|Year : 2017 | Volume
| Issue : 4 | Page : 135-141
Procalcitonin levels to predict bacterial infection in Surgical Intensive Care Unit patients
Jin You Jhan1, Yen Ta Huang2, Cian Huei Shih3, Jhen Da Yang4, Yi Tsen Lin5, Shin-Jie Lin5, Hsiao Hui Yang6, Lee Ying Soo7, Guan Jin Ho8
1 Department of Surgery, Buddhist Tzu Chi General Hospital; Division of Cardiothoracic Surgery, Buddhist Tzu Chi General Hospital, Hualien, Taiwan
2 Department of Surgery; Surgical Intensive Care Unit, Buddhist Tzu Chi General Hospital; Department of Pharmacology, Tzu Chi University, Hualien, Taiwan
3 Nurse Practitioner, Department of Nursing, Surgical Intensive Care Unit, Buddhist Tzu Chi General Hospital; Ph.D. Student, Institute of Medical Sciences, Tzu Chi University, Hualien, Taiwan
4 Nurse Practitioner, Department of Nursing, Surgical Intensive Care Unit, Buddhist Tzu Chi General Hospital, Hualien, Taiwan
5 Nurse Practitioner, Department of Nursing, Surgical Intensive Care Unit, Buddhist Tzu Chi General Hospital; M.S. Student, Institute of Nursing, Tzu Chi University, Hualien, Taiwan
6 Department of Surgery, Buddhist Tzu Chi General Hospital; School of Medicine, Tzu Chi University, Hualien, Taiwan
7 Department of Surgical Intensive Care Unit, Buddhist Tzu Chi General Hospital, Hualien, Taiwan
8 Department of Surgical Intensive Care Unit, Buddhist Tzu Chi General Hospital; School of Medicine, Tzu Chi University, Hualien, Taiwan
|Date of Submission||23-Nov-2016|
|Date of Decision||13-Jan-2017|
|Date of Acceptance||02-Mar-2017|
|Date of Web Publication||19-Jul-2017|
Guan Jin Ho
SICU of Tzu Chi General Hospital, 707, Section 3, Chung Yang Road, Hualien 970
Source of Support: None, Conflict of Interest: None
Background: Infection-induced inflammatory response might be aggravated by surgery insults. The clinical presentation of Surgical Intensive Care Unit (SICU) patients might be different from medical critically ill patients.
Purpose: To evaluate the diagnostic and prognostic values of procalcitonin (PCT) to predict bacterial infection in SICU patients.
Methods: We retrospectively analyzed the 2-year (2013 and 2014) records of 342 adult SICU cases with suspected bacterial infection in SICU of Hualien Tzu Chi Hospital. The past histories, the first infection-related parameters when SICU admission, culture results, infection-related laboratory examinations, and outcomes were collected.
Results: Median of PCT level in patients with negative and any positive culture was 0.84 (interquartile range [IQR] 0.18–6.21) and 2.27 (IQR 0.54–9.93) ng/ml, respectively. Infection from blood, urine, and skin/soft tissue elicited significantly higher PCT levels. PCT in receiver operating characteristic (ROC) curve demonstrated the most accurate to predict bacterial infection (area under the ROC curve [AUC]: 0.61; 95% confidence interval [CI]: 0.54–0.63) and bacteremia (AUC: 0.73; 95% CI: 0.66–0.80) compared to white blood cell count, ratio of neutrophils, and neutrophil-to-lymphocyte count ratio (NLCR). Significantly higher PCT levels (4.12 ng/ml, 1.12–19.99; median, IQR) were observed in mortality cases. Higher PCT levels were significantly accompanied with higher NLCR, as well as higher incidence of leukopenia and bandemia. Using Kaplan–Meier analysis, significantly higher intrahospital mortality was observed in cases with above the cutoff PCT levels of 0.5 and 2 ng/ml cases, respectively.
Conclusion: PCT is a relatively more useful tool to predict bacterial and particularly bloodstream infection compared to other infection-related parameters in routinely clinical practice. Initial PCT levels may be a prognostic factor of SICU patients with bacterial infection.
