Search and Contain: Impact of an Integrated Genomic and Epidemiological Surveillance and Response Program for Control of Carbapenemase-Producing <i>Enterobacterales</i>

Abstract

Background: Multi-resistant organisms (MROs) pose a critical threat to public health. Recently, population-based systems for surveillance and control of MROs such as Carbapenemase-producing Enterobacterales (CPE) have emerged globally and evaluation is needed. In this study, we assess the feasibility and impact of a state-wide CPE surveillance and response program deployed in December 2015 across Victoria, Australia (population 6·5 million). Methods: A prospective population-based multi-modal intervention, including active screening, carrier isolation, centralised case investigation and comparative pathogen genomics was implemented. We assess impact by analysing trend in CPE incidence and clinical presentation, risk factors for acquisition and local transmission, using data from the first three years of implementation (January 2016 to December 2018). Findings: CPE case ascertainment increased over the study period to 1·42 cases/100,000 population, linked to increased screening without a concomitant rise in active clinical infections (0·45-0·60 infections/100,000 population, p=0·640). Occurrence of KPC-2 infection decreased from 0·29 infections/100,000 population prior to intervention to 0·03 infections/100,000 population in 2018 (p=0·003). Comprehensive case investigation enabled identification of novel risk factors, including non-healthcare-related overseas acquisition. Median time between isolate referral and initial centralised genomic and epidemiological assessment for local transmission was 11 days (IQR 9-14). Prospective surveillance identified numerous small transmission networks (median 2, range 1-19 cases), predominantly IMP- and KPC-producing organisms. Genomic and epidemiologically defined clusters had a median pairwise distance of 8 (IQR 4-13) single nucleotide polymorphisms, however low diversity between clusters of the same sequence type suggested genomic cluster definitions alone are insufficient for targeted control measures. Interpretation: Our results demonstrate the value of centralised CPE surveillance and control programs to increase case ascertainment, resolve risk factors and identify putative local transmission through combined genomic and epidemiological surveillance; methodologies are transferable to other low-prevalence settings and MROs globally. Funding Statement: National Health and Medical Research Council (NHMRC) partnership grant (GNT1149991) and the Victorian Government. Declaration of Interests: The authors declare no competing interests. Ethics Approval Statement: All data were collected in accordance with the Victorian Public Health and Wellbeing Act 2008. Ethical approval was obtained from the Human Ethics Advisory Group of the School of Biomedical Sciences, University of Melbourne (Ethics ID 1954615.2).