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Published in: BMC Pulmonary Medicine 1/2019

Open Access 01-12-2019 | Community-Acquired Pneumonia | Research article

Combination of clinical symptoms and blood biomarkers can improve discrimination between bacterial or viral community-acquired pneumonia in children

Authors: Mejbah U. Bhuiyan, Christopher C. Blyth, Rachel West, Jurissa Lang, Tasmina Rahman, Caitlyn Granland, Camilla de Gier, Meredith L. Borland, Ruth B. Thornton, Lea-Ann S. Kirkham, Andrew Martin, Peter C. Richmond, David W. Smith, Adam Jaffe, Thomas L. Snelling

Published in: BMC Pulmonary Medicine | Issue 1/2019

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Abstract

Background

Differentiating bacterial from viral pneumonia is important for guiding targeted management and judicious use of antibiotics. We assessed if clinical characteristics and blood inflammatory biomarkers could be used to distinguish bacterial from viral pneumonia.

Methods

Western Australian children (≤17 years) hospitalized with radiologically-confirmed community-acquired pneumonia were recruited and clinical symptoms and management data were collected. C-reactive protein (CRP), white cell counts (WCC) and absolute neutrophil counts (ANC) were measured as part of routine care. Clinical characteristics and biomarker levels were compared between cases with definite bacterial pneumonia (clinical empyema and/or bacteria detected in blood or pleural fluid), presumed viral pneumonia (presence of ≥1 virus in nasopharyngeal swab without criteria for definite bacterial pneumonia), and other pneumonia cases (pneumonia in the absence of criteria for either definite bacterial or presumed viral pneumonia). The area-under-curve (AUC) of the receiver operating characteristic (ROC) curve for varying biomarker levels were used to characterise their utility for discriminating definite bacterial from presumed viral pneumonia. For biomarkers with AUC > 0.8 (fair discriminator), Youden index was measured to determine the optimal cut-off threshold, and sensitivity, specificity, predictive values (positive and negative) were calculated. We investigated whether better discrimination could be achieved by combining biomarker values with the presence/absence of symptoms.

Results

From May 2015 to October 2017, 230 pneumonia cases were enrolled: 30 with definite bacterial pneumonia, 118 with presumed viral pneumonia and 82 other pneumonia cases. Differences in clinical signs and symptoms across the groups were noted; more definite bacterial pneumonia cases required intravenous fluid and oxygen supplementation than presumed viral or other pneumonia cases. CRP, WCC and ANC were substantially higher in definite bacterial cases. For a CRP threshold of 72 mg/L, the AUC of ROC was 0.82 for discriminating definite bacterial pneumonia from presumed viral pneumonia. Combining the CRP with either the presence of fever (≥38οC) or the absence of rhinorrhea improved the discrimination.

