12. Guidelines For Multi- Drug Resistant TB & Extensively- Drug Resistant TB: Pharmacology Lectures

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12. Guidelines For Multi- Drug Resistant TB & Extensively- Drug Resistant TB: Pharmacology Lectures
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MDR-TB (Multi-Drug Resistant Tuberculosis) and XDR-TB (Extensively Drug-Resistant Tuberculosis) are severe forms of drug-resistant TB caused by Mycobacterium tuberculosis strains that do not respond to conventional first-line anti-TB drugs 💊🦠. MDR-TB is resistant to Rifampin (RIF) and Isoniazid (INH), while XDR-TB is resistant to Rifampin, Isoniazid, Fluoroquinolones (e.g., Levofloxacin, Moxifloxacin), and at least one second-line injectable drug (e.g., Amikacin, Capreomycin, Kanamycin) 🚨🩸. These drug-resistant forms of TB require prolonged treatment (≥18-24 months), multiple drugs, and strict monitoring to prevent treatment failure, transmission, and mortality ⚠️🏥.

🔹 WHO Guidelines for MDR-TB & XDR-TB Treatment:
Shorter MDR-TB Regimen (9-12 months): Used in eligible patients who have not been exposed to second-line drugs and do not have fluoroquinolone resistance 🔄💊.
Longer MDR-TB Regimen (18-24 months): For patients with extensive disease, prior treatment failure, or fluoroquinolone resistance 📉🛑.
All-oral drug regimens are preferred over injectable agents to improve compliance and reduce ototoxicity (hearing loss) from aminoglycosides 🎧🚫.

🔹 Recommended Drug Regimens for MDR-TB/XDR-TB:
Group A (Most effective, must be included): Levofloxacin/Moxifloxacin (Fluoroquinolones), Bedaquiline (ATP Synthase Inhibitor), Linezolid (Protein Synthesis Inhibitor) 🏆🔬.
Group B (Add if needed for regimen completion): Clofazimine, Cycloserine/Terizidone (Cell wall inhibitors, CNS penetration) 🧬🩺.
Group C (Used when Group A & B drugs cannot be used): Ethambutol, Delamanid, Pyrazinamide, Imipenem-Meropenem, Amikacin, PAS (Para-Aminosalicylic Acid) 💥🦠.

🔹 Newer Drugs in MDR/XDR-TB:
Bedaquiline (FDA-approved): A diarylquinoline that inhibits mycobacterial ATP synthase, essential for energy production. It improves MDR-TB cure rates but has QT prolongation risk, requiring ECG monitoring 🫀📉.
Delamanid: Inhibits mycolic acid synthesis, improving treatment success, but also prolongs the QT interval, requiring ECG monitoring 📊🩸.
Pretomanid (used in BPaL regimen): A novel drug combined with Bedaquiline + Linezolid for highly resistant TB cases 🏆💡.

🔹 Challenges in MDR-TB & XDR-TB Treatment:
Prolonged therapy (18-24 months), causing poor patient adherence and high treatment dropout rates ⚠️🩺.
Severe side effects (Ototoxicity, nephrotoxicity, hepatotoxicity, myelosuppression, QT prolongation) requiring frequent monitoring 🎧💀.
Expensive and limited access to second-line and novel TB drugs, especially in resource-limited settings 🌍💰.
Drug interactions with ART (HIV-TB co-infection), requiring careful selection of compatible drugs 🦠💊.

🔹 Preventive Measures & Global Control Strategies:
Rapid Drug Susceptibility Testing (DST) to identify drug resistance early and select appropriate treatment 📉🔬.
Strict adherence to Directly Observed Therapy Short-Course (DOTS) programs to ensure patient compliance 📊🏥.
BCG vaccination and early case detection to prevent transmission 🌍🛡️.
Expanding access to novel MDR-TB/XDR-TB drugs (Bedaquiline, Delamanid, Pretomanid) and improving treatment protocols 💉💊.

🔹 Conclusion: MDR-TB & XDR-TB require aggressive treatment with second-line drugs, careful monitoring, and global TB control measures to prevent further resistance and improve patient survival 🌍💊.

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