1685. Antimicrobial Activity of Aztreonam-Avibactam Against Enterobacterales Causing Infection in United States Hospitals (2019-2021)
Authors: Sader Helio S , Mendes Rodrigo E , Shortridge Dee , Duncan Leonard R , Kantro Valerie , Castanheira Mariana 
Published: December 2022

Abstract

Background
The frequency of metallo-β-lactamase (MBL)-producing Enterobacterales (ENT) is increasing in United States (US). Effective antibiotics to treat infections caused by these organisms are urgently needed. We evaluated the activity of aztreonam-avibactam (ATM-AVI) and comparators against a large collection of clinical ENT isolates from US hospitals.

Methods
27,834 ENT isolates were consecutively collected from 74 US medical centers in 2019-2021 and susceptibility tested by broth microdilution. An ATM-AVI PK/PD breakpoint of ≤8 mg/L was applied for comparison. The antimicrobial susceptibility and frequency of key resistance phenotypes were assessed and stratified by year and infection type: bloodstream (BSI; 5,159 isolates; 18.5%), pneumonia (4,013; 14.4%), skin and skin structure (SSSI; 3,418; 12.3%), urinary tract (UTI; 13,177; 47.3%), or other (2,067; 7.4%). Carbapenem-resistant ENT (CRE) from 2019-2020 were screened for carbapenemase (CPE) genes by whole genome sequencing (WGS).

Results
ATM-AVI inhibited &gt;99.9% of ENT at ≤8 mg/L. Only 3 isolates (0.01%) had an ATM-AVI MIC &gt; 8 mg/L. ENT susceptibility to ceftriaxone varied from 84.0% in 2019 to 82.1% in 2021; it was lowest among isolates from pneumonia (75.3%; Table). CRE rates were 0.8%, 0.9%, and 1.1% in 2019, 2020, and 2021, respectively; 99.6% (260/261) of CRE isolates were inhibited at an ATM-AVI MIC of ≤ 8 mg/L. CRE susceptibility to meropenem-vaborbactam (MEM-VAB) decreased from 91.7% in 2019 to 83.1% in 2020 and 76.5% in 2021 (82.1% overall). CRE, multidrug-resistant, and extensively drug-resistant phenotypes were markedly higher among isolates from pneumonia compared to other infections. The most common CPE among CRE from 2019-2020 (n=163) were KPC (70.6% of CRE), NDM (8.0%), and SME (3.7%). Among non-CPE-producing CRE isolates (n=27; 16.6% of CRE), 100.0% were inhibited at ≤8 mg/L of ATM-AVI and 80.0% were MEM-VAB-susceptible. Isolates with an elevated ATM-AVI MIC ( &gt; 8 mg/L) exhibited PBP3 and/or porin alterations.

Conclusion
ATM-AVI demonstrated potent and consistent activity against ENT across infection types and over time. The activities of the comparator β-lactams decreased slightly during the study period and were lowest among isolates from pneumonia.

Disclosures
Helio S. Sader, MD, PhD, AbbVie: Grant/Research Support|Cidara: Grant/Research Support|Melinta: Grant/Research Support|Nabriva Therapeutics: Grant/Research Support|Pfizer: Grant/Research Support Rodrigo E. Mendes, PhD, AbbVie: Grant/Research Support|Cidara: Grant/Research Support|GSK: Grant/Research Support|Melinta: Grant/Research Support|Nabriva Therapeutics: Grant/Research Support|Office for Assistant Secretary of Defense for Health Affairs: Grant/Research Support|Pfizer: Grant/Research Support|Shionogi: Grant/Research Support|Spero Therapeutics: Grant/Research Support Dee Shortridge, PhD, AbbVie: Grant/Research Support|JMI Laboratory: Employee|Melinta: Grant/Research Support|Menarini: Grant/Research Support|Shionogi: Grant/Research Support Leonard R. Duncan, PhD, AbbVie: Grant/Research Support Valerie Kantro, BA, AbbVie: Grant/Research Support|GSK: Grant/Research Support|Melinta: Grant/Research Support|Shionogi: Grant/Research Support Mariana Castanheira, PhD, AbbVie: Grant/Research Support|Cidara: Grant/Research Support|GSK: Grant/Research Support|Melinta: Grant/Research Support|Pfizer: Grant/Research Support|Shionogi: Grant/Research Support.