Treatment of Extensively Drug-Resistant Tuberculosis (XDR TB)
For patients with XDR TB, treatment should include 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 as core components, for a total duration of 15-24 months after culture conversion. 1, 2
Core Components of XDR TB Treatment Regimen
- Intensive phase (first 5-7 months after culture conversion): At least 5 effective drugs 1, 2
- Continuation phase: At least 4 effective drugs 1, 2
- Total treatment duration: 15-24 months after culture conversion for XDR TB 1
Essential Drugs to Include:
- Bedaquiline - strongly recommended as a core component of any XDR TB regimen 1, 2
- Later-generation fluoroquinolone (levofloxacin or moxifloxacin) - strongly recommended if susceptibility is confirmed 1, 2
- Linezolid - suggested as a core component due to its effectiveness against resistant strains 1, 2, 3
- Clofazimine - suggested as an important component 1, 2
- Cycloserine - suggested as an effective component 1, 2
Additional Drugs to Consider:
- Pyrazinamide - include only if susceptibility is confirmed 1, 2
- Carbapenems (imipenem-cilastatin or meropenem) - must always be used with amoxicillin-clavulanate 1, 2
- Amikacin or streptomycin - only if susceptibility is confirmed and oral options are limited 1, 4
- Delamanid - may be considered, though evidence is limited 1, 2
Drugs to Avoid in XDR TB Treatment
- Kanamycin or capreomycin - not recommended due to poor outcomes 1, 2
- Macrolides (azithromycin and clarithromycin) - not recommended due to lack of efficacy 1, 2
- Amoxicillin-clavulanate alone - should only be used with carbapenems 1, 2
- Ethionamide/prothionamide - avoid if more effective drugs are available 1, 2
Treatment Monitoring and Adjustments
- Monitor sputum cultures monthly to assess treatment response 5
- Drug susceptibility testing (DST) results should guide regimen composition 3, 5
- Regimens containing more potentially effective drugs (at least 6) have been associated with better outcomes 5
Special Considerations
- HIV co-infection: Outcomes are generally poorer; careful management of drug interactions is essential 6
- Surgical intervention: Consider elective partial lung resection (lobectomy or wedge resection) in selected cases where medical therapy alone may be insufficient 1
- Treatment adherence: Critical for preventing further resistance; directly observed therapy is recommended 7
Common Pitfalls to Avoid
- Insufficient number of effective drugs: Using fewer than five effective drugs in the intensive phase leads to poorer outcomes 1, 5
- Inadequate treatment duration: Treating for less than 15 months after culture conversion for XDR TB is associated with higher relapse rates 1, 2
- Relying on drugs with confirmed resistance: Including drugs to which the organism has demonstrated resistance provides minimal benefit 3, 5
- Delaying treatment initiation: Early diagnosis and prompt initiation of appropriate therapy is crucial 6
Emerging Approaches
- New definitions of XDR TB include resistance to bedaquiline and/or linezolid in addition to fluoroquinolones, reflecting the critical importance of these newer agents 3
- Shorter regimens (9-12 months) are being studied but are not yet recommended for XDR TB 1, 7
The management of XDR TB remains challenging, with treatment success rates historically around 30-50% 6. However, the inclusion of newer drugs like bedaquiline and linezolid has shown promise in improving outcomes 3, 7.