title: Clinical Relevance of Pathogens Detected by Multiplex PCR in Blood of Very-Low-Birth Weight Infants with Suspected Sepsis - Multicentre Study of the German Neonatal Network.
abstract: BACKGROUND
  In the German Neonatal Network (GNN) 10% of very-low-birth weight infants (VLBWI) suffer from blood-culture confirmed sepsis, while 30% of VLBWI develop clinical sepsis. Diagnosis of sepsis is a difficult task leading to potential over-treatment with antibiotics. This study aims to investigate whether the results of blood multiplex-PCR (SeptiFast®) for common sepsis pathogens are relevant for clinical decision making when sepsis is suspected in VLBWI.
  
  
  METHODS
  We performed a prospective, multi-centre study within the GNN including 133 VLBWI with 214 episodes of suspected late onset sepsis (LOS). In patients with suspected sepsis a multiplex-PCR (LightCycler SeptiFast MGRADE-test®) was performed from 100 μl EDTA blood in addition to center-specific laboratory biomarkers. The attending neonatologist documented whether the PCR-result, which was available after 24 to 48 hrs, had an impact on the choice of antibiotic drugs and duration of therapy.
  
  
  RESULTS
  PCR was positive in 110/214 episodes (51%) and blood culture (BC) was positive in 55 episodes (26%). Both methods yielded predominantly coagulase-negative staphylococci (CoNS) followed by Escherichia coli and Staphylococcus aureus. In 214 BC-PCR paired samples concordant results were documented in 126 episodes (59%; n = 32 were concordant pathogen positive results, n = 94 were negative in both methods). In 65 episodes (30%) we found positive PCR results but negative BCs, with CoNS being identified in 43 (66%) of these samples. Multiplex-PCR results influenced clinical decision making in 30% of episodes, specifically in 18% for the choice of antimicrobial therapy and in 22% for the duration of antimicrobial therapy.
  
  
  CONCLUSIONS
  Multiplex-PCR results had a moderate impact on clinical management in about one third of LOS-episodes. The main advantage of multiplex-PCR was the rapid detection of pathogens from micro-volume blood samples. In VLBWI limitations include risk of contamination, lack of resistance testing and high costs. The high rate of positive PCR results in episodes of negative BC might lead to overtreatment of infants which is associated with risk of mortality, antibiotic resistance, fungal sepsis and NEC.
authors.affiliation: Department of Pediatrics at the University of Lübeck, Lübeck, Germany.
authors.forename: Birte
authors.initials: B
authors.lastname: Tröger
authors.affiliation: Department of Pediatrics at the University of Lübeck, Lübeck, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Härtel
authors.affiliation: Institute of Medical Microbiology, University of Duisburg-Essen, Essen, Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: Buer
authors.affiliation: Department of Pediatrics at Diakonissen Hospital Flensburg, Flensburg, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Dördelmann
authors.affiliation: Department of Pediatrics, University Hospital Essen, University Duisburg-Essen, Essen, Germany.
authors.forename: Ursula
authors.initials: U
authors.lastname: Felderhoff-Müser
authors.affiliation: Department of Pediatrics at the University of Düsseldorf, Düsseldorf, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Höhn
authors.affiliation: Department of Pediatrics at St. Marien Hospital Bonn, Bonn, Germany.
authors.forename: Nico
authors.initials: N
authors.lastname: Hepping
authors.affiliation: Department of Pediatrics at Hospital of Itzehoe, Itzehoe, Germany.
authors.forename: Georg
authors.initials: G
authors.lastname: Hillebrand
authors.affiliation: Department of Pediatrics at the University of Cologne, Cologne, Germany.
authors.forename: Angela
authors.initials: A
authors.lastname: Kribs
authors.affiliation: Department of Pediatrics at the University of Lübeck, Lübeck, Germany.
authors.forename: Janina
authors.initials: J
authors.lastname: Marissen
authors.affiliation: Neonatology Unit at Südstadt Hospital Rostock, Rostock, Germany.
authors.forename: Dirk
authors.initials: D
authors.lastname: Olbertz
authors.affiliation: Institute of Medical Microbiology, University of Duisburg-Essen, Essen, Germany.
authors.forename: Peter-Michael
authors.initials: PM
authors.lastname: Rath
authors.affiliation: Neonatology Unit at Asclepios Hospital Hamburg-Barmbek, Hamburg, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Schmidtke
authors.affiliation: Neonatology Unit at the Children´s Hospital Hannover Auf der Bult, Hannover, Germany.
authors.forename: Jens
authors.initials: J
authors.lastname: Siegel
authors.affiliation: Department of Pediatrics at the University of Lübeck, Lübeck, Germany.
authors.forename: Egbert
authors.initials: E
authors.lastname: Herting
authors.affiliation: Department of Pediatrics at the University of Lübeck, Lübeck, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Göpel
authors.affiliation: Institute of Medical Microbiology, University of Duisburg-Essen, Essen, Germany.
authors.forename: Joerg
authors.initials: J
authors.lastname: Steinmann
authors.affiliation: Department of Pediatrics, University Hospital Essen, University Duisburg-Essen, Essen, Germany.
authors.forename: Anja
authors.initials: A
authors.lastname: Stein
mesh_terms: D005260:Female; D005858:Germany; D006801:Humans; D007231:Infant, Newborn; D007232:Infant, Newborn, Diseases / Q000097:blood / Q000382:microbiology*; D019102:Infant, Very Low Birth Weight / Q000097:blood*; D008297:Male; D060885:Multiplex Polymerase Chain Reaction; D011446:Prospective Studies; D018805:Sepsis / Q000097:blood / Q000382:microbiology*; D013048:Specimen Handling