What is the best course of action for a female patient with recurrent, purulent large-joint arthritis, negative cultures, elevated synovial White Blood Cell (WBC) count, positive Antinuclear Antibody (ANA) and Rheumatoid Factor (RF), and no autoimmune symptoms, who has failed previous antibiotic therapy with Daptomycin (Cubicin) and Ceftriaxone (Rocephin), and is currently on Ertapenem (Invanz)?

Management of Recurrent Culture-Negative Purulent Large-Joint Arthritis

This patient requires immediate discontinuation of ertapenem, urgent rheumatology consultation, and transition to disease-modifying antirheumatic drug (DMARD) therapy for post-antibiotic Lyme arthritis or seronegative inflammatory arthritis, as she has now failed two complete courses of antibiotics (>8 weeks total) without microbiologic confirmation of infection. 1

Critical Diagnostic Reassessment

Why This Is Not Septic Arthritis

• Culture-negative arthritis after 10+ weeks of broad-spectrum antibiotics (daptomycin, ceftriaxone, and now ertapenem) with persistently purulent fluid strongly suggests non-infectious inflammatory arthritis rather than ongoing infection 2
• The synovial WBC counts of 50,000-65,000 can occur in both septic and inflammatory arthritis; culture negativity after this duration of therapy makes infection highly unlikely 2
• Blood cultures negative on both admissions further argues against bacterial infection 2

Consider Post-Antibiotic Lyme Arthritis

• IDSA/ACR guidelines explicitly address this scenario: patients who fail one course of oral antibiotics (which she received as ceftriaxone IV, equivalent coverage) and one course of IV antibiotics should be referred to rheumatology for non-antibiotic management 1
• The guidelines state that antibiotic therapy for longer than 8 weeks is not expected to provide additional benefit if treatment has included IV therapy 1
• Post-antibiotic Lyme arthritis occurs when persistent synovitis continues despite adequate antibiotic treatment and negative PCR for Borrelia 1

Immediate Management Steps

Stop Current Antibiotics

• Discontinue ertapenem immediately - she has already received >8 weeks of antibiotic therapy without microbiologic confirmation 1
• Continuing antibiotics beyond this point increases toxicity risk without improving outcomes 1

Obtain Additional Diagnostic Studies

• Synovial fluid PCR for Borrelia burgdorferi if not already done, though negative PCR supports post-antibiotic Lyme arthritis diagnosis 1
• Repeat synovial fluid cultures off antibiotics are unlikely to be helpful given the extensive prior antibiotic exposure 3
• Consider synovial biopsy to exclude other causes (crystalline arthropathy, fungal infection, mycobacterial infection) 2
• Anti-CCP antibodies to further evaluate for rheumatoid arthritis given RF positivity 4

Definitive Treatment Algorithm

First-Line: Rheumatology Consultation and DMARD Therapy

• Urgent rheumatology referral for consideration of DMARDs, biologic agents, intra-articular steroids, or arthroscopic synovectomy 1
• For post-antibiotic Lyme arthritis, hydroxychloroquine is specifically recommended as initial DMARD therapy 1
• If rheumatoid arthritis is confirmed (RF+ and anti-CCP+), methotrexate is the anchor DMARD 4

Symptomatic Management During Transition

• NSAIDs are appropriate for symptom control during the diagnostic transition 1
• Intra-articular corticosteroids should be avoided until infection is definitively excluded, but may be considered after rheumatology evaluation 1

Surgical Consideration

• Arthroscopic synovectomy may reduce the duration of joint inflammation if persistent synovitis causes significant pain or functional limitation 1
• This is particularly relevant given her recurrent large effusions 1

Key Clinical Pitfalls to Avoid

Do Not Continue Empiric Antibiotics

• The most common error is prolonging antibiotics beyond 8 weeks without microbiologic confirmation 1
• Preoperative antibiotics significantly decrease operative culture yield (OR 2.12), so if surgical drainage is planned, hold antibiotics first 3
• Research shows that antibiotic therapy <4 weeks increases relapse risk in culture-positive septic arthritis, but this patient has culture-negative disease after extensive therapy 5

Do Not Delay Rheumatology Referral

• Delayed treatment adjustment can lead to irreversible joint damage in inflammatory arthritis 4
• The European League Against Rheumatism recommends against continuing ineffective therapy for >6 months 4

Recognize the Autoimmune Context

• Positive ANA and RF 45 suggest underlying autoimmune predisposition, even without other systemic symptoms 4
• RF-positive patients may benefit from rituximab if biologic therapy becomes necessary 4

Alternative Diagnoses to Exclude

• Fungal or mycobacterial infection: Consider if she has risk factors for immunosuppression beyond what's stated 2
• Crystalline arthropathy: Synovial fluid analysis should have included crystal examination 2
• Reactive arthritis: No genitourinary symptoms reported, but consider if there's occult Chlamydia or other trigger 2

Monitoring Plan After Transition

• Disease activity assessment every 1-3 months using standardized measures if inflammatory arthritis is confirmed 4
• Target clinical remission or low disease activity within 6 months of initiating DMARD therapy 4
• If no improvement after 3 months of DMARD therapy, adjust treatment; if target not reached by 6 months, change therapy 4