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Published in: European Journal of Clinical Microbiology & Infectious Diseases 10/2017

Open Access 01-10-2017 | Original Article

Respiratory viral infections are underdiagnosed in patients with suspected sepsis

Authors: L. R. Ljungström, G. Jacobsson, B. E. B. Claesson, R. Andersson, H. Enroth

Published in: European Journal of Clinical Microbiology & Infectious Diseases | Issue 10/2017

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Abstract

The study aim was to investigate the prevalence and clinical relevance of viral findings by multiplex PCR from the nasopharynx of clinically septic patients during a winter season. During 11 weeks of the influenza epidemic period in January–March 2012, consecutive adult patients suspected to be septic (n = 432) were analyzed with cultures from blood and nasopharynx plus multiplex PCR for respiratory viruses on the nasopharyngeal specimen. The results were compared with those from microbiology analyses ordered as part of standard care. During the winter season, viral respiratory pathogens, mainly influenza A virus, human metapneumovirus, coronavirus, and respiratory syncytial virus were clinically underdiagnosed in 70% of patients positive by the multiplex PCR assay. During the first four weeks of the influenza epidemic, few tests for influenza were ordered by clinicians, indicating low awareness that the epidemic had started. Nasopharyngeal findings of Streptococcus pneumoniae and Haemophilus influenzae by culture correlated to pneumonia diagnosis, and in those patients laboratory signs of viral co-infections were common but rarely suspected by clinicians. The role of respiratory viral infections in patients presenting with a clinical picture of sepsis is underestimated. Specific antiviral treatment might be beneficial in some cases and may reduce spread in a hospital setting. Diagnosing viral infections may promote reduction of unnecessary antibiotic use. It can also be a tool for decisions concerning patient logistics, in order to minimize exposure of susceptible patients and personnel.
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Literature
1.
go back to reference Jain S, Self WH, Wunderink RG, Fakhran S, Balk R, Bramley AM, Reed C, Grijalva CG, Anderson EJ, Courtney DM, Chappell JD, Qi C, Hart EM, Carroll F, Trabue C, Donnelly HK, Williams DJ, Zhu Y, Arnold SR, Ampofo K, Waterer GW, Levine M, Lindstrom S, Winchell JM, Katz JM, Erdman D, Schneider E, Hicks LA, McCullers JA, Pavia AT, Edwards KM, Finelli L (2015) Community-acquired pneumonia requiring hospitalization among U.S. adults. N Engl J Med 373(5):415–427CrossRefPubMedPubMedCentral Jain S, Self WH, Wunderink RG, Fakhran S, Balk R, Bramley AM, Reed C, Grijalva CG, Anderson EJ, Courtney DM, Chappell JD, Qi C, Hart EM, Carroll F, Trabue C, Donnelly HK, Williams DJ, Zhu Y, Arnold SR, Ampofo K, Waterer GW, Levine M, Lindstrom S, Winchell JM, Katz JM, Erdman D, Schneider E, Hicks LA, McCullers JA, Pavia AT, Edwards KM, Finelli L (2015) Community-acquired pneumonia requiring hospitalization among U.S. adults. N Engl J Med 373(5):415–427CrossRefPubMedPubMedCentral
2.
go back to reference Johansson N, Kalin M, Tiveljung-Lindell A, Giske CG, Hedlund J (2010) Etiology of community-acquired pneumonia: increased microbiological yield with new diagnostic methods. Clin Infect Dis 50(2):202–209CrossRefPubMed Johansson N, Kalin M, Tiveljung-Lindell A, Giske CG, Hedlund J (2010) Etiology of community-acquired pneumonia: increased microbiological yield with new diagnostic methods. Clin Infect Dis 50(2):202–209CrossRefPubMed
3.
go back to reference Cillóniz C, Ewig S, Polverino E, Marcos MA, Esquinas C, Gabarrús A, Mensa J, Torres A (2011) Microbial aetiology of community-acquired pneumonia and its relation to severity. Thorax 66(4):340–346CrossRefPubMed Cillóniz C, Ewig S, Polverino E, Marcos MA, Esquinas C, Gabarrús A, Mensa J, Torres A (2011) Microbial aetiology of community-acquired pneumonia and its relation to severity. Thorax 66(4):340–346CrossRefPubMed
4.
go back to reference Mahony JB, Petrich A, Smieja M (2011) Molecular diagnosis of respiratory virus infections. Crit Rev Clin Lab Sci 48(5–6):217–249CrossRefPubMed Mahony JB, Petrich A, Smieja M (2011) Molecular diagnosis of respiratory virus infections. Crit Rev Clin Lab Sci 48(5–6):217–249CrossRefPubMed
5.
go back to reference Johansson N, Kalin M, Hedlund J (2011) Clinical impact of combined viral and bacterial infection in patients with community-acquired pneumonia. Scand J Infect Dis 43(8):609–615CrossRefPubMed Johansson N, Kalin M, Hedlund J (2011) Clinical impact of combined viral and bacterial infection in patients with community-acquired pneumonia. Scand J Infect Dis 43(8):609–615CrossRefPubMed
6.
