Can a patient with multidrug‑resistant bone tuberculosis and a psoas abscess be treated with the BPaLM regimen (bedaquiline, pretomanid, linezolid, moxifloxacin), and what duration is recommended; if not appropriate, what alternative regimen should be used?

BPaLM Regimen for MDR Bone TB with Psoas Abscess

The BPaLM regimen should NOT be started for this patient because osteoarticular tuberculosis (including bone TB with psoas abscess) is an absolute contraindication to BPaLM; instead, initiate an individualized 18–20 month regimen using at least 4 effective drugs from WHO Groups A, B, and C. 1, 2

Why BPaLM is Contraindicated

• Osteoarticular TB is explicitly listed as an absolute contraindication to the BPaLM regimen in WHO guidelines, alongside central nervous system TB and miliary TB. 1, 2
• The evidence base for BPaLM (bedaquiline, pretomanid, linezolid, moxifloxacin) comes from trials that systematically excluded patients with bone and joint TB, so efficacy and safety data do not exist for this population. 1
• Bone TB with psoas abscess represents severe extrapulmonary disease requiring longer treatment duration to prevent relapse and ensure adequate drug penetration into poorly vascularized bone tissue. 3

Recommended Alternative Regimen

Build an individualized 18–20 month regimen using the WHO drug-grouping hierarchy:

Core Drug Selection (Group A – Use All Three if Possible)

• Bedaquiline – 400 mg daily × 2 weeks, then 200 mg three times weekly × 22 weeks, then continue at 200 mg three times weekly through month 18–20. 3, 2
• Levofloxacin (preferred over moxifloxacin for fewer adverse events and less QTc prolongation) – 750–1000 mg daily based on weight. 3
• Linezolid – 600 mg daily; consider dose reduction to 300 mg daily after 2–4 months if toxicity develops (peripheral neuropathy, myelosuppression). 3, 2

Add at Least One Group B Drug

• Clofazimine – 100 mg daily (preferred Group B agent for bone TB due to good tissue penetration and anti-inflammatory properties). 3, 2
• Cycloserine or terizidone – 500–750 mg daily in divided doses if clofazimine alone is insufficient or not tolerated. 3, 2

Consider Group C Drugs to Reach ≥4 Effective Drugs

• Pyrazinamide – 1500–2000 mg daily (retain if DST shows susceptibility; MDR-TB is defined as resistance to isoniazid + rifampicin only, so pyrazinamide may remain active). 3, 2
• Ethambutol – 800–1200 mg daily (if DST confirms susceptibility). 3, 2
• Delamanid – 100 mg twice daily (if additional drugs are needed and available). 3, 2

Avoid Injectable Agents Unless Absolutely Necessary

• Amikacin or streptomycin should only be added if an adequate number of effective oral drugs cannot be assembled, and DST confirms susceptibility. 2
• Kanamycin and capreomycin are strongly discouraged due to poor outcomes and high toxicity. 2

Treatment Duration and Phases

• Intensive phase: 5–7 months after sputum culture conversion (if pulmonary disease is also present) or 6–8 months for isolated extrapulmonary disease. 2
• Continuation phase: Continue with ≥3 effective drugs. 2
• Total duration: 18–20 months minimum; extend to 20–24 months for bone TB given the risk of relapse in osteoarticular disease. 2
• Do not shorten the regimen even after clinical improvement or culture conversion; bone TB requires prolonged therapy to sterilize poorly vascularized tissue. 2

Critical Monitoring Requirements

Baseline Assessment

• Drug susceptibility testing (DST) for fluoroquinolones, bedaquiline, linezolid, and all second-line drugs to guide regimen construction. 3, 2
• Baseline ECG, electrolytes (potassium, magnesium, calcium), CBC, liver function tests, renal function, HIV status, pregnancy test, visual acuity, and audiometry. 2
• MRI or CT of the spine and psoas to document baseline disease extent and guide surgical consultation if needed. 2

Ongoing Monitoring

• ECG at weeks 2,4,8,12, then monthly to detect QTc prolongation from bedaquiline, levofloxacin, and clofazimine; discontinue bedaquiline if QTcF >500 ms or ventricular arrhythmia develops. 1, 2
• Monthly CBC to identify linezolid-induced myelosuppression (anemia, thrombocytopenia); reduce linezolid to 300 mg daily if toxicity occurs. 1, 2
• Monthly peripheral neuropathy and visual acuity assessments for linezolid-induced peripheral and optic neuropathy. 1, 2
• Monthly liver function tests (AST, ALT, bilirubin) for bedaquiline and linezolid hepatotoxicity. 1, 2
• Monthly sputum cultures (if pulmonary disease is present) to assess microbiologic response. 2
• Repeat imaging at 6 and 12 months to document resolution of psoas abscess and bone lesions. 2

Surgical Considerations

• Consult orthopedic or spine surgery for potential drainage of the psoas abscess if it is large (>3–5 cm), causing neurologic compromise, or not responding to medical therapy after 4–6 weeks. 2
• Surgical debridement of necrotic bone may be required if there is extensive vertebral destruction or spinal instability. 2

Common Pitfalls to Avoid

• Do not use BPaLM for bone TB even if the patient meets all other eligibility criteria (fluoroquinolone-susceptible, no prior exposure to second-line drugs); osteoarticular TB is an absolute contraindication. 1, 2
• Do not add a single drug to a failing regimen; this creates functional monotherapy and drives resistance—always add at least two susceptible drugs when modifying treatment. 2
• Do not discontinue therapy early even after clinical improvement or abscess resolution; bone TB requires the full 18–20 month course to prevent relapse. 2
• Do not use fewer than 4 effective drugs in the intensive phase; this predisposes to treatment failure and acquired resistance. 2
• Do not delay treatment waiting for complete DST results; start the regimen empirically based on available resistance data and adjust once full DST returns. 1, 2
• Do not ignore linezolid toxicity; dose reduction to 300 mg daily is acceptable and preserves efficacy while mitigating peripheral neuropathy and myelosuppression. 2

Why Not the 9-Month All-Oral Regimen?

• The 9-month regimen also excludes severe extrapulmonary TB (spinal/CNS/miliary) from eligibility criteria. 3
• Bone TB with psoas abscess requires longer treatment duration (18–20 months) to ensure adequate drug exposure in poorly vascularized bone and prevent relapse. 3, 2