For a child with multidrug‑resistant tuberculosis who has completed a 6‑month course of delamanid and is currently receiving levofloxacin, cycloserine, and clofazimine, should another active drug (e.g., linezolid or bedaquiline) be added to maintain at least three to four effective agents for the remainder of therapy?

Should Another Treatment Be Added After Delamanid Completion?

Yes, you must add bedaquiline immediately to maintain at least four effective drugs in this child's MDR-TB regimen. After stopping delamanid at 6 months, the current three-drug regimen (levofloxacin, cycloserine, clofazimine) falls below WHO minimum standards and significantly increases the risk of treatment failure and acquired resistance 1, 2.

Why the Current Regimen Is Inadequate

The WHO explicitly mandates that MDR/RR-TB treatment must include all three Group A agents (levofloxacin or moxifloxacin, bedaquiline, and linezolid) to ensure at least four effective drugs at treatment initiation, with at least three agents continuing throughout therapy 1. Your patient currently has only one Group A agent (levofloxacin), creating a critically suboptimal regimen 2.

• Group A drugs (highest efficacy, should use all three): Fluoroquinolones (levofloxacin/moxifloxacin), bedaquiline, linezolid 1
• Group B drugs (add at least one): Clofazimine, cycloserine/terizidone 1
• The current regimen has one Group A drug and two Group B drugs—this violates WHO guidelines 2

Immediate Action Required

Add bedaquiline now unless there is documented resistance or contraindication 2, 3. For children aged 6-17 years, bedaquiline may be included with conditional recommendation based on very low certainty evidence, but the benefit of maintaining adequate drug numbers outweighs risks 1.

Bedaquiline Dosing for Children

• Age ≥12 years and weight ≥33 kg: 400 mg daily for 14 days, then 200 mg three times weekly for 22 weeks 1
• Age 6-11 years or weight <33 kg: Consult expert for weight-based dosing 1
• Duration: 24 weeks standard; longer duration may be considered case-by-case 1, 2

Consider Adding Linezolid

While bedaquiline is the priority addition, linezolid should also be strongly considered to complete the full Group A triad 1, 2, 3. The WHO gives a strong recommendation for linezolid inclusion in MDR/RR-TB regimens 1.

Linezolid Dosing for Children

• Age >12 years: 10 mg/kg once daily 1
• Age <12 years: 10 mg/kg twice daily 1
• Duration: Entire treatment course as tolerated 1

Why Delamanid Should Be Stopped

Delamanid is recommended for only 24 weeks (6 months) duration in pediatric MDR-TB, with longer duration considered only when no alternative drug options exist 1. Since your patient has completed 6 months and better alternatives (bedaquiline, linezolid) are available, continuing delamanid is not indicated 1.

• Delamanid showed no additional benefit when added to regimens already containing three highly effective drugs in observational studies 4
• The 24-week duration recommendation is based on conditional evidence with moderate certainty 1

Total Treatment Duration

The complete MDR-TB treatment course should be 18-20 months total (or 15-17 months after culture conversion) for longer regimens 2, 3. Your patient is only 6 months into treatment, so approximately 12-14 months remain.

Critical Monitoring Requirements

For Bedaquiline

• Baseline: ECG for QTc interval assessment 1, 2
• Ongoing: Monthly ECG monitoring for QTc prolongation 1, 2
• Action threshold: QTcF >500 msec or increase >60 msec from baseline requires intervention 2
• Correct electrolyte abnormalities (hypokalemia, hypomagnesemia, hypocalcemia) before and during treatment 2

For Linezolid (if added)

• Baseline: Complete blood count, assess for peripheral neuropathy 1
• Ongoing: Monthly CBC and peripheral neuropathy screening 1, 2
• Dose reduction: Consider reducing to 300 mg daily if toxicity develops (anemia, neuropathy) while maintaining efficacy 2, 5
• Visual monitoring: Monthly visual acuity and color vision screening for optic neuropathy 2

For Clofazimine (already on regimen)

• Baseline and monthly ECG for QTc monitoring, especially when combined with bedaquiline 1
• The combination of bedaquiline, fluoroquinolone, and clofazimine increases QTc prolongation risk 6

Common Pitfalls to Avoid

• Never accept a three-drug regimen as adequate—this violates WHO guidelines and dramatically increases treatment failure risk 2, 3
• Do not delay bedaquiline addition—every day without adequate drug coverage increases resistance development risk 2, 3
• Do not continue delamanid beyond 6 months when better alternatives exist 1
• Do not miss linezolid toxicity monitoring—myelosuppression and peripheral neuropathy are common but manageable with dose reduction 2, 5
• Do not ignore QTc prolongation—the combination of multiple QT-prolonging drugs requires vigilant ECG monitoring 2, 6

Final Regimen Structure

Optimal regimen after adding bedaquiline and linezolid:

• Levofloxacin (Group A)
• Bedaquiline (Group A)
• Linezolid (Group A)
• Clofazimine (Group B)
• Cycloserine (Group B)

This five-drug regimen meets WHO standards with all three Group A agents plus two Group B agents 1, 2, 3.