Conclusions

Combining elevated CRP with the presence or absence of clinical signs/ symptoms differentiates definite bacterial from presumed viral pneumonia better than CRP alone. Further studies are required to explore combination of biomarkers and symptoms for use as definitive diagnostic tool.
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Literature
1.
go back to reference Walker CL, Rudan I, Liu L, Nair H, Theodoratou E, Bhutta ZA, et al. Global burden of childhood pneumonia and diarrhoea. Lancet. 2013;381(9875):1405–16.CrossRef Walker CL, Rudan I, Liu L, Nair H, Theodoratou E, Bhutta ZA, et al. Global burden of childhood pneumonia and diarrhoea. Lancet. 2013;381(9875):1405–16.CrossRef
2.
go back to reference Burgner D, Richmond P. The burden of pneumonia in children: an Australian perspective. Paediatr Respir Rev. 2005;6(2):94–100.CrossRef Burgner D, Richmond P. The burden of pneumonia in children: an Australian perspective. Paediatr Respir Rev. 2005;6(2):94–100.CrossRef
3.
go back to reference Moore H, Burgner D, Carville K, Jacoby P, Richmond P, Lehmann D. Diverging trends for lower respiratory infections in non-aboriginal and aboriginal children. J Paediatr Child Health. 2007;43(6):451–7.CrossRef Moore H, Burgner D, Carville K, Jacoby P, Richmond P, Lehmann D. Diverging trends for lower respiratory infections in non-aboriginal and aboriginal children. J Paediatr Child Health. 2007;43(6):451–7.CrossRef
4.
go back to reference McIntosh K. Community-acquired pneumonia in children. N Engl J Med. 2002;346(6):429–37.CrossRef McIntosh K. Community-acquired pneumonia in children. N Engl J Med. 2002;346(6):429–37.CrossRef
5.
go back to reference Huijskens EG, Koopmans M, Palmen FM, van Erkel AJ, Mulder PG, Rossen JW. The value of signs and symptoms in differentiating between bacterial, viral and mixed aetiology in patients with community-acquired pneumonia. J Med Microbiol. 2014;63(Pt 3):441–52.CrossRef Huijskens EG, Koopmans M, Palmen FM, van Erkel AJ, Mulder PG, Rossen JW. The value of signs and symptoms in differentiating between bacterial, viral and mixed aetiology in patients with community-acquired pneumonia. J Med Microbiol. 2014;63(Pt 3):441–52.CrossRef
6.
go back to reference Isaacs D. Problems in determining the etiology of community-acquired childhood pneumonia. Pediatr Infect Dis J. 1989;8(3):143–8.PubMed Isaacs D. Problems in determining the etiology of community-acquired childhood pneumonia. Pediatr Infect Dis J. 1989;8(3):143–8.PubMed
7.
go back to reference Flood RG, Badik J, Aronoff SC. The utility of serum C-reactive protein in differentiating bacterial from nonbacterial pneumonia in children: a meta-analysis of 1230 children. Pediatr Infect Dis J. 2008;27(2):95–9.PubMed Flood RG, Badik J, Aronoff SC. The utility of serum C-reactive protein in differentiating bacterial from nonbacterial pneumonia in children: a meta-analysis of 1230 children. Pediatr Infect Dis J. 2008;27(2):95–9.PubMed
8.
go back to reference Korppi M, Heiskanen-Kosma T, Leinonen M. White blood cells, C-reactive protein and erythrocyte sedimentation rate in pneumococcal pneumonia in children. Eur Respir J. 1997;10(5):1125–9.CrossRef Korppi M, Heiskanen-Kosma T, Leinonen M. White blood cells, C-reactive protein and erythrocyte sedimentation rate in pneumococcal pneumonia in children. Eur Respir J. 1997;10(5):1125–9.CrossRef
9.
go back to reference Elemraid MA, Rushton SP, Thomas MF, Spencer DA, Gennery AR, Clark JE. Utility of inflammatory markers in predicting the aetiology of pneumonia in children. Diagn Microbiol Infect Dis. 2014;79(4):458–62.CrossRef Elemraid MA, Rushton SP, Thomas MF, Spencer DA, Gennery AR, Clark JE. Utility of inflammatory markers in predicting the aetiology of pneumonia in children. Diagn Microbiol Infect Dis. 2014;79(4):458–62.CrossRef
