{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T15:49:39Z","timestamp":1787759379417,"version":"build-2784847793"},"reference-count":25,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2023,2,3]],"date-time":"2023-02-03T00:00:00Z","timestamp":1675382400000},"content-version":"vor","delay-in-days":2,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100019383","name":"Cipla Ltd","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100019383","id-type":"DOI","asserted-by":"crossref"}]},{"name":"JMI Laboratories"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,2,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>The Clinical and Laboratory Standards Institute (CLSI) lowered the Enterobacterales-susceptible\/-resistant breakpoints for amikacin in 2023 from \u226416\/\u226564\u2005mg\/L to \u22644\/\u226516\u2005mg\/L and the breakpoints for gentamicin and tobramycin from \u22644\/\u226516\u2005mg\/L to \u22642\/\u22658\u2005mg\/L. Because aminoglycosides are frequently used to treat infections caused by multidrug-resistant (MDR) and carbapenem-resistant Enterobacterales (CRE), we evaluated the impact of these changes on the susceptibility rates (%S) of Enterobacterales collected from US medical centers.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A total of 9809 Enterobacterales isolates were consecutively collected (1\/patient) from 37 US medical centers in 2017\u20132021 and susceptibility was tested by broth microdilution. Susceptibility rates were calculated using CLSI 2022, CLSI 2023, and US Food and Drug Administration 2022 criteria. Aminoglycoside-nonsusceptible isolates were screened for genes encoding aminoglycoside-modifying enzymes (AMEs) and 16S rRNA methyltransferases (16RMT).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The CLSI breakpoint changes mostly affected amikacin, especially against MDR (94.0%S to 71.0%S), extended-spectrum \u03b2-lactamase (ESBL)-producing (96.9%S to 79.7%S), and CRE (75.2%S to 59.0%S) isolates. Plazomicin was active against 96.4% of isolates and retained potent activity against CRE (94.0%S), ESBL-producing (98.9%S), and MDR (94.8%S) isolates. Gentamicin and tobramycin showed limited activity against resistant subsets of Enterobacterales. The AME-encoding genes and 16RMT were observed in 801 (8.2%) and 11 (0.1%) isolates, respectively. Plazomicin was active against 97.3% of the AME producers.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The spectrum of activity of amikacin against resistant subsets of Enterobacterales was drastically reduced when interpretative criteria based on pharmacokinetic\/pharmacodynamic parameters that are currently used to establish breakpoints for other antimicrobials were applied. Plazomicin was markedly more active than amikacin, gentamicin, or tobramycin against antimicrobial-resistant Enterobacterales.<\/jats:p><\/jats:sec>","DOI":"10.1093\/ofid\/ofad058","type":"journal-article","created":{"date-parts":[[2023,2,3]],"date-time":"2023-02-03T17:59:10Z","timestamp":1675447150000},"source":"Crossref","is-referenced-by-count":23,"title":["Impact of the Recent Clinical and Laboratory Standards Institute Breakpoint Changes on the Antimicrobial Spectrum of Aminoglycosides and the Activity of Plazomicin Against Multidrug-Resistant and Carbapenem-Resistant Enterobacterales From United States Medical Centers"],"prefix":"10.1093","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7022-6644","authenticated-orcid":false,"given":"Helio S","family":"Sader","sequence":"first","affiliation":[{"name":"JMI Laboratories , North Liberty, Iowa , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8648-1137","authenticated-orcid":false,"given":"Rodrigo E","family":"Mendes","sequence":"additional","affiliation":[{"name":"JMI Laboratories , North Liberty, Iowa , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0457-1543","authenticated-orcid":false,"given":"John H","family":"Kimbrough","sequence":"additional","affiliation":[{"name":"JMI Laboratories , North Liberty, Iowa , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9178-1847","authenticated-orcid":false,"given":"Valerie","family":"Kantro","sequence":"additional","affiliation":[{"name":"JMI Laboratories , North Liberty, Iowa , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0126-1782","authenticated-orcid":false,"given":"Mariana","family":"Castanheira","sequence":"additional","affiliation":[{"name":"JMI Laboratories , North Liberty, Iowa , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,2,3]]},"reference":[{"key":"2023022712292919700_","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1021\/acsinfecdis.9b00441","article-title":"Aminoglycosides: time for resurrection of a neglected class of antibacterials?","volume":"6","author":"Bottger","year":"2020","journal-title":"ACS Infect Dis"},{"key":"2023022712292919700_","doi-asserted-by":"crossref","first-page":"1585","DOI":"10.1517\/14656566.2013.806486","article-title":"Aminoglycoside therapy in infectious diseases","volume":"14","author":"Poulikakos","year":"2013","journal-title":"Expert Opin Pharmacother"},{"key":"2023022712292919700_","doi-asserted-by":"crossref","first-page":"650","DOI":"10.1128\/AAC.39.3.650","article-title":"Experience with a once-daily aminoglycoside program administered to 2,184 adult patients","volume":"39","author":"Nicolau","year":"1995","journal-title":"Antimicrob Agents Chemother"},{"key":"2023022712292919700_","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1016\/j.ijid.2022.01.029","article-title":"Antimicrobial activity of high-dose cefepime-tazobactam (WCK 4282) against a large collection of Gram-negative organisms collected worldwide in 2018 and 2019","volume":"116","author":"Sader","year":"2022","journal-title":"Int J Infect Dis"},{"key":"2023022712292919700_","volume-title":"Performance standards for antimicrobial susceptibilty testing.","author":"CLSI. M100Ed32."