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EDITORIAL
Year : 2021  |  Volume : 8  |  Issue : 5  |  Page : 217-218

Serum procalcitonin: A promising biomarker for ventilator-associated pneumonia in children


Department of Anesthesiology and Critical Care Medicine, Driscoll Children's Hospital, Corpus Christi, Texas, USA and University of Texas Medical Branch, Galveston, Texas, USA

Date of Submission05-Sep-2021
Date of Acceptance11-Sep-2021
Date of Web Publication28-Sep-2021

Correspondence Address:
Dr. Utpal S Bhalala
Driscoll Children's Hospital, 3533 S. Almeda Street, Corpus Christi, TX 78414xs
USA
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jpcc.jpcc_78_21

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How to cite this article:
Samraj RS, Bhalala US. Serum procalcitonin: A promising biomarker for ventilator-associated pneumonia in children. J Pediatr Crit Care 2021;8:217-8

How to cite this URL:
Samraj RS, Bhalala US. Serum procalcitonin: A promising biomarker for ventilator-associated pneumonia in children. J Pediatr Crit Care [serial online] 2021 [cited 2021 Oct 16];8:217-8. Available from: http://www.jpcc.org.in/text.asp?2021/8/5/217/326873



Despite ongoing efforts to prevent ventilator-associated pneumonia (VAP), it continues to be one of the common hospital-acquired infections, with a reported incidence of approximately 10%.[1] A recent meta-analysis estimated a mortality of 13% related to VAP.[2] In addition, VAP prolongs the duration of mechanical ventilation by 7.6–11.5 days and prolongs hospitalization by 11.5–13.1 days.[3] The above-reported numbers from the developed countries are probably even higher in resource-limited countries, making an early diagnosis and prompt treatment imperative in improving outcomes in these settings. There are no gold standards for diagnosing VAP, and currently, the condition is diagnosed on clinical, laboratory, and radiologic criteria. Consequently, there is a higher use of empiric antibiotics for a prolonged period resulting in increased medical costs, emergence of resistant pathogens, prolonged length of stay, and risk of mortality.[4] With the need for an early diagnosis of VAP, Nandan et al. have studied the diagnostic utility of serum procalcitonin (PCT) levels in pediatric VAP.[5]

PCT, a 116-amino acid peptide, is a precursor molecule of calcitonin without any known biologic properties. Serum PCT levels are very low in healthy individuals but get upregulated during bacterial sepsis.[6] A meta-analysis of 12 studies comparing the diagnostic accuracy for bacterial infection of PCT compared to C-reactive protein (CRP) in hospital inpatients found that PCT was more sensitive (88% versus 75%) and specific (81% versus 67%) than CRP for differentiating bacterial from noninfective causes of inflammation.[7] PCT has several desirable features of an ideal biomarker: undetectable in healthy subjects, upregulated in sepsis, rises early (elevated at 3–6 h), and a short half-life of about 1 day.[8] PCT has been widely investigated as a biomarker of bacterial infection, including in disease of the lower respiratory tract. Serum PCT levels have been shown to be helpful in early diagnosis of VAP in adult patients.[9] However, there is a paucity of literature in the pediatric population.

The authors have conducted a prospective observational study to determine the utility of PCT in diagnosing pediatric VAP.[5] The study was designed to exclude children with primary diagnosis of pneumonia, children with nonpulmonary infection, and those with elevated baseline PCT levels, thus eliminating potential confounders. VAP was diagnosed with quantitative bronchoalveolar lavage cultures with ≥105 colony-forming unit count/ml. The incidence of VAP in this study was 49.4%; this was higher than the previously reported incidence of 10%.[1] However, the incidence of infections is expected to be higher in resource-limited developing countries. Previously reported rates of VAP in children range from 1.4 to 7 episodes per 1000 ventilator days in developed countries while it was significantly higher in developing countries, ranging from 16.1 to 89 episodes per 1000 ventilator days.[10] There are limited studies evaluating the diagnostic utility of PCT in VAP. Luyt et al., in their single-center observational study of VAP, reported a 72% sensitivity but only 24% specificity for diagnosing VAP and the authors concluded that PCT rise had poor diagnostic value. However, they used a low PCT cutoff level of 0.5 ng/ml. In addition, the study had several limitations: it included patients (a) with late-onset VAP, (b) who received antibiotics before inclusion into the study and (c) post cardiac surgery patients who have been reported to have elevated PCT levels at baseline after surgery.[11] In contrast to the previous studies, the current study used a higher PCT cutoff level of 10 ng/ml and found a receiver operating characteristic area under curve of 0.785 (95% confidence interval = 0.678–0.870) with a sensitivity of 82.05% and specificity of 75%. Although the optimal cutoff level that might be useful for diagnosing VAP needs to be studied further, it is plausible that a higher cutoff level such as the one used in the present study, might potentially yield a better specificity compared to the previously used lower cutoff levels. Furthermore, with the higher cutoff levels, the authors found that the mean duration of mechanical ventilation was significantly higher in the VAP group than in the non-VAP group (P = 0.0001) and longer duration of antibiotic therapy in the VAP group compared to the non-VAP group (P = 0.0001). This underlines the importance of early diagnosis of VAP and instituting prompt therapy to improve patient outcomes.

