What is the recommended treatment regimen for brucellosis?

Recommended Treatment Regimen for Brucellosis

The optimal treatment of uncomplicated brucellosis should be based on a six-week regimen of doxycycline (100 mg twice daily) combined either with streptomycin (1 g daily) 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 twice daily orally for 6 weeks 1
• Streptomycin: 15 mg/kg daily intramuscularly for 2-3 weeks 1
• This combination has the lowest relapse rate (5.3%) compared to other regimens 2
• Considered the gold standard treatment with the strongest evidence supporting its efficacy 1

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

• Doxycycline: 100 mg twice daily orally for 6 weeks 1
• Rifampicin: 600-900 mg daily as a single morning dose for 6 weeks 1
• Higher relapse rate (16%) compared to DOX-STR 2
• More convenient as both medications are administered orally 1
• May be preferred when streptomycin is unavailable or contraindicated 1

Doxycycline-Gentamicin (DOX-GENT) - Alternative First-Line

• Doxycycline: 100 mg twice daily orally for 6 weeks 1
• Gentamicin: 5 mg/kg daily parenterally in 1 dose for 7 days 1
• Comparable efficacy to DOX-STR regimen 1
• Gentamicin offers advantages over streptomycin in terms of wider availability 1
• Duration of gentamicin administration may need modification (5-14 days) for optimal results 1

Second-Line Treatment Options

Trimethoprim-Sulfamethoxazole (TMP-SMX) Containing Regimens

• TMP-SMX: 800+160 mg twice daily for 6 weeks 1
• Often combined with doxycycline or rifampicin 3
• Cost-effective alternative in certain resource-limited settings 1
• Less effective than first-line regimens but may be considered when first-line options are unavailable 1

Quinolone-Containing Regimens

• Ofloxacin: 400 mg twice daily for 6 weeks, or 1
• Ciprofloxacin: 500 mg twice daily for 6 weeks 1
• Similar efficacy to DOX-RIF but with higher relapse rates 3
• Should be reserved as second or third agents in combination regimens 1

Special Populations

Pregnant Women

• Rifampicin: 900 mg once daily for 6 weeks 4
• Tetracyclines (including doxycycline) are contraindicated during pregnancy 4

Children Under 8 Years

• Rifampicin with co-trimoxazole for 45 days 4, 3
• Alternative: rifampicin for 45 days with gentamicin 5-6 mg/kg/day for the first 5 days 4
• Doxycycline is contraindicated in children under 8 years due to dental staining 4

Treatment Duration and Monitoring

• Standard treatment duration is 6 weeks for most regimens 1
• Shorter treatment durations (less than 4 weeks) are associated with higher relapse rates (22% vs. 4.8%) 3
• Relapse rates range from 5% to 15% of uncomplicated cases even with appropriate treatment 1
• Relapses are usually mild and can be treated successfully with the same regimens 1

Common Pitfalls and Caveats

• Monotherapy has significantly higher relapse rates (13% vs. 4.8%) compared to combination therapy and should be avoided 3
• Triple therapy (aminoglycoside-doxycycline-rifampicin) has not been adequately studied and cannot be recommended as first-line treatment 5
• In regions where brucellosis and tuberculosis coexist, consider the public health implications of using rifampicin, as this may contribute to mycobacterial resistance 1
• The DOX-RIF regimen, while convenient (all oral), has been shown to be less effective than DOX-STR in multiple studies 5, 2
• Therapeutic failure rates are higher with the DOX-RIF regimen (8%) compared to the DOX-STR regimen (2%) 2