European Journal of Cardiovascular Medicine

Sepsis continues to be a significant global health challenge, responsible for millions of deaths each year despite advances in critical care and antimicrobial therapy. It is now recognized as a complex syndrome resulting from a dysregulated host response to infection that causes life-threatening organ dysfunction [1]. The early identification of sepsis in critically ill patients is vital because the timing of diagnosis directly affects prognosis delays in recognition and initiation of treatment are associated with higher mortality rates, prolonged hospital stays, and increased healthcare costs [2]. The clinical presentation of sepsis is often subtle and nonspecific, overlapping with other inflammatory or non-infectious conditions such as trauma, surgery, burns, or autoimmune diseases. Therefore, reliance solely on clinical findings and conventional laboratory parameters like white blood cell count and fever can lead to misdiagnosis or delayed intervention [3].  Biomarkers are measurable indicators of biological or pathological processes, and in sepsis, they serve to reflect the intensity and nature of the host’s inflammatory response [4]. Among the various biomarkers proposed over the years, such as interleukin-6, lactate, and presepsin, CRP and PCT have shown the greatest clinical applicability due to their accessibility, reproducibility, and relatively well-understood kinetics [5].

C-reactive protein (CRP), discovered in 1930, is one of the earliest acute-phase reactants identified. It is synthesized by hepatocytes under the stimulation of cytokines like interleukin-6 (IL-6), interleukin-1β (IL-1β), and tumor necrosis factor-alpha (TNF-α). CRP binds to phosphocholine expressed on the surface of dead or dying cells and certain bacteria, thereby activating the complement system and enhancing phagocytosis [6]. Its serum concentration can increase up to 1000-fold within 24–48 hours of an inflammatory insult. However, while CRP is highly sensitive to inflammation, it lacks specificity; elevations can occur in a wide range of conditions, including viral infections, trauma, autoimmune diseases, and post-surgical recovery [7]. Therefore, CRP alone cannot reliably distinguish sepsis from other causes of systemic inflammation in the intensive care unit (ICU) setting. Nonetheless, trends in CRP levels over time have prognostic value; a sustained or rising CRP level often indicates ongoing infection or treatment failure [8]. Procalcitonin (PCT), on the other hand, has emerged as a more specific marker for bacterial infections. It is a 116-amino acid prohormone of calcitonin that, under physiological conditions, is produced by thyroid parafollicular C cells in trace amounts [9]. During systemic bacterial infections, however, multiple tissues, including the lungs, liver, kidneys, and adipose tissue, begin producing PCT in response to bacterial endotoxins and inflammatory cytokines such as IL-1β and TNF-α. Importantly, viral infections typically do not stimulate PCT synthesis due to the inhibitory effect of interferon-gamma, making it a more specific indicator of bacterial etiology. PCT levels begin to rise within 2–4 hours of infection onset, peak around 6–12 hours, and have a half-life of about 24 hours [10]. Moreover, its concentration correlates with disease severity higher levels are often seen in septic shock and severe sepsis compared to localized infections [11]. The combined use of CRP and PCT enhances the diagnostic and prognostic accuracy in sepsis. CRP, being a broad and early marker of inflammation, can indicate that an inflammatory process is occurring, while PCT provides specificity toward bacterial infection [12]. Studies have shown that monitoring both markers simultaneously can improve early recognition of sepsis and differentiate it from non-infectious systemic inflammatory response syndrome (SIRS) [13].

Objective

This study aims to evaluate and compare the diagnostic and prognostic value of PCT and CRP in critically ill patients suspected of sepsis.

This was a cross-sectional analytical study conducted at Gulbarga Institute of Medical Sciences, Kalaburagi A total of 235 critically ill patients were enrolled in the study. Non-probability consecutive sampling was used to recruit patients who fulfilled the inclusion criteria.

Inclusion Criteria:

• Patients aged 18 years and above admitted to the Intensive Care Unit (ICU).
• Patients with clinical suspicion of infection or sepsis based on systemic inflammatory response criteria.
• Patients with available serum procalcitonin and C-reactive protein levels within the first 24 hours of admission.

Exclusion Criteria:

• Patients already receiving antibiotic therapy for more than 48 hours before admission.
• Patients with chronic inflammatory or autoimmune diseases (such as rheumatoid arthritis or systemic lupus erythematosus).
• Patients with severe hepatic failure or recent major surgery within the last seven days.
• Patients with incomplete medical or laboratory records.

