Multi-drug Resistant Tuberculosis

MDR-TB 101 - Rogue Bacilli Basics

• Definitions & Key Resistance Patterns:

  Type	Resistance Pattern
  MDR-TB	Resistance to at least Isoniazid (H) AND Rifampicin (R)
  RR-TB	Rifampicin Resistant TB; often a proxy for MDR-TB programmatically.
  Pre-XDR-TB	MDR-TB + resistance to any Fluoroquinolone (e.g., Levofloxacin, Moxifloxacin)
  XDR-TB	MDR-TB + resistance to any Fluoroquinolone + at least one other Group A drug (Bedaquiline or Linezolid)

• Epidemiology Snapshot:

  • Global: Approx. 450,000 incident RR-TB cases in 2021 (WHO).
  • India: Highest MDR-TB burden; accounts for ~26% of global cases.
  • Trend: ↑ drug resistance is a major public health threat.

• High-Risk Groups for MDR-TB:

  • Previously treated TB patients (especially relapse, treatment failure, default).
  • Contacts of known MDR-TB/RR-TB patients.
  • People living with HIV.
  • Residents & staff of congregate settings (prisons, shelters).

⭐ The cornerstone definition: MDR-TB signifies resistance to at least Isoniazid (H) AND Rifampicin (R), the two most potent first-line anti-TB drugs.

Resistance & Reveal - TB's Dirty Tricks

MDR-TB: Resistance to ≥ Isoniazid (INH) & Rifampicin (RIF). Resistance via key genetic mutations.

• Rifampicin (RIF):
  • Gene: rpoB (RNA polymerase B subunit)
  • Mechanism: Altered drug target. >95% of RIF resistance.
  • 📌 Really Bad Problem for Rifampicin.
• Isoniazid (INH):
  • Gene: katG (catalase-peroxidase): High-level resistance; prevents prodrug activation.
  • Gene: inhA (promoter/gene): Low-level INH & Ethionamide resistance.
  • 📌 CATs Get IN High places.

Detection (NTEP Algorithm Focus):

• Genotypic (Rapid):
  • NAATs: Xpert MTB/RIF (CBNAAT), LPA.
  • Detects common resistance mutations.
• Phenotypic (Culture-based):
  • Solid (LJ), Liquid (MGIT). Slower; confirms resistance.

⭐ CBNAAT/Xpert MTB/RIF detects M. tuberculosis and Rifampicin resistance (via rpoB gene mutations) rapidly, typically within 2 hours.

Treatment Tactics - Fighting Super TB

• Strict adherence to NTEP guidelines is paramount for MDR-TB.
• Key Regimens (NTEP-aligned):
  • Shorter Oral Bdq-containing Regimen: ~9-11 months. Includes Bedaquiline (Bdq), fluoroquinolone, Linezolid (Lzd), and other agents.
  • Longer All-Oral Regimens: 18-20 months. Individualized (DST-guided); uses newer (Bdq, Pa, Dlm, Lzd) & repurposed drugs.
• Crucial Newer Anti-TB Drugs:
  • Bedaquiline (Bdq): Diarylquinoline; inhibits ATP synthase.
  • Pretomanid (Pa): Nitroimidazole; key in BPaL/BPaLM regimens.
  • Delamanid (Dlm): Nitroimidazole; inhibits mycolic acid synthesis.
  • Linezolid (Lzd): Oxazolidinone; inhibits protein synthesis.
• Essential: Vigilant ADR monitoring & management. 📌 Key ADRs: QT prolongation (Bdq, Dlm, Mfx), myelosuppression (Lzd), hepatotoxicity (Pa, Bdq), optic/peripheral neuropathy (Lzd).

⭐ Bedaquiline, a diarylquinoline, inhibits mycobacterial ATP synthase (subunit c of F₀F₁ ATP synthase); crucial for MDR-TB treatment.

Contain & Conquer - TB Control Ops

• Infection Prevention & Control (IPC):
  • Administrative: Triage, separation, ↓ overcrowding.
  • Environmental: Ventilation (natural/mechanical).
  • Personal: N95 respirators for HCWs.
• NTEP Programmatic Management (PMDT):
  • Decentralized DR-TB centers.
  • Nikshay portal: Case notification, tracking.
  • Nutritional support (Nikshay Poshan Yojana).
• Key Challenges:
  • Treatment adherence, social stigma.
  • Limited access to rapid diagnostics.

⭐ Airborne infection control (AIC) measures are critical in preventing nosocomial transmission of MDR-TB.

High‑Yield Points - ⚡ Biggest Takeaways

• MDR-TB is defined by resistance to at least isoniazid (H) and rifampicin (R).
• XDR-TB is MDR-TB plus resistance to a fluoroquinolone AND a second-line injectable (e.g., amikacin).
• Rapid molecular tests (GeneXpert) detect rifampicin resistance (RR), indicating potential MDR-TB.
• Culture & DST (Drug Susceptibility Testing) confirms MDR-TB and guides therapy.
• Treatment involves shorter all-oral bedaquiline-containing regimens (9-12 months) or longer regimens (18-20 months).
• Key drugs include Bedaquiline, Pretomanid, Linezolid (BPaL), moxifloxacin, and clofazimine.
• Rifampicin Resistance (RR-TB) is generally managed as MDR-TB due to high co-occurrence rates.