Here is a detailed treatment protocol for Pulmonary Tuberculosis (TB), including drug names, doses,

duration, side effects, and schedule based on current WHO and Indian RNTCP/NTEP guidelines:

🧫 Pulmonary Tuberculosis Treatment Protocol (Drug-Sensitive TB)

💊 Standard First-Line Anti-TB Drugs (ATD):

Drug Abbreviation Dose (mg/kg) Max Daily Dose Common Side Effects
Isoniazid H 5 mg/kg 300 mg Hepatitis, neuropathy, rash
Rifampicin R 10 mg/kg 600 mg Hepatitis, flu-like syndrome, red urine
Pyrazinamide Z 25 mg/kg 2000 mg Hepatitis, hyperuricemia, arthralgia
Ethambutol E 15 mg/kg 1600 mg Optic neuritis, visual disturbance

📅 Treatment Schedule (RNTCP/NTEP) for New Pulmonary TB (Category I)

Phase Duration Drugs Frequency

Intensive 2 months HRZE Daily (7 days/wk)
Continuation 4 months HR Daily (7 days/wk)

🕒 Total Duration: 6 months

📦 Weight-Based Dosage (Daily Regimen for Adults):

Weight Band (kg) Isoniazid (H) Rifampicin (R) Pyrazinamide (Z) Ethambutol (E)
25–39 75 mg 150 mg 400 mg 275 mg
40–54 150 mg 300 mg 1000 mg 550 mg
55–69 225 mg 450 mg 1500 mg 825 mg
≥70 300 mg 600 mg 2000 mg 1100 mg

📦 FDCs (Fixed Dose Combinations) are used under NTEP.

A Drug Sensitive TB
Section 1: - DRUG DOSAGE FOR ADULT TB (≥25 kgs body weight)

Weight Category
Number of Tablets (FDCs) (in mg) Injection
(Kgs)
Streptomycin
(in Gm.)
Intensive Phase Continuation
Phase

H R Z E H R E

75 15 400 275 75 150 27

0 5

25-39 2 2 0.5

40-54 3 3 0.75

55-69 4 4 1.0

≥70 5 5 1.0

 Injection Streptomycin to be given for 2 months in patients previously treated with drug
sensitive TB.
 Age > 50 years, maximum dose of streptomycin should be 0.75 gm.

Section 2: - DRUG DOSAGE FOR PAEDIATRIC TB (Age <12 yrs)

Weight Number of Tablets (Dispersible Injection

Category (in FDCs) (in mg) Streptomycin
Kgs.) (in mg)

Intensive Phase Continuation

Phase

H R Z E H R E
 50 75 150 100 50 75 100

4-7 1 1 1 100

8-11 2 2 2 150

12-15 3 3 3 200

16-24 4 4 4 300

25-29 3 + 1A 3 3 +1A 400

30-39 2 +2A 2 2 +2A 500

 A = Adult FDC (H/R/Z/E = 75/150/400/275; H/R/E = 75/150/275)

⚠️Common Side Effects & Monitoring

Drug Side Effects Monitoring Required

Isoniazid Hepatitis, peripheral neuropathy LFTs, give pyridoxine (Vit B6)
Rifampicin Hepatitis, orange-red urine, drug interactions LFTs, drug history
Pyrazinamide Hepatitis, gout, joint pain Uric acid, LFTs
Ethambutol Optic neuritis (loss of vision, red-green discrimination) Monthly vision check

🧾 Additional Notes:
  DOTS (Directly Observed Treatment Short-course) preferred in public health settings.
 Pyridoxine 10–25 mg/day recommended with INH to prevent neuropathy.
 HIV testing and blood glucose testing should be done in all TB patients.
 Sputum AFB testing after 2 months to assess response.

Here is a comprehensive summary of MDR-TB treatment guidelines and modifications required in

pregnancy, renal impairment, and hepatic impairment:

🦠 MDR-TB (Multidrug-Resistant Tuberculosis) Treatment

Guidelines
✅ Definition:

MDR-TB is resistant to both isoniazid (H) and rifampicin (R).

