426. Trends in carbapenem non-susceptible (Carb-NS) Enterobacterales from hospitalized patients in the US from 2014-2020: A comparison between organisms with and without concerns for chromosomal ampC beta-lactamase hyperproduction
Authors: Gupta Vikas , Yu Kalvin , Pogue Jason M , Watts Janet , Clancy Cornelius J 
Published: December 2022

Abstract

Background
Carbapenem-resistant Enterobacterales (ENT) were designated an “Urgent Threat” by the CDC, underscoring need for understanding epidemiological trends over time with these pathogens. We evaluated trends in non-susceptibility to carbapenems (Carb-NS) in ENT in the inpatient setting from 2014-2020 across 314 US facilities nation-wide, with a focus on comparisons between ENT with and without concerns for chromosomal ampC beta-lactamase hyperproduction. Table:Model-estimated inpatient-setting Carb NS % and trends from 2014-2020.Figure:Trends in inpatient % Carb-NS ENT from 2014-2020.

Methods
All adults with a positive ENT culture (first isolate of a species per 30-day period from blood, respiratory, urine, skin/wound, intra-abdominal, or other) in the inpatient setting from 314 US hospitals from 2014 - 2020 were evaluated (BD Insights Research Database, Becton, Dickinson & Company). Carb-NS was defined as intermediate or resistant to ertapenem, imipenem, meropenem or doripenem per commercial panels. Organisms were classified as concerning for hyperproduction of chromosomal ampC b-lactamase (K. aerogenes, E. cloacae, C. freundii; ampC-ENT) and those without such concerns (E coli [EC], K. pneumoniae [KPN], P mirabilis [PM]); non-ampC ENT). Other ENT were excluded. Time series models were used to evaluate the monthly patterns of resistance trends in proportion per isolates tested.

Results
2,513,392 inpatient non-duplicate ENT isolates were evaluated across 314 facilities of which 31,628 (1.3%) were Carb-NS. For Carb-NS ENT, 60.9% (19,277/31,628) were from non-ampC ENT and 30.7% (9,717/31,628) were in ampC ENT; together, these groups made up 91.6% of ENT evaluated. There were significant decreases in overall trends in inpatient ENT by % Carb-NS and % Carb-NS KPN (p &lt; 0.001 for both). There were significant increases (see Table) in inpatient % Carb NS for PM and ampC-ENT (p &lt; 0.0001 for both).

Conclusion
There was significant decrease in overall inpatient % Carb-NS ENT and % Carb-NS KPN from 2014-2020. However, significant increases in % Carb-NS were seen in organisms concerning for hyperproduction of chromosomal ampC. PM, in particular, should be further evaluated for genotypic resistance. Surveillance of Carb-NS isolates should include a broader set of pathogens beyond KPN and EC.

Disclosures
Vikas Gupta, PharmD, Becton, Dickinson and Company: Employee of, and shareholder in, Becton, Dickinson and Company, and the company received funding from GlaxoSmithKline plc. to conduct this study|GlaxoSmithKline plc.: GlaxoSmithKline plc.-sponsored study 212502 Kalvin Yu, MD, FIDSA, Becton, Dickinson and Company: Employee of, and shareholder in, Becton, Dickinson and Company, and the company received funding from GlaxoSmithKline plc. to conduct this study|GlaxoSmithKline plc.: GlaxoSmithKline plc.-sponsored study 212502 jason M. Pogue, PharmD, consultant to Venatorx, Merck, Shionogi, QPex Biopharma, Utility, GSK, and Entasis.: Advisor/Consultant Janet Watts, PhD, Becton, Dickinson and Company: Employee of Becton, Dickinson and Company, and the company received funding from GlaxoSmithKline plc. to conduct this study|GlaxoSmithKline plc.: GlaxoSmithKline plc.-sponsored study 212502 Cornelius J. Clancy, MD, receives research funding paid to his institution from Astellas and Merck: Grant/Research Support|serves as an advisory Board member for Astellas, Cidara, and Scynexis, served on the advisory board for Merck, Qpex Biopharma, and Shionogi: Advisor/Consultant|Venatorx and Needham & Associates: Advisor/Consultant.