Brucellosis Management
Recommended First-Line Treatment
For uncomplicated brucellosis in adults, doxycycline 100 mg twice daily for 6 weeks combined with streptomycin 15 mg/kg daily intramuscularly for 2-3 weeks is the most effective regimen, demonstrating significantly lower relapse rates (5.3%) compared to doxycycline-rifampicin (16% relapse rate). 1, 2, 3
Primary Treatment Options (in order of preference):
1. Doxycycline-Streptomycin (DOX-STR) - Grade AI Recommendation:
- Doxycycline: 100 mg orally twice daily for 6 weeks 1, 2
- Streptomycin: 15 mg/kg daily (maximum 1 g) intramuscularly for 2-3 weeks 1, 4
- This combination has the lowest relapse rate at 5.3% versus 16% with doxycycline-rifampicin 3
- Combined treatment failure and relapse rate: 7.45% versus 24% with doxycycline-rifampicin 3
- Inject into upper outer quadrant of buttock or mid-lateral thigh; alternate injection sites 4
2. Doxycycline-Gentamicin (DOX-GENT) - Grade BI Recommendation:
- Doxycycline: 100 mg orally twice daily for 6 weeks 1, 2
- Gentamicin: 5 mg/kg daily parenterally as single dose for 7 days 1, 2
- Preferred alternative when streptomycin is unavailable or to spare streptomycin for tuberculosis treatment 1
- Relapse rates comparable to WHO-recommended regimens 1
- Offers advantage of shorter parenteral therapy duration (7 days vs 14-21 days) 2
3. Doxycycline-Rifampicin (DOX-RIF) - Grade AI Recommendation:
- Doxycycline: 100 mg orally twice daily for 6 weeks 1, 2
- Rifampicin: 600-900 mg daily as single morning dose for 6 weeks 1, 2
- Second-choice regimen due to higher relapse rates (16% vs 5.3%) 3, 5
- Advantage: entirely oral regimen, no injections required 1
- Caution: In regions with tuberculosis co-endemicity, rifampicin use may contribute to mycobacterial resistance 2, 6
Alternative Regimens
Trimethoprim-Sulfamethoxazole (TMP-SMX) Combinations - Grade CII:
- TMP-SMX: 800+160 mg twice daily for 6 weeks 1
- Cost-effective alternative in resource-limited settings 2
- Should be used in three-drug combination regimens with doxycycline 1
Quinolone-Containing Regimens - Grade CII:
- Ofloxacin: 400 mg twice daily for 6 weeks OR Ciprofloxacin: 500 mg twice daily for 6 weeks 1
- Reserved as second or third agents in combination regimens 1, 2
- Higher cost and risk of promoting antimicrobial resistance 2
- Similar efficacy to doxycycline-rifampicin but with higher relapse rates 5, 7
Special Populations
Children (<8 years old):
- Rifampicin 900 mg once daily for 6 weeks plus cotrimoxazole for 45 days is preferred 8, 9
- Alternative: Rifampicin for 45 days plus gentamicin 5-6 mg/kg/day for first 5 days 8
- Tetracyclines contraindicated due to dental staining 8, 9
Pregnant Women:
- Rifampicin 900 mg once daily for 6 weeks is the drug of choice 8, 9
- Tetracyclines are contraindicated 8, 9
Patients >60 years:
- Reduce streptomycin dosage due to increased toxicity risk 4
- For endocarditis: 500 mg twice daily for entire 2-week period instead of standard dosing 4
Complicated Brucellosis
Brucellar Spondylitis:
- Aminoglycoside-containing regimens may be superior to rifampicin-containing regimens 6, 10
- Treatment duration may need extension beyond standard 6 weeks 6
- Obtain MRI when spinal involvement suspected 10
- Immobilize spine if cervical involvement present to prevent neurological complications 10
Brucellar Endocarditis:
- High mortality complication requiring aggressive management 6
- Surgical intervention required in most cases 6
- Streptomycin 1 g twice daily for first week, then 500 mg twice daily for second week, combined with penicillin 4
Neurobrucellosis:
- Consider doxycycline plus rifampicin with aminoglycoside (gentamicin preferred over streptomycin) 10
Treatment Monitoring and Outcomes
Expected Relapse Rates:
- Even with appropriate treatment: 5-15% relapse rate 2, 6
- Relapses are usually mild and respond to same regimens 2, 6
- Monotherapy associated with 13% relapse rate versus 4.8% with combination therapy 7
- Short-term treatment (<4 weeks) shows 22% relapse rate versus 4.8% with standard duration 7
Critical Pitfalls to Avoid
Do not use monotherapy: Monotherapy with doxycycline alone shows relapse rates up to 39% in older studies, though one well-designed trial showed comparable rates to combination therapy 1
Do not shorten treatment duration: Treatment <4 weeks associated with significantly higher relapse rates (22% vs 4.8%) 7
Do not exceed total streptomycin dose: Maximum cumulative dose of 120 g over entire treatment course unless no other therapeutic options 4
Avoid rifampicin in TB-endemic areas when possible: Consider public health implications of mycobacterial resistance 2, 6, 10