BioProject

Importance: Patients of neonatal intensive care units (NICU) are at risk of transmission events (TE) by bacteria with multidrug-resistance with epidemic potential, such as Enterobacterales, P. aeruginosa, S. marcescens, MSSA and MRSA (MDRO+), which may precede invasive infections. Resolution of MDRO+ transmission clusters (TC) is important to invoke timely and thus effective infection prevention control (IPC) measures . Objective: Exploration of the potential of timely whole genome sequencing (WGS) in resolving putative MDRO+ transmission chains on a NICU, based on routine screening-isolates. Exploration of patient- and environmental-specific risk factors of becoming part of a TC. Design, Setting, Participants: Prospective monocentric cohort study at a level III NICU at the University Hospital of Freiburg, Germany. Enrollment of 434 of 551 patients that were on the NICU for at least 48h and screened at least once in the time between February 15 2019 and November 16 2020. Exposures: Integration of (1) routine culture-based screening for MDRO+ (at admission, and then once a week, in accordance to national guidelines), (2) genetic typing with amplified fragment length polymorphism (AFLP) and WGS with (3) granular clinical and staffing data. Statistical analysis based on multivariate model analysis, using moving averages (MA). Main Outcomes: Primary outcome: Identification of bacterial TE with pathogens of the same species in different patients, which are indistinguishable after AFLP or WGS. Secondary outcomes: Bacterial colonization densities, identification of influential factors of TE, blood stream infection densities (BSI). Results: Among 434 NICU patients (27.9% with birth weight < 1,500 g) 51.8 % were colonized with at least one MDRO+ species; 30.1% were part of at least one TC as revealed by WGS. With 38 unique TC, E. coli was the most common MDRO+ forming clusters whereas K. oxytoca formed the largest clusters involving up to 19 patients. Out of ten bloodstream infections, four originated from TE. Multivariate model analysis revealed three factors influencing TE risk: Increased nurse staffing levels as well as antibiotic administration lowered the risk of being part of a bacterial transmission cluster, while invasive ventilation increased it. Conclusions and Relevance: Prospective WGS of routine screening isolates from newborn infants in intensive care is a powerful tool for resolving MDRO+ transmission chains exceeding ALFP in precision. Despite the related expenditure of resources, systematic strain identification by WGS seems justified in high-risk neonates, given the grave organizational consequences of both delayed TE identification and “false” TE, which inevitably occur in conventional microbiological screening.