},{"key":"2023022712292919700_","author":"US Food and Drug Administration","year":"2019"},{"key":"2023022712292919700_","first-page":"S71","author":"Bhavnani","year":"2018"},{"key":"2023022712292919700_","article-title":"Activity of plazomicin tested against Enterobacterales isolates collected from U.S. hospitals in 2016\u20132017: effect of different breakpoint criteria on susceptibility rates among aminoglycosides","volume":"64","author":"Castanheira","year":"2021","journal-title":"Antimicrob Agents Chemother"},{"key":"2023022712292919700_","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.diagmicrobio.2018.10.023","article-title":"In vitro activity of plazomicin against Enterobacteriaceae isolates carrying genes encoding aminoglycoside-modifying enzymes most common in US census divisions","volume":"94","author":"Castanheira","year":"2019","journal-title":"Diagn Microbiol Infect Dis"},{"key":"2023022712292919700_","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1128\/AAC.43.4.727","article-title":"Aminoglycosides: activity and resistance","volume":"43","author":"Mingeot-Leclercq","year":"1999","journal-title":"Antimicrob Agents Chemother"},{"key":"2023022712292919700_","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/j.drup.2010.08.003","article-title":"Aminoglycoside modifying enzymes","volume":"13","author":"Ramirez","year":"2010","journal-title":"Drug Resist Updat"},{"key":"2023022712292919700_","doi-asserted-by":"crossref","first-page":"980","DOI":"10.1021\/acsinfecdis.8b00001","article-title":"Plazomicin retains antibiotic activity against most aminoglycoside modifying enzymes","volume":"4","author":"Cox","year":"2018","journal-title":"ACS Infect Dis"},{"key":"2023022712292919700_","doi-asserted-by":"crossref","first-page":"4636","DOI":"10.1128\/AAC.00572-10","article-title":"Synthesis and spectrum of the neoglycoside ACHN-490","volume":"54","author":"Aggen","year":"2010","journal-title":"Antimicrob Agents Chemother"},{"key":"2023022712292919700_","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1007\/s40265-019-1054-3","article-title":"Plazomicin: a novel aminoglycoside for the treatment of resistant Gram-negative bacterial infections","volume":"79","author":"Eljaaly","year":"2019","journal-title":"Drugs"},{"key":"2023022712292919700_","volume-title":"Performance standards for antimicrobial susceptibility testing","author":"CLSI","year":"2023"},{"key":"2023022712292919700_","first-page":"S14","article-title":"Global surveillance of antimicrobial resistance: 20 years of experience with the SENTRY program","volume":"6","author":"Fuhrmeister","year":"2019","journal-title":"Open Forum Infect Dis"},{"key":"2023022712292919700_","volume-title":"Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically","author":"CLSI. M07Ed11","year":"2018"},{"key":"2023022712292919700_","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1111\/j.1469-0691.2011.03570.x","article-title":"Multidrug-resistant, extensively drug-resistant and pandrug-resistant bacteria: an international expert proposal for interim standard definitions for acquired resistance","volume":"18","author":"Magiorakos","year":"2012","journal-title":"Clin Microbiol Infect"},{"key":"2023022712292919700_","doi-asserted-by":"crossref","first-page":"S69","DOI":"10.1093\/ofid\/ofz004","article-title":"Application of next-generation sequencing for characterization of surveillance and clinical trial isolates: analysis of the distribution of beta-lactamase resistance genes and lineage background in the United States","volume":"6","author":"Mendes","year":"2019","journal-title":"Open Forum Infect Dis"},{"key":"2023022712292919700_","doi-asserted-by":"crossref","first-page":"873","DOI":"10.1016\/0002-9343(77)90655-6","article-title":"Resistance to gentamicin, tobramycin, and amikacin among clinical isolates of Bacteria","volume":"62","author":"Moellering","year":"1977","journal-title":"Am J Med"},{"key":"2023022712292919700_","doi-asserted-by":"crossref","first-page":"1000","DOI":"10.1128\/jcm.13.5.1000-1003.1981","article-title":"Gentamicin and amikacin disk susceptibility tests with Pseudomonas aeruginosa: definition of minimal inhibitory concentration correlates for susceptible and resistant categories","volume":"13","author":"Barry","year":"1981","journal-title":"J Clin Microbiol"},{"key":"2023022712292919700_","author":"USCAST"},{"key":"2023022712292919700_","author":"EUCAST"},{"key":"2023022712292919700_","doi-asserted-by":"crossref","DOI":"10.1128\/AAC.00313-18","article-title":"In vitro activity of plazomicin against Gram-negative and Gram-positive isolates collected from U. S. hospitals and comparative activity of aminoglycosides against carbapenem-resistant Enterobacteriaceae and isolates carrying carbapenemase genes","volume":"62","author":"Castanheira","year":"2018","journal-title":"Antimicrob Agents Chemother"},{"key":"2023022712292919700_","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1586\/eri.12.25","article-title":"Comparison of the next-generation aminoglycoside plazomicin to gentamicin, tobramycin and amikacin","volume":"10","author":"Zhanel","year":"2012","journal-title":"Expert Rev Anti Infect Ther"}],"container-title":["Open Forum Infectious Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/ofid\/advance-article-pdf\/doi\/10.1093\/ofid\/ofad058\/49087281\/ofad058.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ofid\/article-pdf\/10\/2\/ofad058\/49344929\/ofad058.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ofid\/article-pdf\/10\/2\/ofad058\/49344929\/ofad058.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,3,23]],"date-time":"2023-03-23T22:33:03Z","timestamp":1679610783000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ofid\/article\/doi\/10.1093\/ofid\/ofad058\/7025709"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,2,1]]},"references-count":25,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2023,2,3]]}},"URL":"https:\/\/doi.org\/10.1093\/ofid\/ofad058","relation":{},"ISSN":["2328-8957"],"issn-type":[{"value":"2328-8957","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2023,2,1]]},"published":{"date-parts":[[2023,2,1]]},"article-number":"ofad058"}}