What is the recommended treatment for Brucellosis?

Treatment of Brucellosis

The optimal treatment for uncomplicated brucellosis is a six-week regimen of doxycycline (100 mg twice daily) combined with streptomycin (15 mg/kg daily intramuscularly) for 2-3 weeks, which has demonstrated the lowest relapse rates. 1, 2

First-Line Treatment Options

• Doxycycline-Streptomycin (DOX-STR): Doxycycline 100 mg twice daily orally for 6 weeks plus streptomycin 15 mg/kg daily intramuscularly for 2-3 weeks - considered the gold standard with the lowest relapse rates 1, 2
• Doxycycline-Rifampicin (DOX-RIF): Doxycycline 100 mg twice daily orally for 6 weeks plus rifampicin 600-900 mg daily as a single morning dose for 6 weeks - effective but with higher relapse rates compared to DOX-STR 1, 3
• Doxycycline-Gentamicin (DOX-GENT): Doxycycline 100 mg twice daily orally for 6 weeks plus gentamicin 5 mg/kg daily parenterally in a single dose for 7 days - comparable efficacy to DOX-STR with the advantage of wider availability of gentamicin 1, 3

Treatment Efficacy Comparison

• The DOX-STR regimen has demonstrated superior efficacy with relapse rates of only 5.3% compared to 16% with DOX-RIF in comparative studies 4
• DOX-GENT shows failure/relapse rates ranging from 10% to 20%, which is approximately 5% higher than the WHO-recommended DOX-STR regimen 3, 1
• When treatment failure and relapse are considered together, DOX-STR has shown significantly better outcomes (7.45% failure) compared to DOX-RIF (24% failure) 4

Special Populations

• Pregnant women: Rifampicin 900 mg once daily for 6 weeks is considered the drug of choice 5, 6
• Children under 8 years: Avoid tetracyclines; use rifampicin with trimethoprim-sulfamethoxazole (TMP-SMX) for 45 days, or rifampicin with gentamicin 5-6 mg/kg/day for the first 5 days 5, 6

Complicated Brucellosis Treatment

• Brucellar spondylitis (spinal involvement): May require aminoglycoside-containing regimens and extended treatment beyond the standard 6 weeks 2
• Neurobrucellosis: Consider doxycycline and rifampicin with an aminoglycoside (preferably gentamicin over streptomycin) 7
• Brucellar endocarditis: Requires aggressive management with antimicrobials and often surgical intervention; streptomycin in doses of 1 g twice daily for 2 weeks and 500 mg twice daily for an additional 4 weeks is given in combination with penicillin 8

Treatment Monitoring and Outcomes

• Relapse rates range from 5-15% even with appropriate treatment 1
• Relapses are usually mild and can be treated with the same regimens 1
• Monitor for aminoglycoside toxicity, particularly ototoxicity, which may require early termination of treatment 8

Public Health Considerations

• In regions where brucellosis and tuberculosis coexist, consider the implications of using rifampicin, as this may contribute to mycobacterial resistance 1, 2
• The doxycycline-gentamicin combination offers advantages over doxycycline-streptomycin by sparing streptomycin, a valuable anti-tuberculosis agent 3

Treatment Algorithm

1. For uncomplicated brucellosis in adults: Start with DOX-STR as first choice 1, 2
2. If streptomycin is unavailable or contraindicated: Use DOX-GENT 1
3. If parenteral therapy is not feasible: Use DOX-RIF, but be aware of higher relapse rates 3, 4
4. For complicated cases: Extend treatment duration and consider additional agents based on the site of infection 2
5. Monitor for treatment response and toxicity, particularly with aminoglycosides 8

Human brucellosis requires combination therapy for adequate treatment, with the doxycycline-streptomycin regimen showing the most favorable outcomes in terms of preventing relapse and treatment failure 9, 4.