What is the recommended treatment for Brucellosis?

Treatment of Brucellosis

The optimal treatment for brucellosis is a six-week regimen of doxycycline (100 mg twice daily) combined with either streptomycin (15 mg/kg daily intramuscularly for 2-3 weeks) or rifampicin (600-900 mg daily for six weeks). 1

First-Line Treatment Options

Doxycycline-Streptomycin (DOX-STR) - Preferred Regimen

• Doxycycline: 100 mg orally twice daily for 6 weeks
• Streptomycin: 15 mg/kg daily intramuscularly for 2-3 weeks
• Evidence grade: AI (highest recommendation) 1
• This regimen has demonstrated the lowest relapse rates (5-15%) 1, 2
• Considered the gold standard for uncomplicated brucellosis

Doxycycline-Rifampicin (DOX-RIF) - Alternative First-Line

• Doxycycline: 100 mg orally twice daily for 6 weeks
• Rifampicin: 600-900 mg daily orally for 6 weeks, administered as a single morning dose
• Evidence grade: AI 1
• Higher relapse rate compared to DOX-STR (RR 2.39,95% CI 1.17 to 4.86) 2
• Advantage: Fully oral regimen, better compliance in outpatient settings

Alternative Regimen

Doxycycline-Gentamicin (DOX-GENT)

• Doxycycline: 100 mg orally twice daily for 6 weeks
• Gentamicin: 5 mg/kg daily parenterally in 1 dose for 7 days
• Evidence grade: BI 1
• Comparable efficacy to WHO-recommended regimens 1
• Advantage: Wider availability of gentamicin compared to streptomycin
• Spares streptomycin (valuable anti-tuberculosis agent)

Special Populations

Pregnant Women

• Rifampicin: 900 mg once daily for 6 weeks 3, 4
• Tetracyclines are contraindicated during pregnancy

Children < 8 Years Old

• Preferred regimen: Rifampicin with cotrimoxazole for 45 days 3, 5, 4
• Alternative: Rifampicin for 45 days with gentamicin 5-6 mg/kg/day for first 5 days 3
• Tetracyclines are contraindicated in children under 8 years

Treatment Considerations

Factors Affecting Treatment Choice

1. Severity of infection:

   • Uncomplicated cases: Standard regimens as above
   • Complicated cases (endocarditis, neurobrucellosis): May require longer treatment duration

2. Accessibility to care:

   • If daily IM injections are difficult, consider DOX-RIF regimen
   • DOX-GENT may be preferred over DOX-STR due to wider availability

3. Risk factors for relapse:

   • Male gender
   • Symptom duration >10 days before treatment
   • Baseline ESR >50 mm/h
   • Bacteremia
   • Consider longer treatment duration or DOX-STR regimen

Monitoring During Treatment

• Clinical response (fever resolution typically within 3-7 days)
• Periodic liver function tests when using rifampicin
• Renal function and audiometric testing when using aminoglycosides
• Monitor for adverse effects of doxycycline (photosensitivity, gastrointestinal symptoms)

Common Pitfalls to Avoid

1. Inadequate treatment duration: Treatment for less than 6 weeks is associated with higher relapse rates (22% vs 4.8%) 5
2. Monotherapy: Significantly higher relapse rates compared to combination therapy (13% vs 4.8%) 5
3. Improper streptomycin administration: Intramuscular injections should be given in the gluteus maximus or mid-lateral thigh, with site rotation to prevent local complications 6
4. Failure to recognize complications: Endocarditis, neurobrucellosis, or abscess formation may require surgical intervention in addition to antibiotics 4
5. Overlooking drug interactions: Rifampicin induces hepatic enzymes and may reduce effectiveness of concurrent medications

The evidence strongly supports the DOX-STR regimen as most effective for uncomplicated brucellosis in adults, with DOX-RIF as a reasonable alternative when parenteral therapy is not feasible or practical 1, 2.