What is the drug of choice (DOC) for treating brucella infection in children?

Drug of Choice for Brucellosis in Children

For children under 8 years old, the drug of choice is rifampicin (15-20 mg/kg/day) combined with trimethoprim-sulfamethoxazole (TMP-SMX: 10-12 mg/kg trimethoprim component) given orally for 6 weeks. 1

Age-Based Treatment Algorithm

Children Under 8 Years Old

First-line regimen:

• Rifampicin 15-20 mg/kg/day PLUS TMP-SMX (10-12 mg/kg trimethoprim component) for 6 weeks 1, 2
• This combination avoids tetracycline-related tooth staining and bone growth issues in young children 3
• Cost-effectiveness analysis supports this regimen, avoiding aminoglycoside toxicity and expense 1

Alternative regimen if needed:

• Rifampicin for 6 weeks PLUS gentamicin 5-6 mg/kg/day for the first 5-7 days 3, 1

Children 8 Years and Older

First-line regimen (lowest relapse rates):

• Doxycycline 100 mg twice daily (or 2 mg/kg/day for children <100 lbs) PLUS streptomycin 15 mg/kg daily IM for 2-3 weeks, with doxycycline continued for total of 6 weeks 1, 4
• Alternatively: Doxycycline PLUS gentamicin 5 mg/kg daily IV/IM for 7 days, with doxycycline continued for 6 weeks 1, 4

Second-line regimen (when aminoglycosides contraindicated):

• Doxycycline 100 mg twice daily PLUS rifampicin 600-900 mg daily for 6 weeks 1, 4

Critical Treatment Duration Evidence

• Large multicenter study of 1,100 children showed no significant difference in relapse rates between 3,5, or 8 weeks when using combination therapy 5
• However, 6 weeks remains the standard recommendation to ensure adequate treatment 1, 2

Important Caveats and Pitfalls

Avoid TMP-SMX monotherapy:

• TMP-SMX alone has unacceptably high failure rates (30%) and should ONLY be used in combination with rifampicin 1, 5

Aminoglycoside-containing regimens provide superior outcomes:

• Lowest relapse rates (4-9%) occur with aminoglycoside combinations in children ≥8 years 5, 1
• Gentamicin offers advantage of shorter duration (7 days vs 14 days for streptomycin) and wider availability 4

Special Clinical Situations

Brucellar spondylitis:

• Aminoglycoside-containing regimens may be superior to rifampicin-containing regimens 1, 6
• Always perform MRI when spinal involvement suspected 1, 6

Neurobrucellosis:

• Requires aminoglycoside (preferably gentamicin) combined with doxycycline and rifampicin 6
• Treatment duration extends to 3-6 months 1

Tuberculosis-endemic regions:

• Consider public health implications of rifampicin use, as widespread use may contribute to mycobacterial resistance 1, 4
• In these settings, aminoglycoside-based regimens may be preferable when feasible 1

Expected Outcomes

• All patients should defervesce within 1-3 weeks of appropriate therapy 2
• Relapse rates range 5-15% even with appropriate treatment 1, 4
• Relapses are usually mild and respond well to retreatment with the same regimen 1, 4