Treatment Regimen for Extensively Drug-Resistant (XDR) Tuberculosis
The recommended treatment regimen for XDR-TB should include bedaquiline, a later-generation fluoroquinolone (if susceptible), linezolid, and clofazimine as core components, with treatment duration extended to 15-24 months after culture conversion. 1
Core Treatment Principles
- Only drugs to which the patient's M. tuberculosis isolate has documented or high likelihood of susceptibility should be included in the treatment regimen 2
- Drug susceptibility testing (DST) must be performed on the first isolate to guide appropriate treatment selection 2
- The intensive phase should last 5-7 months after culture conversion, with a total treatment duration of 15-24 months after culture conversion for XDR-TB 1
Essential Drugs for XDR-TB Regimen
Group A (Include All When Possible):
- Bedaquiline - strongly recommended as a core component 2, 1
- Later-generation fluoroquinolone (levofloxacin preferred over moxifloxacin due to fewer adverse events and less QTc prolongation) - if susceptibility is confirmed 3, 2
- Linezolid - conditionally recommended as an effective component 2, 1
Group B (Add One or Both):
- Clofazimine - conditionally recommended 2, 1
- Cycloserine or terizidone - conditionally recommended 3, 2
Group C (Add to Complete Regimen When Group A and B Drugs Cannot Be Used):
- Ethambutol - include only when other more effective drugs cannot be assembled 3, 2
- Delamanid - may be included if needed 3
- Pyrazinamide - include only when susceptibility is confirmed 3, 2
- Carbapenems (imipenem-cilastatin or meropenem) with amoxicillin-clavulanate - conditionally recommended if needed 3
- Amikacin or streptomycin - include only when susceptibility is confirmed 3
- Ethionamide/prothionamide - lower priority option 3
- p-aminosalicylic acid - lower priority option 3
Treatment Duration and Monitoring
- Intensive phase: 5-7 months after culture conversion 2, 1
- Total treatment duration: 15-24 months after culture conversion 2, 1
- Regular sputum cultures should be obtained monthly until conversion, then less frequently 4
- Directly observed therapy (DOT) is strongly recommended to ensure adherence 2
Surgical Considerations
- Elective partial lung resection (lobectomy or wedge resection) may be considered for adults with XDR-TB receiving antimicrobial therapy 3, 2
- Surgery should be performed by experienced surgeons only after the patient has received several months of intensive chemotherapy 2
Special Considerations
- Treatment success rates for XDR-TB using bedaquiline-containing regimens have improved significantly compared to historical rates of 30-50% 5
- HIV co-infection requires careful management of drug interactions and overlapping toxicities 6
- QTc interval prolongation is a concern with several XDR-TB drugs (bedaquiline, fluoroquinolones, clofazimine), requiring ECG monitoring 5
Common Pitfalls to Avoid
- Never add a single drug to a failing regimen as this leads to acquired resistance 2, 1
- When initiating therapy for suspected XDR-TB, add at least two, preferably three, new drugs to which susceptibility can be inferred 2, 1
- Avoid kanamycin and capreomycin as they are associated with poor outcomes 3, 1
- Using fewer than five effective drugs in the intensive phase leads to poorer outcomes 1
- Treating for less than 15 months after culture conversion is associated with higher relapse rates 1
Newer Treatment Options
- The BPaL regimen (bedaquiline, pretomanid, and linezolid) for 6-9 months may be considered under operational research conditions for MDR/RR-TB/pre-XDR-TB patients who have not had prior exposure to bedaquiline or linezolid (defined as < 2 weeks) 3
- In cases where an effective regimen cannot be composed based on existing recommendations, the BPaL regimen may be considered as a last resort under programmatic conditions with higher standards of monitoring 3