What is the recommended treatment for brucellosis?

Treatment of Brucellosis

For uncomplicated brucellosis in adults, doxycycline 100 mg twice daily for 6 weeks combined with streptomycin 15 mg/kg daily intramuscularly for 2-3 weeks is the gold standard treatment with the lowest relapse rates. 1, 2, 3

First-Line Treatment Regimens

The Ioannina recommendations provide clear guidance on optimal treatment, with two regimens receiving the highest level of evidence (AI recommendation):

Preferred Regimen: Doxycycline-Streptomycin (DOX-STR)

• Doxycycline: 100 mg orally twice daily for 6 weeks 1, 2, 3
• Streptomycin: 15 mg/kg daily intramuscularly for 2-3 weeks 1, 2, 3
• This combination demonstrates superior efficacy with relapse rates of approximately 5-7%, significantly lower than alternative regimens 4, 5
• A landmark randomized controlled trial showed doxycycline-streptomycin had a failure rate of only 7.45% compared to 24% with doxycycline-rifampicin 4

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

• Doxycycline: 100 mg orally twice daily for 6 weeks 1, 2, 3
• Rifampicin: 600-900 mg daily as a single morning dose for 6 weeks 1, 2, 3
• This regimen has higher relapse rates (16-24%) compared to doxycycline-streptomycin 4, 5
• Critical caveat: In regions where tuberculosis is endemic, rifampicin use may contribute to mycobacterial resistance and should be avoided when possible 2, 3

Practical Alternative: Doxycycline-Gentamicin (DOX-GENT)

• Doxycycline: 100 mg orally twice daily for 6 weeks 1, 2
• Gentamicin: 5 mg/kg daily parenterally as a single dose for 7 days 1, 2
• This regimen offers comparable efficacy to doxycycline-streptomycin with relapse rates of 10-20% 1, 5
• Advantages: Gentamicin is more widely available than streptomycin, and the shorter parenteral course (7 days vs 14-21 days) improves patient convenience 1, 2
• Meta-analysis shows no significant difference between doxycycline-gentamicin and doxycycline-streptomycin (OR = 1.89; CI95% = 0.81-4.39) 5

Second-Line Treatment Options

Trimethoprim-Sulfamethoxazole Regimens

• TMP-SMX: 800+160 mg twice daily for 6 weeks, typically combined with doxycycline 1, 2
• This is a cost-effective alternative in resource-limited settings with response rates above 90% 2
• Important limitation: When used as monotherapy, TMP-SMX has unacceptably high relapse rates of 46% 1

Quinolone-Containing Regimens

• Ofloxacin: 400 mg twice daily for 6 weeks, or Ciprofloxacin: 500 mg twice daily for 6 weeks 1, 2
• These should be reserved as second or third agents in combination regimens due to higher cost and risk of promoting fluoroquinolone resistance 1, 2
• Quinolone-rifampicin combinations show similar efficacy to doxycycline-rifampicin (OR = 1.23; CI95% = 0.63-2.40) 5

Special Clinical Situations

Complicated Brucellosis

• Brucellar spondylitis: Aminoglycoside-containing regimens may be superior to rifampicin-containing ones 3, 6
• Treatment duration should be extended beyond 6 weeks, typically 3-6 months 3, 7
• MRI should be performed when spinal involvement is suspected 6
• Cervical spine involvement requires immobilization to prevent devastating neurological complications 6

Neurobrucellosis

• If ceftriaxone cannot be used, consider doxycycline and rifampicin with an aminoglycoside (preferably gentamicin over streptomycin) 6
• Treatment duration typically extends to 3-6 months 7

Brucellar Endocarditis

• This is a high mortality complication requiring aggressive management with empirical antimicrobial selection 3
• Parenteral therapy with streptomycin or gentamicin combined with TMP-SMX, rifampicin, and doxycycline is recommended 7
• Surgical intervention (valvular replacement) is required in most cases 3, 7

Pregnant Women

• Rifampicin: 900 mg once daily for 6 weeks is considered the drug of choice 7
• Tetracyclines are contraindicated in pregnancy 7, 8

Children Under 8 Years

• Preferred regimen: Rifampicin with cotrimoxazole (TMP-SMX) for 45 days 7
• Alternative: Rifampicin for 45 days with gentamicin 5-6 mg/kg/day for the first 5 days 7
• Tetracyclines are generally contraindicated in this age group 7, 8

Treatment Monitoring and Expected Outcomes

• Relapse rates: Even with appropriate treatment, expect 5-15% relapse rates in uncomplicated cases 2, 3
• Relapse characteristics: Relapses are usually mild and can be successfully treated with the same regimens 2, 3
• Standard treatment duration: 6 weeks for uncomplicated cases 1, 2, 3

Critical Pitfalls to Avoid

• Never use monotherapy except in highly selected patients with uncomplicated disease and low relapse risk, as monotherapy has unacceptably high relapse rates ranging from 2-46% depending on the agent 1
• Do not use fixed-dose gentamicin (500 mg): Always calculate weight-based dosing at 5 mg/kg daily 2
• Avoid rifampicin in TB-endemic areas when alternative regimens are available to prevent mycobacterial resistance 2, 3
• Do not use triple therapy routinely: Only one study assessed aminoglycoside-doxycycline-rifampicin triple therapy in uncomplicated brucellosis, and this cannot be considered standard therapy until further studies are performed 5