📌 WHO 2024 Preferred Regimen: All-Oral, Shorter Regimen (18–24 months)

🔹 Regimen: BDQ + LFX + LZD + CFZ + Z

 Bedaquiline (BDQ): 400 mg daily for 2 weeks, then 200 mg thrice weekly
 Levofloxacin (LFX): 750–1000 mg/day
 Linezolid (LZD): 600 mg/day (reduce to 300 mg if toxicity)
 Clofazimine (CFZ): 100 mg/day
 Pyrazinamide (Z): 25 mg/kg/day

✅ Duration: 6–9 months intensive + 9–12 months continuation

📌 Longer All-Oral Regimen (when shorter regimen not possible)

Drug Dose Duration

Bedaquiline As above 6 months
Linezolid 600 mg → 300 mg if needed Up to 18 months
Levofloxacin 750–1000 mg/day Full duration
Clofazimine 100 mg/day Full duration
Cycloserine 10–15 mg/kg/day Full duration
Delamanid (optional) 100 mg twice daily Up to 6 months

🔍 Regular monitoring: CBC, LFT, ECG (QT prolongation risk), vision (LZD), neuropathy.
🤰 TB Treatment in Pregnancy
🔹 Safe First-Line Drugs:

 Isoniazid (H) – Yes ✅ (Give pyridoxine 25 mg/day)

 Rifampicin (R) – Yes ✅
 Ethambutol (E) – Yes ✅
 Pyrazinamide (Z) – Safe, WHO approved ✅

✅ Use standard HRZE regimen (6-month course)

🔴 Avoid in Pregnancy:

 Streptomycin – ❌ Ototoxic to fetus

 Fluoroquinolones, aminoglycosides – ❌ Not recommended unless no alternatives (MDR-TB)

🧬 TB with Renal Impairment (CKD/ESRD)

Drug Renal Adjustment
INH (H) No adjustment
RIF (R) No adjustment
PZA (Z) Reduce dose or give thrice weekly if CrCl <30 ml/min
EMB (E) Reduce dose or give thrice weekly
Streptomycin Avoid if possible (ototoxic, nephrotoxic)

🩸 Hemodialysis: Give drugs after dialysis session

🏥 TB with Hepatic Impairment

Degree Management
Mild Monitor LFTs, full regimen if needed
Moderate Avoid PZA, use HRE or RE + Levofloxacin
Severe Use 2-3 non-hepatotoxic drugs (e.g., Streptomycin + EMB + LFX)

⚠️Monitor LFTs every 1–2 weeks during intensive phase

✅ Consider replacing INH or RIF if severe hepatotoxicity develops

ATD-Induced Hepatitis (Anti-TB Drug Hepatotoxicity)

🔍 Definition (per WHO/NTEP/ATS):

Hepatotoxicity is considered significant if:

 ALT/AST > 3x ULN with symptoms (nausea, vomiting, jaundice)

 ALT/AST > 5x ULN without symptoms
 Serum bilirubin >2.0 mg/dL

🚫 Most Common Hepatotoxic TB Drugs:

Drug Hepatotoxicity Risk Notes
Isoniazid (H) High ↑ Risk with age, alcohol
Rifampicin (R) Moderate Cholestatic, enzyme inducer
Pyrazinamide (Z) Highest Dose-dependent hepatotoxic

✅ Non-hepatotoxic ATDs:

 Ethambutol (E)
 Streptomycin (S)
 Levofloxacin (LFX)
 Amikacin, Cycloserine, Linezolid (MDR options)

🚑 Management Protocol of ATD-Induced Hepatitis

🔴 Step 1: Stop All Hepatotoxic Drugs Immediately

 Stop: INH, RIF, PZA

 Continue: Ethambutol + Streptomycin (or Levofloxacin if injectable not preferred)

🩺 Drugs Used During Hepatitis (While Waiting)

 Ethambutol: 15 mg/kg/day
 Streptomycin: 15 mg/kg/day (max 1 g/day)
 Continue this "safe" regimen until hepatic drugs are reintroduced.

Weight Daily Dose (approx.)

40 kg 600 mg
50 kg 750 mg
60 kg and above 1000 mg (max)
Streptomycin Dose in CKD

1. General Guidelines:

 Reduce the dose and/or extend the dosing interval.

 Therapeutic drug monitoring (TDM) is ideal if available (peak 20–35 mcg/mL; trough < 5 mcg/mL).

