178. Endemic Carbapenem Resistance Driven By Clonal and Horizontal Spread of bla IMP-4 Across Diverse Enterobacterales: Jumping Genes, Promiscuous Plasmids and Killer Clones

Abstract

s • OFID 2021:8 (Suppl 1) • S109 Figure 3. Survival analysis comparing patients with carbapenem-resistant Enterobacterales (CRE) that are ertapenem mono-resistant to other CRE (i.e., resistant to ≥1 carbapenem other than ertapenem), either total (A) or stratified by isolate site (B). Ertapenem mono-resistant) isolates were not associated with decreased mortality, and sterile isolate source (i.e., non-urinary isolates) was associated with increased mortality regardless of ertapenem mono-resistance. Conclusion. Ertapenem mono-resistant CRE rarely have carbapenemase genes and have distinct clinical and microbiologic characteristics compared to other CRE. Session: O-35. Trends in Gram-negative Resistance Background. Carbapenem-resistant Enterobacterales (CRE) have become en-demic and cause significant morbidity and mortality globally. The metallo-beta-lacta-mase gene bla IMP-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 bla IMP-4 in clinical and environmental isolates from 2008-2020 at our institution. Methods. We performed whole genome sequencing on 219 bla IMP-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 bla IMP-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, sulfa-methoxazole, 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, bla IMP-4 was present on IncC plasmids in Serratia marcescens and Klebsiella pneumoniae. We noted small outbreaks of Pseudomonas aeruginosa ST111 with chromosomal integration of bla IMP-4 from 2008-2018 (16 isolates) and Enterobacter cloacae complex ST114 with bla IMP-4 on IncFIB(K)/ IncFIA(HI1) plasmids from 2011-2020 (19 isolates). From 2016-2020, there was an explosion of diverse IncHI2 plasmids carrying bla IMP-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 bla IMP-4 , these plasmids carried mcr-9.1, a colistin resistance gene, and resistance determinants to nearly all key classes of Gram-negative antimicrobials.