7.
go back to reference Brittain-Long R, Andersson L-M, Olofsson S, Lindh M, Westin J (2012) Seasonal variations of 15 respiratory agents illustrated by the application of a multiplex polymerase chain reaction assay. Scand J Infect Dis 44(1):9–17CrossRefPubMed Brittain-Long R, Andersson L-M, Olofsson S, Lindh M, Westin J (2012) Seasonal variations of 15 respiratory agents illustrated by the application of a multiplex polymerase chain reaction assay. Scand J Infect Dis 44(1):9–17CrossRefPubMed
8.
go back to reference Smith CM, Sandrini S, Datta S, Freestone P, Shafeeq S, Radhakrishnan P, Williams G, Glenn SM, Kuipers OP, Hirst RA (2014) Respiratory syncytial virus increases the virulence of Streptococcus Pneumoniae by binding to penicillin binding protein 1a. A new paradigm in respiratory infection. Am J Respir Crit Care Med 190(2):196–207CrossRefPubMedPubMedCentral Smith CM, Sandrini S, Datta S, Freestone P, Shafeeq S, Radhakrishnan P, Williams G, Glenn SM, Kuipers OP, Hirst RA (2014) Respiratory syncytial virus increases the virulence of Streptococcus Pneumoniae by binding to penicillin binding protein 1a. A new paradigm in respiratory infection. Am J Respir Crit Care Med 190(2):196–207CrossRefPubMedPubMedCentral
9.
go back to reference Wolf AI, Strauman MC, Mozdzanowska K, Whittle JR, Williams KL, Sharpe AH, Weiser JN, Caton AJ, Hensley SE, Erikson J (2014) Coinfection with Streptococcus Pneumoniae modulates the B cell response to influenza virus. J Virol 88(20):11995–12005CrossRefPubMedPubMedCentral Wolf AI, Strauman MC, Mozdzanowska K, Whittle JR, Williams KL, Sharpe AH, Weiser JN, Caton AJ, Hensley SE, Erikson J (2014) Coinfection with Streptococcus Pneumoniae modulates the B cell response to influenza virus. J Virol 88(20):11995–12005CrossRefPubMedPubMedCentral
10.
go back to reference Lee KH, Gordon A, Foxman B (2016) The role of respiratory viruses in the etiology of bacterial pneumonia an ecological perspective. Evol Med Public Health 2016(1):95–109CrossRefPubMedPubMedCentral Lee KH, Gordon A, Foxman B (2016) The role of respiratory viruses in the etiology of bacterial pneumonia an ecological perspective. Evol Med Public Health 2016(1):95–109CrossRefPubMedPubMedCentral
11.
go back to reference Mina M, Burke R, Klugman K (2014) Estimating the prevalence of coinfection with influenza virus and the atypical bacteria Bordetella pertussis, Chlamydophila pneumoniae, and Mycoplasma pneumoniae. Eur J Clin Microbiol Infect Dis 33(9):1585–1589CrossRefPubMedPubMedCentral Mina M, Burke R, Klugman K (2014) Estimating the prevalence of coinfection with influenza virus and the atypical bacteria Bordetella pertussis, Chlamydophila pneumoniae, and Mycoplasma pneumoniae. Eur J Clin Microbiol Infect Dis 33(9):1585–1589CrossRefPubMedPubMedCentral
12.
go back to reference Burk M, El-Kersh K, Saad M, Wiemken T, Ramirez J, Cavallazzi R (2016) Viral infection in community-acquired pneumonia: a systematic review and meta-analysis. Eur Respir Rev 25(140):178–188CrossRefPubMed Burk M, El-Kersh K, Saad M, Wiemken T, Ramirez J, Cavallazzi R (2016) Viral infection in community-acquired pneumonia: a systematic review and meta-analysis. Eur Respir Rev 25(140):178–188CrossRefPubMed
13.
