Genomic interrogation of the burden and transmission of multidrug-resistant pathogens within and across hospital networks

Abstract

BackgroundMultidrug-resistant organisms (MDROs) disproportionately affect hospitalized patients due to the combination of comorbidities, frequent antimicrobial use, and in-hospital MDRO transmission. Identification of MDRO transmission by hospital microbiology laboratories is difficult due to limitations of existing typing methods.\n\nMethodsWe conducted a prospective multicenter genomics implementation study (8 hospitals, 2800 beds) from 24th April to 18th June 2017 in Melbourne, Australia. Clinical and screening isolates from hospital inpatients were collected for six MDROs (vanA VRE, MRSA, ESBL E. coli [ESBL-Ec] and Klebsiella pneumoniae [ESBL-Kp], and carbapenem-resistant Pseudomonas aeruginosa [CRPa] and Acinetobacter baumannii [CRAb]), sequenced (Illumina NextSeq) and analyzed using open-source tools. MDRO transmission was assessed by genomics (core SNP phylogeny, grouped by species and ST) and compared to epidemiologic data.\n\nResults408 isolates were collected from 358 patients; 47.5% were screening isolates. ESBL-Ec was most common (52.5%), then MRSA (21.6%), vanA VRE (15.7%) and ESBL-Kp (7.6%).\n\nWe define the transmission rate for each MDRO by genomics and epidemiology; 31.6% of all study patients had potential genomic links to other study isolates; 86% of these were confirmed by epidemiologic links (probable or possible transmission). The highest transmission rates occurred with vanA VRE (88.4% of patients).\n\nConclusionsCombining genomics with high-quality epidemiologic data gives substantial insights into the burden and distribution of critical MDROs in hospitals, including in-hospital transmission. By defining transmission rates by genomics, we hope to enable comparisons over time and between sites, and introduce this as a new outcome measure to assess the efficacy of infection control interventions.