Search and Contain: Centralised Prospective Genomic and Epidemiological Surveillance for the Identification and Control of Carbapenemase-Producing Enterobacterales Transmission

Background: Carbapenemase-producing Enterobacterales (CPE) are multi-resistant organisms (MRO), posing a major threat to public health. Following a multi-facility outbreak of KPC-producing Enterobacterales, Victoria, Australia introduced a state-wide public health surveillance and response system for CPE in December 2015. Methods: A prospective multi-modal intervention including active screening, laboratory testing, carrier isolation practices and case investigation was implemented. Isolates and standardised epidemiological data, including travel and hospitalisation history were collected by clinical staff and collated centrally. Combined analysis of phylogenetic and epidemiological data was undertaken to identify time and place(s) of CPE transmission, and targeted interventions deployed. Results: Systematic real-time surveillance and response was deployed, capturing 402 cases comprising 58 diverse combinations of carbapenemase genes and species. NDM and OXA-48-like genes were associated with overseas travel, with non-healthcare-related overseas acquisition observed. Centralised genomic and epidemiological analyses identified multiple small local transmission networks (median 2, range 1-19 cases) across multiple facilities, predominantly KPC- and IMP-producing organisms. Incidence of CPE increased over the surveillance period to 1·42 cases/100,000 population, however active clinical infections remained steady since 2017 (0·45-0·60/infections/100,000 population, p=0·640), indicating an increase in screening, case ascertainment, and resolution of transmission networks. Occurrence of KPC-2 infection decreased from 0·29 infections/100,000 population prior to intervention to 0·03 cases/100,000 in 2018 (p=0·003). Conclusions: Victoria has successfully implemented a centralised combined phylogenomic and epidemiological surveillance and response system for a primarily healthcare-associated MRO. Multi-sector cooperation has contributed to the maintenance of Victoria’s low incidence of CPE, and methodologies may be transferrable to other low-prevalence settings and MROs. Funding Statement: This work is supported by the National Health and Medical Research Council (NHMRC) through a partnership grant (GNT1149991), individual supporting grants (GNT1142613 to J.C.K., GNT1123854 to D.A.W., and GNT1105905 to B.P.H.). N.L.S. and C.R.L. are supported by Australian Government Research Training Program (RTP) scholarships. MDU PHL is funded by the Victorian Government. Declaration of Interests: The authors declare no competing interests. Ethics Approval Statement: All data were collected and analysed as part of routine surveillance through the Victorian Department of Health and Human Services in accordance with the Victorian Public Health and Wellbeing Act 2008 (Vic). No additional ethical approval or consent was required for the project.