MDR-TB and TB Spine Treatment Regimen and Duration
Core Drug Regimen for MDR-TB
For MDR-TB, including TB spine (Pott's disease), use an all-oral regimen containing bedaquiline, a later-generation fluoroquinolone (levofloxacin or moxifloxacin), and linezolid as the three mandatory Group A agents, plus at least one additional effective drug to ensure a minimum of four drugs likely to be effective. 1, 2, 3
Group A Agents (All Three Must Be Included)
- Levofloxacin or moxifloxacin (later-generation fluoroquinolones) - strong recommendation 1, 2
- Bedaquiline - strong recommendation for adults ≥18 years; conditional for ages 6-17 years 1, 2
- Linezolid - strong recommendation 1, 2
Group B Agents (Add at Least One)
- Clofazimine - conditional recommendation 1, 2
- Cycloserine or terizidone - conditional recommendation 1, 2
Group C Agents (Add Only If Needed to Complete Regimen)
- Ethambutol - conditional recommendation 1
- Delamanid - conditional recommendation for ages ≥3 years 1, 2
- Pyrazinamide - only if susceptibility confirmed 1, 2
- Imipenem-cilastatin or meropenem (with amoxicillin-clavulanate) - conditional recommendation 1, 2
- Amikacin or streptomycin - only when susceptibility demonstrated and adequate monitoring available 1, 2
Drugs to AVOID
- Kanamycin and capreomycin - conditional recommendation against use 1, 2
- Ethionamide/prothionamide - use only if bedaquiline, linezolid, clofazimine, or delamanid cannot be used 1, 4
- p-Aminosalicylic acid - use only if better options unavailable 1
- Clavulanic acid alone - strong recommendation against use 1
Treatment Duration for MDR-TB
The total treatment duration for MDR-TB should be 18-20 months, or alternatively 15-17 months after culture conversion, whichever is longer. 1, 2
Standard MDR-TB Duration
- Total duration: 18-20 months for most patients 1
- Alternative calculation: 15-21 months after culture conversion 2, 3
- Intensive phase: 5-7 months after culture conversion if using injectable agents 1, 2
Pre-XDR and XDR-TB Duration
Special Considerations for TB Spine (Pott's Disease)
TB spine should be treated with the same MDR-TB regimen as pulmonary MDR-TB, using the longer duration (18-20 months total or 15-21 months after culture conversion) due to the extrapulmonary nature of the disease. 1, 2, 3
Key Points for Extrapulmonary TB
- Extrapulmonary TB, including TB spine, requires the same drug regimen as pulmonary MDR-TB 5
- The BPaLM regimen (bedaquiline, pretomanid, linezolid, moxifloxacin) for 6 months may be considered for MDR/RR-TB with extrapulmonary involvement if no fluoroquinolone or bedaquiline resistance is documented 5
- However, for TB spine specifically, the longer conventional regimen (18-20 months) is generally preferred given the severity and location of disease 1, 2
Alternative Shorter Regimen (BPaLM)
A 6-month all-oral BPaLM regimen (bedaquiline, pretomanid, linezolid, moxifloxacin) may be used for eligible MDR/RR-TB patients, including those with extrapulmonary disease, if there is no documented fluoroquinolone or bedaquiline resistance. 5
Eligibility Criteria for Shorter Regimen
- Confirmed MDR/RR-TB with no fluoroquinolone resistance 5, 3
- No previous exposure to second-line TB drugs for >1 month 3
- No extensive pulmonary disease or severe extrapulmonary TB 3
Important Caveat
The 2019 ATS/CDC/ERS/IDSA guidelines could not recommend for or against the older 9-12 month standardized regimen because it included kanamycin (now not recommended) and drugs with likely resistance 1, 5
Monitoring Requirements
Baseline Assessment
- ECG for QTc interval (bedaquiline and fluoroquinolones prolong QTc) 3
- Electrolytes (hypokalemia and hypomagnesemia increase QTc risk) 3
- Complete blood count (linezolid causes myelosuppression) 3
- Visual acuity and color vision (linezolid and ethambutol cause optic neuropathy) 3
- Sputum culture 3
Ongoing Monitoring
- Monthly sputum cultures to monitor treatment response 5
- ECG monitoring for QTc prolongation 3
- Visual screening for optic neuropathy 3
- Complete blood count for linezolid toxicity 3
Critical Pitfalls to Avoid
- Using fewer than four effective drugs in the intensive phase increases treatment failure risk 2, 3
- Omitting any Group A agent (fluoroquinolone, bedaquiline, or linezolid) compromises efficacy 3
- Insufficient treatment duration (less than 15 months after culture conversion) increases relapse risk 2, 3
- Using kanamycin or capreomycin when oral alternatives are available increases toxicity without benefit 1, 2, 3
- Missing QTc prolongation can lead to fatal arrhythmias 3
- Inadequate linezolid toxicity monitoring can result in irreversible peripheral neuropathy or optic neuropathy 3
Adjunctive Therapy
Surgical Intervention
- Elective partial lung resection may be considered alongside medical therapy for patients at high risk of treatment failure or relapse based on clinical judgment, bacteriological, and radiographic data 1, 3
- For TB spine, surgical debridement may be necessary for spinal instability, neurological compromise, or large abscesses, but medical therapy remains the cornerstone 1