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TB Drug Classification — India 2025–2026

Based on: WHO (2022), India NTEP Guidelines, Harrison's 21st Ed.

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PART 1: FIRST-LINE DRUGS (Drug-Sensitive TB / DS-TB)

India NTEP uses fixed-dose combinations (FDCs) for all DS-TB patients under the Pradhan Mantri TB Mukt Bharat Abhiyan.

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PART 2: SECOND-LINE DRUGS — WHO/NTEP Classification for DR-TB

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🔴 GROUP A — Highest Priority (Include ALL three unless contraindicated)

India NTEP now prioritizes BPaL/BPaLM regimens (Bedaquiline + Pretomanid + Linezolid ± Moxifloxacin) for pre-XDR and XDR-TB.

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🟡 GROUP B — Add Next (both agents preferable)

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🟢 GROUP C — Add to complete regimen (when Group A/B agents insufficient)

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PART 3: NEWER / REPURPOSED DRUGS (BPaL Regimen — India NTEP 2023 onward)

Pretomanid is a new nitroimidazole approved by WHO (2022) and introduced in India through NTEP's conditional access program. It is not classified in Groups A/B/C but is part of the BPaL framework as a distinct regimen drug.

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PART 4: SUMMARY CLASSIFICATION TABLE

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Key India-Specific Updates (NTEP 2023–2026)

1. Shorter MDR-TB regimen (9 months): BdqLfxCfzZEHhEto — used for confirmed MDR-TB without fluoroquinolone resistance.
2. Longer individualized regimen (18–20 months): Built using Group A → B → C hierarchy.
3. All oral regimens preferred — injectable aminoglycosides (amikacin, kanamycin) have been de-emphasized; kanamycin is no longer recommended by WHO.
4. Kanamycin removed from the classification — no longer recommended due to poor outcomes.
5. DST-guided therapy is mandatory before starting DR-TB treatment under NTEP.
6. PMDT (Programmatic Management of Drug-Resistant TB) is the operational framework under NTEP.

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• Harrison's Principles of Internal Medicine, 21st Edition, p. 5164
• WHO Consolidated Guidelines on Tuberculosis, Module 4: Treatment (2022)
• India NTEP — Technical and Operational Guidelines for TB Control (2023 updated)
• WHO TB Drug Classification Update (2022) — Groups A, B, C framework

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TB Drug Resistance Classification — Updated 2025–2026

WHO 2021 Revised Definitions | India NTEP Aligned

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⚠️ KEY UPDATE: WHO 2021 Redefined XDR-TB & Introduced Pre-XDR-TB

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COMPLETE DRUG RESISTANCE CLASSIFICATION

1. 🟡 Mono-Drug Resistance (MR-TB)

Resistance to one first-line anti-TB drug only (not rifampicin alone)

• India note: Isoniazid mono-resistance (Hr-TB) is treated with 6RZELfx regimen under NTEP.

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2. 🟡 Polydrug Resistance (PDR-TB)

Resistance to more than one first-line drug, but not the combination of isoniazid + rifampicin

• Distinct from MDR-TB
• Requires individualized regimen based on DST

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3. 🔴 Rifampicin-Resistant TB (RR-TB)

Resistance to rifampicin detected by any method (phenotypic or molecular — Xpert MTB/RIF)

• May or may not have isoniazid resistance
• Treated the same as MDR-TB under NTEP/WHO
• Xpert Ultra can detect RR-TB rapidly → triggers DR-TB treatment pathway

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4. 🔴 Multi-Drug Resistant TB (MDR-TB)

Resistance to both isoniazid AND rifampicin, with or without resistance to other drugs

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5. 🟠 Pre-XDR TB (NEW — WHO 2021)

MDR/RR-TB + resistance to any fluoroquinolone (levofloxacin or moxifloxacin)

• Treatment: BPaLM regimen (Bedaquiline + Pretomanid + Linezolid + Moxifloxacin) under India NTEP
• India NTEP adopted Pre-XDR category formally in 2022–23 updates

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6. 🔴 Extensively Drug-Resistant TB (XDR-TB) (REDEFINED — WHO 2021)

MDR/RR-TB + resistance to any fluoroquinolone + resistance to at least one Group A drug (bedaquiline OR linezolid)

"XDR-TB: TB caused by M. tuberculosis resistant to rifampicin, AND resistant to at least one fluoroquinolone (levofloxacin or moxifloxacin), AND to at least one other Group A drug (bedaquiline or linezolid)."