10.
go back to reference Higdon MM, Le T, O'Brien KL, Murdoch DR, Prosperi C, Baggett HC, et al. Association of C-Reactive Protein With Bacterial and Respiratory Syncytial Virus-Associated Pneumonia Among Children Aged <5 Years in the PERCH Study. Clin Infect Dis. 2017;64(suppl_3):S378–S86.CrossRef Higdon MM, Le T, O'Brien KL, Murdoch DR, Prosperi C, Baggett HC, et al. Association of C-Reactive Protein With Bacterial and Respiratory Syncytial Virus-Associated Pneumonia Among Children Aged <5 Years in the PERCH Study. Clin Infect Dis. 2017;64(suppl_3):S378–S86.CrossRef
11.
go back to reference Berg AS, Inchley CS, Fjaerli HO, Leegaard TM, Lindbaek M, Nakstad B. Clinical features and inflammatory markers in pediatric pneumonia: a prospective study. Eur J Pediatr. 2017;176(5):629–38.CrossRef Berg AS, Inchley CS, Fjaerli HO, Leegaard TM, Lindbaek M, Nakstad B. Clinical features and inflammatory markers in pediatric pneumonia: a prospective study. Eur J Pediatr. 2017;176(5):629–38.CrossRef
12.
go back to reference Heiskanen-Kosma T, Korppi M. Serum C-reactive protein cannot differentiate bacterial and viral aetiology of community-acquired pneumonia in children in primary healthcare settings. Scand J Infect Dis. 2000;32(4):399–402.CrossRef Heiskanen-Kosma T, Korppi M. Serum C-reactive protein cannot differentiate bacterial and viral aetiology of community-acquired pneumonia in children in primary healthcare settings. Scand J Infect Dis. 2000;32(4):399–402.CrossRef
13.
go back to reference Korppi M. Non-specific host response markers in the differentiation between pneumococcal and viral pneumonia: what is the most accurate combination? Pediatr Int. 2004;46(5):545–50.CrossRef Korppi M. Non-specific host response markers in the differentiation between pneumococcal and viral pneumonia: what is the most accurate combination? Pediatr Int. 2004;46(5):545–50.CrossRef
14.
go back to reference Virkki R, Juven T, Rikalainen H, Svedstrom E, Mertsola J, Ruuskanen O. Differentiation of bacterial and viral pneumonia in children. Thorax. 2002;57(5):438–41.CrossRef Virkki R, Juven T, Rikalainen H, Svedstrom E, Mertsola J, Ruuskanen O. Differentiation of bacterial and viral pneumonia in children. Thorax. 2002;57(5):438–41.CrossRef
15.
go back to reference Berg AS, Inchley CS, Aase A, Fjaerli HO, Bull R, Aaberge I, et al. Etiology of pneumonia in a pediatric population with high pneumococcal vaccine coverage: a prospective study. Pediatr Infect Dis J. 2016;35(3):e69–75.CrossRef Berg AS, Inchley CS, Aase A, Fjaerli HO, Bull R, Aaberge I, et al. Etiology of pneumonia in a pediatric population with high pneumococcal vaccine coverage: a prospective study. Pediatr Infect Dis J. 2016;35(3):e69–75.CrossRef
16.
go back to reference Jain S, Williams DJ, Arnold SR, Ampofo K, Bramley AM, Reed C, et al. Community-acquired pneumonia requiring hospitalization among U.S. children. N Engl J Med. 2015;372(9):835–45.CrossRef Jain S, Williams DJ, Arnold SR, Ampofo K, Bramley AM, Reed C, et al. Community-acquired pneumonia requiring hospitalization among U.S. children. N Engl J Med. 2015;372(9):835–45.CrossRef
17.
go back to reference Bhuiyan MU, Snelling TL, West R, Lang J, Rahman T, Borland ML, et al. Role of viral and bacterial pathogens in causing pneumonia among Western Australian children: a case-control study protocol. BMJ Open. 2018;8(3):e020646.CrossRef Bhuiyan MU, Snelling TL, West R, Lang J, Rahman T, Borland ML, et al. Role of viral and bacterial pathogens in causing pneumonia among Western Australian children: a case-control study protocol. BMJ Open. 2018;8(3):e020646.CrossRef
18.