2. Recommended Dosing by Kidney Function:

Renal Function eGFR / Creatinine Clearance Suggested Dose Frequency

Normal > 50 mL/min 15 mg/kg (max 1 g) Daily
Mild to Moderate CKD 30–50 mL/min 12–15 mg/kg Every 2–3 days
Severe CKD < 30 mL/min 12 mg/kg Every 3–5 days
Hemodialysis (HD) N/A 12 mg/kg After dialysis sessions

Note: Always cap dose at 1 g per administration, even in normal renal function.

⚠️Precautions

 Baseline and serial audiometry (to monitor ototoxicity)

 Monitor renal function and electrolytes
 Avoid concurrent nephrotoxic or ototoxic drugs if possible.

🔬 Step 2: Monitor and Support

 LFTs every 3–7 days

 Maintain hydration and nutrition
 Avoid hepatotoxic agents (alcohol, paracetamol)
 Consider vitamin K, if INR prolonged

🔁 Step 3: Reintroduction (Rechallenge Protocol)

Start once LFTs return to <2× ULN and patient is asymptomatic

In ATD-induced hepatitis, streptomycin (S) is often added temporarily as a non-hepatotoxic agent while the
main hepatotoxic drugs (INH, Rifampicin, Pyrazinamide) are stopped. Once the liver function normalizes and
the original drugs are gradually reintroduced, streptomycin should be stopped at the appropriate time.
🧾 When and How to Stop Streptomycin in ATD-Induced Hepatitis

🔹 Step-by-Step Guide

✅ Step 1: Start of Hepatitis Management

 Stop H, R, Z (hepatotoxic drugs)

 Continue E + S (Ethambutol + Streptomycin)

✅ Step 2: Monitor LFTs

 Wait until ALT/AST normalize or drop to <2× ULN.

✅ Step 3: Reintroduction Phase

 Reintroduce H and R slowly, as per protocol.

 If tolerated without rise in LFTs for 7–10 days, continue full doses.

✅ Step 4: Decision Point

 If both INH and Rifampicin are tolerated:

🔸 You can now stop streptomycin safely, as the core bactericidal drugs (H and R) are back.
 If Pyrazinamide is reintroduced and tolerated:
🔸 Also stop S, since full HRZ regimen is restored.
 If Pyrazinamide is not reintroduced (due to high hepatotoxicity risk):
🔸 You may continue with HRE for 9 months, and stop streptomycin after full drug coverage is
achieved.

⏰ Typical Duration of Streptomycin

 Usually given for 2–4 weeks during hepatotoxic drug interruption.

 Stop when full-strength HR (±Z) is reestablished and tolerated.

📌 Clinical Tip:

Prolonged use of streptomycin (beyond 4–6 weeks) is not recommended due to:

 Risk of ototoxicity
 Nephrotoxicity
 Poor penetration in intracellular TB compared to HRZ
🔄 Rechallenge Protocol for ATD-Induced Hepatitis

🧪 Precondition: Start only after ALT/AST return to <2× ULN and symptoms resolve.

📅 Day-wise Reintroduction Schedule

Day Drug Dose Monitoring

Observe for 2–3

Day 1 Rifampicin Start with 75–150 mg (¼ to ½ dose)
days

Day 4 Increase Rifampicin to full dose e.g., 450 mg (for <50 kg) or 600 mg Check LFTs

Gradually increase to full dose over 2–

Day 7 Add Isoniazid at 50–100 mg
3 days

Day 10 Isoniazid full dose (300 mg) Continue monitoring

Day Consider adding Pyrazinamide, only if

Avoid if high risk for hepatitis
14+ essential

🔍 LFT Monitoring
  Repeat LFTs every 2–3 days during drug reintroduction.
 If ALT rises >3× ULN with symptoms or >5× ULN without symptoms, stop the last drug added.
 Permanently avoid the offending agent.

🧾 Important Notes

 Reintroduce Rifampicin first because:

o It is less hepatotoxic than isoniazid when used alone.
o It is more bactericidal and important for treatment success.
 Isoniazid is added second.
 Pyrazinamide is often not reintroduced, especially in older or hepatically vulnerable patients.
 Do not reintroduce more than one drug at a time.

