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High pneumococcal DNA load, procalcitonin and suPAR levels correlate to severe disease development in patients with pneumococcal pneumonia

Abstract

Community-acquired pneumonia (CAP) is mostly caused by Streptococcus pneumoniae. Identification of the pathogen causing CAP can be achieved by conventional culture techniques of sputum and/or blood, antigen detection from urine or molecular analysis. However, it remains difficult to determine patients who are at risk of severe disease development (intensive care unit [ICU] admittance and/or death). In this retrospective study, 121 patients admitted to the emergency department with pneumonia symptoms were included. Several markers of infection (pneumococcal DNA load in blood (real-time LytA PCR), white blood cell (WBC) count, C-reactive protein (CRP), procalcitonin (PCT) and soluble urokinase plasminogen activator receptor (suPAR) levels) were assessed for their ability to predict severe disease development. Of 121 patients, 6 were excluded from the study because of an alternative diagnosis, whereas 8 were excluded from biomarker analysis because of the presence of co-morbidities. Of the 115 patients analysed by the LytA PCR, 23 were positive. PCR detected S. pneumoniae DNA in 82% of patients with positive blood culture for S. pneumoniae. PCR missed three samples from patients in which S. pneumoniae was recovered by blood cultures. However, eight additional LytA PCR-positive samples were detected from patients whose blood cultures remained negative. Pneumococcal DNA load was also monitored in time for 31 patients, of whom 11 had positive PCR results. For 10 out of 11 (91%) positive PCR patients, a clear increase in Ct-values was observed, indicating a lower pneumococcal DNA load in the blood as a result of antibiotic therapy. Biomarker analysis was performed in 107 patients, of whom 29 showed severe disease development. Pneumococcal DNA load (p = 0.026), PCT (p = 0.046) and suPAR (p = 0.001) levels most reliably predicted severe disease development. In conclusion, in patients with CAP, higher pneumococcal DNA load, PCT and suPAR values are associated with severe disease development (ICU admission and/or death). These biomarkers may be useful tools for triage of patients suspected of having CAP in the emergency department.

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References

  1. Jain S, Self WH, Wunderink RG, Fakhran S, Balk R, Bramley AM et al (2015) Community-acquired pneumonia requiring hospitalization among U.S. adults. N Engl J Med 373(5):415–427. doi:10.1056/NEJMoa1500245

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. van Gageldonk-Lafeber AB, Wever PC, van der Lubben IM, de Jager CP, Meijer A, de Vries MC et al (2013) The aetiology of community-acquired pneumonia and implications for patient management. Neth J Med 71(8):418–425

    PubMed  Google Scholar 

  3. Grace CJ, Lieberman J, Pierce K, Littenberg B (2001) Usefulness of blood culture for hospitalized patients who are receiving antibiotic therapy. Clin Infect Dis 32(11):1651–1655. doi:10.1086/320527

    Article  CAS  PubMed  Google Scholar 

  4. Waterer GW, Wunderink RG (2001) The influence of the severity of community-acquired pneumonia on the usefulness of blood cultures. Respir Med 95(1):78–82. doi:10.1053/rmed.2000.0977

    Article  CAS  PubMed  Google Scholar 

  5. Said MA, Johnson HL, Nonyane BA, Deloria-Knoll M, O’Brien KL, Team AAPBS et al (2013) Estimating the burden of pneumococcal pneumonia among adults: a systematic review and meta-analysis of diagnostic techniques. PLoS One. 8(4):e60273. doi: 10.1371/journal.pone.0060273.

  6. Sinclair A, Xie X, Teltscher M, Dendukuri N (2013) Systematic review and meta-analysis of a urine-based pneumococcal antigen test for diagnosis of community-acquired pneumonia caused by Streptococcus pneumoniae. J Clin Microbiol 51(7):2303–2310. doi:10.1128/JCM.00137-13

    Article  PubMed  PubMed Central  Google Scholar 

  7. Peters RP, de Boer RF, Schuurman T, Gierveld S, Kooistra-Smid M, van Agtmael MA et al (2009) Streptococcus Pneumoniae DNA load in blood as a marker of infection in patients with community-acquired pneumonia. J Clin Microbiol 47(10):3308–3312. doi:10.1128/JCM.01071-09

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Rello J, Lisboa T, Lujan M, Gallego M, Kee C, Kay I et al (2009) Severity of pneumococcal pneumonia associated with genomic bacterial load. Chest 136(3):832–840. doi:10.1378/chest.09-0258

    Article  PubMed  Google Scholar 

  9. Gilbert D, Gelfer G, Wang L, Myers J, Bajema K, Johnston M et al (2016) The potential of molecular diagnostics and serum procalcitonin levels to change the antibiotic management of community-acquired pneumonia. Diagn Microbiol Infect Dis 86(1):102–107. doi:10.1016/j.diagmicrobio.2016.06.008

    Article  CAS  PubMed  Google Scholar 

  10. Haupt TH, Petersen J, Ellekilde G, Klausen HH, Thorball CW, Eugen-Olsen J et al (2012) Plasma suPAR levels are associated with mortality, admission time, and Charlson comorbidity index in the acutely admitted medical patient: a prospective observational study. Crit Care 16(4):R130. doi:10.1186/cc11434

    Article  PubMed  PubMed Central  Google Scholar 

  11. Ito A, Ishida T, Tachibana H, Ito Y, Takaiwa T (2016) Serial procalcitonin levels for predicting prognosis in community-acquired pneumonia. Respirology 21(8):1459–1464. doi:10.1111/resp.12846

