Whole-genome sequencing to investigate the prevalence and transmission of multidrug-resistant Gram-negative pathogens in an adult intensive care unit in the UK

<b>Background.</b> Rates of multidrug resistance (MDR) in Gram-negative bacteria (GNB), particularly those harbouring extended-spectrum beta-lactamases (ESBL) and/or carbapenemases, are increasing globally. Intensive care unit (ICU) patients are vulnerable to healthcare-associated infection (HCAI). Surveillance for carriage of multidrug-resistant Gram-negative bacteria (MDR GNB) is inconsistent, with differing practices amongst ICUs, hospitals and countries. Furthermore, the impact of asymptomatic carriage on HCAI rates is unclear.<b>Methods.</b> We conducted a 6-month prospective surveillance study of MDR GNB in a UK adult ICU. Screening samples were collected from all study participants on admission, once a week (depending on length of stay) and on discharge from the ICU. Whole-genome sequencing (WGS) was used to examine the population structure and antimicrobial resistance mechanisms of MDR GNB and to determine evidence of recent transmission between patients.<b>Findings.</b> Of 424 participants recruited between June and December 2016, 15% (<i>n</i>=64) were positive for MDR GNB during admission screening to the ICU. The most frequently identified organisms were <i>Pseudomonas aeruginosa</i>, <i>Escherichia coli</i> and <i>Klebsiella pneumoniae</i>. In total, 10% (<i>n</i>=42) of patients acquired an ESBL-producing or carbapenem-resistant MDR GNB during their ICU admission. WGS of the bacterial populations reflected national trends. An undetected outbreak of carbapenemase-producing <i>K. pneumoniae</i>, which had spread to several wards, was identified and controlled. Most positive patients carried identical lineages across multiple body sites.<b>Interpretation.</b> Our findings suggest that prospective screening for MDR GNB in ICU patients could be beneficial and be considered in other UK critical care settings. This would not only improve early detection but also enable the prompt institution of enhanced infection control measures.