✅ Example Timeline Summary

Day Action

1 Start rifampicin low dose

3 Increase rifampicin to full dose

7 Start isoniazid low dose

10 Increase isoniazid to full dose

14+ Consider pyrazinamide or modify to HRE regimen

Reintroduction Protocol After ATD-Induced Hepatitis

Day Drug Dose Action Monitoring

75–150 mg (¼ to ½ of full Observe for symptoms;

Day 1 Rifampicin Start first
dose) monitor LFTs

Day 3– Increase to full dose (450–

Rifampicin If no symptoms or LFT rise Repeat LFTs
4 600 mg)

50–100 mg (start with low Monitor for any signs of

Day 7 Isoniazid Add second drug
dose) hepatitis

Increase to full dose (300

Day 10 Isoniazid If no adverse effects LFTs every 2–3 days
mg)

Day (Optional) Reintroduce only if essential Often avoided unless Close LFT & symptom
 Day Drug Dose Action Monitoring

14+ Pyrazinamide (start low) strictly needed monitoring

🔍 Important Points

 Only one drug is added at a time.

 Pyrazinamide reintroduction is often skipped due to high hepatotoxicity risk.
 Continue non-hepatotoxic drugs (Ethambutol ± Streptomycin/Levofloxacin) throughout.
 If ALT/AST rise again, stop the most recently added drug.

🔴 When to Stop Rechallenge Immediately

 If symptoms of hepatitis recur

 If ALT/AST >3× ULN with symptoms or >5× ULN without symptoms
 Identify and permanently exclude the offending drug

🧪 Monitoring Plan
 LFTs: At baseline, Day 3, 6, 10 of rechallenge
 Monitor symptoms daily: fatigue, nausea, jaundice
 Vision test: If continuing ethambutol
 Audiometry (if using streptomycin beyond 2 weeks)

🧯 When to Stop Streptomycin?

 Once at least 2–3 hepatotoxic drugs are tolerated and patient is stable
 Usually after 2–3 weeks of rechallenge if:
o Rifampicin + Isoniazid ± Pyrazinamide are successfully reintroduced
o LFTs remain stable

❗ Streptomycin should NOT be continued long term due to:

 Risk of ototoxicity (hearing loss)

 Nephrotoxicity
 Injectable burden

🛡️Alternate Strategy if Pyrazinamide Not Reintroduced

 Use HRE for 9 months instead of 6 months
 OR HRE + Levofloxacin for 6–9 months under supervision
Here is the text extracted from the image and a summary of its content:

Management of TB patients with liver disorder

A. If serum ALT >3× ULN before treatment, use:

Regimen Drugs Duration

HRE-9 INH + RIF + EMB 9 months
HREZ(S)-2 HR-7 INH + RIF + EMB + STREP (2 months), then INH + RIF 7 months
RZE-6/9 RIF + EMB + PZA 6–9 months
SHE-2 HE-10 INH + EMB + STREP (2 months), then INH + EMB 10 months
SLE-18/24 STREP + EMB + FQ 18–24 months

B. If hepatitis develops after starting ATDs:

a) ALT/AST 3–5× ULN with symptoms:

 Withhold all hepatotoxic ATDs

 Restart when LFTs normalize:
o First: INH
o Then: RIF
o Last: PZA

b) ALT/AST >5× ULN even without symptoms:

 Withhold all hepatotoxic drugs

INH Preventive Therapy (IPT)

 Adults/Adolescents: INH 300 mg + Pyridoxine 50 mg daily × 6 months

 Children >12 months: INH 10 mg/kg + Pyridoxine 25 mg/day × 6 months

ART & TB: Timing Initiation

 Start ART irrespective of CD4 count or stage

 Start ATT first, then ART between 2 weeks–2 months
 TLE (Tenofovir + Lamivudine + Efavirenz) is preferred

New Drug under RNTCP: Bedaquiline (BDQ)

  Diarylquinoline: inhibits ATP synthase of TB bacteria
 Strong bactericidal, for MDR-TB
 No cross-resistance with H/R
 Adult, pulmonary MDR-TB only (≥18 yrs, non-pregnant females)

