What is the recommended treatment for brucellosis?

Brucellosis Treatment

For uncomplicated brucellosis, the optimal first-line treatment is doxycycline 100 mg twice daily orally for 6 weeks combined with streptomycin 15 mg/kg daily intramuscularly for 2-3 weeks, which achieves the lowest relapse rates. 1, 2

First-Line Treatment Regimens

Preferred Option: Doxycycline-Streptomycin

• Doxycycline 100 mg twice daily orally for 6 weeks PLUS streptomycin 15 mg/kg daily intramuscularly for 2-3 weeks 1, 2
• This combination demonstrates superior efficacy with the lowest relapse rates compared to all other regimens 2, 3
• Meta-analysis shows doxycycline-streptomycin is significantly better than doxycycline-rifampicin (OR = 3.17; 95% CI = 2.05-4.91) 3

Alternative First-Line Option: Doxycycline-Gentamicin

• Doxycycline 100 mg twice daily orally for 6 weeks PLUS gentamicin 5 mg/kg daily parenterally as a single dose for 7 days 1, 2
• The World Health Organization recommends this as first-line with comparable efficacy to doxycycline-streptomycin 1
• Gentamicin offers the advantage of wider availability and shorter duration of parenteral therapy (7 days vs 14-21 days) 1
• No significant difference in outcomes between gentamicin and streptomycin regimens (OR = 1.89; 95% CI = 0.81-4.39) 3
• Use weight-based dosing of 5 mg/kg daily; fixed 500 mg dosing is not recommended 1

Second-Choice Regimen: Doxycycline-Rifampicin

• Doxycycline 100 mg twice daily orally for 6 weeks PLUS rifampicin 600-900 mg daily as a single morning dose for 6 weeks 1, 2
• This all-oral regimen is more convenient but has higher relapse rates than aminoglycoside-containing regimens 2, 3
• Important caveat: In regions where tuberculosis is endemic, avoid rifampicin due to risk of promoting mycobacterial resistance 1, 2

Second-Line Treatment Options

Doxycycline-Trimethoprim-Sulfamethoxazole

• Doxycycline 100 mg twice daily PLUS trimethoprim-sulfamethoxazole 800+160 mg twice daily for 6 weeks 1
• The Centers for Disease Control and Prevention suggests this as a cost-effective alternative in resource-limited settings with response rates above 90% 1
• Comparable efficacy to doxycycline-rifampicin in systematic reviews 4, 3

Quinolone-Containing Regimens

• Ofloxacin or ciprofloxacin combined with doxycycline or rifampicin 1
• The European Centre for Disease Prevention and Control advises reserving these as second or third agents due to higher cost and antimicrobial resistance concerns 1
• Similar efficacy to doxycycline-rifampicin but with higher relapse rates 4, 3

Treatment Duration and Monitoring

Standard Duration

• 6 weeks is the standard treatment duration for uncomplicated brucellosis 1, 2
• Shorter durations (3-4 weeks) are inadequate and associated with unacceptably high relapse rates of 22% vs 4.8% 2, 4

Expected Outcomes

• Relapse rates range from 5-15% even with appropriate treatment 1, 2
• Relapses are usually mild and respond to retreatment with the same regimens 1, 2
• Clinical improvement should be evident within 7-14 days of treatment initiation 5

Special Populations

Children Under 8 Years Old

• Rifampicin 600-900 mg daily PLUS trimethoprim-sulfamethoxazole for 6 weeks 6, 4
• Alternative: Rifampicin for 6 weeks PLUS gentamicin 5-6 mg/kg/day for 5-7 days 6, 4
• Tetracyclines are contraindicated due to dental staining risk 6, 7

Pregnant Women

• Rifampicin 900 mg once daily for 6 weeks as monotherapy 6, 7
• Tetracyclines are contraindicated in pregnancy 6, 7

Complicated Brucellosis

Brucellar Spondylitis (Spinal Involvement)

• Extend treatment duration to 12 weeks (3 months) 2
• Aminoglycoside-containing regimens may be superior to rifampicin-containing regimens 2
• The Infectious Diseases Society of America recommends MRI to confirm spinal involvement before extending therapy 2
• Always assess for back pain in brucellosis patients, as it may indicate spondylitis requiring prolonged treatment 2

Brucellar Endocarditis

• High mortality complication requiring aggressive antimicrobial therapy 2
• Surgical intervention needed in most cases 2, 6

Other Focal Complications

• Neurobrucellosis, cerebral abscess, epidural abscess, or splenic abscess may require surgical intervention if antibiotic-resistant 6, 7
• Treatment duration typically extended to 12-24 weeks 2

Common Pitfalls to Avoid

Monotherapy

• Never use monotherapy for brucellosis 4
• Monotherapy has significantly higher relapse rates (13% vs 4.8% for combination therapy) 4

Inadequate Duration

• Do not shorten treatment below 6 weeks for uncomplicated cases 2, 4
• Short-term regimens (less than 4 weeks) have relapse rates of 22% vs 4.8% for standard duration 4

Symptom Management

• Fever with afternoon temperature swings and profuse sweating is expected during early treatment and represents ongoing inflammatory response, not treatment failure 5
• Acetaminophen can manage fever and discomfort 5
• Full symptom resolution may take several weeks despite appropriate therapy 5