1685. Antimicrobial Activity of Aztreonam-Avibactam Against Enterobacterales Causing Infection in United States Hospitals (2019-2021). (15th December 2022)

• Record Type: Journal Article
• Authors: Sader, Helio S; Mendes, Rodrigo E; Shortridge, Dee; Duncan, Leonard R; Kantro, Valerie; Castanheira, Mariana
• Is Part Of: Open forum infectious diseases. Volume 9:(2022)Supplement 2
• Publication Date: 2022-12-15
• Subjects: Communicable diseases -- Periodicals; Medical microbiology -- Periodicals; Infection -- Periodicals; 616.9
• DOI: 10.1093/ofid/ofac492.1315
• Languages: English
• ISSNs: 2328-8957

Abstract

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 >99.9% of ENT at ≤8 mg/L. Only 3 isolates (0.01%) had an ATM-AVI MIC > 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 ( > 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.