Model Answer
0 min readIntroduction
Multi-Drug Resistant Tuberculosis (MDR-TB) arises when *Mycobacterium tuberculosis* develops resistance to at least isoniazid and rifampicin, the two most potent first-line anti-TB drugs. Treatment of MDR-TB is significantly more complex, prolonged (typically 18-24 months), and expensive than drug-susceptible TB. It necessitates a combination of second-line anti-TB drugs, carefully selected based on drug susceptibility testing (DST). The World Health Organization (WHO) provides updated guidelines for MDR-TB treatment regimens, which are constantly evolving based on new evidence and drug availability. This answer will detail the groups of drugs used in treating MDR-TB, adhering to current WHO recommendations as of my knowledge cutoff.
Drug Groups Used in MDR-TB Treatment
The treatment of MDR-TB typically involves a combination of four or more drugs, categorized into core and supplemental groups. The specific regimen is tailored based on the patient’s drug susceptibility testing results.
1. Core Drugs (Always Included)
- Fluoroquinolones: These are bactericidal drugs that inhibit DNA gyrase and topoisomerase IV, essential for bacterial DNA replication. Examples include:
- Levofloxacin
- Moxifloxacin
- Ciprofloxacin (less preferred due to lower tolerability)
- Second-Line Injectables: These are potent bactericidal drugs, but are associated with significant side effects.
- Amikacin
- Kanamycin
- Capreomycin
- Ethionamide/Prothionamide: These drugs inhibit mycolic acid synthesis, a crucial component of the mycobacterial cell wall. Prothionamide is a derivative of ethionamide.
- Pyrazinamide: While often used in first-line treatment, pyrazinamide can still be effective against some MDR strains and is often included in regimens.
2. Supplemental Drugs (Added Based on DST & Regimen Composition)
- Cycloserine: Inhibits D-alanine racemase, an enzyme involved in cell wall synthesis.
- Para-aminosalicylic acid (PAS): Inhibits folate synthesis.
- Delamanid: A nitro-dihydro-imidazo-oxazole derivative that inhibits mycolic acid synthesis. It is used for extensively drug-resistant TB (XDR-TB) and treatment-intolerant/non-responsive MDR-TB.
- Bedaquiline: A diarylquinoline that inhibits ATP synthase, an essential enzyme for mycobacterial energy production. Primarily used for XDR-TB and treatment-intolerant/non-responsive MDR-TB.
- Linezolid: Inhibits bacterial protein synthesis. Often used in XDR-TB regimens.
3. Treatment Duration and Monitoring
A typical MDR-TB treatment course lasts 18-24 months, divided into an intensive phase (typically 6-8 months) and a continuation phase (12-18 months). Regular monitoring for drug toxicity is crucial, especially for aminoglycosides (amikacin, kanamycin) which can cause ototoxicity (hearing loss) and nephrotoxicity (kidney damage). Liver function tests are also essential due to the hepatotoxicity potential of many anti-TB drugs.
4. Newer Regimens & WHO Recommendations (as of knowledge cutoff)
The WHO has been advocating for shorter, all-oral regimens for MDR-TB, aiming to improve treatment adherence and outcomes. The BPaL regimen (Bedaquiline, Pyrazinamide, Linezolid) is a key example, showing promising results in clinical trials. The use of newer drugs like Delamanid and Bedaquiline is increasingly being incorporated into MDR-TB treatment protocols, particularly for patients with XDR-TB or those who fail initial treatment.
| Drug Group | Examples | Mechanism of Action | Common Side Effects |
|---|---|---|---|
| Fluoroquinolones | Levofloxacin, Moxifloxacin | Inhibit DNA gyrase & topoisomerase IV | Peripheral neuropathy, tendonitis, QT prolongation |
| Second-Line Injectables | Amikacin, Kanamycin | Inhibit protein synthesis | Ototoxicity, nephrotoxicity |
| Ethionamide/Prothionamide | Ethionamide, Prothionamide | Inhibit mycolic acid synthesis | Hepatotoxicity, gastrointestinal upset |
| Newer Drugs | Bedaquiline, Delamanid | Inhibit ATP synthase/Mycolic acid synthesis | QT prolongation, hepatotoxicity |
Conclusion
Treating MDR-TB requires a multifaceted approach utilizing a combination of second-line drugs, guided by drug susceptibility testing and WHO recommendations. While treatment is prolonged and associated with significant side effects, newer drugs and shorter all-oral regimens offer hope for improved outcomes. Continuous monitoring for drug toxicity and adherence to treatment protocols are crucial for successful management of MDR-TB. Further research and development of novel anti-TB drugs are essential to combat the growing threat of drug-resistant tuberculosis globally.
Answer Length
This is a comprehensive model answer for learning purposes and may exceed the word limit. In the exam, always adhere to the prescribed word count.