Synovial fluid α defensin has comparable accuracy to synovial fluid white blood cell count and polymorphonuclear percentage for periprosthetic joint infection diagnosis.

AIMS: The aim of this study was to determine the diagnostic accuracy of α defensin (AD) lateral flow assay (LFA) and enzyme-linked immunosorbent assay (ELISA) tests for periprosthetic joint infection (PJI) in comparison to conventional synovial white blood cell (WBC) count and polymorphonuclear neutrophil percentage (PMN%) analysis. METHODS: Patients undergoing joint aspiration for evaluation of pain after total knee arthroplasty (TKA) or total hip arthroplasty (THA) were considered for inclusion. Synovial fluids from 99 patients (25 THA and 74 TKA) were analyzed by WBC count and PMN% analysis, AD LFA, and AD ELISA. WBC and PMN% cutoffs of ≥ 1,700 cells/mm3 and ≥ 65% for TKA and ≥ 3,000 cells/mm3 and ≥ 80% for THA were used, respectively. A panel of three physicians, all with expertise in orthopaedic infections and who were blinded to the results of AD tests, independently reviewed patient data to diagnose subjects as with or without PJI. Consensus PJI classification was used as the reference standard to evaluate test performances. Results were compared using McNemar's test and area under the receiver operating characteristic curve (AUC) analysis. RESULTS: Expert consensus classified 18 arthroplasies as having failed due to PJI and 81 due to aseptic failure. Using these classifications, the calculated sensitivity and specificity of AD LFA was 83.3% (95% confidence interval (CI) 58.6 to 96.4) and 93.8% (95% CI 86.2 to 98.0), respectively. Sensitivity and specificity of AD ELISA was 83.3% (95% CI 58.6 to 96.4) and 96.3% (95% CI 89.6 to 99.2), respectively. There was no statistically significant difference between sensitivity (p = 1.000) or specificity (p = 0.157) of the two AD assays. AUC for AD LFA was 0.891. In comparison, AUC for synovial WBC count, PMN%, and the combination of the two values was 0.821 (sensitivity p = 1.000, specificity p < 0.001), 0.886 (sensitivity p = 0.317, specificity p = 0.011), and 0.926 (sensitivity p = 0.317, specificity p = 0.317), respectively. CONCLUSION: The diagnostic accuracy of synovial AD for PJI diagnosis is comparable and not statistically superior to that of synovial WBC count plus PMN% combined. Cite this article: Bone Joint J 2021;103-B(6):1119-1126.

Direct Detection and Identification of Prosthetic Joint Infection Pathogens in Synovial Fluid by Metagenomic Shotgun Sequencing.

Metagenomic shotgun sequencing has the potential to transform how serious infections are diagnosed by offering universal, culture-free pathogen detection. This may be especially advantageous for microbial diagnosis of prosthetic joint infection (PJI) by synovial fluid analysis since synovial fluid cultures are not universally positive and since synovial fluid is easily obtained preoperatively. We applied a metagenomics-based approach to synovial fluid in an attempt to detect microorganisms in 168 failed total knee arthroplasties. Genus- and species-level analyses of metagenomic sequencing yielded the known pathogen in 74 (90%) and 68 (83%) of the 82 culture-positive PJIs analyzed, respectively, with testing of two (2%) and three (4%) samples, respectively, yielding additional pathogens not detected by culture. For the 25 culture-negative PJIs tested, genus- and species-level analyses yielded 19 (76%) and 21 (84%) samples with insignificant findings, respectively, and 6 (24%) and 4 (16%) with potential pathogens detected, respectively. Genus- and species-level analyses of the 60 culture-negative aseptic failure cases yielded 53 (88%) and 56 (93%) cases with insignificant findings and 7 (12%) and 4 (7%) with potential clinically significant organisms detected, respectively. There was one case of aseptic failure with synovial fluid culture growth; metagenomic analysis showed insignificant findings, suggesting possible synovial fluid culture contamination. Metagenomic shotgun sequencing can detect pathogens involved in PJI when applied to synovial fluid and may be particularly useful for culture-negative cases.