NEARLY HALF OF CULTURE-NEGATIVE PERIPROSTHETIC JOINT INFECTION SYNOVIAL FLUID SAMPLES HAVE DETECTABLE ANTIBIOTIC LEVELS: A PILOT VALIDATION STUDY

Aims Microbiologic culture is among the most clinically actionable tests in periprosthetic joint infection (PJI), directly informing both diagnosis and organism-specific treatment after arthroplasty. Although antecedent antibiotic exposure has long been suspected to suppress culture growth, the frequency of detectable antibiotics in synovial fluid at the time of aspiration remains poorly defined. The purposes of this pilot study were to validate a practical method for antibiotic detection in synovial fluid and to determine how often antibiotics are present in culture-negative PJI samples. Methods Over a 1-year period, 151 synovial fluid samples qualifying for possible culture-negative PJI after arthroplasty were identified at a single clinical laboratory. Possible culture-negative PJI was defined using the 2018 International Consensus Meeting criteria. A lateral flow assay previously developed for antibiotic detection in biologic fluids was modified for use in synovial fluid. Assay performance was evaluated in a subset of samples by comparison with ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). Results Detectable antibiotics were present in 70 of 151 synovial fluid samples (46%) with possible culture-negative PJI. The most identified antibiotic classes were aminoglycosides (n = 39), beta-lactams (n = 29), tetracyclines (n = 10), and sulfonamides (n = 7), and multiple antibiotic classes were detected within some samples. In the validation subset, the modified lateral flow assay demonstrated 95% concordance with UPLC-MS/MS (21/22 samples agreed), including 18 antibiotic-positive and 3 antibiotic-negative samples. Conclusions Nearly half of synovial fluid samples with possible culture-negative PJI after arthroplasty have detectable antibiotics at the time of testing. The modified lateral flow assay showed high agreement with UPLC-MS/MS, supporting its use as a practical method for synovial fluid antibiotic detection. These findings suggest that occult antibiotic exposure may be an underrecognized contributor to culture-negative PJI. Broader study is warranted to define the prevalence, source, and clinical implications of synovial antibiotic detection across the spectrum of arthroplasty-related PJI evaluation. Future research will utilize the validation in this pilot study to prospectively assess antibiotic levels in the synovial fluid of tested patients to determine the association between antibiotic presence and culture-negativity in the setting of PJI.