Data Collection

After obtaining ethical approval from the institutional review board, written informed consent was taken from patients’ attendants due to the critical condition of the participants. Detailed clinical data were recorded, including age, gender, primary diagnosis, vital signs, comorbidities, and parameters of organ dysfunction. Venous blood samples were collected within 24 hours of ICU admission to measure serum levels of procalcitonin and C-reactive protein. PCT levels were analyzed using an automated immunoassay analyzer (electrochemiluminescence method), and CRP levels were measured using a high-sensitivity immunoturbidimetric assay. Patients were classified as septic or non-septic according to the Sepsis-3 criteria, which define sepsis as life-threatening organ dysfunction caused by a dysregulated host response to infection, indicated by an increase of ≥2 points in the Sequential Organ Failure Assessment (SOFA) score. Blood culture and other relevant investigations (urine, sputum, wound swabs) were also performed to confirm infection.

Data Analysis

Data were analyzed using SPSS version 26. Continuous variables such as age, CRP, and PCT levels were expressed as mean ± standard deviation, while categorical variables like gender, infection source, and sepsis status were presented as frequencies and percentages. Independent-sample t-test was used to compare means between septic and non-septic groups, and the chi-square test was applied to assess associations between categorical variables. A p-value of less than 0.05 was considered statistically significant.

Data were collected from 235 patients. The mean age of participants was 60.3 ± 14.1 years, with the septic group having a significantly older mean age (62.5 ± 13.7 years) compared to the non-septic group (55.6 ± 13.2 years). Gender distribution was fairly similar across both groups, with 60.4% of the total cohort being male. Hypertension was present in 66.4% of the total population, with a higher prevalence in the septic group (69.8%) compared to the non-septic group (58.9%). Diabetes mellitus was observed in 60% of participants, and smoking history was reported by 28.9% of the cohort, with slightly more patients in the septic group. Chronic kidney disease was found in 30.6% of all patients, with a higher prevalence in the septic group (34.6%) compared to the non-septic group (21.9%).

Table 1: Baseline Demographic and Clinical Characteristics of Participants (N = 235)

Procalcitonin levels were markedly higher in the septic group (7.8 ± 4.5 ng/mL) compared to the non-septic group (2.3 ± 1.1 ng/mL), with a p-value of less than 0.001, highlighting its usefulness as a specific marker for bacterial infections. Similarly, C-reactive protein levels were significantly elevated in the septic group (113.5 ± 52.8 mg/L) compared to the non-septic group (77.1 ± 31.9 mg/L), with a p-value also less than 0.001, reinforcing CRP’s role as an indicator of systemic inflammation.

Table 2: Serum Procalcitonin and C-Reactive Protein Levels in Septic and Non-Septic Groups (N = 235)

Procalcitonin demonstrated a sensitivity of 85.6% and specificity of 81.3%, with an AUC of 0.89, indicating excellent diagnostic performance for sepsis detection. In comparison, C-reactive protein showed a sensitivity of 78.9% and specificity of 71.2%, with an AUC of 0.80, suggesting it is a less accurate marker for sepsis but still useful in identifying inflammation.

Table 3: Diagnostic Accuracy of Procalcitonin and C-Reactive Protein for Sepsis Diagnosis

Patients with mild sepsis had a mean procalcitonin level of 4.2 ± 2.3 ng/mL and a mean CRP level of 98.2 ± 47.5 mg/L. In patients with moderate sepsis, procalcitonin levels increased to 7.0 ± 3.5 ng/mL and CRP levels to 110.4 ± 54.7 mg/L. Severe sepsis patients exhibited the highest mean levels of procalcitonin (11.3 ± 5.2 ng/mL) and CRP (137.9 ± 60.1 mg/L). These results demonstrate that both biomarkers correlate with the severity of sepsis and may be useful in assessing the clinical progression of the disease.

Table 4: Relationship Between Procalcitonin and C-Reactive Protein Levels with Sepsis Severity

Non-survivors had significantly higher levels of procalcitonin (8.6 ± 4.9 ng/mL) compared to survivors (4.9 ± 3.0 ng/mL), with a p-value of less than 0.001. Similarly, C-reactive protein levels were higher in non-survivors (125.5 ± 55.6 mg/L) compared to survivors (96.7 ± 43.0 mg/L), with a p-value of 0.015.

