Limited diagnostic value of serum inflammatory biomarkers in the diagnosis of fracture-related infections

Abstract

Aims The aim of this study was to evaluate the diagnostic value of preoperative serum CRP, white blood cell count (WBC), percentage of neutrophils (%N), and neutrophil to lymphocyte ratio (NLR) when using the fracture-related infection (FRI) consensus definition. Methods A cohort of 106 patients having surgery for suspected septic nonunion after failed fracture fixation were studied. Blood samples were collected preoperatively, and the concentration of serum CRP, WBC, and differential cell count were analyzed. The areas under the curve (AUCs) of diagnostic tests were compared using the z-test. Regression trees were constructed and internally cross-validated to derive a simple diagnostic decision tree. Results Using the FRI consensus definition, 46 patients (43%) were identified as infected. Sensitivity, specificity, and AUC of CRP were 67% (95% confidence interval (CI) 52% to 80%), 61% (95% CI 47% to 74%), and 0.64 (95% CI 0.54 to 0.74); of WBC count were 17% (95% CI 9% to 31%), 95% (95% CI 86% to 99%), and 0.57 (95% CI 0.50 to 0.62); of %N 13% (95% CI 6% to 26%), 87% (95% CI 76% to 93%), and 0.50 (95% CI 0.43 to 0.56); and of NLR 28% (95% CI 17% to 43%), 80% (95% CI 68% to 88%), and 0.54 (95% CI 0.46 to 0.63), respectively. A better performance of serum CRP was shown in comparison to the leucocyte count (p = 0.006), %N (p < 0.001), and NLR (p = 0.001). A statistically lower serum CRP level was shown in patients with an infection caused by a low virulence microorganism in comparison to high virulence bacteria (p = 0.008). We found that a simple decision tree approach using only low serum neutrophils (< 3.615 × 109/l) and low CRP (< 2.45 mg/l) may allow better identification of aseptic cases. Conclusion The evaluated serum inflammatory markers showed limited diagnostic value in the preoperative diagnosis of FRI when using the uniform FRI Consensus Definition. Therefore, they should remain as suggestive criteria in diagnosing FRI. Although CRP showed a higher performance in comparison to the other serum markers, it is insufficiently accurate to diagnose a septic nonunion, especially when caused by low virulence microorganisms. Cite this article: Bone Joint J 2020;102-B(7):904–911.

Definition and diagnosis of fracture-related infection

“… 10 In recent studies of infected fractures and non-unions, blood markers had very limited predictive value. 11 , 12 They cannot be used to confirm or exclude an infection.…”

Serum Inflammatory Biomarkers in the Diagnosis of Periprosthetic Joint Infections

“…Lower cut-off values were described by Glehr et al [13] (cut-off: 5.48 G/L) and Klim et al [20] (cut-off 5.68), leading to a higher sensitivity (91% and 90%, respectively) but at the expense of specificity (34% and 39%, respectively). Table 3 shows the recent literature of WBC depending on the used infection definition [2,10,11,13,[15][16][17]20,23,25,29,35].…”

“…In the literature, a broad range of sensitivities from 62% to 100%, and specificities from 64% to 96% [ 2 , 6 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 ] were described. Table 1 shows the results of the recent literature of serum CRP depending on the used infection definition.…”

“…Bacteria can live dormant in this self-made environment without interacting with inflammatory cells of the host immune system, resulting in a limited release of inflammatory serum biomarkers, including serum CRP [ 36 , 37 ]. In our recently published study, 46 (61%) of the 75 PJI patients were culture positive, including 14 infections caused by low-virulence (30%) and 32 by high-virulence microorganisms (70%) [ 2 ]. The median serum CRP levels differed significantly between these groups (17.6 mg/L (IQR 9.5–36.9), 49.2 mg/L (IQR 10.9–231.9), respectively; p = 0.044), with lower values in PJI cases caused by low-virulence pathogens.…”

“…They are easy to obtain, cheap, and are available all over the world. However, they are systemic parameters, and therefore, unspecific [ 2 ]. They need to be complemented by more specific diagnostic test methods, such as synovial fluid analysis, microbiology and histology of deep tissue samples, and sonication fluid analysis.…”