• Treatment: BPaL regimen (Bedaquiline + Pretomanid + Linezolid) — 6 months

⚠️ OLD definition (pre-2021): XDR = MDR + fluoroquinolone resistance + ≥1 injectable (amikacin/kanamycin/capreomycin). This definition is now obsolete.

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SIDE-BY-SIDE COMPARISON: OLD vs. NEW XDR-TB DEFINITION

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COMPLETE UPDATED CLASSIFICATION SUMMARY TABLE

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INDIA NTEP TREATMENT REGIMEN MAPPING (2023–2026)

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Important Points for India Context

1. Kanamycin and capreomycin are no longer recommended — WHO/NTEP removed them from DR-TB regimens.
2. Universal DST (drug susceptibility testing) is mandatory in India before initiating DR-TB treatment — Xpert MTB/RIF for RR, LPA for FQ/SLI, culture DST for Group A drugs.
3. Pretomanid is conditionally available in India through NTEP for BPaL/BPaLM regimens.
4. Bedaquiline is now freely available at DR-TB centres across India under NTEP.
5. The shorter BPaLM regimen (6 months) is a major shift — previously, XDR patients needed 24+ months of treatment.

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• Tuberculosis: Tuberculosis and Comorbidities (p. 12) — XDR-TB 2021 definition
• Prevention and Treatment of Opportunistic Infections in Children with and Exposed to HIV (p. 341) — comparative XDR definitions
• Harrison's Principles of Internal Medicine, 21st Ed. (p. 5164) — Group A/B/C classification
• WHO Consolidated Guidelines on TB, Module 4: Treatment (2022)
• India NTEP Technical & Operational Guidelines (2023 update)
• WHO 2021 Revised Definitions of TB Disease Classification

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TB Management in HIV/AIDS & TB in Pregnancy/Lactation

Sources: Harrison's 21st Ed. | WHO Consolidated TB Guidelines (2022) | TB & Comorbidities Guideline | Treatment of Drug-Resistant TB (WHO)

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PART 1: TB–HIV/AIDS CO-INFECTION MANAGEMENT

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1. General Principles

• TB is the leading cause of death in PLHIV (people living with HIV) globally
• HIV accelerates TB progression: HIV+ individuals have 20–30× higher risk of active TB
• India carries the highest dual TB-HIV burden in the world
• All TB patients must be HIV tested and all HIV patients must be screened for TB at every visit

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2. When to Start ART — Updated WHO Recommendation

"ART should be started as soon as possible within two weeks of initiating TB treatment, regardless of CD4 cell count, among people living with HIV." (Strong recommendation, low-to-moderate certainty evidence)

Exception: When signs/symptoms of TB meningitis are present — delay ART to reduce risk of severe IRIS.

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3. ART Regimen Choice — Drug Interactions with Rifampicin

India NTEP / NACO 2023: Preferred ART for TB-HIV co-infection = TDF + 3TC + DTG (50 mg BD) or TDF + 3TC + EFV 600 mg

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4. MDR-TB in HIV — Special Considerations

"Bedaquiline and/or delamanid might be considered for use in patients with HIV. Although efavirenz can produce a decrease in serum bedaquiline concentrations and this combination is avoided, other ART drugs including protease inhibitors and cobicistat can result in increased serum bedaquiline levels."

QTc prolongation monitoring is mandatory in HIV-TB patients on Bdq/Dlm/Cfz combinations, especially with PI-based ART.

