Activity of aztreonam–avibactam and comparators against difficult-to-treat resistant Enterobacterales from United States medical centres (2020–24) †
Abstract
Background: The occurrence of infections caused by Gram-negative bacteria with difficult-to-treat resistance (DTR) is rapidly increasing, generally requiring the use of recently approved, last-resort antimicrobial agents or old compounds that are more toxic and/or less effective. We evaluated the activity of aztreonam–avibactam and comparators against DTR Enterobacterales.
Methods: A total of 42 295 Enterobacterales isolates were consecutively collected (one per patient) from 85 US medical centres in 2020–24 and susceptibility tested by Clinical Laboratory Standards Institute broth microdilution. The collection included 450 carbapenem-resistant Enterobacterales (CRE) and 284 DTR isolates, which were screened for β-lactamases by whole genome sequencing.
Results: Aztreonam–avibactam was active against 98.2% of DTR (minimum inhibitory concentration for 50%/90% of the collection, 0.25/1 mg/L) and 97.1% of CRE isolates and retained potent activity (≥90.0% susceptibility) against DTR isolates non-susceptible to ceftazidime–avibactam, meropenem–vaborbactam and/or cefiderocol. Cefiderocol was active against 92.8% of DTR isolates, whereas ceftazidime–avibactam, meropenem–vaborbactam, imipenem–relebactam and the aminoglycosides exhibited limited activity against these organisms. Aztreonam–avibactam and cefiderocol were active against 97.8% and 84.4% of DTR metallo-β-lactamase (MBL) producers, respectively. The most common carbapenemase genes identified among DTR isolates were blaKPC (57.7% of isolates) and blaNDM (29.9%). An MBL gene was observed in 31.7% of DTR and 25.1% of CRE isolates.
Conclusions: Aztreonam–avibactam retained potent activity against DTR Enterobacterales from US medical centres, and its activity was not adversely affected by clinically relevant carbapenemases or resistance to agents used to treat multidrug-resistant Enterobacterales. The activities of other β-lactam/β-lactamase inhibitor combinations and cefiderocol were compromised by the increased occurrence of MBL producers.
Related
- In Vitro Activity of Eravacycline, Aztreonam-Avibactam, and Cefiderocol Against Multidrug-Resistant Gram-Negative Clinical Isolates from a Romanian Tertiary Hospital.
- Longitudinal Multicenter Susceptibility Trends of Ceftazidime/Avibactam and Imipenem/Relebactam and Dose Optimization in Critically Ill Patients with Carbapenem-Resistant Enterobacterales Bloodstream Infections
- From sepsis to necrotizing enterocolitis with appendiceal perforation: a case report of successful salvage therapy with aztreonam–avibactam in an extremely preterm infant with NDM-producing Klebsiella pneumoniae
- In Vitro Activity of Aztreonam-Avibactam, Cefiderocol, and Conventional Antimicrobials Against Metallo-β-Lactamase-Producing Gram-Negative Urinary Isolates: A Systematic Review and Local Single-Center Retrospective Evaluation in a Tertiary Care Hospital (2016-2025) and Evaluation of Novel Agents (2021-2025).
- Outcomes of empirical ceftazidime avibactam plus colistin versus colistin regimens in carbapenem resistant gram negative infection under diagnostic uncertainty
BibTeX
@article{sader2026activity,
title = {{Activity of aztreonam–avibactam and comparators against difficult-to-treat resistant Enterobacterales from United States medical centres (2020–24) †}},
author = {Helio S Sader and John H Kimbrough and Dmitri Debabov and Krisztina M Papp-Wallace and Mariana Castanheira},
journal = {JAC-Antimicrobial Resistance},
year = {2026},
month = nov,
doi = {10.1093/jacamr/dlag249},
url = {https://doi.org/10.1093/jacamr/dlag249},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Activity of aztreonam–avibactam and comparators against difficult-to-treat resistant Enterobacterales from United States medical centres (2020–24) †
AU - Helio S Sader
AU - John H Kimbrough
AU - Dmitri Debabov
AU - Krisztina M Papp-Wallace
AU - Mariana Castanheira
PY - 2026
DA - 2026/11/05
JO - JAC-Antimicrobial Resistance
DO - 10.1093/jacamr/dlag249
UR - https://doi.org/10.1093/jacamr/dlag249
AB - Background: The occurrence of infections caused by Gram-negative bacteria with difficult-to-treat resistance (DTR) is rapidly increasing, generally requiring the use of recently approved, last-resort antimicrobial agents or old compounds that are more toxic and/or less effective. We evaluated the activity of aztreonam–avibactam and comparators against DTR Enterobacterales. Methods: A total of 42 295 Enterobacterales isolates were consecutively collected (one per patient) from 85 US medical centres in 2020–24 and susceptibility tested by Clinical Laboratory Standards Institute broth microdilution. The collection included 450 carbapenem-resistant Enterobacterales (CRE) and 284 DTR isolates, which were screened for β-lactamases by whole genome sequencing. Results: Aztreonam–avibactam was active against 98.2% of DTR (minimum inhibitory concentration for 50%/90% of the collection, 0.25/1 mg/L) and 97.1% of CRE isolates and retained potent activity (≥90.0% susceptibility) against DTR isolates non-susceptible to ceftazidime–avibactam, meropenem–vaborbactam and/or cefiderocol. Cefiderocol was active against 92.8% of DTR isolates, whereas ceftazidime–avibactam, meropenem–vaborbactam, imipenem–relebactam and the aminoglycosides exhibited limited activity against these organisms. Aztreonam–avibactam and cefiderocol were active against 97.8% and 84.4% of DTR metallo-β-lactamase (MBL) producers, respectively. The most common carbapenemase genes identified among DTR isolates were blaKPC (57.7% of isolates) and blaNDM (29.9%). An MBL gene was observed in 31.7% of DTR and 25.1% of CRE isolates. Conclusions: Aztreonam–avibactam retained potent activity against DTR Enterobacterales from US medical centres, and its activity was not adversely affected by clinically relevant carbapenemases or resistance to agents used to treat multidrug-resistant Enterobacterales. The activities of other β-lactam/β-lactamase inhibitor combinations and cefiderocol were compromised by the increased occurrence of MBL producers.
SN - 2632-1823
ER -