Diagnostic Algorithm: BDQ-containing Regimen

1. Presumptive MDR-TB → Smear

2. Smear +ve or -ve → CBNAAT or LPA
3. If RR/MDR-TB, treat per BDQ guidelines
4. If INH resistance only, treat accordingly

📌 Summary
1. Liver Disorder TB Regimens:
o Use fewer hepatotoxic drugs
o Extended or injectable-based regimens if severe
2. ATD-Induced Hepatitis:
o Stop all hepatotoxic drugs if ALT >3–5× ULN with symptoms or >5× ULN
o Rechallenge: INH → RIF → PZA
3. INH Preventive Therapy:
o 6-month course with pyridoxine for all high-risk individuals
4. ART with TB:
o Start ATT first, then ART after 2–8 weeks
o Use TLE-based ART
5. New Drug – Bedaquiline:
o For adult MDR-TB (≥18 yrs, not pregnant)
o Strong bactericidal, part of all-oral regimen

Here is a detailed discussion of the updated WHO recommendations on MDR/RR-TB and pre-XDR TB
regimens from the June 2024 Rapid Communication, including the 6-month BPaLM/BPaL regimen, 9-
month all-oral regimen, and longer 18–20 month regimen.

🔹 1. 6-Month BPaLM/BPaL Regimen

Regimen Components:

 B: Bedaquiline (BDQ)
 Pa: Pretomanid
 L: Linezolid
 M: Moxifloxacin (BPaLM) or without M for BPaL

Eligibility Criteria:
  Confirmed MDR/RR-TB
 Pre-XDR-TB (resistance to fluoroquinolones but susceptible to bedaquiline and linezolid)
 Age ≥ 14 years (ongoing trials for younger)
 No prior exposure or resistance to core drugs (esp. bedaquiline, linezolid)

Duration:

 6 months (26 weeks) – all-oral, fixed-dose combination under strict monitoring

Advantages:

 High success rates (~90%)

 Shorter duration improves adherence
 Fully oral (no injectables)

Key Safety Considerations:

 Linezolid toxicity: peripheral neuropathy, myelosuppression

 QT prolongation (due to BDQ)
 Needs baseline and regular monitoring: ECG, LFT, CBC, vision

Dosing Guidance:

Drug Usual Dose

Bedaquiline 400 mg daily × 2 weeks, then 200 mg thrice weekly
Pretomanid 200 mg once daily
Linezolid 600 mg/day (some protocols reduce to 300 mg if toxic)
Moxifloxacin 400 mg once daily (if used)

🔹 2. 9-Month All-Oral MDR/RR-TB Regimen

Regimen Components:

 Bedaquiline (BDQ)
 Levofloxacin (LFX)
 Clofazimine (CFZ)
 High-dose Isoniazid (INHh)
 Pyrazinamide (PZA)
 Ethambutol (EMB)
 ± Ethionamide (ETH) or Linezolid (LZD)

Duration:

 9 months total (4-month intensive phase + 5-month continuation)

Suggested for:

 Patients with MDR/RR-TB with no confirmed resistance to core drugs

  Where rapid DST (drug susceptibility testing) available
 Not suitable if resistance to fluoroquinolones or bedaquiline

Evidence Level:

 Conditional recommendation based on low-certainty evidence

 Included due to operational feasibility in low-resource settings

Advantages:

 Oral-only alternative to injectables

 Easier implementation where new drugs like pretomanid may not be available

🔹 3. Longer 18–20 Month All-Oral Regimen

Component Groups (as per WHO classification):

Group A (must include all 3):

 Levofloxacin (LFX) or Moxifloxacin (MFX)

 Bedaquiline (BDQ)
 Linezolid (LZD)

Group B (add at least 1):

 Clofazimine (CFZ)
 Cycloserine (CS) or Terizidone

Group C (if needed):

 Ethambutol (EMB)
 Delamanid (DLM)
 Pyrazinamide (PZA)
 Imipenem-cilastatin/Meropenem
 Amikacin/Streptomycin (last resort)

Duration:

 18–20 months (minimum 15–17 months after culture conversion)

When to Use:

 When 6-month or 9-month regimens not feasible or contraindicated

 For patients with extensive resistance (e.g. XDR-TB or resistance to BDQ/Pa)
 For pregnant, pediatric, or extrapulmonary TB patients where shorter regimens have limited data

