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ORIGINAL ARTICLE
Year : 2014  |  Volume : 27  |  Issue : 4  |  Page : 717-721

Procalcitonin for discrimination between bacterial and viral lower re spiratory tract infections


Department of Pediatric, Faculty of Medicine, Menoufia University, Menufia, Egypt

Date of Submission10-Sep-2014
Date of Acceptance24-Jun-2014
Date of Web Publication22-Jan-2015

Correspondence Address:
Neamh Mohamed Khattab
Banha Medical Centre, Ministry of Health
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/1110-2098.149709

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  Abstract 

Objective
The aim of this study is to assess whether procalcitonin (PCT) can distinguish between bacterial and viral lower respiratory tract infections (LRTIs).
Background
LRTIs are common diseases in children and are common causes of antibiotic prescription, especially in primary care. It is difficult to distinguish viral from bacterial disease because the clinical presentations of LRTIs because of different causative agents may be similar. Inappropriate use of antibiotics contributes toward the development of antibiotic-resistant bacteria, and increases both the length of stay and the costs of hospitalization. Therefore, a routine test that can safely discriminate between viral and bacterial infection is needed.
Methods
This prospective single study included 45 patients diagnosed clinically with LRTIs (pneumonia and bronchiolitis) and confirmed by radiological laboratory and microbiological investigations and 10 patients as a control group. The participants were categorized into group 1 bacterial infection (pneumonia, 15 patients), group 2 viral infection (bronchiolitis, 30 patients), and group 3 control (10 individuals). Serum PCT levels were determined for the three groups; complete blood count, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) were determined only for group I and group II. Radiological and microbiological investigations were performed for group I and group II.
Results
Although CRP, ESR, and PCT concentrations were significantly different between patients with bacterial and viral LRTIs, the sensitivity and specificity of PCT were higher. PCT had an area under the curve of 0.995 (95% confidence interval, 0.98-1).
Conclusion
LRTI is a major health problem. Serum PCT can improve differentiation between patients with a bacterial or viral LRTI compared with CRP and ESR.

Keywords: Area under curve, C-reactive protein, erythrocyte sedimentation rate, lower respiratory tract infection, procalcitonin


How to cite this article:
Hassan FM, Khattab AA, Midan DA, El-Shazly RM, Khattab NM. Procalcitonin for discrimination between bacterial and viral lower re spiratory tract infections. Menoufia Med J 2014;27:717-21

How to cite this URL:
Hassan FM, Khattab AA, Midan DA, El-Shazly RM, Khattab NM. Procalcitonin for discrimination between bacterial and viral lower re spiratory tract infections. Menoufia Med J [serial online] 2014 [cited 2020 Apr 3];27:717-21. Available from: http://www.mmj.eg.net/text.asp?2014/27/4/717/149709


  Introduction Top


Lower respiratory tract infections (LRTIs) are common causes of antibiotic prescriptions, especially in primary care. It can be difficult to distinguish viral from bacterial causes of the disease because the clinical presentations of LRTIs because of different causative agents may be similar. Inappropriate use of antibiotics contributes toward the development of antibiotic-resistant bacteria, and increases both the length of stay and the costs of hospitalization. Therefore, a routine test that can be safely discriminate between bacterial and viral infections is needed [1]. Procalcitonin (PCT) has been suggested as a candidate for such a test. PCT is a precursor peptide of the hormone calcitonin, and is normally produced by C-cells of the thyroid gland; it can also be produced by several types of cells in response to infection. Some of the most potent inducers of PCT are bacterial endotoxins and exotoxins [2]. An increase in plasma PCT concentrations is observed within 2-4 h after infection. This will continue until appropriate treatment is initiated or until the infection is controlled. The PCT plasma half-life is ~24 h [3]. The increase in plasma PCT in response to bacterial infection is faster than the increase in C-reactive protein (CRP), and the PCT levels return to normal faster than those of CRP when the infection is under control [4].