Keywords: Bacterial infections, critical care, hospital surgery departments, procalcitonin
|How to cite this article:|
Jhan JY, Huang YT, Shih CH, Yang JD, Lin YT, Lin SJ, Yang HH, Soo LY, Ho GJ. Procalcitonin levels to predict bacterial infection in Surgical Intensive Care Unit patients. Formos J Surg 2017;50:135-41
|How to cite this URL:|
Jhan JY, Huang YT, Shih CH, Yang JD, Lin YT, Lin SJ, Yang HH, Soo LY, Ho GJ. Procalcitonin levels to predict bacterial infection in Surgical Intensive Care Unit patients. Formos J Surg [serial online] 2017 [cited 2019 Jan 18];50:135-41. Available from: http://www.e-fjs.org/text.asp?2017/50/4/135/211088
| Introduction|| |
Bacterial infections and followed sepsis are major threats to surgical patients' survival. Early intervention with an appropriate antimicrobial regimen(s) for infected patients is associated with a better outcome. However, some patients with bacterial infections have atypical symptoms or signs. In contrast, only parts of patients with systemic inflammatory response syndrome (SIRS) are resulted from bacterial infections. To find the most arcuate laboratory examination for early identification of bacterial infection in Intensive Care Unit (ICU) practice is very important.
Procalcitonin (PCT), near undetectable in plasma of healthy individuals, is an intracellular precursor of calcitonin produced by C-cells of the thyroid gland. PCT is induced by activated monocytes/macrophages and released into circulation in SIRS. In particular when bacterial infections occur, PCT secretion is stimulated by various cytokines, for example, tumor necrosis factor-α. In viral infections, the PCT production may be downgraded from increased production of interferon-gamma production. Using PCT to guide antibiotic decisions has been extensively studied in patients with bacterial infection. Although PCT is thought as a helpful biomarker for early diagnosis of sepsis in critically ill patients, the positive likelihood ratio in meta-analysis is not good enough. Furthermore, the diagnostic value of C-reactive protein, commonly used to predict bacterial infection in Taiwan, has been demonstrated worse than PCT. The aim of our study is to analyze the clinical significance of PCT in our Surgical ICU (SICU) cases to predict bacterial infections.
| Methods|| |
This is a single-center, 2-year retrospective study, from January 1, 2013, to December 31, 2014. We enrolled all adult (≧18-year-old) cases admitted in SICU of Hualien Tzu Chi Hospital with PCT tests. In clinical practice, we subjectively arranged PCT test for any patient with any symptoms/signs of suspicious infection. In this 15-bed SICU, cases came from the department of general and hepato-biliary-pancreatic surgery, colorectal surgery, cardiovascular and thoracic surgery, plastic surgery, orthopedic surgery, otolaryngology, urology, as well as obstetrics and gynecology. The clinical data including past histories, infection-related laboratory examinations (PCT, white blood cell [WBC] count, ratios of segment plus band form leukocyte [segment + band], and neutrophil-to-lymphocyte count ratio [NLCR]), culture results, and outcomes were collected. We choose the first parameters of infection-related laboratory examinations when bacterial infection was suspected. The patients with insufficient or incomplete data were excluded from the study. We also excluded the patients with positive fungal culture. After chart review, a total of 342 patients were enrolled in this study. The primary outcome is survival rate during admission courses.
According to PCT levels, we divided the data into four ranges (0.05–0.5 ng/ml, 0.5–2 ng/ml, 2–10 ng/ml, and >10 ng/ml) to differentiate the severity. We defined the patients with positive culture (sputum, urine, stool, blood, skin and soft tissue [SST], and drainage culture) as infectious status. The blood culture-positive group twice is bacteremia.