Challenges:
  Longer treatment = more side effects, poor adherence
 Requires extensive monitoring and support

🔹 4. WHO Rapid Communication – June 2024 Highlights

WHO’s June 2024 Rapid Communication outlines key updates ahead of the full 2025 Consolidated
Guidelines:

🔸 New Regimens Introduced:

 BPaLM as preferred 6-month regimen where feasible

 BDLLfxC (Bedaquiline, Delamanid, Levofloxacin, Linezolid, Clofazimine) as an alternative longer
regimen for complex resistance patterns

🔸 Key Updates:

 Emphasis on all-oral regimens (no injectables)

 DST-guided therapy: individualized based on resistance profiles
 New paediatric-friendly formulations expected
 Improved safety monitoring protocols (especially for linezolid and QT risks)
 Surveillance of resistance to newer drugs (esp. BDQ, Pa)

✅ Summary Table of Regimens

Regimen Duration Core Drugs Target Group
BPaLM/BPaL 6 months BDQ, Pa, LZD ± MFX MDR/RR-TB, Pre-XDR, if eligible
BDQ, LFX, CFZ, INHh, PZA, EMB ± MDR/RR-TB without FQ or BDQ
9-month oral 9 months
ETH/LZD resistance
XDR-TB, complex cases, pregnancy,
Longer regimen 18–20 mo Group A + B ± C agents
children

🟩 1. MDR/RR-TB Regimen Summary Chart (Printable)

Regimen
Duration Drugs Used Patient Eligibility Key Notes
Name
MDR/RR-TB or pre-XDR-
Preferred all-oral short
BPaLM 6 months BDQ, Pa, LZD, MFX TB, susceptible to core
regimen
drugs
Same as BPaLM but no
BPaL 6 months BDQ, Pa, LZD Used in FQ-resistant cases
FQ needed
9-month 9 months BDQ, LFX, CFZ, INHh, PZA, MDR/RR-TB, no FQ Conditional
all-oral EMB ± ETH/LZD resistance, no BDQ recommendation
 Regimen
Duration Drugs Used Patient Eligibility Key Notes
Name
resistance
Group A (BDQ, LFX/MFX, XDR-TB, resistance to
Longer 18–20 For patients not eligible
LZD) + Group B (CFZ, CS) ± BDQ or LZD, complex
regimen months for shorter regimens
Group C cases

🟨 2. Drug Dosage Table (Adult)

Drug Usual Adult Dose Key Monitoring
400 mg OD x 2 wks → 200 mg thrice weekly x
Bedaquiline (BDQ) ECG (QTc), LFT
22 wks
Pretomanid (Pa) 200 mg OD LFT, neuropathy
CBC, peripheral neuropathy,
Linezolid (LZD) 600 mg OD (can reduce to 300 mg if toxicity)
vision
Moxifloxacin (MFX) 400 mg OD QTc, tendon effects
Levofloxacin (LFX) 750–1000 mg OD Renal function, CNS effects
Clofazimine (CFZ) 100 mg OD Skin pigmentation, GI issues
Isoniazid high dose Hepatotoxicity, peripheral
10–15 mg/kg/day (up to 900 mg/day)
(INHh) neuropathy
Pyrazinamide (PZA) 25–30 mg/kg/day Hepatotoxicity, uric acid
Ethambutol (EMB) 15–25 mg/kg/day Vision (optic neuritis)
Cycloserine (CS) 250–500 mg BID Mental health, neurotoxicity
Ethionamide (ETH) 250–750 mg/day GI upset, hypothyroidism

🟦 3. Regimen Selection Flowchart

┌──────────────────────────────────────┐
│ Confirmed MDR/RR-TB diagnosis? │
└───────────────┬──────────────────────┘
│
Yes ▼
┌──────────────────────────────┐
│ DST available for BDQ, LZD, │
│ fluoroquinolones (FQ)? │
└───────────────┬──────────────┘
│
Yes ▼
┌────────────────────────────────────────────┐
│ Susceptible to BDQ, LZD ± FQ (MFX)? │
└───────────────┬────────────────────────────┘
│
Yes ▼ No
┌────────────────────┐ ┌───────────────────────────────┐
 │ Use BPaLM (if FQ ✓)│ │ Resistance to BDQ or LZD? │
│ or BPaL (if FQ ✗) │ └───────────────┬──────────────┘
└────────────────────┘ │
Yes ▼ No
┌──────────────────────┐ ┌────────────────────┐
│ Use longer regimen │ │ Use 9-month oral │
│ (18–20 month) │ │ regimen if eligible│
└──────────────────────┘ └────────────────────┘