go back to reference Voiriot G, Visseaux B, Cohen J, Nguyen LBL, Neuville M, Morbieu C, Burdet C, Radjou A, Lescure F-X, Smonig R (2016) Viral-bacterial coinfection affects the presentation and alters the prognosis of severe community-acquired pneumonia. Crit Care 20(1):375CrossRefPubMedPubMedCentral Voiriot G, Visseaux B, Cohen J, Nguyen LBL, Neuville M, Morbieu C, Burdet C, Radjou A, Lescure F-X, Smonig R (2016) Viral-bacterial coinfection affects the presentation and alters the prognosis of severe community-acquired pneumonia. Crit Care 20(1):375CrossRefPubMedPubMedCentral
14.
go back to reference Rappo U, Schuetz AN, Jenkins SG, Calfee DP, Walsh TJ, Wells MT, Hollenberg JP, Glesby MJ (2016) Impact of early detection of respiratory viruses by multiplex PCR on clinical outcomes in adult patients. J Clin Microbiol: JCM. doi:10.1128/JCM.00549-16 Rappo U, Schuetz AN, Jenkins SG, Calfee DP, Walsh TJ, Wells MT, Hollenberg JP, Glesby MJ (2016) Impact of early detection of respiratory viruses by multiplex PCR on clinical outcomes in adult patients. J Clin Microbiol: JCM. doi:10.​1128/​JCM.​00549-16
15.
go back to reference Reddington K, Tuite N, Barry T, O’Grady J, Zumla A (2013) Advances in multiparametric molecular diagnostics technologies for respiratory tract infections. Curr Opin Pulm Med 19(3):298–304CrossRefPubMed Reddington K, Tuite N, Barry T, O’Grady J, Zumla A (2013) Advances in multiparametric molecular diagnostics technologies for respiratory tract infections. Curr Opin Pulm Med 19(3):298–304CrossRefPubMed
16.
go back to reference Esposito S, Principi N (2017) The role of the NxTAG® respiratory pathogen panel assay and other multiplex platforms in clinical practice. Exp Rev Mol Diagn 17(1):9–17 Esposito S, Principi N (2017) The role of the NxTAG® respiratory pathogen panel assay and other multiplex platforms in clinical practice. Exp Rev Mol Diagn 17(1):9–17
17.
go back to reference Andersson ME, Olofsson S, Lindh M (2014) Comparison of the FilmArray assay and in-house real-time PCR for detection of respiratory infection. Scand J Infect Dis 46(12):897–901CrossRefPubMed Andersson ME, Olofsson S, Lindh M (2014) Comparison of the FilmArray assay and in-house real-time PCR for detection of respiratory infection. Scand J Infect Dis 46(12):897–901CrossRefPubMed
18.
go back to reference Green DA, Hitoaliaj L, Kotansky B, Campbell SM, Peaper DR (2016) Clinical utility of on-demand multiplex respiratory pathogen testing among adult outpatients. J Clin Microbiol 54(12):2950–2955CrossRefPubMedPubMedCentral Green DA, Hitoaliaj L, Kotansky B, Campbell SM, Peaper DR (2016) Clinical utility of on-demand multiplex respiratory pathogen testing among adult outpatients. J Clin Microbiol 54(12):2950–2955CrossRefPubMedPubMedCentral
19.
go back to reference Brittain-Long R, Westin J, Olofsson S, Lindh M, Andersson L-M (2010) Prospective evaluation of a novel multiplex real-time PCR assay for detection of fifteen respiratory pathogens—duration of symptoms significantly affects detection rate. J Clin Virol 47(3):263–267CrossRefPubMed Brittain-Long R, Westin J, Olofsson S, Lindh M, Andersson L-M (2010) Prospective evaluation of a novel multiplex real-time PCR assay for detection of fifteen respiratory pathogens—duration of symptoms significantly affects detection rate. J Clin Virol 47(3):263–267CrossRefPubMed
20.
go back to reference Jartti T, Lehtinen P, Vuorinen T, Koskenvuo M, Ruuskanen O (2004) Persistence of rhinovirus and enterovirus RNA after acute respiratory illness in children. J Med Virol 72(4):695–699CrossRefPubMed Jartti T, Lehtinen P, Vuorinen T, Koskenvuo M, Ruuskanen O (2004) Persistence of rhinovirus and enterovirus RNA after acute respiratory illness in children. J Med Virol 72(4):695–699CrossRefPubMed
21.
