What is the first‑line treatment for an adult patient with uncomplicated brucellosis presenting with knee pain and a history of raw‑milk ingestion?

First-Line Treatment for Uncomplicated Brucellosis with Knee Pain

The correct answer is B) Doxycycline + Rifampicin for 6 weeks, which represents one of two equally acceptable first-line regimens with an AI recommendation (highest strength of evidence). 1

Recommended First-Line Regimens

The Ioannina recommendations published in PLoS Medicine establish two regimens with AI (highest) recommendation strength for uncomplicated brucellosis in adults: 1

• Doxycycline-Streptomycin (DOX-STR): Doxycycline 100 mg twice daily orally for 6 weeks PLUS Streptomycin 15 mg/kg daily intramuscularly for 2-3 weeks 1
• Doxycycline-Rifampicin (DOX-RIF): Doxycycline 100 mg twice daily orally for 6 weeks PLUS Rifampicin 600-900 mg daily as a single morning dose for 6 weeks 1

Both regimens carry AI recommendations, meaning they have good evidence from properly randomized controlled trials supporting their use and should generally be offered. 1

Why Doxycycline-Rifampicin is the Answer

Among the provided options, only option B matches a first-line AI-recommended regimen exactly. 1, 2 While doxycycline-streptomycin shows slightly lower relapse rates in meta-analyses (OR = 3.17 favoring streptomycin over rifampicin), 3 the doxycycline-rifampicin combination remains a gold-standard first-line option due to: 1

• Convenience: Entirely oral administration versus requiring intramuscular injections 1
• Availability: Rifampicin is more widely available than streptomycin in many settings 1
• Comparable efficacy: Both achieve similar clinical cure rates despite modest differences in relapse rates 1, 3

Why Other Options Are Incorrect

Option A: Trimethoprim-Sulfamethoxazole + Rifampicin for 6 weeks

• Carries only a CII recommendation (poor evidence, optional use) 1
• Associated with relapse rates as high as 46% in well-designed trials when used without doxycycline 1
• Reserved as a cost-effective alternative in resource-limited settings or for children under 8 years old 2, 4

Option C: Ciprofloxacin for 4 weeks

• Monotherapy is inadequate for brucellosis with unacceptably high relapse rates (13% vs. 4.8% for combination therapy) 4
• Quinolone-containing regimens carry only CII recommendation and should be reserved as second or third agents in combination regimens 1, 2
• Duration of 4 weeks is insufficient; standard treatment requires 6 weeks minimum 2, 4

Option D: Ceftriaxone for 4 weeks

• Ceftriaxone is not a standard regimen for uncomplicated brucellosis 1, 2
• Reserved primarily for neurobrucellosis or other complicated cases requiring CNS penetration 5
• Duration of 4 weeks is inadequate; even uncomplicated cases require 6 weeks 2, 4

Critical Considerations for This Patient

Knee Pain Assessment

The patient's knee pain likely represents osteoarticular involvement (arthritis), which is common in brucellosis but does not necessarily constitute "complicated" disease requiring extended therapy. 6 However, you must: 6

• Carefully assess for back pain, as this may indicate brucellar spondylitis requiring 12 weeks of treatment rather than 6 weeks 6
• Consider MRI of the spine if any back pain is present, as spinal involvement changes management significantly 6
• If isolated peripheral arthritis (knee only, no spinal involvement): standard 6-week regimen is appropriate 1, 2

Important Caveats

• Relapse rates of 5-15% occur even with optimal treatment and are usually mild, treatable with the same regimen 2, 6
• In regions where tuberculosis is endemic, consider the public health implications of using rifampicin, as this may contribute to mycobacterial resistance 2, 6
• Aminoglycoside-containing regimens (doxycycline-gentamicin for 7 days) offer a BI recommendation as an alternative, with wider availability than streptomycin 1, 2
• Never use treatment courses shorter than 6 weeks for uncomplicated brucellosis, as this dramatically increases relapse rates (22% vs. 4.8%) 4