Table of Contents    
ORIGINAL ARTICLE
Year : 2020  |  Volume : 11  |  Issue : 2  |  Page : 93-99  

Comparative study of procalcitonin and C-reactive protein in patients with sepsis


1 Department of Microbiology, Krishna Institute of Medical Sciences, Deemed to be University, Karad, Maharashtra, India
2 Department of Medicine, Krishna Institute of Medical Sciences, Deemed to be University, Karad, Maharashtra, India

Date of Submission01-Jan-2020
Date of Acceptance26-Feb-2020
Date of Web Publication22-Jul-2020

Correspondence Address:
Harsha Virendra Patil
Department of Medicine, Krishna Institute of Medical Sciences, Deemed to be University, Malkapur, Karad, Satara, Maharashtra
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jnsbm.JNSBM_1_20

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   Abstract 


Background: The early diagnosis and appropriate therapy of sepsis is a challenge in intensive care units in spite of the advances in critical care medicine. Aim of the study: The aim is to study and compare procalcitonin (PCT) and C-reactive protein (CRP) levels in patients admitted with the diagnosis of sepsis to the critical care unit. Materials and Methods: This was a prospective observational study conducted at the teaching hospital over a period of 1 year. All patients with evidence of sepsis were enrolled for this study and were underwent relevant history, laboratory biochemical and imaging investigations including PCT and CRP levels. Results: A total of 64 patients with the diagnosis of sepsis were enrolled in this study. A total of 43 (67.19%) were male and 21 (32.81%) were female. The mean and standard deviation for the Acute Physiology and Chronic Health Evaluation II (APACHE-II) score was 18 (±7), Sepsis-Related Organ Failure Assessment (SOFA) score was 9 (±5), papillary thyroid cancer as 19.07 (±7.02 ng/ml), and CRP was 33.5 (±15.7 mg/l). About 56.25% of patients had PCT in the range of 2–10 ng/ml, 28.13% had >10 ng/ml, and 14.06% had between 0.5 and 1.9 ng/ml. A total of 43 (67.19%) patients had a positive culture for organisms and 21 (32.81%) had sterile with no growth on culture with P < 0.001. The mean (20.74 ± 7.13). PCT levels were significantly high in Gram-negative organisms compared to (9.71 ± 0.96). Gram-positive organisms with P < 0.02. APACHE-II score, SOFA score, and CRP had a positive correlation with serum PCT levels and negative correlation with creatinine, pH, Glasgow Coma Scale and PaO2level. Multivariate analysis revealed that the serum PCT level was better correlated with the variable of sepsis than to CRP (P < 0.01). Conclusion: The present study concludes that the PCT was statistically significantly correlated with the severity of sepsis, APACHE-II, and SOFA score than CRP. The higher level of PCT was associated with Gram-negative sepsis and mortality.

Keywords: Acute Physiology and Chronic Health Evaluation-II score, C-reactive protein, Gram-negative organism, procalcitonin, sepsis, Sepsis-Related Organ Failure Assessment score


How to cite this article:
Patil HV, Patil VC. Comparative study of procalcitonin and C-reactive protein in patients with sepsis. J Nat Sc Biol Med 2020;11:93-9

How to cite this URL:
Patil HV, Patil VC. Comparative study of procalcitonin and C-reactive protein in patients with sepsis. J Nat Sc Biol Med [serial online] 2020 [cited 2020 Sep 24];11:93-9. Available from: http://www.jnsbm.org/text.asp?2020/11/2/93/290476




