Clinical characteristics of culture-negative periprosthetic joint infections: findings from an international periprosthetic joint infection registry

<b>Background</b>: Culture-negative periprosthetic joint infections (CN-PJIs) remain a major problem in the field of orthopedic infections. The clinical features of CN-PJI and its risk factors remain poorly defined. The purpose of this study was to elucidate the characteristics of CN-PJI. <b>Methods</b>: This was a retrospective multi-center cohort study as part of the Orthopaedic Device Infection Network (ODIN). Using real-world data from five institutions across Australia, the Netherlands and the USA, 563 cases of PJI (470 culture positive, 93 culture negative) were queried between 1995 and 2021. Patients with CN-PJI had negative cultures on pre-operative aspiration, blood or intra-operative cultures. Demographics, history of surgery on the infected joint, presenting symptoms, operative details, laboratory values and intra-operative findings were recorded. Multivariable regression was used to determine the association between these variables and culture negativity. <b>Results</b>: The prevalence of CN-PJI was 16.5 %. Bivariate analysis revealed that patients with CN-PJI were more likely to be female, have a revision arthroplasty or prior PJI, have a longer duration of symptoms and were less likely to present with fever, wound dehiscence or wound necrosis; they also had lower hemoglobin and serum CRP ( <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mi>p</mml:mi></mml:math> <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mo><</mml:mo></mml:math> <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mn>0.05</mml:mn></mml:math> for all). Using multivariable regression, the only factor significantly associated with CN-PJI was a duration of symptoms of <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mo>></mml:mo></mml:math> 12 weeks (OR 2.24, 95 % CI 1.008-4.964, <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mi>p</mml:mi></mml:math> <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mo>=</mml:mo></mml:math> <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mn>0.048</mml:mn></mml:math> ). <b>Conclusions</b>: Patients with prolonged symptoms were twice as likely to have negative cultures, supporting the traditional belief that CN-PJI presents more insidiously. These clinical data should be used to guide the selection of advanced investigations.