{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T15:49:37Z","timestamp":1787759377098,"version":"build-2784847793"},"reference-count":27,"publisher":"Cambridge University Press (CUP)","issue":"5","license":[{"start":{"date-parts":[[2022,7,13]],"date-time":"2022-07-13T00:00:00Z","timestamp":1657670400000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["cambridge.org"],"crossmark-restriction":true},"short-container-title":["Infect. Control Hosp. Epidemiol."],"published-print":{"date-parts":[[2023,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec id=\"S0899823X22001611_as1\"><jats:title>Objective:<\/jats:title><jats:p>We compared the activity of 8 novel \u03b2-lactam and tetracycline-derivative antibiotics against a cohort of clinical carbapenem-resistant Enterobacterales (CRE) isolates and investigated the incremental susceptibility benefit of the addition of an aminoglycoside, fluoroquinolone, or polymyxin to the \u03b2-lactam agents to assist with empiric antibiotic decision making.<\/jats:p><\/jats:sec><jats:sec id=\"S0899823X22001611_as2\"><jats:title>Methods:<\/jats:title><jats:p>A collection of consecutive CRE clinical isolates from unique patients at 3 US hospitals (2016\u20132021) was assembled. Broth microdilution was performed to obtain antimicrobial susceptibility testing results. Mechanisms of carbapenem resistance were investigated through short-read and long-read whole-genome sequencing.<\/jats:p><\/jats:sec><jats:sec id=\"S0899823X22001611_as3\"><jats:title>Results:<\/jats:title><jats:p>Of the 603 CRE isolates, 276 (46%) were carbapenemase producing and 327 (54%) were non\u2013carbapenemase producing, respectively. The organisms most frequently identified were <jats:italic>Klebsiella pneumoniae<\/jats:italic> (38%), <jats:italic>Enterobacter cloacae<\/jats:italic> complex (26%), and <jats:italic>Escherichia coli<\/jats:italic> (16%). We obtained the following percent susceptibility to novel \u03b2-lactam agents: ceftazidime-avibactam (95%), meropenem-vaborbactam (92%), imipenem-relebactam (84%), and cefiderocol (92%). Aminoglycosides and the polymyxins provided greater incremental coverage as second agents, compared to fluoroquinolones. Amikacin and plazomicin exhibited the greatest additive value. Ceftazidime-avibactam, meropenem-vaborbactam, and cefiderocol were active against 94% of the 220 KPC-producing isolates. Cefiderocol was active against 83% of the 29 NDM-producing isolates. Ceftazidime-avibactam had 100% activity against the 9 OXA-48-like\u2013producing isolates. Tigecycline had the highest activity compared to other tetracyclines against KPC, NDM, or OXA-48-like\u2013producing isolates.<\/jats:p><\/jats:sec><jats:sec id=\"S0899823X22001611_as4\"><jats:title>Conclusion:<\/jats:title><jats:p>Selection among novel agents requires a nuanced understanding of the molecular epidemiology of CRE. This work provides insights into the comparative activity of novel agents and the additive value of a second antibiotic for empiric antibiotic decision making.<\/jats:p><\/jats:sec>","DOI":"10.1017\/ice.2022.161","type":"journal-article","created":{"date-parts":[[2022,7,13]],"date-time":"2022-07-13T07:25:04Z","timestamp":1657697104000},"page":"762-767","update-policy":"https:\/\/doi.org\/10.1017\/policypage","source":"Crossref","is-referenced-by-count":27,"title":["Comparing the activity of novel antibiotic agents against carbapenem-resistant Enterobacterales clinical isolates"],"prefix":"10.1017","volume":"44","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4143-6324","authenticated-orcid":false,"given":"Pranita D.","family":"Tamma","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4262-7173","authenticated-orcid":false,"given":"Yehudit","family":"Bergman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily B.","family":"Jacobs","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6303-086X","authenticated-orcid":false,"given":"Jae Hyoung","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shawna","family":"Lewis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara E.","family":"Cosgrove","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia J.","family":"Simner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"for the Centers for Disease Control and Prevention Epicenters Program","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"56","published-online":{"date-parts":[[2022,7,13]]},"reference":[{"key":"S0899823X22001611_ref5","unstructured":"5. Plazomicin. US Food and Drug Adminstration website. https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2018\/210303Orig1s000lbl.pdf. Accessed May 30, 2022."},{"key":"S0899823X22001611_ref13","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciab176"},{"key":"S0899823X22001611_ref27","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkl224"},{"key":"S0899823X22001611_ref11","doi-asserted-by":"crossref","first-page":"e01923","DOI":"10.1128\/AAC.01923-18","article-title":"Applying rapid whole-genome sequencing to predict phenotypic antimicrobial susceptibility testing results among carbapenem-resistant Klebsiella pneumoniae clinical isolates","volume":"63","author":"Tamma","year":"2019","journal-title":"Antimicrob Agents Chemother"},{"key":"S0899823X22001611_ref2","unstructured":"2. Meropenem-vaborbactam. US Food and Drug Adminstration website. https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2017\/209776lbl.pdf. Accessed May 30, 2022."