   Introduction Top


Sepsis is a life-threatening and contributing significantly, about one-third to the mortality in intensive care units (ICUs). Devoid of appropriate treatment, sepsis can progress to multiorgan dysfunction and septic shock. Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection.[1] Sepsis is a global health-care problem, characterized by inflammation in response to microbial infection leading to organ dysfunction. Sepsis is defined as systemic inflammatory response syndrome (SIRS) with an infectious process and associated with high morbidity and mortality rates if initial therapy is delayed. Numerous biomarkers (interleukins [IL]-2 and IL-6 and tumor necrosis factor-α), leukotrienes, acute-phase proteins (C-reactive protein [CRP]), and adhesion molecules, have been evaluated with variable results, predicting the severity of sepsis and guiding its management.[2] Recently, procalcitonin (PCT) has been suggested as a novel biomarker that is useful in guiding therapeutic decision making in the management of sepsis. This study was designed to compare the efficacy of PCT and CRP as a diagnostic marker of sepsis and relate these biomarkers with blood culture, parameters, and scores of sepsis in a tertiary care hospital. PCT is an innovative laboratory marker, has been recently proven valuable worldwide in this regard. We hypothesized that PCT and CRP concentrations are different in patients with of sepsis.


   Materials and Methods Top


Aim of the study

To study and compare PCT and CRP levels in patients admitted with the diagnosis of sepsis to the critical care unit. All patients admitted to medical ICU with evidence of sepsis were enrolled for this study and were underwent relevant history, laboratory biochemical, and imaging investigations. This was a time-bound study for 1 year.

Study design

This was a prospective observational and noninterventional study conducted at the teaching hospital.

Inclusion criteria

All consecutive patients with evidence of sepsis with age ≥18 years were enrolled for this study.

Study settings

This study was conducted over a period of 1 year (January 2018–December 2018) in Krishna Institute of Medical Sciences a tertiary care teaching hospital. This study was conducted in KIMS Hospital over a period of 1 year (January 2018–December 2018). The Institutional Ethical Committee approval was taken (protocol number:

055/2018–2019). The informed and written consent was taken from patients before enrolling for the study. A total of 64 patients were included in this study satisfying the inclusion criteria. The American College of Chest Physician's (ACCP) criterion for the diagnosis of sepsis (≥2 of the following)(a) temperature >38°C/<36°C, (b) heart rate >90 bpm (c) respiratory rate >20 breaths/min or paCO2<32 mm Hg, and (d) white blood cell (WBC) count >12,000 cells/mm3 or <4000 cells/mm3 or >10% immature (band) forms. Patients were diagnosed and classified into the following four groups, namely using criteria for SIRS, sepsis, severe sepsis, and septic shock based on the 1991 ACCP/Society of Critical Care Medicine consensus conference [Table 1].[3]
Table 1: Classification of sepsis according to ACCP/Society of Critical Care Medicine consensus - 1991

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Sepsis was clinically defined as a diagnosed infection and at least two of four SIRS criteria which include: (a) body temperature >38°C or <36°C, (b) heart rate >90 beats/min, (c) respiratory rate >20 breaths/min or an arterial partial pressure of carbon dioxide <4.3 kPa (32 mmHg), (d) white blood cell count >12,000 or <4000/mm3, or the presence of >10% immature neutrophils.[1] The infection was defined based on infection sites, clinical features, clinical microbiology, and imaging tests. The Acute Physiology and Chronic Health Evaluation II (APACHE II) and Sepsis-related Organ Failure Assessment (SOFA) scores were calculated using data from the first 24 h after admission. We also recorded the ICU and hospital length of stay. The patients were subsequently followed till discharge or death.[2]

Measurement of C-reactive protein, procalcitonin, and laboratory parameters

Within 12 h after ICU admission, 10 mL of blood was sampled for complete blood count, PCT, CRP, blood culture, renal function test, liver function test, and required investigations. PCT rapid quantitative test is a fluorescence immunoassay used to measure serum PCT level. To study the values of PCT obtained, they were divided into four groups based on the severity of sepsis, thus helping in diagnosing sepsis patients.[4] (PCT >10 ng/ml: Severe bacterial sepsis or septic shock, PCT 2–10 ng/ml: Severe systemic inflammatory response, most likely due to sepsis, PCT 0.5–1.9 ng/ml: SIRS; a systemic infection cannot be excluded and PCT <0.5 ng/ml: Local bacterial infection possible; sepsis unlikely). CRP concentrations were measured in a serum sample using a turbidimetric immunoassay test. Blood cultures were done by the automated BacT/Alert BioMerieux system with strict aseptic precautions.