The diagnostic values of PCT and other parameters were assessed by the receiver operating characteristic (ROC) curves and the area under the ROC curve (AUC). Results for categorical are presented as proportions (%) and compared by Chi-square tests. Results for normally and nonnormally distributed continuous variables are presented as mean (± standard deviation) and median (25%–75% interquartile range [IQR]), respectively. For normal distribution analysis, we used Kolmogorov–Smirnov test to examine any continuous variables. Normally and nonnormally distributed continuous variables were compared by Student t-tests and Mann–Whitney U-test, respectively. Variables were considered statistically significant if P < 0.05. Statistical tests of the data and figures were performed by SPSS 22 software (IBM Corporation, Armonk, NY, USA) and GraphPad Prism 6 (GraphPad Software, La Jolla, CA, USA).
The study was conducted in accordance with the Declaration of Helsinki and was approved by the local ethics committee of the institute. Informed written consent was obtained from all patients prior to their enrollment in this study.
| Results|| |
In these 342 SICU patients with suspected infection, the median of age was 62 years old (IQR 53–76) and male gender accounted for 71.1%. About underlying diseases, ratios of diabetes mellitus, cirrhotic liver, and end-stage renal disease (ESRD) cases were 30.4%, 17.5%, and 9.1%, respectively. The positive culture results were 56.5% (65/115), 31.6% (56/177), 40% (50/125), 82.4% (89/108), 77.5% (124/160), and 45.8% (11/24) from blood, urine, drainage, wound, sputum, and stool, respectively. Median of ICU admission days was 6 (IQR 3–10) days. There was no correlation between the length of ICU admission days and PCT levels (P = 0.394 analyzed by Pearson's correlation coefficient). The intrahospital mortality was 22.5%. We compared the infection-related parameters between survivors and nonsurvivors during admission course; only PCT levels reached statistically significant difference [Figure 1]. Significantly higher PCT levels were observed in mortality case who were suspected bacterial infection in SICU.
|Figure 1: Distribution of (a) white blood cell count, (b) ratios of segmented plus band form leukocytes, (c) neutrophil-to-lymphocyte count ratio, (d) procalcitonin levels in survivors and nonsurvivors. Red lines indicate median, while blue error bars indicate interquartile range. Each dot in the figures indicates individual value|
Click here to view
Diagnostic performance of procalcitonin and other infection-related parameters
The ROC curves and the detailed AUCs of WBC count, ratios of segmented plus band form WBC, NLCR, and PCT to predict the positive culture and bacteremia are shown in [Figure 2]a and [Figure 2]b, respectively. The difference of AUC between WBC count and 0.5, which means the test is no better than tossing a coin, did not reach statistical significance to predict bacterial infection in SICU patients. In contrast, only AUC of PCT was significantly higher than 0.5 to predict bacteremia in SICU patients. [Figure 2]c and [Figure 2]d demonstrates the comparison of any two parameters to predict bacterial infection and bacteremia. Compared to WBC count, AUCs of PCT and NLCR showed significantly higher to predict bacterial infection [Figure 2]c. AUC of PCT showed significantly higher than any other parameters to predict bacteremia [Figure 2]d.
|Figure 2: Diagnostic value of procalcitonin levels and other parameters to predict bacterial infection and bacteremia. Receiver operating characteristic curves and the area under the receiver operating characteristic curve predict (a) bacterial infection and (b) bacteremia, respectively. Intragroup comparison of area under the receiver operating characteristic curve to predict (c) bacterial infection and (d) bacteremia, respectively. Error bar = standard error of mean|
Click here to view
Difference of procalcitonin levels from individual culture site
We also analyzed the PCT levels from individual culture site [Table 1]. In our study, median of PCT level was 0.84 (IQR: 0.18–6.21) ng/ml when patients without any positive culture. Patients with any positive culture had significantly higher PCT levels (2.27 ng/ml, 0.54–9.93; median, IQR). Among all culture site obtainment, patients with bacteremia had the highest PCT levels (9.05 ng/ml, 1.80–58.23; median, IQR). The difference of PCT levels between cases with positive and negative cultures from blood, urine, and skin reached statistical significance. Higher PCT levels were observed in SICU patients with bacteremia, urinary tract infection (UTI), and SST infection (SSTI).
