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

Abstract

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. To assess the potential of whole-genome sequencing in resolving suspected transmission chains of MDRO+ and to identify associated risk factors for cluster involvement. 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. 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. 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. 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). 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.