What is the recommended treatment for a patient suspected of having Brucella melitensis infection?

Treatment of Brucella melitensis Infection

For suspected or confirmed Brucella melitensis infection, initiate doxycycline 100 mg twice daily for 6 weeks combined with either streptomycin 15 mg/kg IM daily for 2-3 weeks (lowest relapse rate) or gentamicin 5 mg/kg IV daily for 7 days (wider availability, comparable efficacy). 1, 2

First-Line Treatment Regimens

The optimal approach depends on aminoglycoside availability and patient factors:

Preferred 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 has the lowest documented relapse rate among all regimens 1
• Streptomycin's limited availability makes this less practical in many settings 2

WHO-Recommended Alternative (Most Practical)

• Doxycycline 100 mg PO twice daily for 6 weeks PLUS Gentamicin 5 mg/kg IV daily as single dose for 7 days 1, 2
• Gentamicin offers comparable efficacy with wider availability and shorter parenteral therapy duration 1, 2
• Critical dosing note: Use weight-based dosing (5 mg/kg daily); fixed 500 mg dosing is not recommended 1
• Experimental data confirms gentamicin/doxycycline combination significantly improves therapeutic efficacy compared to monotherapy 3

All-Oral Alternative (When Aminoglycosides Contraindicated)

• Doxycycline 100 mg PO twice daily for 6 weeks PLUS Rifampicin 600-900 mg PO daily as single morning dose for 6 weeks 1, 2
• This regimen is appropriate when aminoglycosides cannot be administered 2
• Important caveat: In regions where tuberculosis and brucellosis coexist, rifampicin use carries public health implications regarding mycobacterial resistance development 1, 2

Second-Line Options

When first-line regimens are not feasible:

• Trimethoprim-sulfamethoxazole (TMP-SMX) 800+160 mg PO twice daily for 6 weeks can serve as a cost-effective alternative in resource-limited settings or as a third agent in complicated cases 1, 2
• Fluoroquinolone-containing regimens (ofloxacin or ciprofloxacin) should be reserved as second or third agents due to higher cost and antimicrobial resistance concerns 1, 2
• Critical warning: Ciprofloxacin monotherapy, even at high doses (750-1000 mg twice daily) for 42 days, results in unacceptably high relapse rates (83% in one study) despite in-vitro activity 4

Treatment Duration and Expected Outcomes

• Standard treatment duration is 6 weeks for most regimens 1, 2
• Even with appropriate treatment, relapse rates range from 5-15% in uncomplicated cases 1, 2
• Relapses are typically mild and respond to retreatment with the same regimens 1, 2
• The aminoglycoside component (streptomycin or gentamicin) requires only 2-3 weeks or 7 days respectively, not the full 6-week course 1, 2

Special Clinical Situations

Complicated Brucellosis (Spondylitis, Neurobrucellosis)

• Aminoglycoside-containing regimens may be superior to rifampicin-containing ones for spinal or neurological involvement 2
• MRI should be performed when spinal involvement is suspected 2
• Immobilization is crucial for cervical spine involvement to prevent devastating neurological complications 2

CIED or Endocarditis

• Device removal is typically recommended, though extended antibiotic therapy (3+ months) with doxycycline, rifampin, TMP-SMX, and initial aminoglycosides has been attempted in high-risk surgical candidates 5
• Lifelong suppressive therapy after device retention carries significant relapse risk upon discontinuation 5

Common Pitfalls to Avoid

1. Do not use fluoroquinolone monotherapy - high failure rates despite in-vitro susceptibility 4
2. Do not use fixed-dose gentamicin (500 mg) - weight-based dosing (5 mg/kg) is essential 1
3. Do not shorten treatment duration below 6 weeks - increases relapse risk significantly 1, 2
4. Do not assume streptomycin resistance means all aminoglycosides are ineffective - gentamicin remains effective against streptomycin-resistant B. melitensis Rev 1 strains 3
5. Monitor renal function closely with aminoglycosides - acute kidney injury requiring dialysis has been reported, particularly with prolonged courses 5