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

IntroductionIn 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.MethodsWe 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.ResultsPCR 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.ConclusionsMultiplex-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.

Using anaerobic blood cultures for infants younger than 90 days rarely showed anaerobic infections but increased yields of bacterial growth

“…This study also demonstrates the relatively low sensitivity of blood cultures for detecting bacteraemia in this age group. Other studies hold promise for advanced polymerase chain reaction‐based methods that may be more sensitive than current methods .…”

Evaluation of updated sepsis scoring systems and systemic inflammatory response syndrome criteria and their association with sepsis in equine neonates

“…A vital component in improving outcome in human adult septic patients is early detection of bacteremia as well as rapid implementation of antimicrobial therapy . Blood culture remains the gold standard to confirm sepsis and provides valuable antimicrobial susceptibility information . However, blood culture techniques have several limitations including temporal delay in result reporting (48–72 hours), low chance of isolation of some pathogens and only fair sensitivity .…”

“…4 Blood culture remains the gold standard to confirm sepsis and provides valuable antimicrobial susceptibility information. 5 However, blood culture techniques have several limitations including temporal delay in result reporting (48-72 hours), low chance of isolation of some pathogens and only fair sensitivity. [6][7][8][9] Furthermore, positive blood cultures have been documented in healthy neonatal foals or can be positive in association with other disease processes that allow bacterial translocation, both of which might cause transient bacteremia, but not reflect true infection.…”

Molecular epidemiology of Staphylococcus epidermidis in neonatal intensive care units

“…Coagulase‐negative staphylococci (CoNS), particularly Staphylococcus epidermidis, are among the first and most ubiquitous commensals of skin and gut , but have emerged over recent decades as the most common causative microorganisms of late‐onset sepsis (LOS) in very preterm neonates .…”