What is the recommended treatment for brucellosis (Brucella infection)?

Treatment of Brucellosis

The recommended first-line treatment for brucellosis is doxycycline (100 mg twice daily orally for 6 weeks) plus streptomycin (15 mg/kg daily intramuscularly for 2-3 weeks), which has the lowest relapse rates and highest efficacy. 1

First-Line Treatment Regimens

Doxycycline-Streptomycin (DOX-STR) - Preferred Regimen

• Doxycycline: 100 mg twice daily orally for 6 weeks
• Streptomycin: 15 mg/kg daily intramuscularly for 2-3 weeks
• Evidence level: AI (highest recommendation) 1
• Multiple studies have demonstrated this regimen has significantly lower relapse rates (5.3%) compared to other combinations 2

Alternative First-Line Regimens

1. Doxycycline-Gentamicin (DOX-GENT)

   • Doxycycline: 100 mg twice daily orally for 6 weeks
   • Gentamicin: 5 mg/kg daily parenterally for 7 days
   • Evidence level: BI 1
   • Consider when streptomycin is unavailable or contraindicated

2. Doxycycline-Rifampicin (DOX-RIF)

   • Doxycycline: 100 mg twice daily orally for 6 weeks
   • Rifampicin: 600-900 mg daily for 6 weeks
   • Evidence level: AI 1
   • Higher relapse rate (16%) compared to DOX-STR (5.3%) 2
   • Not recommended in regions where tuberculosis and brucellosis coexist due to risk of developing mycobacterial resistance 1

Special Populations

Children Under 8 Years

• Tetracyclines are contraindicated
• Recommended regimen: Rifampicin with cotrimoxazole (trimethoprim-sulfamethoxazole) for 45 days 1, 3
• Alternative: Rifampicin for 45 days with gentamicin 5-6 mg/kg/day for the first 5 days 3

Pregnant Women

• Tetracyclines are contraindicated
• Recommended: Rifampicin 900 mg once daily for 6 weeks 3

Patients with Renal Impairment

• Dosage adjustment is essential for aminoglycosides
• Methods include increasing interval between doses or reducing dose while maintaining an 8-hour interval
• Monitor serum gentamicin levels 1

Complicated Brucellosis

Osteoarticular Infections

• Doxycycline plus rifampicin for 3-6 months
• Add streptomycin for the first 2-3 weeks 1

Neurobrucellosis

• TMP-SMX plus rifampicin for 3-6 months 1

Endocarditis

• Parenteral treatment with streptomycin or gentamicin combined with TMP-SMX, rifampicin, and doxycycline
• Often requires valve replacement 1
• Streptomycin dosing for endocarditis: 1g twice daily for first week, 500mg twice daily for second week 4

Treatment Duration

• Uncomplicated brucellosis: 6 weeks
• Localized infections (endocarditis, neurobrucellosis, osteomyelitis): 3-6 months 1
• Short-duration treatments (<4 weeks) have significantly higher relapse rates (22% vs 4.8%) 5

Important Considerations

Monitoring

• Follow-up is recommended for at least 2 years after treatment to detect recurrences 1
• Monitor for adverse effects, particularly with aminoglycosides (ototoxicity, nephrotoxicity)

Common Pitfalls

1. Inadequate treatment duration - treatments shorter than 6 weeks lead to higher relapse rates
2. Inappropriate monotherapy - monotherapy has higher relapse rates (13%) compared to combination therapy (4.8%) 5
3. Using rifampicin in TB-endemic areas - may contribute to mycobacterial resistance 1
4. Failure to adjust aminoglycoside dosing in patients with renal impairment
5. Overlooking complicated disease requiring longer treatment duration

Streptomycin Administration

• Administer via intramuscular route only
• Preferred site: upper outer quadrant of buttock or mid-lateral thigh
• In children: mid-lateral muscles of thigh preferred
• Alternate injection sites
• Maximum total dose should not exceed 120g over course of therapy 4

The evidence strongly supports doxycycline-streptomycin as the most effective regimen for brucellosis treatment, with multiple studies showing lower relapse rates compared to other combinations. While doxycycline-rifampicin is more convenient as an all-oral regimen, its higher relapse rate makes it a second-choice option when streptomycin cannot be used.