Pilot study of a combined genomic and epidemiologic surveillance program for hospital-acquired multidrug-resistant pathogens across multiple hospital networks in Australia

Abstract

Objectives: To conduct a pilot study implementing combined genomic and epidemiologic surveillance for hospital-acquired multidrug-resistant organisms (MDROs) to predict transmission between patients and to estimate the local burden of MDRO transmission. Design: Pilot prospective multicenter surveillance study. Setting: The study was conducted in 8 university hospitals (2,800 beds total) in Melbourne, Australia (population 4.8 million), including 4 acute-care, 1 specialist cancer care, and 3 subacute-care hospitals. Methods: All clinical and screening isolates from hospital inpatients (April 24 to June 18, 2017) were collected for 6 MDROs: vanA VRE, MRSA, ESBL Escherichia coli (ESBL-Ec) and Klebsiella pneumoniae (ESBL-Kp), and carbapenem-resistant Pseudomonas aeruginosa (CRPa) and Acinetobacter baumannii (CRAb). Isolates were analyzed and reported as routine by hospital laboratories, underwent whole-genome sequencing at the central laboratory, and were analyzed using open-source bioinformatic tools. MDRO burden and transmission were assessed using combined genomic and epidemiologic data. Results: In total, 408 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%). Most MDROs (88.3%) were isolated from patients with recent healthcare exposure. Combining genomics and epidemiology identified that at least 27.1% of MDROs were likely acquired in a hospital; most of these transmission events would not have been detected without genomics. The highest proportion of transmission occurred with vanA VRE (88.4% of patients). Conclusions: Genomic and epidemiologic data from multiple institutions can feasibly be combined prospectively, providing substantial insights into the burden and distribution of MDROs, including in-hospital transmission. This analysis enables infection control teams to target interventions more effectively.

Genomic surveillance of antimicrobial resistant bacterial colonisation and infection in intensive care patients

“…While four of the six 3GCR-GN transmission clusters involved E. coli , these included just four of 24 distinct E. coli STs, and did not include the globally distributed ST131, ST10 or ST38. This is consistent with a recent report showing that these E. coli STs were commonly identified from patients in other Melbourne hospitals, but rarely associated with nosocomial transmission [ 15 ]. Hence our data adds to the growing evidence base [ 15 , 18 – 20 , 46 ] that ESBL- E. coli are mainly spread in the community setting.…”

“…This is consistent with a recent report showing that these E. coli STs were commonly identified from patients in other Melbourne hospitals, but rarely associated with nosocomial transmission [ 15 ]. Hence our data adds to the growing evidence base [ 15 , 18 – 20 , 46 ] that ESBL- E. coli are mainly spread in the community setting.…”

“…3b-c). Using a threshold of ≤20 SNVs for transmission of 3GCR-GN (based on recent studies [10,15,16,33]) we identified six putative 3GCR-GN transmission clusters each involving 2-3 patients (maximum 8 SNVs, Table 2). With a single exception, all patients within clusters were epidemiologically linked (overlapping ICU stays or ≤ 14 days between stays).…”

“…Interpretation of VRE pairwise SNVs is more complex because several healthcare-associated lineages are known to be circulating in Melbourne and the regional hospital network. Consequently, it is not uncommon to find near-identical isolates in patients from different wards, hospitals or cities without epidemiological links [7,8,15]. We therefore used a more conservative threshold of ≤3 SNVs to define putative recent VRE transmissions (based on empirical distribution, see Supplementary Figure 3), which identified four clusters of 2-7 patients each (Table 2).…”

“…Asymptomatic gut colonisation is considered a key risk factor for enterococcal, Enterobacteriaceae and other GN infections [9][10][11][12][13] and in the case of VRE has been associated with longer ICU stay and treatment costs [12,14]. A number of hospitals have implemented rectal screening programs to identify patients colonised with VRE and/or carbapenemase-producing Enterobacteriaceae in high-risk wards such as intensive care units (ICUs), oncology and hematology wards [7,8,15,16]. However, few facilities conduct routine screening for ESBL-Enterobacteriaceae or other high-risk carbapenem-susceptible GNs in part due to a lack of evidence to inform the interpretation of these results and to appropriately target infection control measures.…”