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

Background Rates of multidrug resistance (MDR) in Gram-negative bacteria (GNB), particularly those harbouring extended-spectrum beta-lactamases (ESBL) and/or carbapenamases (CP) 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. Methods We conducted a six-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 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. Findings Of 424 participants recruited between June and December 2016, 15% (n=64) were positive for MDRGNB during admission screening to ICU. The most frequently identified organisms were Pseudomonas aeruginosa, Escherichia coli and Klebsiella pneumoniae. 10% (n=42) of patients acquired an ESBL-producing or carbapenem-resistant MDR GNB during their ICU admission. Whole-genome sequencing of the bacterial populations reflected national trends. An undetected outbreak of carbapenemase-producing K. pneumoniae, which had spread to several wards, was identified, and controlled. Most positive patients carried identical lineages across multiple body sites. Interpretation 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 enable prompt institution of enhanced infection control measures. Data Summary: All genomic sequence data have been deposited in the European Nucleotide Archive under the respective project identifiers. Sequences new to this project can be found under projects PRJEB20809 and PRJEB14854 with accession numbers for each isolate detailed in Supplementary Data Table. All previously published data can be found publicly using the accession numbers detailed in Supplementary Data Table. All supporting data, code and protocols have been provided within the article or through supplementary data files. Impact Statement: In the UK there has been an increase in the prevalence of multidrug-resistant Gram-negative bacterial infections (MDR GNB) over the past decade. Patients requiring complex and demanding medical care are disproportionately affected by these pathogens. Bacterial populations carried asymptomatically undermine efforts to reduce MDR pathogen burden and are not subject to the same mandatory surveillance requirements for Gram-negative bloodstream infections in the UK. The impact of the asymptomatic carriage of MDR GNB on critically ill patients remains unclear.