What is the recommended treatment for a patient diagnosed with Brucellosis, considering their medical history and potential for re-exposure?

Brucellosis Treatment

For uncomplicated brucellosis, treat with doxycycline 100 mg twice daily for 6 weeks PLUS streptomycin 15 mg/kg IM daily for 2-3 weeks, as this regimen has the lowest relapse rates and superior efficacy compared to all other options. 1, 2

First-Line Treatment Regimens

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 3, 1, 2
• This combination demonstrates the lowest relapse rates (5-15%) and is considered the gold standard 3, 4
• The Cochrane meta-analysis of 694 patients confirmed this regimen is significantly more effective than doxycycline-rifampicin, with lower treatment failure (RR 1.91 favoring streptomycin) and relapse rates (RR 2.39 favoring streptomycin) 4

Alternative First-Line Regimen (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, 2
• Gentamicin offers comparable efficacy to streptomycin with the advantage of shorter parenteral therapy duration and wider availability 1
• Use weight-based dosing (5 mg/kg daily), 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 First-Line Regimen (Oral Alternative)

• Doxycycline 100 mg PO twice daily for 6 weeks PLUS Rifampicin 600-900 mg PO daily as single morning dose for 6 weeks 3, 1, 2
• This all-oral regimen has higher relapse rates than aminoglycoside-containing regimens but offers convenience 3, 4
• The Cochrane review showed this combination had nearly double the relapse rate compared to doxycycline-streptomycin 4
• Critical caveat: In regions where tuberculosis and brucellosis coexist, avoid rifampicin when possible due to risk of promoting mycobacterial resistance with significant public health implications 3, 1, 2

Second-Line Treatment Options

• Trimethoprim-Sulfamethoxazole (800/160 mg) PO twice daily for 6 weeks can be combined with rifampicin or doxycycline in resource-limited settings 1
• Quinolone-containing regimens (ciprofloxacin or ofloxacin) plus rifampicin for 6 weeks should be reserved as second or third agents due to higher cost and antimicrobial resistance concerns 1, 4
• The quinolone-rifampicin combination showed no significant difference in relapse rates compared to doxycycline-rifampicin, but slightly better tolerability 4

Complicated Brucellosis

Brucellar Spondylitis (Spinal Involvement)

• Extend treatment duration to 12 weeks (3 months) 2
• Aminoglycoside-containing regimens may be superior to rifampicin-containing regimens 2
• Obtain MRI if patient reports back pain, as this may represent spinal involvement requiring extended therapy 2

Brucellar Endocarditis

• This high-mortality complication requires aggressive management with empirical antimicrobial selection 3, 2
• Surgical intervention is necessary in the majority of cases 3, 2
• Consider multi-drug regimens including streptomycin or gentamicin combined with TMP-SMX, rifampicin, and doxycycline 5

Neurobrucellosis

• Treat with TMP-SMX plus rifampicin for 3-6 months 5
• Longer treatment durations (12-24 weeks) are required 2

Special Populations

Pregnant Women

• Rifampicin 900 mg PO once daily for 6 weeks is the drug of choice 6
• Tetracyclines are contraindicated in pregnancy 6, 5
• Monotherapy with rifampicin may be acceptable until delivery in patients without risk factors for relapse or focal disease, with standard combination therapy postpartum if relapse occurs 3

Children Under 8 Years Old

• Rifampicin for 45 days PLUS Trimethoprim-Sulfamethoxazole (TMP-SMX) for 45 days 6, 5
• Alternative: Rifampicin for 45 days PLUS Gentamicin 5-6 mg/kg/day for first 5 days 6
• Tetracyclines are contraindicated in children under 8 years 6, 5

Treatment Duration and Monitoring

• Standard treatment duration is 6 weeks for uncomplicated brucellosis 3, 1, 2
• Shorter durations (3 weeks) are inadequate and associated with unacceptably high relapse rates 2
• Clinical improvement should be evident within 7-14 days of treatment initiation 7
• Fever, chills, and sweating may persist during early treatment and represent ongoing inflammatory response rather than treatment failure 7

Relapse Management

• Relapse rates range from 5-15% even with appropriate treatment 3, 1, 2
• Relapses are usually mild and can be treated successfully with the same regimens 3, 1
• Full symptom resolution may take several weeks even with appropriate therapy 7

Post-Exposure Prophylaxis (For Healthcare/Laboratory Workers)

• High-risk exposures: Doxycycline PLUS Rifampicin for 3 weeks 3
• Alternative for those who cannot tolerate doxycycline: TMP-SMX PLUS Rifampicin for 3 weeks 3
• Symptom surveillance includes weekly symptom checks and daily fever monitoring for 24 weeks after last exposure 3
• Serologic testing at regular intervals for 24 weeks after exposure for high-risk individuals 3

Critical Clinical Pearls

• Never use monotherapy for acute brucellosis except in specific circumstances (pregnant women, low-risk uncomplicated cases) 3, 5
• Consider switching from doxycycline-rifampicin to doxycycline-streptomycin or doxycycline-gentamicin if symptoms persist or worsen after 2 weeks of therapy 7
• Serologic testing is not helpful for early treatment response assessment 7
• Seek immediate attention for new neurological symptoms, high fever unresponsive to antipyretics, or new focal symptoms suggesting disease progression 7