  Patients and methods Top


Study design

This is a prospective single-center study that was carried out in the pediatric department in Menoufiya University Hospital between December 2012 and February 2013. The study included 45 patients who were diagnosed clinically and confirmed by laboratory [complete blood count (CBC), erythrocyte sedimentation rate (ESR), CRP], microbiological (sputum culture), and radiological (chest radiography) investigations to have LRTI and also included 10 control participants. They were grouped as follows: group 1 included 15 patients with bacterial LRTI, group 2 included 30 patients with viral LRTI, and group 3 included 10 control participants.

Inclusion criteria of the study

  1. Age below 16 years.
  2. Signs and symptoms of LRTI (fever, cough, chest pain, dyspnea altered breath sounds on auscultation, and/or presence of infiltrate on chest radiography).
  3. Patients with suspected infection, who had at least two of the following clinical signs of sepsis: temperature >38.3°C or < 36°C, heart rate more than 90/minute, respiratory rate more than 20/minute, chills, altered mental status, systolic blood pressure less than 90 mmHg, mean arterial pressure less than 65 mmHg, and hyperglycemia (plasma glucose>6.8 mmol/l) in the absence of diabetes mellitus.


Patients who did not fulfill these inclusion criteria were excluded.

All patients included in the study were subjected to a complete assessment of history and a full clinical examination including a general examination and a local chest examination. Laboratory investigations included CBC, ESR, CRP and serum PCT level, radiological investigation (chest radiography), and microbiological investigation (sputum culture).

CRP was measured using Abbott Aeroset with a lower detection limit of 5 mg/l. PCT was measured using the ELISA (Kryptor PCT) with a detection limit of 0.02 mg/l.

Statistical analysis

Quantitative data were described statistically as mean ± SD (x0 ± SD) and analyzed using the Mann-Whitney U-test for non-normally distributed variables. The analysis of variance test (f-test) was used for comparison of more than two groups of normally distributed variables and the Kruskal-Wallis test was used for comparison of more than two groups of non-normally distributed variables. Qualitative data were expressed as number and percentage [N (%)] and analyzed using the c2 -test and the Student t-test for numerical data. Pearson correlation (r) was used to detect an association between and qualitative data variables, whereas Spearman correlation was used to detect an association between qualitative and quantitative variables. The receiver operating characteristic (ROC) curve was used to detect the cutoff value with the highest sensitivity and specificity for ESR, CRP, and PCT for numerical data.

The data collected were tabulated and analyzed using statistical package for the social science software (SPSS Inc., Chicago, Illinois, USA), version 15 for Microsoft windows [5].


  Results Top


In this work, 45 studied patients with suspected infection and more than two clinical signs of infection were divided into two groups; the first group included 15 patients who were diagnosed with bacterial LRTI. The second group included 30 patients with a viral LRTI for further analysis. No patient was diagnosed with both bacterial and viral infection. Ten children were selected as controls.

The demographic data are shown in [Table 1]. CRP and ESR were significantly higher in group 1 compared with group 2. In terms of CBC results shown in [Table 2], there was a highly significant difference between group I and group II in the lymphocytic count, being higher in group II. There was a highly significant difference between group I and group II in the granulocytic count, being higher in group I. There was a significant difference between groups I and II in the platelet count, being higher in group I. The most frequent causative organism in sputum culture was Streptococcus pneumoniae (60%). PCT was higher in group 1 with the bacterial infection than group 2 with viral infection as shown in [Table 3] and [Figure 1]. The ROC of CRP had an area under the curve (AUC) of 0.95 [95% confidence interval (CI), 0.88-1.02]. The ROC of ESR had an AUC of 0.80 (95% CI, 0.75-0.91) and the ROC of PCT had an AUC of 0.995 (95% CI, 0.98-1). The cutoff point of PCT was 1.7 (with a sensitivity of 93.3%, a specificity of 90%, and an accuracy of 90.9%). The cutoff point for CRP was 6, with a sensitivity of 86.7%, a specificity of 62.5%, and an accuracy of 69%. The cutoff point of ESR was 10, with a sensitivity of 80%, a specificity of 95%, and an accuracy of 90.9%. Comparison of the validity of ESR, CRP, and PCT showed no significant difference between the sensitivity of PCT and ESR and CRP in detecting cases of bacterial LRTI [Figure 2]. The specificity and accuracy of PCT were significantly higher than CRP in detecting cases of bacterial LRTI as shown in [Table 4].
Figure 1: Serum PCT level of the studied groups. PCT, procalcitonin.

