Helio S Sader, John H Kimbrough, Timothy B Doyle, Marisa L Winkler, Mariana Castanheira
{"title":"美国人口普查部门分层的碳青霉烯耐药肠杆菌的频率、抗菌药物敏感性和分子特征：来自INFORM计划（2018-2022）的结果。","authors":"Helio S Sader, John H Kimbrough, Timothy B Doyle, Marisa L Winkler, Mariana Castanheira","doi":"10.1093/ofid/ofaf005","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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. <i>Klebsiella pneumoniae</i> 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 <i>Klebsiella pneumoniae</i> 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.</p><p><strong>Conclusions: </strong>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.</p>","PeriodicalId":19517,"journal":{"name":"Open Forum Infectious Diseases","volume":"12 4","pages":"ofaf005"},"PeriodicalIF":3.8000,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11986335/pdf/","citationCount":"0","resultStr":"{\"title\":\"Frequency, Antimicrobial Susceptibility, and Molecular Characterization of Carbapenem-Resistant Enterobacterales Stratified by United States Census Divisions: Results From the INFORM Program (2018-2022).\",\"authors\":\"Helio S Sader, John H Kimbrough, Timothy B Doyle, Marisa L Winkler, Mariana Castanheira\",\"doi\":\"10.1093/ofid/ofaf005\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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. <i>Klebsiella pneumoniae</i> 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 <i>Klebsiella pneumoniae</i> 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.</p><p><strong>Conclusions: </strong>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.</p>\",\"PeriodicalId\":19517,\"journal\":{\"name\":\"Open Forum Infectious Diseases\",\"volume\":\"12 4\",\"pages\":\"ofaf005\"},\"PeriodicalIF\":3.8000,\"publicationDate\":\"2025-04-11\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11986335/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Open Forum Infectious Diseases\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1093/ofid/ofaf005\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/4/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q2\",\"JCRName\":\"IMMUNOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Open Forum Infectious Diseases","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1093/ofid/ofaf005","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/4/1 0:00:00","PubModel":"eCollection","JCR":"Q2","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
Frequency, Antimicrobial Susceptibility, and Molecular Characterization of Carbapenem-Resistant Enterobacterales Stratified by United States Census Divisions: Results From the INFORM Program (2018-2022).
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.
期刊介绍：
Open Forum Infectious Diseases provides a global forum for the publication of clinical, translational, and basic research findings in a fully open access, online journal environment. The journal reflects the broad diversity of the field of infectious diseases, and focuses on the intersection of biomedical science and clinical practice, with a particular emphasis on knowledge that holds the potential to improve patient care in populations around the world. Fully peer-reviewed, OFID supports the international community of infectious diseases experts by providing a venue for articles that further the understanding of all aspects of infectious diseases.
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