High Resolution, Whole Genome Tracking of Pathogen Transmission and Infection in the Neonatal ICU (NICU) - SUMMARY Despite reliable use of infection prevention bundles, hospital-acquired infection rates have plateaued in neonatal intensive care units (NICUs). Our preliminary data from whole genome pathogen sequencing at Children’s Hospital of Philadelphia (CHOP) suggests that many serious infections are traceable to strains (highly related clones) that reside in the ICU and are transmitted amongst patients over time. In this proposal, we aim to determine patient, pathogen, and environment-specific factors that may contribute to infection risk. In Aim 1, we aim to use whole genome sequencing (WGS) of bacteria identified from patient colonization, systemic infection, and colonization of the environment, along with diagnostic allele (DA) surveillance, to determine the transmission and persistence dynamics associated with bacterial infection within two NICUs with distinct clinical and demographic characteristics. We will also assess the impact of patient case-mix and the contribution of NICU layout and environmental characteristics on observed patterns of colonization and infection. We will use the data from WGS to test DA sequencing tests as a strategy that can be scaled for broad use as rapid tests in NICUs to measure strain transmission. In Aim 2 we will assess the impact of providing near real time DA sequencing to guide targeted deployment of infection prevention strategies by the NICU to diminish the persistence and transmission of ‘high risk’ strains. The results of this investigation will demonstrate the feasibility and efficacy of DA sequencing guided targeted interventions to decrease bacterial transmission and/or colonization and thereby reduce risk of invasive infection. The findings from this study will be critical to our overall efforts to decrease the risk of hospital-acquired infection, among our most vulnerable ICU patients.