance ( RR ) - resistance to rifampicin with or without resistance to other anti TB drugs

9. All oral H mono/poly DR TB regimen (6) Lfx R E Z Extended to 9 months in : Extensive disease Uncontrolled comorbidities Extrapulmonary TB Sputum smear positivity at the end of 4th month Extended to one year in : CNS, Skeletal and miliary TB Sputum positive at the end of 5th month - treatment failure

10. MDR/RR TB - Shorter MDR TB regimen □ Intensive phase : (4-6) Mfxh Km/Am Eto Cfz Z Hh E After 4 months : * In case sputum smear remains positive ⇨ LPA, Culture DST If no additional resistance ⇨ intensive phase extended maximum upto 6 months ( injectable are given three times a week in the extended IP) If additional resistance ⇨ regimen is altered accordingly *In case sputum smear becomes negative ⇨ Continuation phase □ Continuation phase : ( 5) Mfxh Cfz Z E sputum positive at the end of 6th month - treatment failure

11. MDR/RR TB - All oral longer MDR TB regimen (18-20) Bdq(6) Lfx Lzd Cfz Cs At the end of 6th month, If culture becomes negative, Linezolid dose is tapered from 600 mg to 300 mg If culture remains positive, Linezolid 600 mg dose is extended for one more month (maximum upto 8 months only) Culture positive after 8 months - treatment failure

12. Newer drugs - Bedaquiline and Delomanid Bedaquiline and Delamanid would be given only for 6 months (24 weeks) Inclusion criteria : ⊙ Patients with MDR/RR TB : > 6 years for Delomanid and ≥ 18 years for Bedaquiline ⊙ Females who are non pregnant, not on hormonal birth control methods ⊙ Patients with controlled stable arrythmia Exclusion criteria : ⊙ Pregnant and lactating mother ⊙ Uncontrolled cardiac arrhythmia

13. Newer drugs ( cont.) Bedaquiline : Week 0-2 : 400 mg daily + other drugs Week 3-24 : 200 mg thrice a week + other drugs Week 25 to end of treatment : no Bedaquiline - other second line drugs only Delamanid : > 12 years : 100 mg BD for 24 weeks + other drugs 6 to 11 years : 50 mg BD for 24 weeks + other drugs

14. Management of XDR TB All oral longer MDR TB Regimen is given for 20 months (20)  Bdq(6)  Lfx  Lzd  Cfz  Cs

15. New Recommendations For MDR/RR TB : Shorter all oral Bedaquiline containing regimen of 9-12 months duration Intensive phase : (4-6) Bdq Lfx Cfz Z E Hh Eto Continuation phase : ( 5) Lfx Cfz Z E For MDR TB with additional Fluoroquinolone resistance : BPaL (Bedaquiline, Pretomanid and Linezolid) regimen for 6 to 9 months