Statistical analysis

Data were analyzed for mean, percentage, standard deviation, Chi-square test, multiple correlation, and multivariate analysis by using the Statistical Package for the Social Sciences-21 (SPSS) for Windows (SPSS, Chicago, IL, USA).


   Results Top


A total of 64 patients with the diagnosis of sepsis were enrolled in this study. Total 43 (67.19%) were male and 21 (32.81%) were female, with a male:female ratio being 2:1 (P < 0.05).

The mean and standard deviation for was APACHE-II score was 18 (±7), SOFA score was 9 (±5), papillary thyroid cancer (PTC) was 19.07 (±7.02 ng/ml), and CRP was 33.5 (±15.7 mg/l) [Table 2].
Table 2: Mean (±standard deviation) of numerical values

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About 56.25% of patients had PCT in the range of 2–10 ng/ml, 28.13% had >10 ng/ml, and 14.06% had between 0.5 and 1.9 ng/ml (P < 0.05) [Table 3].
Table 3: Frequency distribution of procalcitonin according to levels (n=64)

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A total of 43 (67.19%) patients had a positive culture for organisms and 21 (32.81%) had sterile with no growth on culture with P < 0.001. The mean (20.74 ± 7.13). PCT levels were significantly high in Gram-negative organisms (Klebsiella, Pseudomonas aeruginosa, Acinetobacter baumannii, Escherichia coli) compared to (9.71 ± 0.96) Gram-positive organisms (Staphylococcus aureus and coagulase-positive staphylococci [COPS]) with P < 0.02. The mean CRP level was not significantly differ among the organism (P < 0.23) [Table 4] [Graph 1].
Table 4: Cultures of various samples with their positivity regarding organism growth

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A total of 16 (37.21%) samples from blood, 15 (34.88%) from sputum, 11 (25.58%) from urine and 1 (2.33%) from stool were positive for bacterial growth in the present study with predominance of blood and sputum positivity on culture (P < 0.05) [Table 5] and [Graph 2].
Table 5: Organism isolated from clinical sample with their procalcitonin levels

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Of total 43 culture-positive samples 25.6% were A. baumannii, 34.88% were E. coli, 11.6% were P. aeruginosa, 9.3% were Klebsiella spp., 11.6% were S. aureus 4.65% were COPS and 2.33% were C. albicans [Table 6].
Table 6: Distribution of culture positivity for bacterial growth

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APACHE-II score, SOFA score, CRP and serum creatinine had positive correlation with serum PCT levels and negative correlation with creatinine, pH, Glasgow Coma Scale (GCS), and PaO2 level [Graph 2]a and [Graph 2]b.

Of the total 64 patients with Sepsis 9 (14.06%) succumbed during treatment with mean high mean PCT 35 (±7.9) and mean CRP of 23.5 (±9.4). The mean of PCT was significantly higher than the mean of CRP in patients with mortality with P < 0.001. Multivariate analysis revealed that the serum PCT level was better correlated with the variable of sepsis compared to CRP after controlling age and gender (P < 0.01).