go back to reference Cherian T, Mulholland EK, Carlin JB, Ostensen H, Amin R, de Campo M, et al. Standardized interpretation of paediatric chest radiographs for the diagnosis of pneumonia in epidemiological studies. Bull World Health Organ. 2005;83(5):353–9.PubMedPubMedCentral Cherian T, Mulholland EK, Carlin JB, Ostensen H, Amin R, de Campo M, et al. Standardized interpretation of paediatric chest radiographs for the diagnosis of pneumonia in epidemiological studies. Bull World Health Organ. 2005;83(5):353–9.PubMedPubMedCentral
19.
go back to reference World Health Organization (WHO). Manual for the Laboratory Identification and Antimicrobial Susceptibility Testing of Bacterial Pathogens of Public Health Importance in the Developing World. 2003. World Health Organization (WHO). Manual for the Laboratory Identification and Antimicrobial Susceptibility Testing of Bacterial Pathogens of Public Health Importance in the Developing World. 2003.
20.
go back to reference World Health Organization (WHO). The mangement of acute respiratory infections in children: practical guidelines for outpatient care. 1995. World Health Organization (WHO). The mangement of acute respiratory infections in children: practical guidelines for outpatient care. 1995.
21.
go back to reference Reed C, Madhi SA, Klugman KP, Kuwanda L, Ortiz JR, Finelli L, et al. Development of the respiratory index of severity in children (RISC) score among young children with respiratory infections in South Africa. PLoS One. 2012;7(1):e27793.CrossRef Reed C, Madhi SA, Klugman KP, Kuwanda L, Ortiz JR, Finelli L, et al. Development of the respiratory index of severity in children (RISC) score among young children with respiratory infections in South Africa. PLoS One. 2012;7(1):e27793.CrossRef
22.
go back to reference Carter JV, Pan J, Rai SN, Galandiuk S. ROC-ing along: evaluation and interpretation of receiver operating characteristic curves. Surgery. 2016;159(6):1638–45.CrossRef Carter JV, Pan J, Rai SN, Galandiuk S. ROC-ing along: evaluation and interpretation of receiver operating characteristic curves. Surgery. 2016;159(6):1638–45.CrossRef
23.
24.
go back to reference Korppi M, Don M, Valent F, Canciani M. The value of clinical features in differentiating between viral, pneumococcal and atypical bacterial pneumonia in children. Acta Paediatr. 2008;97(7):943–7.CrossRef Korppi M, Don M, Valent F, Canciani M. The value of clinical features in differentiating between viral, pneumococcal and atypical bacterial pneumonia in children. Acta Paediatr. 2008;97(7):943–7.CrossRef
25.
go back to reference Ruuskanen O, Lahti E, Jennings LC, Murdoch DR. Viral pneumonia. Lancet. 2011;377(9773):1264–75.CrossRef Ruuskanen O, Lahti E, Jennings LC, Murdoch DR. Viral pneumonia. Lancet. 2011;377(9773):1264–75.CrossRef
26.
go back to reference Juven T, Ruuskanen O, Mertsola J. Symptoms and signs of community-acquired pneumonia in children. Scand J Prim Health Care. 2003;21(1):52–6.CrossRef Juven T, Ruuskanen O, Mertsola J. Symptoms and signs of community-acquired pneumonia in children. Scand J Prim Health Care. 2003;21(1):52–6.CrossRef
27.
go back to reference Wei L, Liu W, Zhang XA, Liu EM, Wo Y, Cowling BJ, et al. Detection of viral and bacterial pathogens in hospitalized children with acute respiratory illnesses, Chongqing, 2009-2013. Medicine (Baltimore). 2015;94(16):e742.CrossRef Wei L, Liu W, Zhang XA, Liu EM, Wo Y, Cowling BJ, et al. Detection of viral and bacterial pathogens in hospitalized children with acute respiratory illnesses, Chongqing, 2009-2013. Medicine (Baltimore). 2015;94(16):e742.CrossRef
28.
go back to reference Korppi M, Kiekara O, Heiskanen-Kosma T, Soimakallio S. Comparison of radiological findings and microbial aetiology of childhood pneumonia. Acta Paediatr. 1993;82(4):360–3.CrossRef Korppi M, Kiekara O, Heiskanen-Kosma T, Soimakallio S. Comparison of radiological findings and microbial aetiology of childhood pneumonia. Acta Paediatr. 1993;82(4):360–3.CrossRef
