What is the treatment approach for multidrug-resistant tuberculosis (MDR-TB)?

Treatment of Multidrug-Resistant Tuberculosis (MDR-TB)

For multidrug-resistant tuberculosis (MDR-TB), treatment requires a regimen of at least five effective drugs in the intensive phase and four drugs in the continuation phase, with bedaquiline and a later-generation fluoroquinolone (levofloxacin or moxifloxacin) forming the core of the regimen. 1

Core Treatment Strategy

Building an Effective Regimen

• Build a regimen using five or more drugs to which the isolate is susceptible (or has low likelihood of resistance), preferably with drugs that have not been used to treat the patient previously 2, 1
• Only include drugs to which the patient's M. tuberculosis isolate has documented or high likelihood of susceptibility 2
• TB expert medical consultation is strongly recommended when treating MDR-TB 2

Priority Drugs for MDR-TB Regimens

1. First-line (highest priority) drugs to include:

   • Bedaquiline 1
   • Later-generation fluoroquinolone (levofloxacin or moxifloxacin) 1, 3
   • Linezolid 1

2. Second-line drugs to consider:

   • Clofazimine 1
   • Cycloserine or terizidone 1

3. Additional drugs if needed to complete the regimen:

   • Delamanid 2, 1
   • Pyrazinamide (only if susceptibility confirmed) 2, 1
   • Ethambutol (only if susceptibility confirmed) 2, 3
   • Imipenem-cilastatin or meropenem (with amoxicillin-clavulanate) 2, 1

Treatment Duration

• Intensive phase: 5-7 months after culture conversion 1
• Total treatment duration: 15-21 months after culture conversion 1
• For pre-XDR and XDR TB: 15-24 months after culture conversion 1

Drugs NOT Recommended for MDR-TB

• Kanamycin and capreomycin (injectable agents) 2, 1
• Macrolides (azithromycin and clarithromycin) 2, 1
• Amoxicillin-clavulanate when used without a carbapenem 2, 1
• Ethionamide/prothionamide should be avoided if more effective drugs are available 1, 4

Special Considerations

Injectable Agents

• Injectable agents (amikacin and streptomycin) should only be used when:
  • The isolate is confirmed susceptible 2
  • More effective or less toxic therapies cannot be assembled to achieve five effective drugs 2, 1

Drug Susceptibility Testing

• Drug susceptibility testing (DST) is critical for guiding appropriate therapy 5, 6
• When DST results are not available, use epidemiological data and information about the source case (especially for children) 2
• Molecular testing can provide rapid results for resistance to first and second-line drugs 5, 7

Treatment Monitoring

• Monitor treatment response clinically (decrease in cough and systemic symptoms, weight gain), radiographically, and bacteriologically 2
• Monthly cultures help identify early evidence of treatment failure 2
• If sputum cultures remain positive after 3 months or if there is bacteriological reversion from negative to positive, repeat DST 2

Common Pitfalls to Avoid

• Using fewer than five effective drugs in the intensive phase 1
• Including drugs to which the isolate is resistant 2, 5
• Insufficient treatment duration (less than 15 months after culture conversion) 1
• Failure to monitor and manage adverse effects, which can lead to poor adherence 2, 8
• Not consulting with TB experts for complex cases of drug resistance 2, 9

Management of Adverse Effects

• Most patients experience difficulty tolerating one or more drugs used to treat MDR-TB 2
• Patient education about potential adverse effects is essential 2
• Investigate and address all adverse effects promptly 2
• Nausea and vomiting are common and can often be managed without discontinuing therapy 2
• QTc interval prolongation is a concern with some drugs (including bedaquiline and fluoroquinolones) but is generally manageable with monitoring 8

By following this structured approach to MDR-TB treatment, clinicians can optimize outcomes while minimizing toxicity, preventing further resistance development, and ultimately reducing mortality and improving quality of life for patients with this challenging disease.