Synovial Fluid Cutibacterium acnes Antigen Is Detected Among Shoulder Samples with High Inflammation and Early Culture Growth

Abstract

Background: An emerging paradigm suggests that positive Cutibacterium acnes shoulder cultures can result from either true infection or contamination, with true infections demonstrating a host inflammatory response and early culture growth. This clinical retrospective study examines the relationship between C. acnes antigen, C. acnes culture results, and inflammation. Methods: From January 2021 to July 2023, 1,365 periprosthetic synovial fluid samples from 347 institutions were tested for shoulder infection at a centralized clinical laboratory. A biomarker scoring system based on the 2018 International Consensus Meeting (ICM) definition was utilized to assign each sample an inflammation score. Associations between inflammation, culture results, and C. acnes antigen results were assessed utilizing cluster and correlation analyses. Results: Of 1,365 samples, 1,150 were culture-negative and 215 were culture-positive (94 C. acnes and 121 other organisms). Among the 94 C. acnes culture-positive samples, unsupervised clustering revealed 2 distinct sample clusters (silhouette coefficient, 0.83): a high-inflammation cluster (n = 67) and a low-inflammation cluster (n = 27). C. acnes antigen levels demonstrated moderate-strong positive correlation with inflammation (Spearman ρ, 0.60), with 166-fold higher levels of C. acnes antigen in high-inflammation samples (16.6 signal/cutoff [S/CO]) compared with low-inflammation samples (0.1 S/CO) (p < 0.0001). The days to C. acnes culture positivity demonstrated weak-inverse correlation with inflammation (Spearman ρ = −0.38), with 1.5-fold earlier growth among the 67 high-inflammation samples (6.7 compared with 10.4 days; p < 0.0001). Elevated C. acnes antigen was observed in only 4 (0.38%) of 1,050 low-inflammation culture-negative samples and in only 5 (4.9%) of 103 high-inflammation non-C. acnes-positive cultures. However, 19.0% of high-inflammation, culture-negative samples demonstrated elevated C. acnes antigen. Conclusions: Synovial fluid C. acnes antigen was detected among shoulder samples with high inflammation and early culture growth, supporting the emerging paradigm that these samples represent true infection. Future research should explore antigen testing to differentiate contamination from infection and to identify culture-negative C. acnes infections. Level of Evidence: Diagnostic Level III. See Instructions for Authors for a complete description of levels of evidence.