{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T20:39:22Z","timestamp":1788986362757,"version":"build-2803163510"},"reference-count":28,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2023,1,6]],"date-time":"2023-01-06T00:00:00Z","timestamp":1672963200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Menarini"},{"name":"MSD"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antibiotics"],"abstract":"<jats:p>Background: Avibactam, relebactam and vaborbactam are \u03b2-lactamase inhibitors that proved their efficiency against KPC-producing Enterobacterales. Regarding their inhibitor activity towards Ambler\u2019s class A extended spectrum \u03b2-lactamases (ESBL) and Ambler\u2019s class C cephalosporinase (AmpC), they should be active on most of the carbapenem-resistant non-carbapenemase-producing Enterobacterales (CR non-CPE). Objectives: Determine the in vitro activity of ceftazidime-avibactam, imipenem-relebactam and meropenem-vaborbactam and comparators against CR non-CPE. Methods: MICs to ceftazidime\/avibactam, imipenem\/relebactam, meropenem\/vaborbactam, but also temocillin, ceftolozane\/tazobactam, ertapenem, colistin, eravacycline and tigecycline were determined by broth microdilution (ThermoFisher) on a collection of 284 CR non-CPE (inhibition zone diameter &lt; 22 mm to meropenem). Whole genome sequencing was performed on 90 isolates to assess the genetic diversity as well as resistome. Results: According to EUCAST breakpoints, susceptibility rates of ceftazidime, imipenem, meropenem and ertapenem used at standard dose were 0.7%, 45.1%, 14.8% and 2.5%, respectively. Increased exposure of ceftazidime, imipenem and meropenem led to reach 3.5%, 68.3% and 67.7% susceptibility, respectively. Using the EUCAST clinical breakpoints, susceptibility rates of ceftazidime\/avibactam, imipenem\/relebactam and meropenem\/vaborbactam were 88.4%, 81.0% and 80.6%, respectively. Susceptibility rates of temocillin, ceftolozane\/tazobactam, tigecycline, eravacycline, and colistin were 0%, 4.6%, 27.8%, 54.9% and 90.1%. MICs distributions with and without the presence of the inhibitor demonstrated a better ability of avibactam and relebactam compared to vaborbactam to restore susceptibility to the associated \u03b2-lactam. Conclusions: This study demonstrated the in vitro efficacy of ceftazidime\/avibactam, imipenem\/relebactam and to a lesser extent meropenem\/vaborbactam against CR non-CPE. Moreover, to test all \u03b2-lactams\/\u03b2-lactamases inhibitors combinations without a priori for CRE, non-CPE is crucial since resistance to one of the \u03b2-lactam\/\u03b2-lactamase inhibitor combinations does not predict resistance to another molecule, depending on the resistance mechanisms involved.<\/jats:p>","DOI":"10.3390\/antibiotics12010102","type":"journal-article","created":{"date-parts":[[2023,1,6]],"date-time":"2023-01-06T03:19:54Z","timestamp":1672975194000},"page":"102","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["In Vitro Activity of Imipenem-Relebactam, Meropenem-Vaborbactam, Ceftazidime-Avibactam and Comparators on Carbapenem-Resistant Non-Carbapenemase-Producing Enterobacterales"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2307-3232","authenticated-orcid":false,"given":"R\u00e9my A.","family":"Bonnin","sequence":"first","affiliation":[{"name":"Team \u201cResist\u201d UMR1184 \u201cImmunology of Viral, Auto-Immune, Hematological and Bacterial Diseases (IMVA-HB)\u201d, INSERM, Faculty of Medicine, Paris-Saclay University, 94270 Le Kremlin-Bic\u00eatre, France"},{"name":"Associated French National Reference Center for Antibiotic Resistance: Carbapenemase-Producing Enterobacteriales, 94270 Le Kremlin-Bic\u00eatre, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandrine","family":"Bernabeu","sequence":"additional","affiliation":[{"name":"Team \u201cResist\u201d UMR1184 \u201cImmunology of Viral, Auto-Immune, Hematological and Bacterial Diseases (IMVA-HB)\u201d, INSERM, Faculty of Medicine, Paris-Saclay University, 94270 Le Kremlin-Bic\u00eatre, France"},{"name":"Department of Bacteriology-Hygiene, Assistance Publique des H\u00f4pitaux de Paris, Bic\u00eatre Hospital, 94270 Le Kremlin-Bic\u00eatre, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u00e9cile","family":"Emeraud","sequence":"additional","affiliation":[{"name":"Team \u201cResist\u201d UMR1184 \u201cImmunology of Viral, Auto-Immune, Hematological and Bacterial Diseases (IMVA-HB)\u201d, INSERM, Faculty of Medicine, Paris-Saclay University, 94270 Le Kremlin-Bic\u00eatre, France"},{"name":"Associated French National Reference Center for Antibiotic Resistance: Carbapenemase-Producing Enterobacteriales, 94270 Le Kremlin-Bic\u00eatre, France"},{"name":"Department of Bacteriology-Hygiene, Assistance Publique des H\u00f4pitaux de Paris, Bic\u00eatre Hospital, 94270 Le Kremlin-Bic\u00eatre, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9937-9572","authenticated-orcid":false,"given":"Thierry","family":"Naas","sequence":"additional","affiliation":[{"name":"Team \u201cResist\u201d UMR1184 \u201cImmunology of Viral, Auto-Immune, Hematological and Bacterial Diseases (IMVA-HB)\u201d, INSERM, Faculty of Medicine, Paris-Saclay University, 94270 Le Kremlin-Bic\u00eatre, France"},{"name":"Associated French National Reference Center for Antibiotic Resistance: Carbapenemase-Producing Enterobacteriales, 94270 Le Kremlin-Bic\u00eatre, France"},{"name":"Department of Bacteriology-Hygiene, Assistance Publique des H\u00f4pitaux de Paris, Bic\u00eatre Hospital, 94270 Le Kremlin-Bic\u00eatre, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7698-2798","authenticated-orcid":false,"given":"Delphine","family":"Girlich","sequence":"additional","affiliation":[{"name":"Team \u201cResist\u201d UMR1184 \u201cImmunology of Viral, Auto-Immune, Hematological and Bacterial Diseases (IMVA-HB)\u201d, INSERM, Faculty of Medicine, Paris-Saclay University, 94270 Le Kremlin-Bic\u00eatre, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agn\u00e8s B.","family":"Jousset","sequence":"additional","affiliation":[{"name":"Team \u201cResist\u201d UMR1184 \u201cImmunology of Viral, Auto-Immune, Hematological and Bacterial Diseases (IMVA-HB)\u201d, INSERM, Faculty of Medicine, Paris-Saclay University, 94270 Le Kremlin-Bic\u00eatre, France"},{"name":"Associated French National Reference Center for Antibiotic Resistance: Carbapenemase-Producing Enterobacteriales, 94270 Le Kremlin-Bic\u00eatre, France"},{"name":"Department of Bacteriology-Hygiene, Assistance Publique des H\u00f4pitaux de Paris, Bic\u00eatre Hospital, 94270 Le Kremlin-Bic\u00eatre, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6596-7384","authenticated-orcid":false,"given":"Laurent","family":"Dortet","sequence":"additional","affiliation":[{"name":"Team \u201cResist\u201d UMR1184 \u201cImmunology of Viral, Auto-Immune, Hematological and Bacterial Diseases (IMVA-HB)\u201d, INSERM, Faculty of Medicine, Paris-Saclay University, 94270 Le Kremlin-Bic\u00eatre, France"},{"name":"Associated French National Reference Center for Antibiotic Resistance: Carbapenemase-Producing Enterobacteriales, 94270 Le Kremlin-Bic\u00eatre, France"},{"name":"Department of Bacteriology-Hygiene, Assistance Publique des H\u00f4pitaux de Paris, Bic\u00eatre Hospital, 94270 Le Kremlin-Bic\u00eatre, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"773","DOI":"10.1016\/j.idc.2020.05.001","article-title":"Resistance to Novel \u03b2-Lactam-\u03b2-Lactamase Inhibitor Combinations: The \u201cPrice of Progress\u201d","volume":"34","author":"Mack","year":"2020","journal-title":"Infect. 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