   Discussion Top


Blood culture is considered as the gold standard for the confirmation of bacteraemia and subsequently test the antimicrobial sensitivity, but the delayed process of bacterial culture delays the diagnosis of sepsis. PCT is an amino acid polypeptide precursor for the hormone calcitonin. It was first identified in 1975 and first linked to infectious disease in 1983 when increased serum levels of immune-reactive calcitonin were described in patients with staphylococcal toxic shock syndrome. High serum PCT levels in sepsis that the current research on PCT in bacterial disease accelerated. PCT offers favorable kinetics for a biomarker. The PCT as a biomarker proved successfully its clinical usefulness in determining the presence of sepsis. It clearly showed the significance of the early diagnosis of bacterial infected sepsis. The serum concentration of PCT, CRP, IL-6, and lactate was elevated according to the severity of illness. Along with PCT, other (including, CRP, IL) biomarkers are used in the diagnosis of sepsis. Compared to CRP, PCT has better diagnostic and prognostic value and will clearly distinguish viral and bacterial infection. The serum PCT level rises rapidly in sepsis than CRP levels and peaks within a very short time, the level of PCT returns to normal range faster than CRP which makes it a better biomarker for sepsis. Several studies mentioned the advantages of the PCT as a biomarker for sepsis. We compared our results with various studies from India and overseas.[5] Recently, PCT has been suggested as a novel biomarker that may be useful in guiding therapeutic decision-making in the management of sepsis. In the present study, a total of 64 patients with the diagnosis of sepsis were enrolled in this study. A total of 67.19% were male and 32.81% were female. In the present study, total 56.25% of patients had PCT in the range of 2–10 ng/ml, 28.13% had >10 ng/ml, and 14.06% had between 0.5 and 1.9 ng/ml in a patient with sepsis. Forty-six trials evaluating the efficacy of PCT concentrations 39 trials yielding positive results in diagnosing sepsis.[2] The peak PCT concentrations occur early after injury in both patients with sepsis and with multiple organ dysfunction syndrome (MODS) and mortality in patients with abdominal sepsis (P < 0.01).[2] Hu et al. observed that PCT and CRP are useful markers and should be used to evaluate serious bacterial infections with a fever of unknown origin.[6] Similarly, in the present study, 67.19% of patients had a positive culture for organisms and 32.81% had sterile with P < 0.001. In the present study of total 43 culture-positive samples 25.6% were A. baumannii, 34.88% were E. coli, 11.6% were P. aeruginosa, 9.3% were Klebsiella spp., 11.6% were S. aureus 4.65% were COPS and 2.33% were Candida albicans with the significantly high level of PCT and CRP. Similarly, Tang et al. stated that both PCT and CRP are helpful in detecting pneumonia caused by different types of infection.[7] Tanrıverdi et al. concluded that the PCT was better than CRP for predicting a bacterial infection; these findings are similar to the present study (P < 0.01).[8] Titova et al. quoted that the PCT had about the same accuracy as CRP and WBC in predicting pneumonia in patients hospitalized with acute exacerbations of chronic obstructive pulmonary disease.[9] In the present study, PCT levels were significantly high (20.74 ± 7.13) in Gram-negative organisms compared to (9.71 ± 0.96) Gram-positive organisms (P < 0.02). The mean CRP level was not significantly differ among the organism (P < 0.23). In the current study in multivariate analysis revealed that the serum PCT level was better correlated with the variable of sepsis compared to CRP after controlling age and gender (P < 0.01). Similarly, Nargis et al. quoted that the serum PCT and CRP values in cases with sepsis, severe sepsis and septic shock were significantly higher (P < 0.01) and PCT was found to be superior to CRP in the identification and to assess the severity of sepsis.[10] Sharma and Duggal in their study quoted that the PCT along with CRP, is a better diagnostic tool for sepsis.[11] Tian et al. found that PCT levels were valuable in discriminating sepsis from SIRS and determining sepsis severity in critically ill patients. We observed APACHE-II score, SOFA score, CRP and serum creatinine had a positive correlation with serum PCT levels and negative correlation with creatinine, pH, GCS, and PaO2 level.[12] Castelli et al. reported that the maximum PCT concentrations were found at higher score levels (SOFA score >12) compared to CRP.[13] Similarly, Qin et al. reported that the PCT, CRP, and SOFA score in the combination of them has higher evaluation value in patients with sepsis.[14] Wang and Chen found that compared with CRP, PCT was more significantly correlated with the APACHE II score and SOFA score. PCT can be a better indicator for the evaluation of the degree of sepsis.[15] Ocakli et al. quoted, PCT may be a better marker for therapeutic decisions in advanced chronic inflammatory diseases.[16] Mustafić et al. stated that there was a significant correlation between PCT and SOFA, and APACHE II score in nonsurviving septic patients indicates that PTC combined with clinical score could be useful for assessing the severity of infection, these findings are similar to the present study.[17] Huang et al. found positive statistical correlation between PCT and SOFA score (r = 0.979, P < 0.05), similar to the present study (r = 0.12). PCT was a useful marker for the diagnosis of infectious SIRS after the cardiac operation as compared with WBC and CRP.[18] In the present study, 14.06% of patients with sepsis succumbed during treatment with mean high mean PCT 35 (±7.9) and mean CRP of 23.5 (±9.4). The mean of PCT was significantly higher than the mean of CRP in patients with mortality with P < 0.001. In the present study in multivariate analysis revealed that the serum PCT level was better correlated with the variable of sepsis compared to CRP (P < 0.01). Castelli et al. reported that PCT and CRP may be useful together with bacteriological data in sepsis diagnosis. PCT and SOFA closer correlate with the infection severity; PCT is the better parameter to estimate severity, prognosis or further course of the disease; these findings are similar to the present study.[19] Wang et al. observed that the prognostic value of PCT is better than that of CRP and CPIS score for evaluation of community-acquired pneumonia (CAP).[20] Liu et al. reported that the detection of PCT in combination with high-sensitivity (hs)-CRP facilitates the early diagnosis of pneumonia and sepsis.[21] Guo et al. stated that the dynamic CRP and PCT changes may potentially be used in the future to predict the prognosis of hospitalized patients with CAP.[22] Luzzani et al. stated that the PCT is a better marker of sepsis with organ dysfunction than CRP.[23] Zhang et al. quoted that hs-CRP is not inferior to PCT in the diagnosis of sepsis and septic shock.[24] Ruan et al., in their meta-analysis study, quoted that the combination of PCT and CRP improves the accuracy of the diagnosis of sepsis.[25] Sinha et al. quoted that the PCT ≥2 ng/ml had a statistically significant correlation with the sepsis (P < 0.0001).[26] Nasimfar et al. stated that the serum PCT level can be measured as a marker of bacterial infections with CRP, erythrocyte sedimentation rate and WBC count.[27] Pravin Charles et al. quoted that the PCT with CRP and other tests for the septic screen can aid in better diagnosis of sepsis.[28] Imran Siddiqui et al. reported that in comparison to PCT and CRP, high plasma lactic acid levels are associated with the development of all-cause MODS and worse outcome in critically ill patients [Table 7].[29]
Table 7: Comparison of various studies with present study