29.
go back to reference O'Grady KA, Torzilo PJ, Frawley K, Chang AB. The radiological diagnosis of pneumonia in children. Pneumonia. 2014;5:38–51.CrossRef O'Grady KA, Torzilo PJ, Frawley K, Chang AB. The radiological diagnosis of pneumonia in children. Pneumonia. 2014;5:38–51.CrossRef
30.
go back to reference 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. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 2004;39(2):206–17.CrossRef 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. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 2004;39(2):206–17.CrossRef
31.
go back to reference Agnello L, Bellia C, Di Gangi M, Lo Sasso B, Calvaruso L, Bivona G, et al. Utility of serum procalcitonin and C-reactive protein in severity assessment of community-acquired pneumonia in children. Clin Biochem. 2016;49(1):47–50.CrossRef Agnello L, Bellia C, Di Gangi M, Lo Sasso B, Calvaruso L, Bivona G, et al. Utility of serum procalcitonin and C-reactive protein in severity assessment of community-acquired pneumonia in children. Clin Biochem. 2016;49(1):47–50.CrossRef
32.
go back to reference Fan RR, Howard LM, Griffin MR, Edwards KM, Zhu Y, Williams JV, et al. Nasopharyngeal pneumococcal density and evolution of acute respiratory illnesses in young children, Peru, 2009-2011. Emerg Infect Dis. 2016;22(11):1996–9.CrossRef Fan RR, Howard LM, Griffin MR, Edwards KM, Zhu Y, Williams JV, et al. Nasopharyngeal pneumococcal density and evolution of acute respiratory illnesses in young children, Peru, 2009-2011. Emerg Infect Dis. 2016;22(11):1996–9.CrossRef
33.
go back to reference Rhedin S, Lindstrand A, Hjelmgren A, Ryd-Rinder M, Ohrmalm L, Tolfvenstam T, et al. Respiratory viruses associated with community-acquired pneumonia in children: matched case-control study. Thorax. 2015;70(9):847–53.CrossRef Rhedin S, Lindstrand A, Hjelmgren A, Ryd-Rinder M, Ohrmalm L, Tolfvenstam T, et al. Respiratory viruses associated with community-acquired pneumonia in children: matched case-control study. Thorax. 2015;70(9):847–53.CrossRef
34.
go back to reference Clark JE. Determining the microbiological cause of a chest infection. Arch Dis Child. 2015;100(2):193–7.CrossRef Clark JE. Determining the microbiological cause of a chest infection. Arch Dis Child. 2015;100(2):193–7.CrossRef
35.
go back to reference Murdoch DR, Morpeth SC, Hammitt LL, Driscoll AJ, Watson NL, Baggett HC, et al. The Diagnostic Utility of Induced Sputum Microscopy and Culture in Childhood Pneumonia. Clin Infect Dis. 2017;64(suppl_3):S280–S8.CrossRef Murdoch DR, Morpeth SC, Hammitt LL, Driscoll AJ, Watson NL, Baggett HC, et al. The Diagnostic Utility of Induced Sputum Microscopy and Culture in Childhood Pneumonia. Clin Infect Dis. 2017;64(suppl_3):S280–S8.CrossRef
36.
go back to reference World Health Organization (WHO). Global antimicrobial resistance surveillance system (GLASS) report: early implementation 2016-2017. 2017. World Health Organization (WHO). Global antimicrobial resistance surveillance system (GLASS) report: early implementation 2016-2017. 2017.
Metadata
Title
Combination of clinical symptoms and blood biomarkers can improve discrimination between bacterial or viral community-acquired pneumonia in children
Authors
Mejbah U. Bhuiyan
Christopher C. Blyth
Rachel West
Jurissa Lang
Tasmina Rahman
Caitlyn Granland
Camilla de Gier
Meredith L. Borland
Ruth B. Thornton
Lea-Ann S. Kirkham
Andrew Martin
Peter C. Richmond
David W. Smith
Adam Jaffe
Thomas L. Snelling
Publication date
01-12-2019
Publisher
BioMed Central
Published in
BMC Pulmonary Medicine / Issue 1/2019
Electronic ISSN: 1471-2466
DOI
https://doi.org/10.1186/s12890-019-0835-5

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