Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 Apr 11;12(4):ofaf005.
doi: 10.1093/ofid/ofaf005. eCollection 2025 Apr.

Frequency, Antimicrobial Susceptibility, and Molecular Characterization of Carbapenem-Resistant Enterobacterales Stratified by United States Census Divisions: Results From the INFORM Program (2018-2022)

Helio S Sader  1 , John H Kimbrough  1 , Timothy B Doyle  1 , Marisa L Winkler  1 , Mariana Castanheira  1
Affiliations

Frequency, Antimicrobial Susceptibility, and Molecular Characterization of Carbapenem-Resistant Enterobacterales Stratified by United States Census Divisions: Results From the INFORM Program (2018-2022)

Helio S Sader et al. Open Forum Infect Dis. .

Abstract

Background: Recently approved β-lactamase inhibitor combinations, such as ceftazidime-avibactam, meropenem-vaborbactam, and imipenem-relebactam, have demonstrated a broad spectrum of activity against carbapenem-resistant Enterobacterales (CRE) from US hospitals, but resistance may emerge with the increasing use of these compounds. Aztreonam-avibactam was recently approved in Europe and it is under clinical development in the United States. We evaluated the activity of aztreonam-avibactam and comparators against CREs from US hospitals.

Methods: A total of 45 497 Enterobacterales isolates were consecutively collected from 79 US medical centers (36 states) and susceptibility tested by broth microdilution. Aztreonam-avibactam was tested with avibactam at a fixed 4 mg/L and a susceptible breakpoint of ≤4 mg/L was applied for comparison. CRE isolates were screened for carbapenemase by whole-genome sequencing.

Results: Aztreonam-avibactam inhibited >99.9% of Enterobacterales at ≤4 mg/L. CRE frequencies varied from 0.2% (New England) to 2.4% (Middle Atlantic). Aztreonam-avibactam was active (minimum inhibitory concentration ≤4 mg/L) against 98.6% (408/414) of CREs overall, whereas susceptibility to ceftazidime-avibactam and meropenem-vaborbactam were lowest in the Mountain division (67.7% and 74.2%, respectively) and highest (100.0%) in West North Central. Klebsiella pneumoniae carbapenemase was the most common carbapenemase (65.5% of CREs), followed by New Delhi MBL (10.6%) and oxacillinase-48-like (2.7%). The occurrence of Klebsiella pneumoniae carbapenemase among CREs varied from 14.3% (New England) to 77.8% (East South Central), whereas the frequency of MBLs ranged from ≤3.0% (4 divisions) to 19.4% in Mountain and 42.9% in New England.

Conclusions: Aztreonam-avibactam showed potent activity against CRE, including MBL producers. Resistance to ceftazidime-avibactam and meropenem-vaborbactam was observed among CRE because of increasing occurrence of MBL-producing isolates.

Keywords: CRE; KPC; NDM; OXA-48; metallo-beta-lactamase.

PubMed Disclaimer

Conflict of interest statement

Potential conflicts of interest. None of the authors has a conflict of interest. Element Iowa City (JMI Laboratories) was contracted to perform services in 2022–2024 for AimMax Therapeutics, Amicrobe, Inc., Appili Therapeutics, Armata Pharmaceuticals, Astellas Pharma, Inc., Basilea Pharmaceutica AG, Biosergen AB, Bugworks, Cerba Research NV, Cidara Therapeutics, Cipla USA Inc., ContraFect Corporation, CorMedix Inc., Crestone, Inc., Curza Global, LLC, Diamond V, Discuva Ltd., Entasis Therapeutics, Enveda Biosciences, Evopoint Biosciences, Fedora Pharmaceuticals, Fox Chase Chemical Diversity Center, Genentech, Gilead Sciences, Inc., GSK plc, Iterum Therapeutics plc, Janssen Biopharma, Johnson & Johnson, Kaleido Biosciences, LifeMine Therapeutics, Medpace, Inc, Lysovant Sciences, Inc, Meiji Seika Pharma, Melinta Therapeutics, Menarini Group, Merck & Co., MicuRx Pharmaceutical Inc., Mundipharma International Ltd., Mutabilis, Nabriva Therapeutics, National Cancer Institute, National Institutes of Health, Ohio State University, Omnix Medical Ltd., Paratek Pharmaceuticals, Pfizer, PolyPid Ltd., PPD, Prokaryotics, Inc., Pulmocide Ltd, Qpex Biopharma, Revagenix, Roche Holding AG, Roivant Sciences, Scynexis, Inc., Shionogi & Co., Ltd., Sinovent Pharmaceuticals, Inc., Spero Therapeutics, Sumitovant Biopharma, Inc., TenNor Therapeutics, U.S. Food and Drug Administration, VenatoRx Pharmaceuticals, Washington University, Watershed Medical, LLC, Wockhardt, and Zoetis, Inc.

Figures

Figure 1.
Figure 1.
Aztreonam-avibactam (ATM-AVI) minimum inhibitory concentration (MIC) distributions for Enterobacterales and carbapenem-resistant Enterobacterales (CRE) isolates from US medical centers (2018–2022).
Figure 2.
Figure 2.
Activities of aztreonam-avibactam (ATM-AVI), ceftazidime-avibactam (CAZ-AVI), meropenem-vaborbactam (MEM-VAB), imipenem-relebactam (IMI-REL), and cefiderocol against carbapenem-resistant Enterobacterales (CRE) isolates from US medical centers (2018–2022). Census Divisions: 1, New England; 2, Middle Atlantic; 3, East North Central; 4, West North Central; 5, South Atlantic; 6, East South Central; 7, West South Central; 8, Mountain; 9, Pacific.
Figure 3.
Figure 3.
Frequency of carbapenemases among carbapenem-resistant Enterobacterales (CRE) isolates stratified by US Census Division. Census Divisions: 1, New England; 2, Middle Atlantic; 3, East North Central; 4, West North Central; 5, South Atlantic; 6, East South Central; 7, West South Central; 8, Mountain; 9, Pacific.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Martin A, Fahrbach K, Zhao Q, Lodise T. Association between carbapenem resistance and mortality among adult, hospitalized patients with serious infections due to Enterobacteriaceae: results of a systematic literature review and meta-analysis. Open Forum Infect Dis 2018; 5:ofy150. - PMC - PubMed
    1. Paniagua-Garcia M, Bravo-Ferrer JM, Perez-Galera S, et al. Attributable mortality of infections caused by carbapenem-resistant Enterobacterales: results from a prospective, multinational case-control-control matched cohorts study (EURECA). Clin Microbiol Infect 2024; 30:223–30. - PubMed
    1. Zhou R, Fang X, Zhang J, et al. Impact of carbapenem resistance on mortality in patients infected with Enterobacteriaceae: a systematic review and meta-analysis. BMJ Open 2021; 11:e054971. - PMC - PubMed
    1. Barbier F, Hraiech S, Kerneis S, et al. Rationale and evidence for the use of new beta-lactam/beta-lactamase inhibitor combinations and cefiderocol in critically ill patients. Ann Intensive Care 2023; 13:65. - PMC - PubMed
    1. Tamma PD, Heil EL, Justo JA, Mathers AJ, Satlin MJ, Bonomo RA. Infectious Diseases Society of America 2024 guidance on the treatment of antimicrobial-resistant Gram-negative infections. Clin Infect Dis 2024; ciae403 [in press]. - PubMed