Prospective whole-genome sequencing uncovers factors influencing bacterial transmission in neonates (PROtect NEO)
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Importance
Infants in neonatal intensive care units are at risk of transmission events by bacteria with multidrug-resistance and/or epidemic potential (“multidrug-resistant organisms plus”, MDRO+), which may precede invasive infections. Prospective high-level resolution of MDRO+ transmission clusters may alleviate high risk situations through targeted infection prevention control measures.
Objectives
1) Exploration of whole-genome sequencing in resolving putative MDRO+ transmission chains. 2) Analysis of risk factors for becoming part of a transmission cluster.
Design, Setting, Participants
Prospective monocentric cohort study at a level III neonatal intensive care unit at the Medical Center – University of Freiburg, Germany. Inclusion of 434 of 551 preterm and term infants admitted for at least 48h and screened at least once between February 15 2019 and November 16 2020.
Exposures
Integration of (1) culture-based screening, (2) genetic typing with amplified fragment length polymorphism and whole-genome sequencing and (3) granular clinical and staffing data. Statistical analysis of time-dependent risk factors based on advanced multivariate model analysis.
Main Outcomes
Primary: Identification of MDRO+ transmission events, indistinguishable by amplified fragment length polymorphism or whole-genome sequencing. Secondary: MDRO+ colonization rates; identification of factors influencing transmission events; MDRO+ blood stream infection rates.
Results
Among 434 participants 51.8 % (95% CI, 47.1%-56.5%) were colonized with at least one MDRO+; 32.5% (95% CI, 28.3%-37.0%) were colonized by transmission. Among 38 unique transmission clusters, E. coli was the most common cluster-forming MDRO+. Four of ten MDRO+ blood stream infections originated from transmission events. Multivariate analysis revealed three factors influencing the risk of becoming part of a transmission cluster: Increased nurse staffing levels and antibiotic administration lowered the risk of becoming part of a bacterial transmission cluster, while vascular catheter usage increased it.
Conclusions and Relevance
Prospective whole-genome sequencing of routine screening isolates from neonatal intensive care unit infants is powerful for detecting MDRO+ transmission chains, exceeding amplified fragment length polymorphism in precision and seems justified in high-risk neonates to uncover specific risk factors for MDRO+ transmission. Delayed and “false” identification of transmission events, which inevitably occur in conventional microbiological screening, have grave organizational consequences.
