What is the recommended treatment regimen for Brucella infection?

Brucellosis Management

Recommended First-Line Treatment

For uncomplicated brucellosis, doxycycline 100 mg twice daily orally for 6 weeks combined with streptomycin 15 mg/kg daily intramuscularly for 2-3 weeks is the preferred regimen, offering the lowest relapse rates. 1, 2

Treatment Algorithm for Uncomplicated Brucellosis

Primary Regimen (Lowest Relapse Rate)

• Doxycycline 100 mg PO twice daily for 6 weeks PLUS Streptomycin 15 mg/kg IM daily for 2-3 weeks 1, 2
• This combination demonstrates superior efficacy with relapse rates of only 5.3% compared to 16% with doxycycline-rifampicin 3
• Meta-analysis confirms this regimen is significantly more effective than alternatives (OR = 3.17 favoring streptomycin over rifampicin) 4

Alternative First-Line Regimens (When Streptomycin Unavailable)

• Doxycycline 100 mg PO twice daily for 6 weeks PLUS Gentamicin 5 mg/kg IV/IM daily as single dose for 7 days 1
• WHO recommends this as first-line with comparable efficacy to streptomycin, offering the advantage of wider availability and shorter parenteral therapy duration 1
• Note: Use weight-based dosing (5 mg/kg), NOT fixed 500 mg dosing 1
• Failure/relapse rates are approximately 10-20%, which is about 5% higher than streptomycin-containing regimens 1

Second-Choice Oral Regimen

• Doxycycline 100 mg PO twice daily for 6 weeks PLUS Rifampicin 600-900 mg PO daily (single morning dose) for 6 weeks 1, 2
• This all-oral regimen has higher relapse rates (16% vs 5.3%) and combined failure rates of 24% vs 7.45% compared to doxycycline-streptomycin 3
• Important caveat: In regions where tuberculosis coexists with brucellosis, avoid rifampicin due to risk of promoting mycobacterial resistance 1, 2

Cost-Effective Alternative (Resource-Limited Settings)

• Trimethoprim-Sulfamethoxazole 800+160 mg PO twice daily for 6 weeks (combined with doxycycline or rifampicin) 1
• CDC reports response rates above 90% when used appropriately 1
• Systematic reviews show similar efficacy to doxycycline-rifampicin 5

Complicated Brucellosis

Brucellar Spondylitis (Spinal Involvement)

• Aminoglycoside-containing regimens are superior to rifampicin-containing regimens 2, 6
• Extend treatment duration beyond standard 6 weeks 2
• Perform MRI when spinal involvement is suspected 6
• If cervical spine involvement: immobilize spine immediately to prevent devastating neurological complications 6

Neurobrucellosis

• Consider doxycycline + rifampicin + aminoglycoside (preferably gentamicin over streptomycin) if ceftriaxone cannot be used 6
• MRI is mandatory when spinal involvement suspected 6

Brucellar Endocarditis

• High mortality complication requiring aggressive management 2
• Empirical antimicrobial selection with surgical intervention needed in most cases 2

Pediatric Considerations (Age <8 Years)

• Trimethoprim-Sulfamethoxazole plus Rifampicin for 6 weeks is the regimen of choice 5
• Alternative: Gentamicin for 5 days plus trimethoprim-sulfamethoxazole for 6 weeks 5
• Avoid doxycycline due to dental staining risk in children under 8 years 5

Treatment Monitoring and Relapse Management

• Standard treatment duration is 6 weeks for uncomplicated cases 1, 2
• Relapse rates range from 5-15% even with appropriate treatment 1, 2
• Relapses are usually mild and respond successfully to the same initial regimen 1, 2
• Monotherapy shows significantly higher relapse rates (13% vs 4.8%) and should be avoided 5
• Short-term treatment (<4 weeks) results in 22% relapse rate vs 4.8% with standard duration 5

Regimens to Avoid or Reserve

• Quinolone-containing regimens (ofloxacin, ciprofloxacin) should be reserved as second or third agents only due to higher cost and antimicrobial resistance concerns 1
• Triple therapy (aminoglycoside-doxycycline-rifampicin) cannot be considered first-line until better studied 4
• Monotherapy with any agent is inadequate and leads to unacceptably high relapse rates 5