Correlation between Erythrocyte Sedimentation Rate/C-Reactive Protein Ratio and Procalcitonin Values in Postoperative Spondylodiscitis : Potential Biomarker Comparison
Article information
Abstract
Objective
Postoperative spondylodiscitis is a rare but serious complication of spinal surgery. The difficulty in establishing an early diagnosis necessitates the evaluation of novel biomarkers. This study aims to determine the diagnostic value of procalcitonin (PCT), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), ESR/CRP, and ESR/PCT ratios in the diagnosis of postoperative spondylodiscitis and to compare the sensitivity and specificity of these parameters.
Methods
This retrospective study was conducted by evaluating 55 patients who underwent two-level lumbar instrumentation (foraminotomy-medial facetectomy and microdiscectomy, autologous graft with fusion) between 2019 and 2023. Laboratory values of 28 patients diagnosed with postoperative spondylodiscitis and 27 control patients with no signs of infection were analyzed. The cut-off values, sensitivity, specificity, positive and negative predictive values, and area under the curve (AUC) of CRP, ESR, PCT, ESR/CRP, and ESR/PCT ratios were calculated using receiver operating characteristic (ROC) analysis.
Results
CRP, ESR, and PCT levels were significantly elevated in patients with spondylodiscitis (p<0.05). The ESR/PCT ratio demonstrated 96% specificity and was considered a supportive marker for the diagnosis of spondylodiscitis. However, the ESR/CRP ratio did not show a significant difference between the two groups (p=0.222). The cut-off value for CRP was determined as 43.7 mg/L, with a specificity of 100%. The cut-off value for ESR was 46 mm/hr, with a sensitivity of 92.9%. The cut-off value for PCT was found to be 0.034 ng/mL, with a sensitivity of 96.2%.
Conclusion
CRP and ESR/PCT ratios were found to be effective in supporting the diagnosis of postoperative spondylodiscitis due to their high specificity. On the other hand, ESR and PCT demonstrated higher sensitivity, making them more successful in distinguishing non-infected individuals. However, no single biomarker was deemed sufficient on its own, emphasizing the necessity of clinical evaluation alongside laboratory findings. Prospective studies are needed in the future to enhance the diagnostic accuracy of these biomarkers.
INTRODUCTION
Postoperative spinal infections (POEs) are undesired complications of spinal surgery. Postoperative spondylodiscitis is a primary infection of the nucleus pulposus, accompanied by secondary involvement of the cartilaginous endplate and vertebral bone. Although rare, postoperative spondylodiscitis can lead to major morbidity and may be associated with severe long-term sequelae [7]. Studies in the literature report that the incidence of POE following spinal surgery varies between 0.7% and 12%, depending on the type of surgery and the studied population [12]. The presence of infection places patients at high risk for pseudoarthrosis, chronic pain, the need for revision surgery, adverse neurological sequelae, poor long-term prognosis, and even mortality [18]. Once diagnosed, treatment should be carefully planned and meticulously implemented to eradicate the infection while preserving spinal stability and instrumentation integrity. However, differentiating postoperative spondylodiscitis in the early postoperative period is challenging, as classic signs of infection—such as fever, leukocytosis, pain, and erythema at the surgical site—can often be observed due to normal postoperative changes, even in the absence of an infection.
When faced with this clinical dilemma, a reliable tool is needed to predict postoperative infectious complications in these patients. In cases of suspected postoperative infection, laboratory tests such as white blood cell (WBC) count, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) are commonly used to assess the presence of infection. However, none of these markers are exclusively specific to infection [1].
Procalcitonin (PCT) has been used to differentiate bacterial infections from non-bacterial infections. Since most spinal infections are pyogenic, PCT can aid in the early detection of spinal infections [11]. However, as PCT alone is not sufficient for the diagnosis of spondylodiscitis, additional diagnostic tests are required to support the diagnosis.