Clinical data analysis divided by four intervals of procalcitonin levels
According to the previous report, PCT levels are divided into four groups: 0.05–0.5, 0.51–2, 2.01–10, and more than 10.01 ng/ml, which indicates the mimic condition of local infection, systemic infection, sepsis, and septic shock, respectively. The analysis is showed in [Table 2]. About underlying conditions, P values regarding the incidence of past history with ESRD among four groups was just 0.05. ESRD patients who were suspected bacterial infection seemed to have higher PCT levels. Compared to other laboratory examinations regarding bacterial infection, higher PCT levels were accompanied with higher NLCR, as well as higher incidence of leukopenia and bandemia with statistically significance difference. Pearson's correlation coefficient was significantly positive between PCT levels and NLCR (r = 0.20, P < 0.0001).
|Table 2: Clinical data analysis divided by the severity according to PCT levels|
Click here to view
Survival curves using different cutoff levels of procalcitonin
We demonstrated the difference of intrahospital survival rate by Kaplan–Meier curves with different cutoff levels of PCT (0.5, 2, and 10 ng/ml, respectively) based on above description. Analyzed by log-rank test, intrahospital survival rates were significantly different with cutoff PCT levels of 0.5 and 2 ng/ml [Figure 3]a and [Figure 3]b. Intrahospital survival rate did not reach statistically significant difference between below and above 10 ng/ml of PCT levels [Figure 3]c.
|Figure 3: Kaplan–Meier curves of intrahospital mortality using cutoff procalcitonin levels of (a) 0.5, (b) 2, (c) 10 ng/ml|
Click here to view
| Discussion|| |
In our study, PCT was better to predict bacterial infection and bacteremia in SICU patients. PCT levels were higher in mortality cases who admitted to SICU due to suspected or confirmed bacterial infection. Patients with bacteremia, UTI, and SSTI had higher PCT levels. Once PCT level >0.5 ng/ml, survival rate was deteriorated. We reviewed original articles from PubMed and found that only a few studies ,,,, investigating the diagnostic value of PCT from patients in Taiwan. Similarly, there were only two studies , demonstrated PCT as a prognostic or severity marker in infected Taiwan patients.
The AUC values to predict bacterial infection in our investigation is lower than other studies focusing on standard care patients or patients with autoimmune disease., Increased nonspecific inflammatory response in the early phase of surgical insults seems to trigger much higher inflammatory response after surgical infections, which results in false positive of PCT levels. One study reported the usefulness of PCT as a marker of systemic infection in emergency department patients with the cutoff value of 0.5 ng/ml. In our study, median of PCT level higher than 0.5 ng/ml in patients without any positive culture may explain the higher inflammatory response in SICU patients. Therefore, the lower diagnostic accuracy of PCT levels to predict bacterial infection in SICU patients than those in medical and noncritically ill populations seems reasonable. In contrast, the AUC values to predict bacteremia in our study are similar to other reports, and AUC values of bacteremia prediction in these reports (including our study) appear higher than other infection diseases., The relationship between bloodstream infection and cytokine releases might be more directly. In our study, PCT levels in patients with bacteremia are higher than some studies.,, Again, it may explain the higher inflammatory response in SICU patients. Renal elimination is one of the major routes for the elimination of PCT, so it is reasonable that higher PCT level is found in ESRD cases in our study. Lower PCT levels were observed in cases with fungal infection, so we excluded patients with positive fungal culture in this study.
NLCR is an easily available biomarker, which can be calculated from a complete blood count. NLCR has previously been shown to predict outcomes in oncological patients and has subsequently been tested in a number of malignancies including lung, ovary, and breast. In acute inflammatory phase, neutrophilia and lymphopenia are presented on laboratory examination. NLCR is also considered as a biomarker of bacterial infections. In our study, although significant, the correlation between PCT levels and NLCR was poor. NLCR is the second powerful tool to predict bacterial and bloodstream infection in SICU patients in our study. More exaggerated inflammatory response in surgical patients may be one of the explanations.
