Whole-genome sequencing enhances existing pathogen and antimicrobial-resistance surveillance schemes within a neonatal unit

In some neonatal units, the screening of isolates for antimicrobial-resistant organisms is a matter of routine, with theoretical benefits including the prevention or early detection of outbreaks. This study sought to use whole-genome sequencing (WGS) retrospectively to characterize the genomic epidemiology of Gram-negative organisms obtained from a screening programme in a 32-bed unit providing intensive, high-dependency and special care at City Hospital, Birmingham, UK, identifying occult transmission events and clinically important antimicrobial-resistance (AMR) genes. WGS was performed for 155 isolates collected from rectal and umbilical screening swabs over a 2 month period from 44 individual neonates. Genomic epidemiological analysis showed possible transmission events involving Escherichia coli, Enterobacter cloacae, Klebsiella oxytoca and Klebsiella pneumoniae not detected by routine screening, with eight putative clusters involving different individuals identified. Within phylogenetic clusters, the relatedness of organisms - as determined by the abundance of SNPs - varied widely, indicating that a variety of transmission routes may be implicated. While clinically important AMR genes were not present in the putative transmission clusters, our observation of suspected interspecies horizontal transfer of bla CTX-M-15 within individuals highlights the potential for their spread between organisms as well as individuals in this environment, with implications for surveillance. Our data show that WGS may reveal occult Gram-negative transmission events, demonstrating the potential of sequencing-based surveillance systems for nosocomial pathogens. Challenges remain in understanding how to utilize WGS surveillance to maximum effect in real-world settings.