    Article  PubMed  Google Scholar 

  12. Ruiz-Gonzalez A, Utrillo L, Bielsa S, Falguera M, Porcel JM (2016) The diagnostic value of serum C-reactive protein for identifying pneumonia in hospitalized patients with acute respiratory symptoms. J Biomark 2016:2198745. doi:10.1155/2016/2198745

    Article  PubMed  PubMed Central  Google Scholar 

  13. Wittenhagen P, Kronborg G, Weis N, Nielsen H, Obel N, Pedersen SS et al (2004) The plasma level of soluble urokinase receptor is elevated in patients with Streptococcus Pneumoniae bacteraemia and predicts mortality. Clin Microbiol Infect 10(5):409–415. doi:10.1111/j.1469-0691.2004.00850.x

    Article  CAS  PubMed  Google Scholar 

  14. Loonen AJ, de Jager CP, Tosserams J, Kusters R, Hilbink M, Wever PC et al (2014) Biomarkers and molecular analysis to improve bloodstream infection diagnostics in an emergency care unit. PLoS One 9(1):e87315. doi:10.1371/journal.pone.0087315

    Article  PubMed  PubMed Central  Google Scholar 

  15. Rasmussen LJ, Ladelund S, Haupt TH, Ellekilde G, Poulsen JH, Iversen K et al (2016) Soluble urokinase plasminogen activator receptor (suPAR) in acute care: a strong marker of disease presence and severity, readmission and mortality. A retrospective cohort study. Emerg Med J. doi:10.1136/emermed-2015-205444

    PubMed  PubMed Central  Google Scholar 

  16. Peters RP, van Agtmael MA, Gierveld S, Danner SA, Groeneveld AB, Vandenbroucke-Grauls CM et al (2007) Quantitative detection of Staphylococcus aureus and enterococcus faecalis DNA in blood to diagnose bacteremia in patients in the intensive care unit. J Clin Microbiol 45(11):3641–3646. doi:10.1128/JCM.01056-07

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Huijsmans CJ, Poodt J, Damen J, van der Linden JC, Savelkoul PH, Pruijt JF et al (2012) Single nucleotide polymorphism (SNP)-based loss of heterozygosity (LOH) testing by real time PCR in patients suspect of myeloproliferative disease. PLoS One 7(7):e38362. doi:10.1371/journal.pone.0038362

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Mellroth P, Daniels R, Eberhardt A, Ronnlund D, Blom H, Widengren J et al (2012) LytA, major autolysin of Streptococcus Pneumoniae, requires access to nascent peptidoglycan. J Biol Chem 287(14):11018–11029. doi:10.1074/jbc.M111.318584

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Loonen AJ, Bos MP, van Meerbergen B, Neerken S, Catsburg A, Dobbelaer I et al (2013) Comparison of pathogen DNA isolation methods from large volumes of whole blood to improve molecular diagnosis of bloodstream infections. PLoS One 8(8):e72349. doi:10.1371/journal.pone.0072349

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Zhydkov A, Christ-Crain M, Thomann R, Hoess C, Henzen C, Werner Z et al (2015) Utility of procalcitonin, C-reactive protein and white blood cells alone and in combination for the prediction of clinical outcomes in community-acquired pneumonia. Clin Chem Lab Med 53(4):559–566. doi:10.1515/cclm-2014-0456

    Article  CAS  PubMed  Google Scholar 

  21. Sakka SG, Kochem AJ, Disque C, Wellinghausen N (2009) Blood infection diagnosis by 16S rDNA broad-spectrum polymerase chain reaction: the relationship between antibiotic treatment and bacterial DNA load. Anesth Analg 109(5):1707–1708. doi:10.1213/ANE.0b013e3181b79904

    Article  PubMed  Google Scholar 

  22. Hong DY, Park SO, Kim JW, Lee KR, Baek KJ, Na JU et al (2016) Serum procalcitonin: an independent predictor of clinical outcome in health care-associated pneumonia. Respiration 92(4):241–251. doi:10.1159/000449005

    Article  CAS  PubMed  Google Scholar 

  23. Minnaard MC, de Groot JA, Hopstaken RM, Schierenberg A, de Wit NJ, Reitsma JB et al (2016) The added value of C-reactive protein measurement in diagnosing pneumonia in primary care: a meta-analysis of individual patient data. CMAJ. doi:10.1503/cmaj.151163

    PubMed  Google Scholar 

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Acknowledgements

We want to thank Jasper Ewalts for collecting blood and plasma samples and Robert Vanderloo for determining procalcitonin levels in the plasma samples. We thank suPARnostic (Copenhagen, Denmark) for providing discount on the suPAR kits used. No other funding was obtained.

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Correspondence to A. J. C. van den Brule.

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Loonen, A.J.M., Kesarsing, C., Kusters, R. et al. High pneumococcal DNA load, procalcitonin and suPAR levels correlate to severe disease development in patients with pneumococcal pneumonia. Eur J Clin Microbiol Infect Dis 36, 1541–1547 (2017). https://doi.org/10.1007/s10096-017-2963-2

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  • DOI: https://doi.org/10.1007/s10096-017-2963-2

Keywords

  • Blood Culture
  • White Blood Cell Count
  • Receiver Operating Characteristic
  • Negative Blood Culture
  • Blood Culture Result