Genomics for molecular epidemiology and detecting transmission of carbapenemase-producing Enterobacterales in Victoria, Australia, 2012-2016.

Abstract

Background Carbapenemase-producing Enterobacterales (CPE) are being increasingly reported in Australia, and integrated clinical and genomic surveillance is critical to effectively manage this threat. We sought to systematically characterize CPE in Victoria, Australia from 2012-2016. Methods Suspected CPE were referred to the state public health laboratory in Victoria, Australia from 2012-2016, and examined using phenotypic, multiplex PCR, and whole genome sequencing (WGS) methods, and compared with epidemiological metadata. Results Carbapenemase genes were detected in 361 isolates from 291 patients (30.8% of suspected CPE isolates), mostly from urine (42.1%) or screening samples (34.8%). IMP-4 (28.0% of patients), KPC-2 (25.3%), NDM (24.1%) and OXA carbapenemases (22.0%) were most common; Klebsiella pneumoniae (48.8% of patients) and Escherichia coli (26.1%) were the dominant species. Carbapenemase-inactivation method (CIM) testing reliably detected carbapenemase-positive isolates (100% sensitivity, 96.9% specificity), identifying an additional five CPE amongst 159 PCR-negative isolates (IMI and SME carbapenemases).When epidemiologic investigations were performed, all pairs of patients designated 'highly likely' or 'possible' local transmission had ≤23 pairwise single-nucleotide polymorphisms (SNPs) by genomic transmission analysis; conversely, all patient pairs designated 'highly unlikely' local transmission had ≥26 pairwise SNPs. Using this proposed threshold, possible local transmission was identified involving a further 16 patients for whom epidemiologic data was unavailable. Conclusions Systematic application of genomics has uncovered the emergence of polyclonal CPE as a significant threat in Australia, providing important insights to inform local public health guidelines and interventions. Using our workflow, pairwise SNP distances between CPE isolates of ≤23 SNPs suggests local transmission.