✅ Notes:

 Pregnancy, CNS TB, osteoarticular TB, and children <14 years: Avoid BPaLM/BPaL till more data
available.
 For XDR-TB or resistance to BDQ/LZD, longer regimens using Group A + B ± C should be used.
 Always individualize based on DST and patient factors.
 Close toxicity monitoring is mandatory with all regimens, especially for linezolid and QT-prolonging
drugs.

Selection of the appropriate drug-resistant TB (DR-TB) regimen requires detailed drug susceptibility testing
(DST) and other diagnostic tools to assess resistance patterns, patient factors, and eligibility. Here is a
comprehensive overview of the available tests for regimen selection, including types of DST, molecular
tools, and how to use them in decision-making.

🟩 1. Drug Susceptibility Testing (DST): The Foundation

DST determines whether Mycobacterium tuberculosis is susceptible or resistant to anti-TB drugs.

🔸 Types of DST:

Type Description Pros Cons

Culture-based test where TB bacilli Reliable for most Slow (2–8 weeks), needs
Phenotypic DST
are grown in the presence of drugs drugs, gold standard biosafety lab
May miss unknown
Genotypic DST Detects genetic mutations associated Fast (hours–1 day),
mutations, not all drugs
(molecular DST) with resistance point-of-care possible
covered

🟨 2. WHO-Recommended Molecular DST Tools

✅ Line Probe Assays (LPAs)

Name Detects resistance to Remarks

First-line LPA Detects katG, inhA, rpoB
Isoniazid (INH), Rifampicin (RIF)
(MTBDRplus) mutations
Second-line LPA Fluoroquinolones (LFX, MFX), Injectables (e.g., Detects gyrA, rrs, eis, and
(MTBDRsl) Amikacin), Linezolid (newer versions) 23S rRNA mutations
  Turnaround: 1–2 days
 Can be done directly from sputum in smear-positive patients

✅ Xpert MTB/RIF & Xpert MTB/XDR (GeneXpert platform)

Test Detects Turnaround Remarks

Frontline test for initial TB
Xpert MTB/RIF TB + Rifampicin resistance ~2 hours
diagnosis
Xpert TB + RIF, INH, FQ, AMK, KM, ETH Expands DST to second-line
~90 minutes
MTB/XDR resistance drugs

 Highly useful for rapid triage and initial regimen planning

 Recommended at point-of-care or district level labs

✅ Whole Genome Sequencing (WGS) / Targeted NGS (tNGS)

Type Use Remarks

WGS Detects resistance to all known anti-TB drugs Comprehensive, best for complex resistance (XDR)
tNGS Focused on key resistance genes Faster and cheaper than WGS

 Performed in reference labs or national programs

 Useful in pre-XDR/XDR cases or treatment failure

🟦 3. Phenotypic Culture-Based DST

Platforms:

 MGIT 960 system (automated liquid culture)

 Lowenstein-Jensen (solid media)

Drugs Tested:

 RIF, INH, LFX, MFX, BDQ, LZD, Pa, PZA, CFZ, AMK, ETH, CS, etc.

Key Points:

 Time-consuming (2–6 weeks)

 Gold standard for confirming resistance
 Needed when molecular results are inconclusive

🟪 4. Drug Resistance Testing Available for Specific Drugs

 Drug Available DST Type Notes
Rifampicin Xpert, LPA, phenotypic rpoB mutation – high confidence
Isoniazid LPA (katG, inhA), phenotypic High-dose INH can be used if only inhA mutation
Fluoroquinolones LPA (gyrA), Xpert XDR, phenotypic Critical for choosing BPaLM vs long regimens
Bedaquiline WGS, phenotypic (limited) Resistance rare, but increasing
Linezolid LPA (23S rRNA), WGS Increasing LZD resistance, needs routine testing
Pretomanid WGS (ddn, fbiA-C) Not widely available, monitored in research settings

