Limited Predictive Value of Serum Inflammatory Markers for Diagnosing Fracture-Related Infections: results of a large retrospective multicenter cohort study

Abstract. Introduction: Diagnosing Fracture-Related Infections (FRI) based on clinical symptoms alone can be challenging and additional diagnostic tools such as serum inflammatory markers are often utilized. The aims of this study were 1) to determine the individual diagnostic performance of three commonly used serum inflammatory markers: C-Reactive Protein (CRP), Leukocyte Count (LC) and Erythrocyte Sedimentation Rate (ESR), and 2) to determine the diagnostic performance of a combination of these markers, and the additional value of including clinical parameters predictive of FRI.

Methods: This cohort study included patients who presented with a suspected FRI at two participating level I academic trauma centers between February 1^st 2009 and December 31^st 2017. The parameters CRP, LC and ESR, determined at diagnostic work-up of the suspected FRI, were retrieved from hospital records. The gold standard for diagnosing or ruling out FRI was defined as: positive microbiology results of surgically obtained tissue samples, or absence of FRI at a clinical follow-up of at least six months. The diagnostic accuracy of the individual serum inflammatory markers was assessed. Analyses were done with both dichotomized values using hospital thresholds as well as with continuous values. Multivariable logistic regression analyses were performed to obtain the discriminative performance (Area Under the Receiver Operating Characteristic, AUROC) of (1) the combined inflammatory markers, and (2) the added value of these markers to clinical parameters.

Results: A total of 168 patients met the inclusion criteria and were included for analysis. CRP had a 38% sensitivity, 34% specificity, 42% positive predictive value (PPV) and 78% negative predictive value (NPV). For LC this was 39%, 74%, 46% and 67% and for ESR 62%, 64%, 45% and 76% respectively. The diagnostic accuracy was 52%, 61% and 80% respectively. The AUROC was 0.64 for CRP, 0.60 for LC and 0.58 for ESR. The AUROC of the combined inflammatory markers was 0.63. Serum inflammatory markers combined with clinical parameters resulted in AUROC of 0.66 as opposed to 0.62 for clinical parameters alone.

Conclusion: The added value of CRP, LC and ESR for diagnosing FRI is limited. Clinicians should be cautious when interpreting the results of these tests in patients with suspected FRI.