The False-Positive Rate of Synovial Fluid Culture at a Single Clinical Laboratory Using Culture Bottles

Introduction Synovial fluid (SF) cultures can yield false-positive or negative results when diagnosing periprosthetic joint infection (PJI). False-positives may arise during sample collection or from laboratory contamination. Understanding false-positive SF culture rates is crucial for interpreting PJI laboratory data, yet clinical laboratories rarely report these rates. This study aimed to define the false-positive SF culture rate at a major specialized clinical laboratory. Methods This study retrospectively analyzed prospectively collected data at a single clinical laboratory that receives SF for clinical testing for PJI. A total of 180,317 periprosthetic SF samples from the hip, knee, and shoulder were identified from January 2016 to December 2023, which met the inclusion criteria for this study. Samples were classified by both a modified 2018 International Consensus Meeting (ICM) score and an inflammation score that combined the SF-C-reactive protein, alpha-defensin, SF-white blood cell count, and SF-polymorphonuclear% into one standardized metric. Logistic regression was utilized to evaluate the impact of various collection-based characteristics on culture positivity, including inflammation biomarkers, the source joint, quality control metrics, and days of specimen transport to the laboratory. SF culture false-positivity was calculated based on the ICM category of "not-infected" or low inflammation score. Results Overall, 13.3% (23,974/180,317) of the samples were associated with a positive culture result: 12.5% for knee samples, 20.3% for hip samples, and 14.7% for shoulder samples. The false-positive SF culture rate among 131,949 samples classified as "not-infected" by the modified 2018 ICM definition was 0.47% (95%CI: 0.43 to 0.51%). Stratification by joint revealed a false-positive rate of 0.34% (95%CI: 0.31 to 0.38%) for knee samples, 1.24% (95%CI: 1.05 to 1.45%) for hip samples, and 3.02% (95%CI: 2.40 to 3.80%) for shoulder samples, with p < 0.0001 for all comparisons. The false-positive SF culture rate among 90,156 samples, representing half of all samples with the lowest standardized inflammation scores, was 0.47% (95%CI: 0.43 to 0.52%). Stratification by joint revealed a false-positive rate of 0.33% (95%CI: 0.29 to 0.37%) for knee samples, 1.45% (95%CI: 1.19 to 1.77%) for hip samples, and 3.09% (95%CI: 2.41 to 3.95%) for shoulder samples, with p<0.0001 for all comparisons. Multivariate logistic regression demonstrated the joint source (hip, shoulder) and poor sample quality as collection-based factors associated with a false-positive culture. Evaluation of a cohort of samples selected to minimize collection-based causes of false-positive culture demonstrated a false-positive rate of 0.30%, representing the ceiling limit for laboratory-based SF culture false-positivity. Conclusions This study utilizes two methods to estimate the false-positive SF culture rate at a single specialized clinical laboratory, demonstrating an overall false-positive rate of approximately 0.5%. Stratification of samples by source joint demonstrated that periprosthetic SF from the shoulder and hip have a substantially higher false-positive culture rate than that of the knee. The lowest false-positive SF culture rate (0.30%) was observed among samples from the knee-passing quality control. Culture positivity due to contamination at this specific laboratory is less than 0.30% because all specimens undergo identical processing.