In a child with multidrug‑resistant tuberculosis treated with delamanid, levofloxacin, cycloserine, and clofazimine, after stopping delamanid at six months, what is the appropriate next step in management?

Management After Stopping Delamanid at 6 Months in Pediatric MDR-TB

Continue the current regimen of levofloxacin, cycloserine, and clofazimine for the remainder of the 18-20 month total treatment course, ensuring at least 3-4 effective drugs remain active after delamanid discontinuation. 1

Immediate Post-Delamanid Regimen Assessment

Your child has completed the standard 6-month course of delamanid and must now continue with the remaining drugs to complete the full MDR-TB treatment duration. 1

Critical requirement: The regimen must maintain at least 3-4 effective drugs for the remainder of treatment, which in this case includes levofloxacin (Group A fluoroquinolone), cycloserine, and clofazimine. 2, 1

Consider Adding Additional Agents

The current three-drug regimen (levofloxacin, cycloserine, clofazimine) may be insufficient by WHO standards, which recommend all three Group A agents plus at least one Group B agent. 2

Strongly consider adding:

• Linezolid at 10 mg/kg once daily (if child >12 years) or twice daily (if <12 years) to strengthen the regimen and meet WHO recommendations for at least 4 effective drugs. 2, 3
• Bedaquiline (if child ≥6 years and ≥20 kg) can be included and extended beyond 6 months with careful monitoring if needed to ensure adequate drug coverage. 2, 1

Total Treatment Duration

The complete treatment course is 18-20 months from initiation, or 15-17 months after culture conversion, whichever is longer. 1

• Delamanid's 6-month completion does NOT signal the end of treatment—the other drugs must continue for the full duration. 1
• Treatment should not be stopped early even though delamanid has been completed. 1

Essential Monitoring After Delamanid Discontinuation

Cardiac Monitoring (Critical with Clofazimine + Levofloxacin)

Perform baseline and monthly ECGs specifically for QTc interval prolongation throughout the remaining treatment. 3

• Measure QTc manually using Bazett's formula in leads II, V5, and V6. 3

• Action thresholds:

  • QTc 450-500 ms: Correct electrolytes immediately, increase ECG frequency to every 2 weeks, obtain cardiology consultation. 3
  • QTc ≥500 ms: Discontinue clofazimine immediately and arrange urgent cardiology consultation. 3
  • QTc increase >60 ms from baseline: Re-evaluate electrolytes and consider dose reduction. 3

• Check monthly electrolytes (potassium, calcium, magnesium) and correct abnormalities promptly to reduce QTc risk. 3

Hematologic and Neurologic Monitoring

Monthly complete blood counts to detect myelosuppression, especially if linezolid is added. 1, 3

Monthly visual acuity and color vision screening for optic neuropathy (linezolid-related if added). 1

Regular assessment for peripheral neuropathy: numbness, tingling, pain in extremities (cycloserine and linezolid-related). 1

Microbiologic Monitoring

Monthly sputum cultures (or gastric aspirates if unable to produce sputum) to confirm sustained culture conversion. 1

Drug susceptibility testing should guide any regimen modifications at this juncture, particularly confirmatory testing for fluoroquinolone, bedaquiline, and linezolid susceptibility. 1

Common Pitfalls to Avoid

Never accept fewer than 3 effective drugs after delamanid stops—this violates WHO guidelines and risks treatment failure. 1

Do not forgo QTc monitoring simply because the child appears well; the clofazimine-levofloxacin combination carries genuine risk of dangerous QT prolongation. 3

Avoid reliance on automated ECG QTc calculations—manual measurement provides greater accuracy in pediatric patients. 3

Never overlook electrolyte disturbances (low potassium, calcium, magnesium) as they markedly increase propensity for QT prolongation. 3

If Regimen Modification Becomes Necessary

If clofazimine must be discontinued due to QTc prolongation ≥500 ms, reinforce the regimen to contain at least four effective second-line drugs by adding: 3

• Linezolid (10 mg/kg twice daily if <12 years; once daily if >12 years) with monitoring for myelosuppression and neuropathy. 3
• Para-aminosalicylic acid (PAS) at 150 mg/kg, which does not contribute to QTc prolongation. 3

Treatment Success Indicators

Continue treatment until:

• 18-20 months total duration from treatment initiation is completed. 1
• At least 15-17 months have elapsed after documented culture conversion. 1
• Clinical, radiological, and microbiological improvement is sustained. 1