Studies have investigated whether the ESR/CRP ratio can assist in determining infectious processes, particularly in postoperative infections [14]. In this study, we aimed to evaluate the effectiveness of PCT levels and the ESR/CRP ratio in diagnosing infection in patients with suspected postoperative spondylodiscitis following lumbar surgery. Additionally, we compared the diagnostic efficacy of other infection markers.
MATERIALS AND METHODS
This study was conducted with the approval of the Clinical Research Ethics Committee of Ordu University (approval No. 301). Patients who underwent two-level lumbar instrumentation (foraminotomy-medial facetectomy and microdiscectomy, autologous graft with fusion) at our hospital between 2019 and 2023 and were followed up with a preliminary diagnosis of postoperative spondylodiscitis were retrospectively analyzed. In defining the infection group, patients who reported severe low back pain (more severe than preoperative back pain) during outpatient follow-up between postoperative weeks 1 and 4 were considered. These patients underwent contrast-enhanced lumbar magnetic resonance imaging (MRI) on the same day. Cases in which the radiology report indicated findings consistent with spondylodiscitis were subsequently referred to the infectious diseases department, and the diagnosis of spondylodiscitis was confirmed following specialist consultation. Therefore, in this study, the diagnosis of spondylodiscitis was established based on clinical findings, MRI results consistent with infection, and confirmation by the infectious diseases specialist. We defined the control group as patients who presented for outpatient follow-up between postoperative weeks 1 and 4 and had no complaints. The number of patients in the infection group was 28, while the control group consisted of 27 patients.
All surgeries were performed under the same sterile conditions in accordance with the recommendations of our hospital’s infection protocol committee, and prophylactic administration of 1 g cefazolin was provided. Patients who presented between postoperative days 5 and 30 were included in the study. Only patients with available PCT, CRP, and ESR values in their medical records were analyzed. Patients with rheumatic diseases that could affect ESR levels, as well as those with postoperative systemic infections that could influence ESR, CRP, or PCT values, were excluded from the study.
Statistical analysis
Statistical analyses were performed using the MedCalc statistical software package (version 20.009; MedCalc Software Ltd., Ostend, Belgium). Descriptive statistics were presented as count, mean, standard deviation (SD), median, and 25th and 75th percentiles. The normality of numerical data was assessed using the Shapiro-Wilk test. Since the numerical variables did not follow a normal distribution, comparisons between groups were conducted using the Mann-Whitney U test. Data distributions were visually represented using box-and-whisker plots. A receiver operating characteristic (ROC) curve analysis was performed to determine the cut-off values, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and area under the curve (AUC) for CRP, ESR, PCT, ESR/CRP ratio, and ESR/PCT ratio. Additionally, graphical comparisons of the AUC values for these parameters were presented. A p-value <0.05 was considered statistically significant.
RESULTS
A total of 55 patients who underwent lumbar microdiscectomy and stabilization surgery were included in the study. The values of 28 patients who developed postoperative spondylodiscitis were compared with those of 27 control group patients who showed no signs of infection. The values for the control group were obtained from blood samples collected between the 1st and 4th postoperative weeks. The analysis revealed no significant difference in WBC levels between the two groups (p=0.553). Similarly, there was no significant difference in neutrophil and leukocyte ratios (p>0.05). However, CRP, ESR, and PCT levels were significantly elevated in patients with spondylodiscitis (p<0.05). While the ESR/CRP ratio did not show a significant difference between the two groups (p=0.222), the ESR/PCT ratio showed a significant difference (p=0.04) (Table 1).
When examining the diagnostic values of CRP, ESR, and PCT, the cut-off value for CRP was determined to be >43.7, with a specificity of 100%. The cut-off value for ESR was >46, with a sensitivity of 92.9%, while the cut-off value for PCT was >0.034, with a sensitivity of 96.2%. For the ratio-based parameters, the cut-off value for ESR/CRP was 1.22, with a specificity of 88.9%, whereas the cut-off value for ESR/PCT was 1535, with a specificity of 96% (Table 2 and Fig. 1).