🟫 5. Other Required Baseline Tests (Non-DST) Before Starting

Regimens
Test Purpose
ECG QT interval monitoring (BDQ, MFX, CFZ)
CBC Linezolid-induced cytopenia monitoring
LFT (Liver Function Test) BDQ, Pa, PZA hepatotoxicity
RFT (Renal Function Test) For dosing (LFX, AMK, CS)
Visual acuity test LZD, EMB (neuropathy, optic neuritis)
Peripheral neuropathy screening Baseline for LZD use
HIV test Determine co-management and drug interactions

✅ Summary: Decision-Making with Testing

Patient with confirmed TB → Run Xpert MTB/RIF →
└─> RIF resistance?
└─ Yes → MDR-TB → Do FL-LPA, SL-LPA, or Xpert XDR
└─> FQ/BDQ/LZD susceptible → Short regimen (BPaLM)
└─> FQ resistance, BDQ/LZD susceptible → BPaL
└─> BDQ/LZD resistance or complex case → Longer regimen

✅ Stepwise Checklist for DR-TB Regimen Selection

🔷 Step 1: Confirm TB Diagnosis

 ✅ Sputum positive or GeneXpert MTB detected

 ✅ Perform Xpert MTB/RIF → check for Rifampicin resistance (RR)

🔷 Step 2: Confirm MDR-TB / Pre-XDR / XDR

 ✅ If Rifampicin-resistant, initiate further testing:

o 🔸 First-Line LPA (FL-LPA) → Isoniazid resistance?
o 🔸 Second-Line LPA (SL-LPA) or Xpert MTB/XDR → Resistance to:
 Fluoroquinolones (FQ)
  Amikacin/Kanamycin
 Ethionamide
 Linezolid (if available)

🔷 Step 3: Review Patient Eligibility for Short Regimens

Criteria ✓/✗
Age ≥ 14 years
No previous exposure to BDQ, LZD, or Pa
No resistance to BDQ, LZD, FQ (as needed)
Not pregnant
Pulmonary TB only (not CNS, miliary)

🔷 Step 4: Choose Regimen Based on DST

DST Result Recommended Regimen

Susceptible to BDQ, LZD, FQ ✅ 6-month BPaLM
Susceptible to BDQ, LZD, but FQ-resistant ✅ 6-month BPaL
Susceptible to BDQ + FQ, but not eligible for BPaLM (age,
✅ 9-month oral regimen
pregnancy, etc.)
✅ 18–20 month longer all-oral regimen (Group
Resistance to BDQ or LZD, or complex XDR pattern
A+B±C)

🔷 Step 5: Baseline Tests Before Initiation

Test Purpose
CBC Linezolid safety
LFT, RFT BDQ, Pa, PZA, EMB dosing/safety
ECG QT interval monitoring
HIV Test Drug interaction + ART planning
Pregnancy test (if applicable) Regimen decision
Visual screening EMB, LZD safety

🔷 Step 6: Monitor Monthly

 Clinical response, sputum culture (monthly till conversion)

 CBC, LFT, ECG, peripheral neuropathy check
 Adherence and AE monitoring
🖨️ Flowchart for DR-TB Regimen Selection
+-----------------------------+
| Confirm TB Diagnosis (Xpert)|
+-------------+---------------+
|
+--------------v----------------+
| RIF Resistance Detected? |
+--------------+----------------+
|
Yes ▼
+-------------------------------+
| Diagnose MDR/RR-TB |
| Run FL-LPA & SL-LPA / Xpert XDR|
+---------------+---------------+
|
+-----------v-----------+
| Assess FQ, BDQ, LZD Resistance |
+-----------+-----------+
|
+------------------------+--------------------------+
| | |
▼ ▼ ▼
All susceptible FQ-resistant only BDQ or LZD-resistant /
not eligible
▼ ▼ ▼
+------------+ +---------------+ +--------------------+
| 6-month | | 6-month BPaL | | 18–20 month longer |
| BPaLM | | | | regimen (Group A+B)|
+------------+ +---------------+ +--------------------+