What is the treatment for drug-resistant tuberculosis (TB)?

Treatment for Drug-Resistant Tuberculosis

For drug-resistant tuberculosis, treatment should include at least five effective drugs in the intensive phase and four drugs in the continuation phase, with a total treatment duration of 15-21 months after culture conversion (15-24 months for pre-XDR and XDR-TB). 1

Core Regimen Components

Essential Drugs (Strongly Recommended)

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

Additional Recommended Drugs (Conditionally Recommended)

• Linezolid 1
• Clofazimine 1
• Cycloserine 1

Additional Considerations

• Pyrazinamide: Include when the M. tuberculosis isolate is not resistant to it 1
• Ethambutol: Include only when other more effective drugs cannot be assembled to achieve a total of five drugs 1

Treatment Duration

• Intensive phase: 5-7 months after culture conversion 1
• Continuation phase: Continue until total treatment duration reaches 15-21 months after culture conversion 1
• For pre-XDR and XDR-TB: 15-24 months after culture conversion 1

Drugs NOT Recommended

• Amoxicillin-clavulanate: Not recommended except when used with a carbapenem 1
• Macrolides (azithromycin, clarithromycin): Not recommended 1
• Ethionamide/prothionamide: Not recommended if more effective drugs are available 1
• P-aminosalicylic acid: Not recommended if more effective drugs are available 1
• Kanamycin or capreomycin: Not recommended 1

Injectable Agents (When Needed)

• Amikacin or streptomycin: Consider when susceptibility is confirmed 1
• Carbapenems (with amoxicillin-clavulanic acid): Consider when needed 1

Special Considerations

Isoniazid-Resistant TB (Not MDR)

• Add a later-generation fluoroquinolone to a 6-month regimen of daily rifampin, ethambutol, and pyrazinamide 1
• Pyrazinamide duration can be shortened to 2 months in selected situations (non-cavitary disease, lower burden disease, or toxicity) 1

Dosing Approach for Ethionamide (When Used)

• Start at 250 mg daily and gradually titrate up as tolerated 2
• Typical effective dose is between 0.5-1.0 g daily (average 0.75 g) 2
• May divide doses to improve tolerance 2
• Administer with meals to minimize gastrointestinal side effects 2

Treatment Monitoring

• Monthly clinical evaluations are recommended 3
• Monitor for adverse effects such as hepatotoxicity, optic neuritis, and peripheral neuropathy 3
• Prophylactic pyridoxine is recommended, especially with drugs like cycloserine and ethionamide 3

Critical Pitfalls to Avoid

1. Never add a single drug to a failing regimen - add at least two drugs to which the organism is likely susceptible 3
2. Failure to ensure adherence - directly observed therapy is strongly recommended 1, 2
3. Inadequate drug susceptibility testing - treatment should be guided by susceptibility results 1, 2
4. Inadequate number of effective drugs - always aim for at least 5 effective drugs in the intensive phase 1

Role of Surgery

• Elective partial lung resection (lobectomy or wedge resection) should be considered for patients with MDR-TB when clinical judgment, supported by bacteriological and radiographic data, suggests a strong risk of treatment failure or relapse with medical therapy alone 1

Drug-resistant TB treatment requires careful selection of multiple effective drugs based on susceptibility testing, appropriate duration of therapy, close monitoring for adverse effects, and strategies to ensure adherence. Consultation with TB experts is essential for managing these complex cases.