go back to reference Wiemken T, Peyrani P, Bryant K, Kelley R, Summersgill J, Arnold F, Carrico R, McKinney W, Jonsson C, Carrico K (2013) Incidence of respiratory viruses in patients with community-acquired pneumonia admitted to the intensive care unit: results from the severe influenza pneumonia surveillance (SIPS) project. Eur J Clin Microbiol Infect Dis 32(5):705–710CrossRefPubMed Wiemken T, Peyrani P, Bryant K, Kelley R, Summersgill J, Arnold F, Carrico R, McKinney W, Jonsson C, Carrico K (2013) Incidence of respiratory viruses in patients with community-acquired pneumonia admitted to the intensive care unit: results from the severe influenza pneumonia surveillance (SIPS) project. Eur J Clin Microbiol Infect Dis 32(5):705–710CrossRefPubMed
22.
go back to reference Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, Bellomo R, Bernard GR, Chiche J-D, Coopersmith CM (2016) The third international consensus definitions for sepsis and septic shock (sepsis-3). JAMA 315(8):801–810CrossRefPubMedPubMedCentral Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, Bellomo R, Bernard GR, Chiche J-D, Coopersmith CM (2016) The third international consensus definitions for sepsis and septic shock (sepsis-3). JAMA 315(8):801–810CrossRefPubMedPubMedCentral
23.
go back to reference Edman-Wallér J, Ljungström L, Jacobsson G, Andersson R, Werner M (2016) Systemic symptoms predict presence or development of severe sepsis and septic shock. Infectious Diseases 48(3):209–214CrossRefPubMed Edman-Wallér J, Ljungström L, Jacobsson G, Andersson R, Werner M (2016) Systemic symptoms predict presence or development of severe sepsis and septic shock. Infectious Diseases 48(3):209–214CrossRefPubMed
24.
go back to reference Denis E, Martis N, Guillouet-de Salvador F, Demonchy E, Degand N, Carles K, Roger P-M (2016) Bacteraemic urinary tract infections may mimic respiratory infections: a nested case–control study. Eur J Clin Microbiol Infect Dis 35:1601–1605CrossRefPubMed Denis E, Martis N, Guillouet-de Salvador F, Demonchy E, Degand N, Carles K, Roger P-M (2016) Bacteraemic urinary tract infections may mimic respiratory infections: a nested case–control study. Eur J Clin Microbiol Infect Dis 35:1601–1605CrossRefPubMed
25.
go back to reference Ljungström LR, Steinum O, Brink M, Gårdlund B, Martner J, Sjölin J (2011) Diagnostik och diagnoskodning av svår sepsis och septisk chock. ICD10 bör kompletteras med tilläggskoder Läkartidning en 108:276 Ljungström LR, Steinum O, Brink M, Gårdlund B, Martner J, Sjölin J (2011) Diagnostik och diagnoskodning av svår sepsis och septisk chock. ICD10 bör kompletteras med tilläggskoder Läkartidning en 108:276
26.
go back to reference Loens K, Van Heirstraeten L, Malhotra-Kumar S, Goossens H, Ieven M (2009) Optimal sampling sites and methods for detection of pathogens possibly causing community-acquired lower respiratory tract infections. J Clin Microbiol 47(1):21–31CrossRefPubMed Loens K, Van Heirstraeten L, Malhotra-Kumar S, Goossens H, Ieven M (2009) Optimal sampling sites and methods for detection of pathogens possibly causing community-acquired lower respiratory tract infections. J Clin Microbiol 47(1):21–31CrossRefPubMed
28.
go back to reference Falsey AR, Becker KL, Swinburne AJ, Nylen ES, Formica MA, Hennessey PA, Criddle MM, Peterson DR, Baran A, Walsh EE (2013) Bacterial complications of respiratory tract viral illness: a comprehensive evaluation. J Infect Dis 208(3):432–441CrossRefPubMedPubMedCentral Falsey AR, Becker KL, Swinburne AJ, Nylen ES, Formica MA, Hennessey PA, Criddle MM, Peterson DR, Baran A, Walsh EE (2013) Bacterial complications of respiratory tract viral illness: a comprehensive evaluation. J Infect Dis 208(3):432–441CrossRefPubMedPubMedCentral
29.
