What is the recommended treatment regimen for brucellosis?

Treatment of Brucellosis

First-Line Treatment for Uncomplicated Brucellosis in Adults

The optimal treatment for uncomplicated brucellosis is doxycycline 100 mg twice daily orally for 6 weeks combined with streptomycin 15 mg/kg daily intramuscularly for 2-3 weeks, as this regimen demonstrates the lowest relapse rates. 1, 2, 3

Primary Recommended Regimens (in order of preference):

1. Doxycycline-Streptomycin (DOX-STR) - Preferred regimen:

• Doxycycline 100 mg twice daily orally for 6 weeks 1, 2
• Streptomycin 15 mg/kg daily (maximum 1 g) intramuscularly for 2-3 weeks 1, 4
• This combination has the lowest relapse rates (5-10%) compared to other regimens 5, 6
• Streptomycin should be injected in the upper outer quadrant of the buttock or mid-lateral thigh, with alternating injection sites 4

2. Doxycycline-Gentamicin (DOX-GENT) - Preferred alternative:

• Doxycycline 100 mg twice daily orally for 6 weeks 1, 2
• Gentamicin 5 mg/kg daily parenterally as a single dose for 7 days 1, 2
• Offers comparable efficacy to DOX-STR with relapse rates of 10-20% 1, 5
• Advantages include wider availability of gentamicin and sparing streptomycin for tuberculosis treatment 1, 2
• Important: Use weight-based dosing (5 mg/kg), not fixed 500 mg doses 2

3. Doxycycline-Rifampicin (DOX-RIF) - Second-choice regimen:

• Doxycycline 100 mg twice daily orally for 6 weeks 1, 2
• Rifampicin 600-900 mg daily as a single morning dose for 6 weeks 1, 2
• This regimen has higher relapse rates (15-30%) compared to aminoglycoside-containing regimens 5, 6
• Critical caveat: In regions where tuberculosis is endemic, avoid rifampicin to prevent mycobacterial resistance 2, 3

Alternative Regimens for Specific Situations

Trimethoprim-Sulfamethoxazole (TMP-SMX) combinations:

• TMP-SMX 800+160 mg twice daily for 6 weeks combined with rifampicin 1, 7
• May be used as a cost-effective alternative in resource-limited settings 2
• Monotherapy with TMP-SMX shows unacceptably high relapse rates (46%) and should be avoided 1

Quinolone-containing regimens:

• Ofloxacin 400 mg twice daily or ciprofloxacin 500 mg twice daily for 6 weeks in combination with doxycycline 1
• Should be reserved as second or third agents due to higher cost and risk of promoting antimicrobial resistance 2, 7
• Not recommended for routine use to preserve efficacy against respiratory pathogens 1

Treatment of Complicated Brucellosis

Brucellar spondylitis (spinal involvement):

• Aminoglycoside-containing regimens (DOX-STR or DOX-GENT) may be superior to rifampicin-containing regimens 8, 3
• Treatment duration may need extension beyond 6 weeks 3
• MRI should be performed when spinal involvement is suspected 8
• Immobilization of the spine is crucial if cervical involvement is present 8

Neurobrucellosis:

• If ceftriaxone cannot be used, combine doxycycline and rifampicin with an aminoglycoside (preferably gentamicin over streptomycin) 8

Brucellar endocarditis:

• Requires aggressive management with empirical antimicrobial selection and surgical intervention in most cases 3
• High mortality complication requiring combination therapy 3

Special Populations

Pregnant women:

• Rifampicin 900 mg once daily for 6 weeks is considered the drug of choice 9
• Tetracyclines are contraindicated 9

Children < 8 years old:

• Rifampicin combined with TMP-SMX for 45 days is the preferred regimen 9, 7
• Alternative: Rifampicin for 45 days with gentamicin 5-6 mg/kg/day for the first 5 days 9
• Tetracyclines are contraindicated 9

Patients > 60 years old:

• Reduce streptomycin dosage due to increased risk of toxicity 4

Treatment Monitoring and Expected Outcomes

Relapse rates:

• Even with appropriate treatment, relapse rates range from 5-15% in uncomplicated cases 2, 3
• Relapses are usually mild and can be treated successfully with the same regimens 2, 3
• Monotherapy shows significantly higher relapse rates (13% vs. 4.8%) compared to combination therapy 7
• Short-term treatment (< 4 weeks) shows unacceptably high relapse rates (22% vs. 4.8%) 7

Treatment duration:

• Standard duration is 6 weeks for uncomplicated cases 1, 2, 3
• Complicated cases may require 3-6 months of therapy 10

Common Pitfalls to Avoid

• Never use monotherapy (except rifampicin in pregnancy) - relapse rates are unacceptably high 1, 7
• Never shorten treatment duration below 6 weeks for uncomplicated cases 7
• Avoid fixed-dose gentamicin - always use weight-based dosing (5 mg/kg) 2
• Do not use rifampicin in TB-endemic areas without considering public health implications 2, 3
• Monitor for ototoxicity with aminoglycosides, especially in elderly patients 4