Using genomics to identify hospital transmission of carbapenem-resistant Enterobacteriales

Introduction: Colonisation and healthcare associated infection (HCAI) with Carbapenem-resistant Enterobacteriales (CRE) is concerning for vulnerable patients. Genomics can trace transmission routes and support antimicrobial stewardship. blaOXA-48- and blaNDM-mediated colonisation and HCAI was seen in patients in a North London tertiary referral hospital. This study aimed to identify whether genomics could be used to track the movement and transmission of CREs within clinical and environmental samples. Methods: 28 isolates were cultured from patient screens or swabs, who tested positive for OXA-48-like variants using the NG-Test® CARBA-5 test and whole genome sequenced (WGS) using Oxford Nanopore Technologies (ONT). 216 environmental swabs and wastewater samples were collected from the ward. 47 isolates (matching clinical isolate genera; Klebsiella, Enterobacter, Citrobacter and Escherichia) were isolated from the environmental samples and WGS performed. Metagenomic sequencing was undertaken on 36 environmental wastewater and swab samples. Data were analysed for AMR genes and transmission. Results: Twenty-five clinical isolates were sequenced. 21/25 (84%) clinical isolates had >1 blaOXA gene and 19/25 (76%) harboured >1 blaNDM gene. Enterobacteriales were most commonly isolated from environmental wastewater samples 27/52 (51.9%), then stick swabs 5/43 (11.6%) and sponge swabs 5/115 (4.3%). 11/60 (18%) environmental isolates harboured at >1 blaOXA gene and 1.9% (1/60) harboured blaNDM-1. blaOXA genes were found in 2/36 (5.5%) metagenomic environmental samples. Discussion: Potential for putative patient-patient and patient-ward transmission was shown. ONT sequencing can expedite clinical decisions whilst awaiting reference laboratory results, providing economic and patient care benefits. Metagenomic sampling needs optimization to improve sensitivity.