DISCUSSION
Diagnosing spondylodiscitis in the early postoperative period is challenging because initial clinical findings—such as lower back pain, MRI findings, and biochemical markers—often resemble those seen in non-infected patients. Pain typically emerges between 1 week and 1 month postoperatively, mimicking preoperative symptoms and leading to diagnostic confusion [2]. The increased signal intensity and edema observed on MRI may not necessarily indicate infection but rather reflect normal postoperative changes, resulting in a high rate of false-positive findings in MRI [5]. Therefore, a careful clinical evaluation of patients is essential. Biochemical markers play a crucial role in aiding diagnosis, allowing for early initiation of treatment before significant clinical deterioration occurs [17].
The primary biochemical markers include WBC count, CRP, ESR, and PCT [18]. Although WBC, CRP, and ESR have limited utility in assessing surgical site infections, PCT is particularly important for detecting pyogenic infections [19]. Less than 50% of postoperative infection cases exhibit an increase in WBC count [5].
Although ESR was first described more than a century ago, it remains widely used today [8,9]. ESR measures the rate at which red blood cells aggregate (in mm/hr) and is primarily influenced by the concentration of circulating acute-phase proteins, particularly fibrinogen [6]. While ESR is more sensitive than WBC in detecting inflammatory processes, it is not equally specific for postoperative infections. Depending on the extent of the surgical procedure, ESR levels may take approximately 2 to 4 weeks to peak and can take 21 to 90 days to return to normal levels [5]. In our study, the cut-off value for ESR was determined to be 46 mm/hr, with a sensitivity of 92.9%, indicating that ESR has high sensitivity in diagnosing postoperative spondylodiscitis. However, the specificity of 77.8% suggests that ESR alone may not be sufficient for detecting infections. As noted in the literature, ESR tends to show more pronounced changes in chronic conditions, reinforcing the need for its evaluation alongside other markers in early postoperative spondylodiscitis cases.
CRP was first identified in 1930 in a patient with pneumococcal pneumonia [20]. It is synthesized by hepatocytes following stimulation by cytokines released during infection and tissue inflammation, particularly interleukin-6 (IL-6). CRP plays a role in host defense mechanisms and exhibits both inflammatory and anti-inflammatory effects [1]. CRP levels peak on the second to third postoperative day and reliably return to normal between postoperative days 14 and 21, decreasing by approximately half every 3 days [15]. If CRP levels rise again after this period, particularly showing a second “bump” (a secondary increase occurring days or weeks after the initial rise due to the normal postoperative inflammatory response), it has been reported to be highly correlated with infection, with a sensitivity of 82% [10]. In our study, the cut-off value for CRP was determined to be 43.7 mg/L, with a specificity of 100%. CRP levels above this threshold provide strong diagnostic support for patients suspected of spondylodiscitis who meet the exclusion criteria and show no other signs of infection.
PCT, a prohormone of calcitonin, has emerged as an effective biomarker for the diagnosis of bacterial infections [11]. PCT secretion begins within the first 4 hours of infection exposure and reaches its peak within 8 hours, whereas CRP secretion starts 4–6 hours after infection exposure and peaks only after 36 hours [19]. Nie et al. [16] reported that PCT is a more reliable biomarker for the early prediction of postoperative infectious complications in patients with acute traumatic spinal cord injury and is considered crucial for the timely initiation of antibiotic therapy. Similarly, in our study, the cut-off value for PCT was determined to be 0.034 ng/mL, with a sensitivity of 96.2%, indicating that this biomarker has high diagnostic sensitivity for postoperative spondylodiscitis.