Table 5: Mortality and Procalcitonin/C-Reactive Protein Levels

Sepsis remains a leading cause of morbidity and mortality in critically ill patients, and timely identification is crucial to improving outcomes. This study aimed to assess the utility of serum procalcitonin (PCT) and C-reactive protein (CRP) levels in the early identification of sepsis among critically ill patients. Our results show that both PCT and CRP levels are significantly higher in septic patients compared to non-septic patients, with PCT demonstrating superior diagnostic accuracy. These findings are consistent with prior research, which has highlighted the role of these biomarkers in improving the early diagnosis and management of sepsis. Procalcitonin has been increasingly recognized as a more specific biomarker for bacterial infections compared to CRP, which is a general marker of inflammation [14]. In our study, the mean PCT levels were significantly elevated in septic patients (7.8 ± 4.5 ng/mL) compared to non-septic patients (2.3 ± 1.1 ng/mL), with a high sensitivity of 85.6% and specificity of 81.3%. This is in line with the findings of several studies, which have demonstrated that PCT is a more reliable marker for bacterial infections, particularly in the context of sepsis (Nauclér et al., 2016; Schuetz et al., 2017). The early rise of PCT within a few hours of infection onset and its higher levels in septic shock provide clinicians with a more accurate diagnostic tool compared to traditional markers such as CRP, which can be elevated in a variety of inflammatory conditions [15].

While CRP is sensitive to inflammation, it lacks the specificity needed to differentiate between bacterial and non-bacterial infections. In our study, the mean CRP levels in septic patients (113.5 ± 52.8 mg/L) were significantly higher than those in non-septic patients (77.1 ± 31.9 mg/L), but its diagnostic accuracy (AUC = 0.80) was inferior to that of PCT. These findings support the notion that CRP, while useful as a general marker of inflammation, is not specific enough for the early detection of sepsis [17-19]. As demonstrated by previous studies, CRP levels can be elevated in a wide range of conditions, including viral infections, trauma, and autoimmune diseases, thereby limiting its ability to differentiate sepsis from other inflammatory syndromes. Both PCT and CRP levels have been shown to correlate with the severity of sepsis. In our study, we observed a progressive increase in both PCT and CRP levels with the worsening severity of sepsis. Patients with mild sepsis had the lowest levels of PCT (4.2 ± 2.3 ng/mL) and CRP (98.2 ± 47.5 mg/L), while those with severe sepsis had the highest levels (PCT: 11.3 ± 5.2 ng/mL, CRP: 137.9 ± 60.1 mg/L). This is consistent with the findings of other studies that have demonstrated the association between elevated PCT and CRP levels and worse outcomes, including higher rates of organ dysfunction and mortality [20]. These results suggest that both biomarkers serve not only as diagnostic tools but also reflect the extent of inflammatory response and may be used to monitor disease progression in critically ill patients. Our study also found that elevated PCT and CRP levels were associated with increased mortality. Non-survivors had significantly higher PCT (8.6 ± 4.9 ng/mL) and CRP (125.5 ± 55.6 mg/L) levels compared to survivors. This aligns with previous research that has indicated elevated PCT levels as a predictor of poor outcomes in septic patients [21].

Limitations

Although our study provides valuable insights into the role of biomarkers in sepsis detection, there are several limitations. First, the study was conducted in a single center, and the sample size may not fully represent the diversity of critically ill patients in different settings. Additionally, we did not assess other potential biomarkers or microbiological data in detail, which could have further elucidated the relationship between these biomarkers and different types of infections. Future studies with a larger cohort, including multicenter trials, are needed to confirm our findings and evaluate the role of PCT and CRP in combination with other biomarkers for the diagnosis and prognosis of sepsis.

It is concluded that procalcitonin (PCT) and C-reactive protein (CRP) are valuable biomarkers in the early identification, severity assessment, and prognosis of sepsis in critically ill patients. Our study demonstrates that both biomarkers are significantly elevated in septic patients compared to non-septic patients, with PCT showing superior diagnostic accuracy. PCT exhibited higher sensitivity and specificity, making it a more reliable marker for bacterial infections, while CRP, although useful, was less specific and had lower diagnostic accuracy in distinguishing sepsis from other inflammatory conditions. Both PCT and CRP levels were positively correlated with the severity of sepsis, with higher levels observed in patients with severe sepsis.

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