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5. Cotrimoxazole Preventive Therapy (CPT)

"Routine co-trimoxazole prophylaxis should be given to all people living with HIV with active TB disease regardless of CD4 cell count." (Strong recommendation, high-certainty evidence)

• Prevents PCP, toxoplasmosis, bacterial infections, and malaria (in endemic areas)
• Dose: Co-trimoxazole 960 mg OD (single-strength or double-strength per weight)

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6. Immune Reconstitution Inflammatory Syndrome (IRIS)

"IRIS occurs in ~10% of HIV-infected TB patients. Usually developing 1–3 months after initiation of ART... The earlier ART is started and the lower the baseline CD4+ T-cell count, the greater the risk of IRIS."

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7. Isoniazid Preventive Therapy (IPT) / TB Preventive Therapy (TPT) in HIV

• All PLHIV with no active TB should receive TPT (TB Preventive Therapy)
• India NTEP / WHO recommendation:

TPT should be given after excluding active TB by clinical screening + CXR.

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8. Summary Algorithm — TB-HIV Management

TB Diagnosed in HIV+ Patient
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Start Anti-TB Therapy (ATT) immediately
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Is it TB Meningitis?
   YES → Start ART at 4–8 weeks
   NO  → Start ART within 2 WEEKS
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Choose ART: TDF + 3TC + DTG (50mg BD) OR EFV 600mg
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Add Co-trimoxazole prophylaxis (regardless of CD4)
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Monitor for IRIS (1–3 months post-ART)
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Screen household contacts → Offer TPT if no active TB

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PART 2: TB IN PREGNANCY AND LACTATION

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1. Impact of TB on Pregnancy

Active TB in pregnancy must be treated — untreated TB is far more dangerous to mother and fetus than any anti-TB drug.

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2. Drug-Sensitive TB (DS-TB) in Pregnancy

"The regimen of choice for pregnant women is 9 months of treatment with isoniazid and rifampin supplemented by ethambutol for the first 2 months. Although WHO has recommended routine use of pyrazinamide in pregnant women, this drug has not been recommended in the United States because of insufficient data documenting its safety in pregnancy."

WHO vs. US Approach:

India NTEP follows WHO — pyrazinamide IS used, making the standard regimen 2HRZE/4HR (6 months).

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3. Drug Safety in Pregnancy — Individual Drug Review

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4. MDR-TB in Pregnancy

• Most challenging scenario — majority of preferred Group A drugs have limited safety data
• Individualized DST-guided regimen is essential
• Recommended approach per WHO 2022:

India NTEP: MDR-TB in pregnancy is managed at DR-TB centres with multidisciplinary team (pulmonologist + obstetrician + neonatologist).

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5. TB in Lactation (Breastfeeding)

"Treatment for TB is not a contraindication to breastfeeding; most of the drugs administered will be present in small quantities in breast milk, albeit at concentrations far too low to provide any therapeutic or prophylactic benefit to the child."

Key point: Drug levels in breast milk are sub-therapeutic — they protect neither the infant from TB nor cause clinical toxicity. Breastfeeding is encouraged while on standard ATT.

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6. Neonatal Considerations

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7. Summary Table — DS-TB Regimens in Special Populations

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• Harrison's Principles of Internal Medicine, 21st Ed. — p. 5147 (IRIS), p. 5185 (Pregnancy/Lactation)
• Tuberculosis: Tuberculosis and Comorbidities — p. 12, 18 (WHO recommendations — ART timing, CPT, XDR definitions)
• Treatment of Drug-Resistant Tuberculosis (WHO) — p. 36 (HIV-MDR-TB drug interactions)
• WHO Consolidated Guidelines on TB Module 4: Treatment (2022)
• India NTEP / NACO 2023 Co-infection Guidelines
• Supporting Breastfeeding During Maternal or Child Hospitalization — lactation drug safety principles