The combined evaluation of ESR and CRP can be used as a predictive method for diagnosing POEs and monitoring treatment response. Recently, research on the ESR/CRP ratio in infection diagnosis has increased, particularly in orthopedic surgery. Christopher et al. [3] demonstrated that the ESR/CRP ratio could serve as a useful diagnostic tool for distinguishing between acute and chronic periprosthetic infections. Their study suggested that when CRP levels (measured in mg/L) exceed ESR levels, it may indicate an acute infection. Littlejohn et al. [13] conducted a study on patients with systemic lupus erythematosus (SLE) and found that the ESR/CRP ratio was effective in differentiating fever caused by inflammation from fever due to infection. They proposed that ESR is more reliable for detecting inflammation, while low CRP levels might be associated with autoantibodies produced by the body. Similarly, Daios et al. [4] investigated West Nile virus infections in 2020 and reported that the ESR/CRP ratio was higher in neuroinvasive disease caused by West Nile virus compared to non-West Nile virus-related neuroinvasive diseases, suggesting that this ratio could serve as a biomarker. In our study, despite the ESR/CRP ratio demonstrating a specificity of 88.9% in diagnosing postoperative spondylodiscitis, its sensitivity was found to be only 46.4%, indicating that this parameter may not be sufficient as a standalone biomarker. Therefore, unlike findings in the literature where the ESR/CRP ratio has been shown to be significant in orthopedic and rheumatic diseases, we believe that it is not a meaningful biomarker for differentiating postoperative spondylodiscitis.
In our study, the ESR/PCT ratio was found to show a significant difference between postoperative spondylodiscitis patients and the control group. Although the ESR/PCT ratio demonstrated a specificity of 96%, its sensitivity was only 30.8%, indicating that due to its low sensitivity, it may not be sufficient as a standalone biomarker. However, its high specificity suggests that the ESR/PCT ratio could serve as a supportive parameter in the diagnosis of spondylodiscitis.
Based on these findings, the ESR/PCT ratio may be considered a supportive biomarker for the diagnosis of spondylodiscitis; however, due to its low sensitivity, it may not be sufficient as a standalone diagnostic tool. Therefore, it is suggested that the ESR/PCT ratio should be interpreted alongside other biomarkers. In light of these results, CRP and the ESR/PCT ratio were found to be more effective in identifying spondylodiscitis patients due to their high specificity. On the other hand, ESR and PCT demonstrated superior performance in distinguishing non-infected individuals due to their high sensitivity
Limitation
This study has several limitations. First, its single-center and retrospective design restricts the generalizability of the findings. Although the incidence of spondylodiscitis in our cohort was consistent with the rates reported in the literature, the relatively small sample size may have reduced the statistical power and limited the robustness of our conclusions. Future multicenter, prospective studies with larger patient populations are warranted to validate these results and provide stronger evidence.
CONCLUSION
Postoperative spondylodiscitis is a significant complication that is difficult to diagnose in the early period and can lead to severe physical limitations in patients. The challenges in diagnosis necessitate the investigation of new diagnostic methods and biomarkers in this field. In our study, the newly defined parameters and determined cut-off values were evaluated as additional biomarkers that may aid in the diagnosis of postoperative spondylodiscitis.
In conclusion, while biomarkers such as CRP, ESR, PCT, and ESR/PCT contribute significantly to the diagnosis of postoperative spondylodiscitis, no single marker is sufficient on its own, and they should always be interpreted alongside clinical evaluation. Future prospective studies could help optimize the cut-off values of these biomarkers, thereby improving their diagnostic accuracy.
Notes
Conflicts of interest
No potential conflict of interest relevant to this article was reported.
Informed consent
Informed consent was obtained from all individual participants included in this study.
Author contributions
Conceptualization : ÖFŞ, MİY; Data curation : ABG; Formal analysis : ABG; Funding acquisition : ÖFŞ, BT; Methodology : ÖFŞ, AY; Project administration : ÖFŞ, OU, BT; Visualization : OU, MİY; Writing - original draft : ÖFŞ, OU; Writing - review & editing : ÖFŞ, OU, ABG
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