Comorbidity Burden and Preoperative Inflammatory Markers Associated with Intraoperative Culture Positivity in Surgically Treated Suspected Native Knee Septic Arthritis

Background/Objectives: Culture-negative results are common in surgically treated suspected native knee septic arthritis, but the absence of a uniform reference standard can complicate interpretation. We evaluated whether comorbidity burden and routinely available preoperative inflammatory markers were associated with intraoperative culture positivity. Methods: This retrospective cohort included 104 adults who underwent open or arthroscopic irrigation and debridement for clinically suspected native knee septic arthritis between May 2020 and December 2025. The primary analysis used age-adjusted Firth bias-reduced logistic regression with the Charlson Comorbidity Index (CCI), C-reactive protein (CRP), peripheral white blood cell count (WBC), and age. A sensitivity analysis was restricted to patients with an observed synovial WBC of at least 50,000 cells/mm3. Results: Intraoperative cultures were positive in 29/104 patients (27.9%). In the age-adjusted Firth model, lower CCI (odds ratio [OR] 0.63 per point, 95% confidence interval [CI] 0.46–0.86), higher CRP (OR 1.39 per 50 mg/L, 95% CI 1.07–1.82), and higher WBC (OR 2.37 per 5 × 109/L, 95% CI 1.32–4.26) were associated with culture positivity; age was not independently associated. In the restricted sensitivity analysis (n = 44; 17 positive cultures), effect directions were preserved, although estimates were less precise. Conclusions: Within this selected surgical cohort, lower comorbidity burden and stronger preoperative CRP and peripheral leukocyte responses were associated with culture positivity. These exploratory associations require external validation and do not establish infection in individual culture-negative cases or replace standardized diagnostic sampling.