1688. Aztreonam-Avibactam Activity against a Large Collection of Carbapenem-Resistant Enterobacterales (CRE) collected in Hospitals from Europe, Asia, and Latin America (2019-2021)
Authors: Sader Helio S , Carvalhaes Cecilia G , Kantro Valerie , Castanheira Mariana , Mendes Rodrigo E 
Published: December 2022

Abstract

Background
Aztreonam-avibactam (ATM-AVI) is being developed to treat infections caused by Gram-negative bacteria. We evaluated the in vitro activities of ATM-AVI and comparators against a global (ex-US) collection of carbapenem-resistant Enterobacterales (CRE), including ceftazidime-avibactam (CAZ-AVI) resistant (R) isolates.

Methods
24,924 isolates were consecutively collected (1/patient) from 69 medical centers in 36 countries in 2019-2021. Isolates were susceptibility tested by CLSI broth microdilution and CRE isolates (n=1,098; 4.4%) were further evaluated. CRE isolates were from Europe (EU; n=681), Latin America (LATAM; n=240) and Asia-Pacific region (APAC; n=177). An ATM-AVI PK/PD breakpoint of ≤8 mg/L was applied for comparison. CRE isolates from 2019-2020 were screened for carbapenemase (CPE) genes by whole genome sequencing (WGS). Susceptibility results were stratified by geography and CPE gene.

Results
ATM-AVI inhibited 99.6% of CREs at ≤ 8 mg/L (MIC50/90, 0.25/0.5 mg/L), including 98.9% (345/349) of CAZ-AVI-R isolates (Table). ATM-AVI activity was consistent across geographic regions (98.9-100.0% inhibited at ≤8 mg/L), but susceptibility to comparators varied markedly. Susceptibility rates for CAZ-AVI, meropenem-vaborbactam and imipenem-relebactam were 73.6%, 59.1% and 55.5% in EU, 74.1%, 78.3% and 68.0% in LATAM, and 38.6%, 39.8% and 31.4% in APAC, respectively. The most active comparator was tigecycline (MIC50/90, 0.5/2 mg/L; 93.4% susceptible [S]). ATM-AVI retained activity against isolates non-S to colistin (99.7% inhibited at ≤ 8 mg/L) or tigecycline (98.6% inhibited at ≤8 mg/L). A CPE gene was identified in 608 of 692 isolates (87.9%) submitted to WGS. The most common CPEs were KPC (40.9% of CREs), NDM (26.9%), and OXA-48-like (20.1%); 37 isolates (5.3%) had &gt; 1 CPE gene. ATM-AVI inhibited 100.0% of CPE-producers at ≤ 8 mg/L independent of CPE type or geography, whereas current available β-lactamase inhibitors combinations exhibited limited activity against isolates producing MBL or OXA-48-like.

Conclusion
ATM-AVI activity was not adversely affected by clinically relevant CPEs. Our results support the development of ATM-AVI to treat infections caused by CRE, including MBL producers.

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 Cecilia G. Carvalhaes, MD, PhD, AbbVie: Grant/Research Support|Cidara: Grant/Research Support|Melinta: Grant/Research Support|Pfizer: 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 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.