2802. Frequency, Antimicrobial Susceptibility, and Molecular Characterization of Carbapenem-Resistant Enterobacterales Stratified by United States Census Divisions: Results from the INFORM Program (2018-2022)
Authors: Sader Helio S , Kimbrough John H , Doyle Timothy , Carvalhaes Cecilia G , Castanheira Mariana 
Published: November 2023

Abstract

Background
Recently approved β-lactamase inhibitor combinations (BLIs), such as ceftazidime-avibactam (CAZ-AVI) and meropenem-vaborbactam (MEM-VAB), have demonstrated a broad spectrum of activity against carbapenem-resistant Enterobacterales (CRE) from US hospitals, but resistance may emerge with the increasing use of these compounds. Aztreonam-avibactam (ATM-AVI) has shown potent activity against CRE, including MBL producers, and is under clinical development. We evaluated the activity of ATM-AVI and comparators against CREs from US hospitals.

Methods
45,497 Enterobacterales (ENT) isolates were consecutively collected from 79 US medical centers (36 states) and susceptibility tested by CLSI broth microdilution. ATM-AVI was tested with AVI at a fixed 4 mg/L and a susceptible (S) breakpoint of ≤ 8 mg/L was applied for comparison. CRE isolates were screened for carbapenemase (CPE) by whole genome sequencing.

Results
ATM-AVI inhibited &gt; 99.9% of ENT at ≤4 mg/L and only 4 isolates (&lt; 0.01%) showed ATM-AVI MICs &gt; 8 mg/L. CAZ-AVI (MIC50/90, 0.12/0.25 mg/L) and MEM-VAB (MIC50/90, 0.03/0.06 mg/L) were active against 99.9% and 99.8% of ENT isolates, respectively. CRE rates varied from 0.2% (New England [NE]) to 2.4% (Middle Atlantic; Table). ATM-AVI was active (MIC ≤ 8 mg/L) against 99.5% (412/414) of CREs, whereas susceptibility to CAZ-AVI and MEM-VAB were lowest in the Mountain [MO] division (67.7% and 74.2%, respectively) and highest (100.0%) in West North Central. ATM-AVI retained activity against ENT non-S to CAZ-AVI and/or MEM-VAB (n=73; MIC50/90, 0.25/2 mg/L; 98.6% inhibited at ≤8 mg/L). KPC was the most common CPE (65.5% of CREs), followed by NDM (8.2%) and OXA-48–like (3.6%). A CPE gene was not observed in 20.8% of CREs. The occurrence of KPC among CREs varied from 14.3% (1/7; NE) to 77.8% (14/18; East South Central [ESC]); whereas the frequency of metallo-β-lactamases (MBLs) ranged from ≤ 3.0% (South Atlantic, East North Central, ESC and Pacific) to 19.4% (6/31) in MO and 42.9% (3/7) in NE.

Conclusion
ATM-AVI showed potent activity against CRE, including MBL producers, from all US Census Divisions. Resistance to CAZ-AVI and MEM-VAB among CRE was observed in the NE and MO Census Divisions due to increasing occurrence of MBL-producing isolates.

Disclosures
Helio S. Sader, MD, PhD, FIDSA, AbbVie: Grant/Research Support|Basilea: Grant/Research Support|Cipla: Grant/Research Support|Paratek: Grant/Research Support|Pfizer: Grant/Research Support|Shionogi: Grant/Research Support John H. Kimbrough, PhD, AbbVie: Grant/Research Support|Basilea: Grant/Research Support|Pfizer: Grant/Research Support|Shionogi: Grant/Research Support Timothy Doyle, MS, AbbVie: Grant/Research Support Cecilia G. Carvalhaes, MD, PhD, AbbVie: Grant/Research Support|bioMerieux: Grant/Research Support|Cipla: Grant/Research Support|CorMedix: Grant/Research Support|Melinta: Grant/Research Support|Pfizer: Grant/Research Support Mariana Castanheira, PhD, AbbVie: Grant/Research Support|Basilea: Grant/Research Support|bioMerieux: Grant/Research Support|Cipla: Grant/Research Support|CorMedix: Grant/Research Support|Entasis: Grant/Research Support|Melinta: Grant/Research Support|Paratek: Grant/Research Support|Pfizer: Grant/Research Support|Shionogi: Grant/Research Support