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There is evidence that sonication of explanted prosthetic hip and knee arthroplasty components with culture of the sonication fluid may enhance diagnostic sensitivity. Previous studies on the use of implant sonicate cultures have evaluated diagnostic thresholds but did not elaborate on the clinical importance of positive implant sonicate cultures in the setting of presumed aseptic revisions and did not utilize consensus statements on periprosthetic joint infection (PJI) diagnosis when defining their gold standard for infection.(1) How do implant sonicate cultures compare with preoperative synovial fluid cultures and intraoperative tissue cultures in the diagnosis of PJI in both THA and TKA when compared against Musculoskeletal Infection Society (MSIS) criteria for PJI? (2) Utilizing implant sonicate cultures, what is the relative prevalence of bacterial species identified in PJIs? (3) What is the incidence of positive implant sonicate cultures in the setting of presumed aseptic revision hip and knee arthroplasty procedures, and what treatments did they receive?Between 2012 and 2016 we performed implant sonicate fluid cultures on surgically removed implants from 565 revision THAs and TKAs. Exclusion criteria including insufficient data to determine Musculoskeletal Infection Society (MSIS) classification, fungal-only cultures, and absence of reported colony-forming units decreased the number of procedures to 503. Procedures represented each instance of revision surgery (sometimes multiple in the same patient). Of those, a definitive diagnosis of infection was made using the MSIS criteria in 178 of 503 (35%), whereas the others (325 of 503 [65%]) were diagnosed as without infection. A total of 53 of 325 (16%) were considered without infection based on MSIS criteria but had a positive implant sonicate culture. Twenty-five of 53 (47%) of these patients were followed for at least 2 years. The diagnosis of PJI was determined using the MSIS criteria.Sensitivity of implant sonicate culture was greater than synovial fluid culture and tissue culture (97% [89%-99%] versus 57% [44%-69%], p < 0.001; 97% [89%-99%] versus 70% [58%-80%], p < 0.001, respectively). The specificity of implant sonicate culture was not different from synovial fluid culture or tissue culture with the numbers available (90% [72%-97%] versus 100% [86%-100%], p = 0.833; 90% [72%-97%] versus 97% [81%-100%], p = 0.317, respectively). Coagulase-negative Staphylococcus was the most prevalent organism for both procedure types. In PJIs, the five most frequent bacteria identified by synovial fluid, tissue, and/or implant sonicate cultures were coagulase-negative Staphylococcus (26% [89 of 267]), methicillin-susceptible Staphylococcus aureus (19% [65 of 267]), methicillin-resistant S.aureus (12% [43 of 267]), α-hemolytic Streptococci (5% [19 of 267]), and Enterococcusfaecalis (5% [19 of 267]). Fifty-three of 325 (16%) presumed aseptic revisions had a positive sonication culture. Thirty-four percent (18 of 53) of culture-positive aseptic revision patients received antibiotic treatment for infection and 8% (4 of 53) underwent a secondary revision.The routine use of implant sonicate cultures in arthroplasty revisions improves the diagnostic sensitivity for detecting the presence of bacteria in both clinical and occult infections. Future studies will need to refine colony-forming unit thresholds for determining clinical infection and indications for treatment.Level III, diagnostic study.