Prospective Whole-Genome Sequencing to Identify Bacterial Transmission and Its Modifiers in Neonates.

Importance: Infants in neonatal intensive care units (NICUs) are at risk of acquiring organisms with multidrug resistance or high epidemic potential (MDRO+), which may precede invasive infections. High-resolution analysis of transmission cultures of MDRO+ may help mitigate these risks through targeted infection prevention measures. Objectives: To assess the potential of whole-genome sequencing in resolving suspected transmission chains of MDRO+ and to identify associated risk factors for cluster involvement. Design, Setting, and Participants: This prospective monocentric cohort study was conducted at a level III NICU at the Medical Center-University of Freiburg, Freiburg, Germany. Of 551 admitted infants, 434 were included because they remained on the ward for 48 hours or more and received 1 or more screenings between February 15, 2019, and November 16, 2020. Statistical analysis was conducted from December 1, 2021, to November 10, 2024. Exposures: Time-dependent patient- and ward-level factors, medical device use, nursing effort score, invasive procedures, antibiotic use, prevalence of MDRO+, and staffing metrics were analyzed for association with transmission chains. Main Outcomes and Measures: The primary outcome was transmission of MDRO+, defined as colonization or invasion with genetically indistinguishable bacteria, defined by amplified fragment length polymorphism or whole-genome sequencing. Secondary outcomes included colonization rates, bloodstream infections, and risk factors associated with transmission. Results: The study included 434 infants (median gestational age, 34.6 weeks [IQR, 31.4-38.3 weeks]; 242 boys [55.8%]; median birth weight, 2165 g [IQR, 1410-2965 g]). Overall, 225 patients (51.8% [95% CI, 47.1%-56.5%]) were colonized with at least 1 MDRO+. Of 418 unique colonizations, 142 (34.0% [95% CI, 29.6%-38.6%]) were linked with transmission by whole-genome sequencing. Thirty-seven unique transmission clusters were identified, most frequently involving Escherichia coli (n = 11). Four of 10 bloodstream infections with MDRO+ (40.0%) were linked with transmission events. Increased full-time nurse staffing (odds ratio [OR], 0.28 [95% CI, 0.21-0.38]; P < .001) and prior antibiotic use (OR, 0.41 [95% CI, 0.26-0.63]; P < .001) were associated with decreased transmission risk, while vascular catheter use was associated with increased transmission risk (OR, 1.65 [95% CI, 1.26-2.17]; P < .001). Conclusions and Relevance: This cohort study involving infants in the NICU suggests that bacterial sequencing can accurately detect bacterial transmission events. Multivariate analysis suggests that the bacterial transmission risk on a NICU can be modified.