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The increase in antimicrobial resistance is of concern for human and animal health, especially when resistance is conferred to extended-spectrum cephalosporins, which are used to treat serious infections in both human and veterinary medicine. Bacteria carrying extended-spectrum cephalosporin resistance genes, including bla CTX-M and bla CMY , are frequently found in dairy manure.

Background The spread of carbapenemase-producing Enterobacterales (CPE) is global threat. Numerous outbreaks of CPE have been reported during the COVID-19 pandemic. We describe the impact of of the SARS-CoV-2 pandemic on the emergence of CPE in south-central Ontario, Canada. Incidence of clinical isolates of CPE and isolates with different CPE genes in Toronto/Peel region, 2017–2021. The upper panel shows the incidence of patients with clinical isolates of CPE by year and quarter from q4 2007 to q1 2022. The lower panel shows the incidence of patients with clinical isolates with different carbapenemase genes by fiscal year during the same period. Methods TIBDN has performed population-based surveillance for CPE in Toronto/Peel region (pop 4.5M) from first identified isolate in 2007. All laboratories test/refer all carbapenem non-susceptible Enterobacterial isolates for identification of CPE. Hospital charts are reviewed and patients/physicians interviewed. Population data are obtained from Statistics Canada. Results From 10/2007 to 3/31/2022, 1367 persons colonized or infected with CPE were identified. Their median age was 68.7yrs (IQR 54–78yrs); 761 (56%) were male. 772 (56%) were colonized when first identified; 115 (8.4%) were bacteremic at identification or subsequently developed bacteremia. The most common organisms were E. coli (651, 48%), K. pneumoniae (436, 32%), Enterobacter spp. (146, 11%), Citrobacter spp (62, 5%); the most common genes were NDM±OXA-48 (722, 53%), OXA-48-like (341, 25%), KPC (225, 16%), VIM (44, 3%). The incidence of CPE infections increased steadily until 3/2020 then declined by 61% and remained stable until 3/2022 (Figure, upper panel). The decline was greater for E. coli (56% decrease), K. pneumoniae (62%) than for Enterobacter spp. (30%) and other species (19%). It occurred in all genes in 2020; however, KPC containing organisms increased again in 2021 (Figure, lower panel). Conclusion The advent of the COVID-19 pandemic was associated with an immediate, substantial decline in the incidence of patients with CPE in our population area. This decline occurred in both isolates with genes usually occurring in cases imported from other countries, and in those usually occurring in cases associated with transmission within Canadian hospitals. Decreased travel and enhanced infection prevention and control in hospitals may both have contributed to reductions in CPE during the pandemic. Disclosures All Authors: No reported disclosures.

Objectives This study assessed in vitro activities of cefepime/taniborbactam and comparator antimicrobial agents against ertapenem-non-susceptible Enterobacterales (ENSE) clinical isolates collected from the CANWARD study 2007–19, and associations between MIC and various mechanisms of β-lactam resistance identified using WGS. Methods A total of 179 ENSE (MIC ≥ 1 mg/L) isolates underwent susceptibility testing using reference CLSI broth microdilution. WGS was performed using the Illumina NextSeq platform. Carbapenemases, ESBLs and other β-lactamases were identified using ResFinder 4.0. Alterations in ompC/F and ftsI (PBP3) were identified by comparing extracted sequences to the appropriate NCBI reference gene. Porin alterations were analysed with Provean v1.1.3. Specific alterations of interest in PBP3 included a YRIN or YRIK insertion after P333. Results Cefepime/taniborbactam was highly active (MIC50/MIC90, 0.5/2 mg/L; 177/179 isolates inhibited at ≤ 8 mg/L) against ENSE with various antimicrobial resistance phenotypes. Thirteen (7.3%) of the 179 ENSE isolates demonstrated cefepime/taniborbactam MIC values ≥ 4 mg/L and possessed combinations of β-lactam resistance mechanisms, including a carbapenemase and/or ESBL and/or other β-lactamase genes, as well as alterations in OmpC and/or OmpF and/or PBP3. Of the two Escherichia coli isolates that demonstrated a cefepime/taniborbactam MIC of 32 mg/L, one possessed NDM-5, OXA-181 and TEM-1B, an OmpC alteration and P333_Y334insYRIN in PBP3, while the second contained CTX-M-71, a truncated OmpF and a large alteration in OmpC (F182_R195delinsMTTNGRDDVFE). Conclusions Cefepime/taniborbactam was highly active against ENSE with various antimicrobial resistance phenotypes/genotypes. ENSE isolates with cefepime/taniborbactam MIC values ≥ 4 mg/L possessed combinations of β-lactam resistance mechanisms, including β-lactamase genes, as well as alterations in OmpC and/or OmpF and/or PBP3.

The usefulness of carbapenems for gram-negative infections is becoming compromised by organisms harboring carbapenemases, enzymes which can hydrolyze the drug. Currently KPC (class A), NDM (class B), and OXA-48 types (class D) are the most globally widespread carbapenemases. However, among the GES-type class A extended-spectrum β-lactamases (ESBLs) there are variants that hydrolyze carbapenems, with blaGES-5 being the most common. Two Escherichia coli and two Serratia marcescens harboring blaGES-5 on plasmids were isolated by the Canadian Nosocomial Infection Surveillance Program (CNISP) from four different patients in a single hospital over a 2-year period. Complete sequencing of the blaGES-5 plasmids indicated that all four had nearly identical backbones consisting of genes for replication, partitioning, and stability, but contained variant accessory regions consisting of mobile elements and antimicrobial resistance genes. The plasmids were of a novel replicon type, but belonged to the MOBQ1 group based on relaxase sequences, and appeared to be mobilizable, but not self-transmissible. Considering the time periods of bacterial isolation, it would appear the blaGES-5 plasmid has persisted in an environmental niche for at least 2 years in the hospital. This has implications for infection control and clinical care when it is transferred to clinically relevant gram-negative organisms.