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

Key Points

Question  Can prospective whole-genome sequencing identify bacterial transmission events and associated factors in a neonatal intensive care unit?

Findings  In this cohort study, 51.8% of participants were colonized with at least 1 bacterial strain with antibiotic resistance or epidemic potential, and 34.0% of colonizations were linked to transmission. Increased full-time nurse staffing and prior antibiotic exposure were associated with a lower risk of transmission-linked colonization, while vascular catheter use was associated with an increased risk.

Meaning  This study suggests that whole-genome sequencing can identify bacterial transmission events and help identify modifying factors for colonization in newborn infants in intensive care.

Abstract

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.