What is the treatment for brucellosis?

Treatment of Brucellosis

The optimal treatment for brucellosis consists of doxycycline 100 mg twice daily for 6 weeks combined with streptomycin 15 mg/kg daily intramuscularly for 2-3 weeks (DOX-STR), which is considered the first-line regimen with the lowest relapse rates. 1

First-Line Treatment Options

Preferred Regimen:

• Doxycycline-Streptomycin (DOX-STR)
  • Doxycycline: 100 mg twice daily orally for 6 weeks
  • Streptomycin: 15 mg/kg daily intramuscularly for 2-3 weeks
  • Evidence level: AI (highest recommendation) 2
  • Clinical response rate: 95.4% (highest among treatment options) 3
  • Lowest relapse rate: 4.6% 3

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 2
   • Advantage: Wider availability of gentamicin compared to streptomycin 2
   • Can be considered 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 (single morning dose)
   • Evidence level: AI 2
   • Higher relapse rate compared to DOX-STR (RR 2.39,95% CI 1.17 to 4.86) 4
   • Caution: In regions where brucellosis and tuberculosis coexist, rifampicin use may contribute to mycobacterial resistance 1

Special Populations

Children (<8 years old):

• Preferred regimen: Rifampicin with cotrimoxazole for 45 days 5
• Alternative: Rifampicin for 45 days with gentamicin 5-6 mg/kg/day for the first 5 days 5

Pregnant Women:

• Preferred regimen: Rifampicin 900 mg once daily for 6 weeks 5
• Tetracyclines are contraindicated during pregnancy

Treatment Duration and Monitoring

• Standard duration: 6 weeks for uncomplicated brucellosis
• Extended duration: 3-6 months for localized infections (endocarditis, neurobrucellosis, osteomyelitis) 1
• Short-term treatment regimens (<4 weeks) are associated with significantly higher relapse rates 1
• Follow-up for at least 2 years after treatment to monitor for recurrence 1

Complications and Treatment Failure

• Relapse rates range from 5-15% even with appropriate treatment 1
• Treatment failure is more common with:
  • Monotherapy (13% vs. 4.8% with combination therapy) 6
  • Short-term regimens (<4 weeks) (22% vs. 4.8% with standard duration) 6
  • DOX-RIF compared to DOX-STR (RR 1.91,95% CI 1.07 to 3.42) 4

Second-Line Treatment Options

• Quinolone-containing regimens (ciprofloxacin or ofloxacin plus rifampicin)

  • Evidence level: CII 2
  • Similar efficacy to DOX-RIF but with higher relapse rates 6
  • Consider when first-line agents are contraindicated

• Trimethoprim-sulfamethoxazole (TMP-SMX) containing regimens

  • Evidence level: CII 2
  • More cost-effective in developing countries 2
  • Can be used in combination with other agents

Common Pitfalls and Caveats

1. Inadequate treatment duration: Ensure full 6-week course of doxycycline to prevent relapse
2. Inappropriate monotherapy: Always use combination therapy for better outcomes
3. Overlooking drug interactions: Monitor for interactions between doxycycline and rifampicin
4. Neglecting follow-up: Regular monitoring is essential to detect relapse early
5. Antimicrobial resistance concerns: Consider local tuberculosis prevalence when using rifampicin

The DOX-STR regimen remains the gold standard for brucellosis treatment due to its superior efficacy and lower relapse rates compared to other regimens. When streptomycin administration is not feasible, DOX-GENT offers a comparable alternative with more convenient administration.