go back to reference Boivin G, De Serres G, Hamelin M-E, Côté S, Argouin M, Tremblay G, Maranda-Aubut R, Sauvageau C, Ouakki M, Boulianne N (2007) An outbreak of severe respiratory tract infection due to human metapneumovirus in a long-term care facility. Clin Infect Dis 44(9):1152–1158CrossRefPubMed Boivin G, De Serres G, Hamelin M-E, Côté S, Argouin M, Tremblay G, Maranda-Aubut R, Sauvageau C, Ouakki M, Boulianne N (2007) An outbreak of severe respiratory tract infection due to human metapneumovirus in a long-term care facility. Clin Infect Dis 44(9):1152–1158CrossRefPubMed
30.
go back to reference Strålin K, Törnqvist E, Kaltoft MS, Olcén P, Holmberg H (2006) Etiologic diagnosis of adult bacterial pneumonia by culture and PCR applied to respiratory tract samples. J Clin Microbiol 44(2):643–645CrossRefPubMedPubMedCentral Strålin K, Törnqvist E, Kaltoft MS, Olcén P, Holmberg H (2006) Etiologic diagnosis of adult bacterial pneumonia by culture and PCR applied to respiratory tract samples. J Clin Microbiol 44(2):643–645CrossRefPubMedPubMedCentral
31.
go back to reference Bjarnason A, Lindh M, Westin J, Andersson L-M, Baldursson O, Kristinsson K, Gottfredsson M (2016) Utility of oropharyngeal real-time PCR for S. pneumoniae and H. influenzae for diagnosis of pneumonia in adults. Eur J Clin Microbiol Infect Dis 36:529–536 1–8CrossRefPubMedPubMedCentral Bjarnason A, Lindh M, Westin J, Andersson L-M, Baldursson O, Kristinsson K, Gottfredsson M (2016) Utility of oropharyngeal real-time PCR for S. pneumoniae and H. influenzae for diagnosis of pneumonia in adults. Eur J Clin Microbiol Infect Dis 36:529–536 1–8CrossRefPubMedPubMedCentral
32.
go back to reference Herberg JA, Kaforou M, Wright VJ, Shailes H, Eleftherohorinou H, Hoggart CJ, Cebey-López M, Carter MJ, Janes VA, Gormley S (2016) Diagnostic test accuracy of a 2-transcript host RNA signature for discriminating bacterial vs viral infection in febrile children. JAMA 316(8):835–845CrossRefPubMed Herberg JA, Kaforou M, Wright VJ, Shailes H, Eleftherohorinou H, Hoggart CJ, Cebey-López M, Carter MJ, Janes VA, Gormley S (2016) Diagnostic test accuracy of a 2-transcript host RNA signature for discriminating bacterial vs viral infection in febrile children. JAMA 316(8):835–845CrossRefPubMed
33.
go back to reference Suarez NM, Bunsow E, Falsey AR, Walsh EE, Mejias A, Ramilo O (2015) Superiority of transcriptional profiling over procalcitonin for distinguishing bacterial from viral lower respiratory tract infections in hospitalized adults. J Infect Dis 212(2):213–222CrossRefPubMedPubMedCentral Suarez NM, Bunsow E, Falsey AR, Walsh EE, Mejias A, Ramilo O (2015) Superiority of transcriptional profiling over procalcitonin for distinguishing bacterial from viral lower respiratory tract infections in hospitalized adults. J Infect Dis 212(2):213–222CrossRefPubMedPubMedCentral
34.
go back to reference Santolaya ME, Alvarez AM, Acuña M, Avilés CL, Salgado C, Tordecilla J, Varas M, Venegas M, Villarroel M, Zubieta M (2016) Efficacy and safety of withholding antimicrobial treatment in children with cancer, fever and neutropenia, with a demonstrated viral respiratory infection: a randomized clinical trial. Clin Microbiol Infect 23:173–178CrossRefPubMed Santolaya ME, Alvarez AM, Acuña M, Avilés CL, Salgado C, Tordecilla J, Varas M, Venegas M, Villarroel M, Zubieta M (2016) Efficacy and safety of withholding antimicrobial treatment in children with cancer, fever and neutropenia, with a demonstrated viral respiratory infection: a randomized clinical trial. Clin Microbiol Infect 23:173–178CrossRefPubMed
Metadata
Title
Respiratory viral infections are underdiagnosed in patients with suspected sepsis
Authors
L. R. Ljungström
G. Jacobsson
B. E. B. Claesson
R. Andersson
H. Enroth
Publication date
01-10-2017
Publisher
Springer Berlin Heidelberg
Published in
European Journal of Clinical Microbiology & Infectious Diseases / Issue 10/2017
Print ISSN: 0934-9723
Electronic ISSN: 1435-4373
DOI
https://doi.org/10.1007/s10096-017-2990-z

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