title: 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.
authors.affiliation: Laboratory of Molecular Diagnostics, Jeroen Bosch Hospital, P.O Box 90153, 5200 ME, 's-Hertogenbosch, The Netherlands.|Fontys University of Applied Sciences, Department of Applied Natural Sciences, Section Diagnostics and Test Development, Eindhoven, The Netherlands.
authors.forename: A J M
authors.initials: AJM
authors.lastname: Loonen
authors.affiliation: Laboratory of Molecular Diagnostics, Jeroen Bosch Hospital, P.O Box 90153, 5200 ME, 's-Hertogenbosch, The Netherlands.
authors.forename: C
authors.initials: C
authors.lastname: Kesarsing
authors.affiliation: Department of Clinical Chemistry and Haematology, Jeroen Bosch Hospital, P.O Box 90153, 5200 ME, 's-Hertogenbosch, The Netherlands.
authors.forename: R
authors.initials: R
authors.lastname: Kusters
authors.affiliation: Jeroen Bosch Academy, P.O Box 90153, 5200 ME, 's-Hertogenbosch, The Netherlands.
authors.forename: M
authors.initials: M
authors.lastname: Hilbink
authors.affiliation: Department of Medical Microbiology and Infection Control, Jeroen Bosch Hospital, P.O Box 90153, 5200 ME, 's-Hertogenbosch, The Netherlands.
authors.forename: P C
authors.initials: PC
authors.lastname: Wever
authors.affiliation: Laboratory of Molecular Diagnostics, Jeroen Bosch Hospital, P.O Box 90153, 5200 ME, 's-Hertogenbosch, The Netherlands. a.v.d.brule@jbz.nl.
authors.forename: A J C
authors.initials: AJC
authors.lastname: van den Brule
mesh_terms: D015415:Biomarkers; D001772:Blood Cell Count; D002116:Calcitonin / Q000097:blood*; D004269:DNA, Bacterial; D005260:Female; D006801:Humans; D008297:Male; D011018:Pneumonia, Pneumococcal / Q000175:diagnosis / Q000378:metabolism* / Q000382:microbiology*; D012372:ROC Curve; D055293:Receptors, Urokinase Plasminogen Activator / Q000097:blood*; D012189:Retrospective Studies; D012720:Severity of Illness Index; D013296:Streptococcus pneumoniae / Q000235:genetics*
chemical_list: D015415:Biomarkers; D004269:DNA, Bacterial; D055293:Receptors, Urokinase Plasminogen Activator; D002116:Calcitonin
keywords: Blood Culture; Blood Culture Result; Negative Blood Culture; Receiver Operating Characteristic; White Blood Cell Count