This study has some limitations. First, we did not collect enough clinical data regarding patients' severity, for example, APACHE II score or SOFA score. Lack of pathogen analysis was a weakness in this investigation because the presentation of PCT levels is different from Gram-positive and negative pathogens., PCT variations after antibiotic therapy may influence the outcome of patients with acute infectious diseases.,, There are no fixed intervals to check PCT in our clinical practice, so we were not able to determine the PCT variations.
| Conclusion|| |
Although not good enough for SICU patients, PCT is a relatively more useful diagnostic tool to predict bacterial and particularly bloodstream infection compared to other infection-related parameters in routinely clinical practice in our study. Initial PCT levels may be a prognostic factor of SICU patients with bacterial infection. A new diagnostic parameter for improving the predictive accuracy of bacterial infection in SICU patients should be explored in the future.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Kollef MH, Sherman G, Ward S, Fraser VJ. Inadequate antimicrobial treatment of infections: A risk factor for hospital mortality among critically ill patients. Chest 1999;115:462-74.
Maruna P, Nedelníková K, Gürlich R. Physiology and genetics of procalcitonin. Physiol Res 2000;49 Suppl 1:S57-61.
Karzai W, Oberhoffer M, Meier-Hellmann A, Reinhart K. Procalcitonin – A new indicator of the systemic response to severe infections. Infection 1997;25:329-34.
Gendrel D, Raymond J, Coste J, Moulin F, Lorrot M, Guérin S, et al.
Comparison of procalcitonin with C-reactive protein, interleukin 6 and interferon-alpha for differentiation of bacterial vs. viral infections. Pediatr Infect Dis J 1999;18:875-81.
Carr JA. Procalcitonin-guided antibiotic therapy for septic patients in the surgical Intensive Care Unit. J Intensive Care 2015;3:36.
Wacker C, Prkno A, Brunkhorst FM, Schlattmann P. Procalcitonin as a diagnostic marker for sepsis: A systematic review and meta-analysis. Lancet Infect Dis 2013;13:426-35.
Simon L, Gauvin F, Amre DK, Saint-Louis P, Lacroix J. Serum procalcitonin and C-reactive protein levels as markers of bacterial infection: A systematic review and meta-analysis. Clin Infect Dis 2004;39:206-17.
Gürol G, Çiftci IH, Terizi HA, Atasoy AR, Ozbek A, Köroglu M. Are there standardized cutoff values for neutrophil-lymphocyte ratios in bacteremia or sepsis? J Microbiol Biotechnol 2015;25:521-5.
Wu JY, Chen HC, Lee SH, Chan RC, Lee CC, Chang SS. Diagnostic role of procalcitonin in patients with suspected appendicitis. World J Surg 2012;36:1744-9.
Su CP, Chen TH, Chen SY, Ghiang WC, Wu GH, Sun HY, et al.
Predictive model for bacteremia in adult patients with blood cultures performed at the emergency department: A preliminary report. J Microbiol Immunol Infect 2011;44:449-55.
Li CH, Yang RB, Pang JH, Chang SS, Lin CC, Chen CH, et al.
Procalcitonin as a biomarker for bacterial infections in patients with liver cirrhosis in the emergency department. Acad Emerg Med 2011;18:121-6.
Lai CC, Chen SY, Wang CY, Wang JY, Su CP, Liao CH, et al.
Diagnostic value of procalcitonin for bacterial infection in elderly patients in the emergency department. J Am Geriatr Soc 2010;58:518-22.
Chan YL, Tseng CP, Tsay PK, Chang SS, Chiu TF, Chen JC. Procalcitonin as a marker of bacterial infection in the emergency department: An observational study. Crit Care 2004;8:R12-20.
Lee CC, Chen SY, Tsai CL, Wu SC, Chiang WC, Wang JL, et al.
Prognostic value of mortality in emergency department sepsis score, procalcitonin, and C-reactive protein in patients with sepsis at the emergency department. Shock 2008;29:322-7.
