title: A prospective multicenter evaluation of direct molecular detection of blood stream infection from a clinical perspective.
abstract: Rapid diagnosis and appropriate antimicrobial therapy are of major importance to decrease morbidity and mortality in patients with blood stream infections (BSI). Blood culture, the current gold standard for detecting bacteria in blood, requires at least 24-48 hours and has limited sensitivity if obtained during antibiotic treatment of the patient. The aim of this prospective multicenter study was to clinically evaluate the application of a commercial universal 16S/18S rDNA PCR, SepsiTest™ (PCR-ST), directly on whole blood.
  
  
  
  In total 236 samples from 166 patients with suspected sepsis were included in the study. PCR-ST results were compared to blood culture, the current gold standard for detecting BSI. Because blood cultures can give false-negative results, we performed an additional analysis to interpret the likelihood of bloodstream infection by using an evaluation based on clinical diagnosis, other diagnostic tests and laboratory parameters.
  
  
  
  Clinical interpretation of results defined the detected organism to be contaminants in 22 of 43 positive blood cultures (51.2 %) and 21 of 47 positive PCR-ST results (44.7 %). Excluding these contaminants resulted in an overall sensitivity and specificity of the PCR-ST of 66.7 and 94.4 % respectively. Of the 36 clinically relevant samples, 11 BSI were detected with both techniques, 15 BSI were detected with PCR-ST only and 10 with blood culture only. Therefore, in this study, SepsiTest™ detected an additional 71 % BSI compared to blood culture alone.
  
  
  
  More clinically relevant BSI were diagnosed by molecular detection, which might influence patient treatment. An improved SepsiTest™ assay suited for routine use can have additional value to blood culture in diagnosing bacteremia in septic patients.
authors.affiliation: Department of Medical Microbiology and Infection control, VU University Medical Center, Amsterdam, The Netherlands.|Laboratory for Medical Microbiology, Immunology and Infection Control, Elisabeth-TweeSteden Hospital, Tilburg, The Netherlands.
authors.forename: A E
authors.initials: AE
authors.lastname: Nieman
authors.affiliation: Department of Medical Microbiology and Infection control, VU University Medical Center, Amsterdam, The Netherlands.|Department of Medical Microbiology, Maastricht University Medical Center, Maastricht, The Netherlands.
authors.forename: P H M
authors.initials: PHM
authors.lastname: Savelkoul
authors.affiliation: Department of Intensive Care Medicine, VU University Medical Center, Amsterdam, The Netherlands.|Department of Intensive Care, Medisch Spectrum Twente, Enschede, The Netherlands.
authors.forename: A
authors.initials: A
authors.lastname: Beishuizen
authors.affiliation: Institute of Medical Microbiology and Hospital Hygiene, University Clinic of Heinrich-Heine University Düsseldorf, Düsseldorf, Germany.
authors.forename: B
authors.initials: B
authors.lastname: Henrich
authors.affiliation: Institute of Medical Microbiology and Hospital Hygiene, University Clinic of Heinrich-Heine University Düsseldorf, Düsseldorf, Germany.
authors.forename: B
authors.initials: B
authors.lastname: Lamik
authors.affiliation: Institute of Medical Microbiology and Hospital Hygiene, University Clinic of Heinrich-Heine University Düsseldorf, Düsseldorf, Germany.
authors.forename: C R
authors.initials: CR
authors.lastname: MacKenzie
authors.affiliation: Department of Anesthesiology, University Clinic of Heinrich-Heine University Düsseldorf, Düsseldorf, Germany.
authors.forename: D
authors.initials: D
authors.lastname: Kindgen-Milles
authors.affiliation: Department of Microbiology, Merheim Zentrallabor, MVZ synlab Leverkusen GmbH, Leverkusen, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Helmers
authors.affiliation: Department of Microbiology, Merheim Zentrallabor, MVZ synlab Leverkusen GmbH, Leverkusen, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Diaz
authors.affiliation: Department of Anesthesiology and Intensive Care Medicine, Medical Center Cologne-Merheim, University Witten/Herdecke, Cologne, Germany.
authors.forename: S G
authors.initials: SG
authors.lastname: Sakka
authors.affiliation: Department of Medical Microbiology and Infection control, VU University Medical Center, Amsterdam, The Netherlands. r.schade@vumc.nl.
authors.forename: R P
authors.initials: RP
authors.lastname: Schade
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016470:Bacteremia / Q000175:diagnosis* / Q000382:microbiology; D001419:Bacteria / Q000235:genetics*; D000071997:Blood Culture; D003141:Communicable Diseases; D004275:DNA, Ribosomal / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction / Q000379:methods*; D011446:Prospective Studies; D012336:RNA, Ribosomal, 16S / Q000235:genetics; D012337:RNA, Ribosomal, 18S / Q000235:genetics; D012680:Sensitivity and Specificity; D018805:Sepsis / Q000175:diagnosis / Q000382:microbiology
chemical_list: D004275:DNA, Ribosomal; D012336:RNA, Ribosomal, 16S; D012337:RNA, Ribosomal, 18S
keywords: 16S; Bacteremia; Blood stream infection; Molecular; PCR; SepsiTest™; Sepsis