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IL-6 and IL-10 performance better than CRP and PCT in identifying patients with high-risk febrile illness. Standard blood culture techniques require time with results typically not available for at least 24–48 h, highlighting the need for rapid diagnosis and risk stratification where biomarkers could be of use. PCT has been investigated as the biomarker that holds the most assure for bloodstream infections in recent research.[32] Serological tests are indispensable in the diagnosis of early infection. At present, only PCT and CRP are commonly used in clinical practice. Recently, serum amyloid A1 (SAA1) and heparin-binding protein (HBP) have been shown to be new biomarkers because SAA1 is highly sensitive and specific for viral infections, and HBP is predictive for septic shock.[33] The present study support the majority of the research conducted in India and overseas in regard to the utility of PCT in sepsis.


   Conclusion Top


The present study revealed that the severity of sepsis was correlated with the proportionate increased level of serum procalcitonin and CRP as well, with better correlation was found between the PCT levels and APACHE-II and SOFA scores. The parameters of sepsis, organ dysfunction, and mortality were significantly correlated with the serum PCT level. Patients with mortality in the present population had significantly high levels of PCT levels compared to CRP. To conclude it was obvious from the present study that the serum procalcitonin will help in the diagnosis, management, and prognosis of the disease in a patient with sepsis which can be complimented by other parameters of sepsis including SOFA score and CRP.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7]



 

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