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Figure 2: ROC curve of PCT. PCT, procalcitonin; ROC, receiver operating characteristic.

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Table 1: Hematological data of the studied groups

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Table 2: Serum levels of procalcitonin in the studied groups

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Table 3: Comparison of the validity of PCT alone and that of CRP and PCT and ESR and PCT in detecting cases of bacterial LRTI

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Table 4: Shows comparison between validity of PCT alone and that of CRP &PCT and ESR &PCT in detecting cases of bacterial LRTI

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  Discussion Top


Morbidity and mortality associated with LRTIs remain significant despite improved diagnostic and therapeutic treatment strategies in recent years. The early initiation of antibiotic therapy has a major impact on the clinical outcome of critically ill patients [6].

Several laboratory diagnostic tests are currently used to establish an etiologic diagnosis. However, difficulty in obtaining relevant specimens, the low sensitivity or specificity of the used tests, high costs, and the absence of test results within the critical window for initiating adequate treatment often result in the prescription of antibiotic therapy in the absence of a bacterial infection. This may have potentially deleterious consequences such as anaphylactic reactions, antibiotic resistance, and high costs. Rapid tests that provide additional insight into the bacterial/viral etiology of infection may guide the appropriate use of antibiotics and are urgently needed [7].

Antibiotics are the cornerstones in the treatment of bacterial infections and early antibiotic administration has been a crucial part of the surviving sepsis campaign [8].

However, a marked increase in antibiotic resistance has emerged without the prospect of development of novel classes of antimicrobial agents. Therefore, reduction of unnecessary use of antibiotics is mandatory [9].

Unfortunately, the symptoms and signs used routinely in the diagnosis of LRTI have limited value in predicting the requirement of antibiotic therapy [10].

PCT can be used as a diagnostic prognostic factor of pneumonia. The PCT level can help guide antibiotic therapy. In this trial, 'on the basis of serum PCT concentrations, use of antibiotics was more or less discouraged ( < 0.1 mg/l or 0.25 mg/l) or encouraged (>0.5 mg/l or >0.25 mg/l), respectively' [11].

This study was designed to evaluate the level of serum PCT and improve the discriminating ability in cases of a proven bacterial or viral LRTI and to correlate their concentrations as a marker of disease severity and clinical outcomes.

In this work, the 55 patients studied were divided into three groups: the first group included 15 patients who were diagnosed with bacterial LRTI. The second group included 30 patients with a viral LRTI for further analysis. No patients were diagnosed with both a bacterial and a viral infection. The third group included 10 children as a control group.

The study showed that age was highly significant differently between both groups. Sex was not significantly different between the two groups. Proper [12] reported that male sex is an additional risk for LRTIs.

The patients studied presented with various clinical manifestations. However, they showed no statistically significant difference among both groups in fever. High-grade fever and cough were the most common presenting symptoms.

Micheal and Richard [13] found that fever is the most common manifestation of infection in children.

In terms of the laboratory data, lymphocytes and granulocytes differed highly significantly. The platelet count was significantly elevated in patients with viral LRTI than patients with bacterial LRI. However, there were no statistically significant differences in white blood cell, red blood cell, and hemoglobin levels between both groups.

EI-Khayat et al. [14] reported similar results on lymphocytes, hemoglobin level, and platelet count in their patients.

McWilliam and Riordan [15] in a prospective study, reported the limited utility of CRP testing in differentiating the etiology of infection because of low sensitivity and specificity. Further investigation of the effects of CRP testing in the clinical setting may provide support for the implementation of such a test. Antibiotic prescription is guided by diagnostic evidence as well as physician judgment, and CRP testing may prove to be influential in removing some diagnostic uncertainty.

