1. 178. Endemic Carbapenem Resistance Driven By Clonal and Horizontal Spread of blaIMP-4 Across Diverse Enterobacterales: Jumping Genes, Promiscuous Plasmids and Killer Clones
- Author
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Macesic, N, Blakeway, L, Jenney, AW, Peleg, A, Macesic, N, Blakeway, L, Jenney, AW, and Peleg, A
- Abstract
Background Carbapenem-resistant Enterobacterales (CRE) have become endemic and cause significant morbidity and mortality globally. The metallo-beta-lactamase gene blaIMP-4 is a key CRE resistance determinant in Australia and Asia but its genomic context remains unknown. We aimed to determine the genomic epidemiology of blaIMP-4 in clinical and environmental isolates from 2008 – 2020 at our institution. Methods We performed whole genome sequencing on 219 blaIMP-4-carrying isolates from 134 patients (219 short-read and 75 long-read). Multi-locus sequence types (MLSTs), resistance determinants and plasmid replicons were assessed. High-quality de novo hybrid assemblies were used to identify location of blaIMP-4 gene. We conducted phylogenetic analysis for key MLSTs and plasmids. Results Bla IMP-4 was noted on a class I integron also harboring aminoglycoside, sulfamethoxazole, chloramphenicol and quaternary ammonium compound resistance genes. This integron was able to migrate over time to 10 bacterial species (42 STs) and 6 different plasmid types (Figure 1 and Figure 2). From 2008-2020, blaIMP-4 was present on IncC plasmids in Serratia marcescens and Klebsiella pneumoniae. We noted small outbreaks of Pseudomonas aeruginosa ST111 with chromosomal integration of blaIMP-4 from 2008-2018 (16 isolates) and Enterobacter cloacae complex ST114 with blaIMP-4 on IncFIB(K)/IncFIA(HI1) plasmids from 2011-2020 (19 isolates). From 2016-2020, there was an explosion of diverse IncHI2 plasmids carrying blaIMP-4. This was driven by clonal expansion of E. cloacae complex ST93/ST190 (79 isolates), with spillover of IncHI2 plasmids to Klebsiella spp (13 isolates), Citrobacter spp (2 isolates), S. marcescens (1 isolate), Escherichia coli (4 isolates). In addition to blaIMP-4, these plasmids carried mcr-9.1, a colistin resistance gene, and resistance determinants to nearly all key classes of Gram-negative antimicrobials. Figure 1. Bacterial species harboring blaIMP-4 2008-2020 BlaIMP
- Published
- 2021