What is the next best step in managing a female patient with recurrent, purulent large-joint arthritis, currently on ertapenem (a carbapenem antibiotic) and prednisone (a corticosteroid), with improved C-reactive protein (CRP) and white blood cell count (WBC), but with a history of negative cultures, positive antinuclear antibody (ANA) and rheumatoid factor (RF), and no other autoimmune symptoms?

Infectious Disease Workup for Recurrent Purulent Large-Joint Arthritis

From an infectious disease standpoint, this patient has completed appropriate antimicrobial therapy with clinical and laboratory improvement, and further ID workup should focus on excluding disseminated gonococcal infection through repeat genitourinary testing, obtaining synovial fluid cultures during any future flares, and considering rheumatology referral now, as the positive ANA and RF with recurrent culture-negative arthritis increasingly suggests an underlying autoimmune inflammatory arthritis rather than persistent infection.

Immediate Next Steps from ID Perspective

Complete Infectious Workup

• Repeat genitourinary testing for gonorrhea and chlamydia using both cervical/urethral swabs and pharyngeal/rectal swabs if not already done, as disseminated gonococcal infection can present with migratory polyarthritis and culture-negative synovial fluid 1
• Obtain synovial fluid analysis and culture during any future joint flares before initiating antibiotics, as the pattern of recurrent culture-negative purulent arthritis (WBC 50,000-65,000) is unusual for bacterial infection 2
• Consider testing for Lyme disease serology if there is any epidemiologic exposure, as Lyme arthritis can present with recurrent large-joint arthritis 1

Assess Current Antibiotic Response

• Continue ertapenem to complete the planned course given the improving CRP (20→10) and normalized WBC, as ertapenem provides broad-spectrum coverage including anaerobes and most Enterobacteriaceae 3
• Monitor inflammatory markers (CRP, ESR) every 4-6 weeks to ensure continued improvement and guide duration of therapy 2, 1
• Plan to discontinue ertapenem after completing the current course unless new infectious evidence emerges, as prolonged carbapenem use (beyond 2-4 weeks for most infections) raises antimicrobial resistance concerns 3, 4

Critical Diagnostic Pivot Point

Why This Likely Represents Autoimmune Arthritis

The clinical pattern strongly suggests inflammatory arthritis rather than persistent infection:

• Two episodes of culture-negative purulent arthritis despite adequate synovial fluid sampling (WBC 50,000-65,000) 2
• Positive autoimmune markers (ANA, RF 45) in the setting of recurrent inflammatory arthritis 2, 1
• Rapid recurrence one week after completing antibiotics, which is atypical for adequately treated bacterial arthritis 1
• Multi-joint involvement (right knee, left knee, left wrist) with migratory pattern suggests reactive or autoimmune process 2

Additional Autoimmune Testing Needed

• Anti-CCP antibodies to evaluate for rheumatoid arthritis, as RF is positive 2, 1
• HLA-B27 testing given the large-joint oligoarthritis pattern, which could represent reactive arthritis or spondyloarthropathy 2
• Repeat inflammatory markers (ESR, CRP) to establish baseline inflammatory burden for rheumatology 2, 1

Management Algorithm Moving Forward

If Inflammatory Markers Continue Improving on Current Therapy

• Complete the current ertapenem course as planned 3
• Refer to rheumatology within 2 weeks for evaluation of inflammatory arthritis, as early recognition is critical to avoid erosive joint damage 2, 1
• Continue prednisone 5 mg daily temporarily, but recognize this dose is inadequate for inflammatory arthritis if that is the diagnosis 1, 5

If New Joint Flare Occurs

• Obtain synovial fluid analysis and culture immediately before escalating antibiotics 2
• If synovial fluid cultures remain negative, strongly consider this is autoimmune inflammatory arthritis requiring immunosuppression rather than infection 2, 1
• Escalate prednisone to 10-20 mg daily if inflammatory arthritis is confirmed, as 5 mg is insufficient for active disease 2, 1, 5

Common Pitfalls to Avoid

Overtreating with Antibiotics

• Prolonged antibiotic courses without documented infection can lead to antimicrobial resistance and delay appropriate immunosuppressive therapy 3, 4
• Culture-negative arthritis after two separate episodes makes persistent bacterial infection unlikely, especially with negative blood cultures on both admissions 2, 1

Undertreating Inflammatory Arthritis

• Prednisone 5 mg daily is inadequate for active inflammatory arthritis; therapeutic doses are 10-20 mg daily for moderate disease 2, 1, 5
• Delaying rheumatology referral can result in irreversible joint damage, as inflammatory arthritis requires early aggressive treatment 2, 1

Missing Disseminated Gonococcal Infection

• Single negative urine NAAT is insufficient to exclude disseminated gonococcal infection; pharyngeal and rectal swabs are needed as these sites can harbor infection even with negative genitourinary testing 1
• Gonococcal arthritis classically presents with migratory polyarthritis and culture-negative synovial fluid, making it a critical differential 1

Specific ID Recommendations

From an infectious disease standpoint, no further antimicrobial therapy is indicated after completing the current ertapenem course unless:

1. New positive cultures are obtained from synovial fluid or blood 2, 1
2. Repeat genitourinary testing (including pharyngeal/rectal swabs) is positive for gonorrhea 1
3. Clinical deterioration occurs with rising inflammatory markers despite completing antibiotics 2, 1

The patient should be transitioned to rheumatology care for management of likely inflammatory arthritis, with consideration for disease-modifying antirheumatic drugs (DMARDs) if unable to taper prednisone below 10 mg daily after 3 months 2, 1, 5.