In the current study, it was found that CRP, ESR first hour, and ESR second hour were more elevated in patients with bacterial LRTI than in patients with viral LRTI. There was an increase in serum PCT in patients with bacterial LRTI than in patients with viral LRTI and the control group. ESR did no aid in the diagnosis of infection because of its variation in hematocrit levels, delayed increase, and finally, in reverting to a normal value, which is very low, despite clinical recovery [16].

Khan et al. [16], in a prospective study, found that the diagnostic accuracy of PCT had a maximum sensitivity of 83% and specificity of 72% at a cut-off of 2 ng/ml. CRP showed a maximum sensitivity of 57% and specificity of 82% at a cut-off of 6 mg/l. PCT has shown greater specificity than CRP in differentiating between viral and bacterial etiologies because of the significant association between PCT and CRP and pneumococcal pneumonia. PCT can be utilized as an early marker (more so than CRP) for the diagnosis of bacterial pneumonia.

In this work, there was a highly significant positive correlation between CRP, ESR first hour, and ESR second hour and group I ( P < 0.001), and a significant positive correlation between hemoglobin and group II (P < 0.05).

Schuetz et al. [17] reported that antibiotic use can be reduced by ~50% if physicians were encouraged not to prescribe antibiotics for patients with low serum PCT levels. In another study from the same group, it was shown that determination of PCT can be used safely to guide antibiotic treatment with respect to duration. Physicians were encouraged to discontinue antibiotic treatment when PCT had decreased below a certain predefined cut-off level; this approach resulted in a marked reduction in antibiotic use without affecting outcome.


  Conclusion Top


LRTI is one of the major health problems worldwide. There is no single test that can reliably diagnose LRTI. It still relies on high clinical suspicion. In our study, serum PCT level was elevated in bacterial LRTI more than in viral LRTI; thus, this could be a prediction of microbiological etiology in patients with LRTI compared with CRP as a single marker. Therefore, PCT is a reliable marker for early diagnosis and better management of LRTI.


  Acknowledgements Top


Conflicts of interest

There is no conflicts of interest.

 
  References Top

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World Health Organization Anti-Infective Drug Resistance Surveillance and Containment Team. WHO global strategy for containment of antimicrobial resistance. Geneva: World Health Organization; 2001.  Back to cited text no. 7
    
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Dellinger RP, Levy MM, Carlet JM, Bion J, Parker MM, Jaeschke, et al. Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock: 2008. Crit Care Med2008; 36:296-327.  Back to cited text no. 8
    
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Schuetz P, Christ-Crain M, Thomann R, Falconnier C, Wolbers M, Widmer I, et al. ProHOSP Study Group Effect of procalcitonin-based guidelines vs standard guidelines on antibiotic use in lower respiratory tract infections: the ProHOSP randomized controlled trial. JAMA 2009; 302 :1059-1066.  Back to cited text no. 11
    
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Proper CG. Respiratory tract infection in: Behrman RE, Kliegman RM, Jenson HB (eds). Nelson Text Book of pediatrics 17th ed, Saunders, Philadilphia, 2004.  Back to cited text no. 12
    
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McWilliam S, Riordan A. How to use: C-reactive protein. Arch Dis Child Educ Pract Ed 2010; 95 :55-58.  Back to cited text no. 15
    
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Khan DA, Rahman A, Khan FA. Is procalcitonin better than C-reactive protein for early diagnosis of bacterial pneumonia in children? J Clin Lab Anal 2010; 24 :1-5.  Back to cited text no. 16
    
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Schuetz P, Christ-Crain M, Thomann R, Falconnier C, Wolbers M, Widmer I, et al. ProHOSP Study Group Effect of procalcitonin-based guidelines vs standard guidelines on antibiotic use in lower respiratory tract infections: the ProHOSP randomized controlled trial. JAMA 2009; 302 :1059-1066.  Back to cited text no. 17
    


    Figures

  [Figure 1], [Figure 2]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4]


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