Evaluation of Acid Production as a Metabolic Phenotype in Cutibacterium acnes Shoulder Periprosthetic Joint Infections.

Abstract

Cutibacterium acnes (C. acnes) is the most frequently isolated organism in shoulder periprosthetic joint infection (PJI), yet distinguishing contamination from infection remains challenging. Current diagnostic frameworks rely on culture positivity and consensus criteria but provide limited insight into bacterial metabolic activity. Since C. acnes produces short-chain fatty acids influencing host inflammation, acid production may represent a relevant metabolic phenotype beyond simple biomass. An exploratory cohort of 40 clinical C. acnes isolates were selected from a larger repository using stratified randomization based on hemolysis and aerotolerance, with all clindamycin-resistant isolates force-included. Cultures were grown anaerobically in glucose-supplemented media, with pH and optical density at 600 nm (OD₆₀₀) measured at baseline and after 72 hours. Acid production was defined as change in pH (ΔpH), and growth as change in optical density (ΔOD₆₀₀). Clinical infection status was classified according to the 2018 International Consensus Meeting criteria. Eleven isolates (27.5%) were clindamycin resistant. Resistant isolates produced significantly less acid than susceptible isolates (ΔpH -1.22 vs -1.42; P = 0.04), despite similar growth (P = 0.31). Regression analysis showed growth accounted for only 27% of acid production variability (R² = 0.27), indicating ΔpH reflects metabolic characteristics largely independent of biomass accumulation. Isolates from definite infections demonstrated a trend toward reduced acid production compared with non-definite cases, although this did not reach statistical significance. Receiver operating characteristic analysis demonstrated modest discrimination of definite infection by ΔpH, with an area under the curve of 0.72. Clindamycin-resistant C. acnes exhibited lower acid production despite similar bacterial growth. However, acid production alone demonstrated modest diagnostic discrimination for definite infection in this exploratory cohort. While these findings do not currently support the use of metabolic phenotyping for independent clinical decision-making, metabolic phenotyping may provide a complementary approach to growth-based detection in future research. Larger studies incorporating direct biofilm characterization are warranted.