},{"key":"S0899823X22001611_ref4","unstructured":"4. Cefiderocol. US Food and Drug Adminstration website. https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2019\/209445s000lbl.pdf. Accessed May 30, 2022."},{"key":"S0899823X22001611_ref6","unstructured":"6. Eravacycline. US Food and Drug Adminstration website. https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2018\/211109lbl.pdf. Accessed May 30, 2022."},{"key":"S0899823X22001611_ref12","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciaa1478"},{"key":"S0899823X22001611_ref15","first-page":"20499361211011373","article-title":"Antimicrobial stewardship and antibiograms: importance of moving beyond traditional antibiograms","volume":"8","author":"Klinker","year":"2021","journal-title":"Ther Adv Infect Dis"},{"key":"S0899823X22001611_ref17","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciw636"},{"key":"S0899823X22001611_ref18","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02497-17"},{"key":"S0899823X22001611_ref20","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciy492"},{"key":"S0899823X22001611_ref22","doi-asserted-by":"publisher","DOI":"10.1093\/ofid\/ofab371"},{"key":"S0899823X22001611_ref8","unstructured":"8. CRE technical information. Centers for Disease Control and Prevention website. https:\/\/www.cdc.gov\/hai\/organisms\/cre\/technical-info.html#Definition. Accessed May 30, 2022."},{"key":"S0899823X22001611_ref23","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciz1131"},{"key":"S0899823X22001611_ref25","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01733-10"},{"key":"S0899823X22001611_ref26","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/cir611"},{"key":"S0899823X22001611_ref19","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkaa503"},{"key":"S0899823X22001611_ref21","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02313-19"},{"key":"S0899823X22001611_ref14","doi-asserted-by":"publisher","DOI":"10.1017\/ice.2015.196"},{"key":"S0899823X22001611_ref1","unstructured":"1. Ceftazidime-avibactam. US Food and Drug Adminstration website. www.accessdata.fda.gov\/drugsatfda_docs\/label\/2019\/206494s005,s006lbl.pdf. Accessed May 30, 2022."},{"key":"S0899823X22001611_ref7","unstructured":"7. Omadacycline. US Food and Drug Adminstration website. https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2018\/209816_209817lbl.pdf. Accessed May 30, 2022."},{"key":"S0899823X22001611_ref10","unstructured":"10. Antibacterial susceptibility test interpretive criteria. US Food and Drug Administration website. www.fda.gov\/drugs\/development-resources\/antibacterial-susceptibility-test-interpretive-criteria. Accessed February 28, 2022."},{"key":"S0899823X22001611_ref16","volume-title":"Analysis and Presentation of Cumulative Antimicrobial Susceptibility Test Data","year":"2022"},{"key":"S0899823X22001611_ref24","doi-asserted-by":"publisher","DOI":"10.1016\/j.idc.2020.05.001"},{"key":"S0899823X22001611_ref3","unstructured":"3. Imipenem-cilastatin-relebactam. US Food and Drug Adminstration website. https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2019\/212819s000lbl.pdf. Accessed May 30, 2022."},{"key":"S0899823X22001611_ref9","unstructured":"9. Clinical and Laboratory Standards Institute. Performance Standards for Antimicrobial Susceptibility Testing\u2014Thirty-second Edition. M100. Wayne, PA: CLSI; 2022."}],"container-title":["Infection Control &amp; Hospital Epidemiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.cambridge.org\/core\/services\/aop-cambridge-core\/content\/view\/S0899823X22001611","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,24]],"date-time":"2023-05-24T08:19:40Z","timestamp":1684916380000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.cambridge.org\/core\/product\/identifier\/S0899823X22001611\/type\/journal_article"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,7,13]]},"references-count":27,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2023,5]]}},"alternative-id":["S0899823X22001611"],"URL":"https:\/\/doi.org\/10.1017\/ice.2022.161","relation":{},"ISSN":["0899-823X","1559-6834"],"issn-type":[{"value":"0899-823X","type":"print"},{"value":"1559-6834","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,7,13]]},"assertion":[{"value":"\u00a9 The Author(s), 2022. Published by Cambridge University Press on behalf of The Society for Healthcare Epidemiology of America","name":"copyright","label":"Copyright","group":{"name":"copyright_and_licensing","label":"Copyright and Licensing"}},{"value":"This is an Open Access article, distributed under the terms of the Creative Commons Attribution licence (http:\/\/creativecommons.org\/licenses\/by\/4.0\/), which permits unrestricted re-use, distribution and reproduction, provided the original article is properly cited","name":"license","label":"License","group":{"name":"copyright_and_licensing","label":"Copyright and Licensing"}},{"value":"This content has been made available to all.","name":"free","label":"Free to read"}]}}