What is the best course of treatment for a female patient with recurrent, purulent large-joint arthritis, positive Antinuclear Antibody (ANA) and Rheumatoid Factor (RF), and no clear evidence of bacterial infection, who has been treated with Daptomycin (Cubicin) and Ceftriaxone, and is currently on ertapenem and prednisone?

Transition to Rheumatologic Management with DMARD Therapy

This patient has completed over 10 weeks of broad-spectrum antibiotics with persistently culture-negative purulent arthritis and should be referred to rheumatology for initiation of disease-modifying antirheumatic drug (DMARD) therapy, as further antibiotic therapy is not expected to provide additional benefit. 1

Rationale for Stopping Antibiotics

• The IDSA/ACR guidelines explicitly state that patients who have failed one course of oral antibiotics and one course of IV antibiotics should be referred to rheumatology for non-antibiotic management, as antibiotic therapy for longer than 8 weeks is not expected to provide additional benefit. 2, 1

• Culture-negative arthritis after 10+ weeks of broad-spectrum antibiotics (daptomycin, ceftriaxone, and ertapenem) with persistently purulent fluid (WBC 50,000-65,000) strongly suggests non-infectious inflammatory arthritis rather than ongoing infection. 1

• The negative blood cultures on both admissions, negative urine PCR/NAAT for gonorrhea and chlamydia, and lack of bacterial growth from synovial fluid despite purulent appearance all support a non-infectious etiology. 2

Immediate Management Steps

Discontinue Ertapenem

• Complete the current course of ertapenem as prescribed, but do not extend antibiotic therapy beyond this. 2, 1

Optimize Corticosteroid Dosing

• The current 5 mg prednisone dose is appropriate for bridging therapy while awaiting rheumatology evaluation. 3
• Low-dose prednisone (≤10 mg/day) is safe and effective in suppressing inflammation and retarding bony erosions in inflammatory arthritis. 3
• Ensure calcium supplementation (800-1,000 mg/day) and vitamin D (400-800 units/day) are initiated immediately. 3

Rheumatologic Workup and Treatment

Initial DMARD Selection

• Hydroxychloroquine is specifically recommended as initial DMARD therapy for post-antibiotic culture-negative arthritis, with methotrexate being the anchor DMARD if rheumatoid arthritis is confirmed. 1

• Given the positive ANA and RF 45, along with recurrent large-joint arthritis, this presentation is consistent with either seronegative/early seropositive RA or post-infectious inflammatory arthritis. 2, 4

Additional Therapeutic Options

• The IDSA/ACR guidelines recommend consideration of DMARDs, biologic agents, intra-articular steroids (once infection definitively excluded), or arthroscopic synovectomy for persistent culture-negative purulent arthritis. 2, 1

• NSAIDs are appropriate for symptom control during the diagnostic transition. 1

• Intra-articular corticosteroids should be avoided until infection is definitively excluded, though given the extensive negative workup and prolonged antibiotic course, this threshold has likely been met. 1, 5

Monitoring Strategy

Disease Activity Assessment

• Monitor disease activity every 1-3 months using standardized measures (DAS28, CDAI, or SDAI) with the goal of achieving clinical remission or low disease activity within 6 months of initiating DMARD therapy. 1, 4

Treatment Adjustment Algorithm

• If no improvement after 3 months of DMARD therapy, treatment should be adjusted. 1
• If the target is not reached by 6 months, therapy should be changed to a different DMARD or biologic agent. 1, 4

Surgical Consideration

• Arthroscopic synovectomy may reduce the duration of joint inflammation if persistent synovitis causes significant pain or functional limitation, particularly given the recurrent large effusions in this patient. 1
• This should be considered if medical management fails to control symptoms after 6 months of optimized DMARD therapy. 2, 1

Critical Pitfalls to Avoid

• Do not continue antibiotics beyond the current ertapenem course—prolonged antibiotic therapy will not benefit this patient and increases risk of adverse effects and antibiotic resistance. 2, 1

• Do not delay rheumatology referral—early DMARD initiation is crucial to prevent joint damage and disability in inflammatory arthritis. 4

• Do not taper prednisone too rapidly—if used, taper slowly using 1 mg decrements every 2-4 weeks to the lowest effective dose. 3