Diagnosis of VAP continues to be a challenge for the clinician in the absence of a noninvasive definitive test. Clinical criteria have been reported to have an ideal sensitivity of 100%, however, with a very low specificity of 15% in diagnosing VAP. Bronchoalveolar lavage culture has a specificity of 88%.[12] However, the use of bronchial lavage cultures entails an inherent risk due to its invasive nature and reporting of the bacterial culture often takes several days. In addition, it is not widely available, especially in resource-limited countries. The current study identifies a potential role for PCT, using higher cutoff levels, in diagnosing VAP, especially when used in the appropriate clinical situation.[5]

In summary, the study has provided a timely and important examination of utility of PCT in early detection of VAP in children. Their findings highlight the need for a rapidly available biomarker for resource-limited settings. This would help in early institution of therapy, thereby improving outcomes as well as avoiding unnecessary use of empiric antibiotics. Follow-up, large-scale studies are needed to evaluate (a) utility of PCT in diagnosing VAP in children, (b) optimal cutoff value and (c) possibility of serial PCT levels in antibiotic stewrdship.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Wang Y, Eldridge N, Metersky ML, Verzier NR, Meehan TP, Pandolfi MM, et al. National trends in patient safety for four common conditions, 2005-2011. N Engl J Med 2014;370:341-51.  Back to cited text no. 1
    
2.
Melsen WG, Rovers MM, Groenwold RH, Bergmans DC, Camus C, Bauer TT, et al. Attributable mortality of ventilator-associated pneumonia: A meta-analysis of individual patient data from randomised prevention studies. Lancet Infect Dis 2013;13:665-71.  Back to cited text no. 2
    
3.
Muscedere JG, Day A, Heyland DK. Mortality, attributable mortality, and clinical events as end points for clinical trials of ventilator-associated pneumonia and hospital-acquired pneumonia. Clin Infect Dis 2010;51 Suppl 1:S120-5.  Back to cited text no. 3
    
4.
Huang HB, Peng JM, Weng L, Wang CY, Jiang W, Du B. Procalcitonin-guided antibiotic therapy in Intensive Care Unit patients: A systematic review and meta-analysis. Ann Intensive Care 2017;7:114.  Back to cited text no. 4
    
5.
Nandan D, Nimesh M, Kumar S, Manik L, Sudarshan J, Duggal N. Serum procalcitonin as an early inflammatory marker in pediatric ventilator-associated pneumonia: A prospective Observational Study. J Pediatr Crit Care 2021;8:229-33.  Back to cited text no. 5
  [Full text]  
6.
Müller B, White JC, Nylén ES, Snider RH, Becker KL, Habener JF. Ubiquitous expression of the calcitonin-i gene in multiple tissues in response to sepsis. J Clin Endocrinol Metab 2001;86:396-404.  Back to cited text no. 6
    
7.
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.  Back to cited text no. 7
    
8.
Creamer AW, Kent AE, Albur M. Procalcitonin in respiratory disease: Use as a biomarker for diagnosis and guiding antibiotic therapy. Breathe (Sheff) 2019;15:296-304.  Back to cited text no. 8
    
9.
Duflo F, Debon R, Monneret G, Bienvenu J, Chassard D, Allaouchiche B. Alveolar and serum procalcitonin: Diagnostic and prognostic value in ventilator-associated pneumonia. Anesthesiology 2002;96:74-9.  Back to cited text no. 9
    
10.
Cernada M, Brugada M, Golombek S, Vento M. Ventilator-associated pneumonia in neonatal patients: An update. Neonatology 2014;105:98-107.  Back to cited text no. 10
    
11.
Luyt CE, Combes A, Reynaud C, Hekimian G, Nieszkowska A, Tonnellier M, et al. Usefulness of procalcitonin for the diagnosis of ventilator-associated pneumonia. Intensive Care Med 2008;34:1434-40.  Back to cited text no. 11
    
12.
Bradley JS. Considerations unique to pediatrics for clinical trial design in hospital-acquired pneumonia and ventilator-associated pneumonia. Clin Infect Dis 2010;51 Suppl 1:S136-43.  Back to cited text no. 12
    




 

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