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Antimicrobial Activities of Aztreonam-Avibactam and Comparator Agents against Enterobacterales Analyzed by ICU and
Denis Piérard1, Elizabeth D Hermsen2, Michal Kantecki3
1Department of Microbiology and Infection Control, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, B-1090 Brussels, Belgium.
Abstract:
Increasing antimicrobial resistance among multidrug-resistant (MDR), extended-spectrum β-lactamase (ESBL)- and carbapenemase-producing Enterobacterales (CPE), in particular metallo-β-lactamase (MBL)-positive strains, has led to limited treatment options in these isolates. This study evaluated the activity of aztreonam-avibactam (ATM-AVI) and comparator antimicrobials against Enterobacterales isolates and key resistance phenotypes stratified by wards, infection sources and geographic regions as part of the ATLAS program between 2016 and 2020. Minimum inhibitory concentrations (MICs) were determined per Clinical and Laboratory Standards Institute (CLSI) guidelines. The susceptibility of antimicrobials were interpreted using CLSI and European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoints. A tentative pharmacokinetic/pharmacodynamic breakpoint of 8 µg/mL was considered for ATM-AVI activity. ATM-AVI inhibited ≥99.2% of Enterobacterales isolates across wards and ≥99.7% isolates across infection sources globally and in all regions at ≤8 µg/mL. For resistance phenotypes, ATM-AVI demonstrated sustained activity across wards and infection sources by inhibiting ≥98.5% and ≥99.1% of multidrug-resistant (MDR) isolates, ≥98.6% and ≥99.1% of ESBL-positive isolates, ≥96.8% and ≥90.9% of carbapenem-resistant (CR) isolates, and ≥96.8% and ≥97.4% of MBL-positive isolates, respectively, at ≤8 µg/mL globally and across regions. Overall, our study demonstrated that ATM-AVI represents an important therapeutic option for infections caused by Enterobacterales, including key resistance phenotypes across different wards and infection sources.
Insights
Aztreonam-avibactam (ATM-AVI) shows high efficacy against resistant Enterobacterales, including multidrug-resistant (MDR) and carbapenemase-producing strains. This antimicrobial is a promising option for treating challenging infections across various hospital settings.
Area of Science:
- Clinical microbiology
- Infectious diseases
- Antimicrobial resistance
Background:
- Rising resistance in Enterobacterales, particularly multidrug-resistant (MDR), extended-spectrum β-lactamase (ESBL), and carbapenemase-producing Enterobacterales (CPE), limits treatment options.
- Metallo-β-lactamase (MBL)-positive strains pose a significant challenge due to their resistance mechanisms.
Purpose of the Study:
- To evaluate the in vitro activity of aztreonam-avibactam (ATM-AVI) against Enterobacterales isolates with key resistance phenotypes.
- To assess ATM-AVI's efficacy across different hospital wards, infection sources, and geographic regions.
Main Methods:
- Minimum inhibitory concentrations (MICs) were determined for ATM-AVI and comparators against Enterobacterales isolates collected between 2016-2020 (ATLAS program).
- Susceptibility was interpreted using CLSI and EUCAST breakpoints, with a tentative PK/PD breakpoint of 8 µg/mL for ATM-AVI.
- Isolates were stratified by ward, infection source, and geographic region.
Main Results:
- ATM-AVI demonstrated potent activity, inhibiting ≥99.2% of all Enterobacterales isolates at ≤8 µg/mL globally.
- High sustained activity was observed against key resistance phenotypes: MDR (≥98.5%), ESBL-positive (≥98.6%), carbapenem-resistant (CR) (≥96.8%), and MBL-positive (≥96.8%) isolates.
- ATM-AVI efficacy remained consistent across different wards, infection sources, and geographic regions.
Conclusions:
- ATM-AVI exhibits excellent in vitro activity against a broad range of Enterobacterales, including highly resistant strains.
- ATM-AVI represents a crucial therapeutic option for managing infections caused by challenging Enterobacterales phenotypes.
- The study supports ATM-AVI's role in combating antimicrobial resistance across diverse clinical settings.
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