Tseng JS, Chan MC, Hsu JY, Kuo BI, Wu CL. Procalcitonin is a valuable prognostic marker in ARDS caused by community-acquired pneumonia. Respirology 2008;13:505-9.
Ratzinger F, Schuardt M, Eichbichler K, Tsirkinidou I, Bauer M, Haslacher H, et al.
Utility of sepsis biomarkers and the infection probability score to discriminate sepsis and systemic inflammatory response syndrome in standard care patients. PLoS One 2013;8:e82946.
Joo K, Park W, Lim MJ, Kwon SR, Yoon J. Serum procalcitonin for differentiating bacterial infection from disease flares in patients with autoimmune diseases. J Korean Med Sci 2011;26:1147-51.
Cui P, Fang X. Pathogenesis of infection in surgical patients. Curr Opin Crit Care 2015;21:343-50.
Hausfater P, Garric S, Ayed SB, Rosenheim M, Bernard M, Riou B. Usefulness of procalcitonin as a marker of systemic infection in emergency department patients: A prospective study. Clin Infect Dis 2002;34:895-901.
Romualdo LG, Torrella PE, González MV, Sánchez RJ, Holgado AH, Freire AO, et al.
Diagnostic accuracy of presepsin (soluble CD14 subtype) for prediction of bacteremia in patients with systemic inflammatory response syndrome in the emergency department. Clin Biochem 2014;47:505-8.
Jeong S, Park Y, Cho Y, Kim HS. Diagnostic utilities of procalcitonin and C-reactive protein for the prediction of bacteremia determined by blood culture. Clin Chim Acta 2012;413:1731-6.
Leli C, Ferranti M, Moretti A, Al Dhahab ZS, Cenci E, Mencacci A. Procalcitonin levels in Gram-positive, Gram-negative, and fungal bloodstream infections. Dis Markers 2015;2015:701480.
Oussalah A, Ferrand J, Filhine-Tresarrieu P, Aissa N, Aimone-Gastin I, Namour F, et al.
Diagnostic accuracy of procalcitonin for predicting blood culture results in patients with suspected bloodstream infection: An observational study of 35,343 consecutive patients (A STROBE-compliant article). Medicine (Baltimore) 2015;94:e1774.
Lu XL, Xiao ZH, Yang MY, Zhu YM. Diagnostic value of serum procalcitonin in patients with chronic renal insufficiency: A systematic review and meta-analysis. Nephrol Dial Transplant 2013;28:122-9.
Templeton AJ, McNamara MG, Šeruga B, Vera-Badillo FE, Aneja P, Ocaña A, et al.
Prognostic role of neutrophil-to-lymphocyte ratio in solid tumors: A systematic review and meta-analysis. J Natl Cancer Inst 2014;106:dju124.
Abramson N, Melton B. Leukocytosis: Basics of clinical assessment. Am Fam Physician 2000;62:2053-60.
Lowsby R, Gomes C, Jarman I, Lisboa P, Nee PA, Vardhan M, et al.
Neutrophil to lymphocyte count ratio as an early indicator of blood stream infection in the emergency department. Emerg Med J 2015;32:531-4.
Magrini L, Travaglino F, Marino R, Ferri E, De Berardinis B, Cardelli P, et al.
Procalcitonin variations after emergency department admission are highly predictive of hospital mortality in patients with acute infectious diseases. Eur Rev Med Pharmacol Sci 2013;17 Suppl 1:133-42.
Pieralli F, Vannucchi V, Mancini A, Antonielli E, Luise F, Sammicheli L, et al.
Procalcitonin kinetics in the first 72 hours predicts 30-day mortality in severely ill septic patients admitted to an intermediate care unit. J Clin Med Res 2015;7:706-13.
Charles PE, Kus E, Aho S, Prin S, Doise JM, Olsson NO, et al.
Serum procalcitonin for the early recognition of nosocomial infection in the critically ill patients: A preliminary report. BMC Infect Dis 2009;9:49.
[Figure 1], [Figure 2], [Figure 3]
[Table 1], [Table 2]