{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T03:06:33Z","timestamp":1777431993838,"version":"3.51.4"},"reference-count":42,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2022,6,20]],"date-time":"2022-06-20T00:00:00Z","timestamp":1655683200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100018336","name":"National Institute for Health Research Health Protection Research Unit","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100018336","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100018336","name":"NIHR HPRU","doi-asserted-by":"crossref","award":["NIHR200915"],"award-info":[{"award-number":["NIHR200915"]}],"id":[{"id":"10.13039\/100018336","id-type":"DOI","asserted-by":"crossref"}]},{"name":"NIHR Research Methods Fellowship","award":["NIHR-RM-FI-2017-08-002-001"],"award-info":[{"award-number":["NIHR-RM-FI-2017-08-002-001"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,8,25]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Reported bacteraemia outcomes following inactive empirical antibiotics (based on in vitro testing) are conflicting, potentially reflecting heterogeneity in causative species, MIC breakpoints defining resistance\/susceptibility, and times to rescue therapy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We investigated adult inpatients with Escherichia coli bacteraemia at Oxford University Hospitals, UK, from 4 February 2014 to 30 June 2021 who were receiving empirical amoxicillin\/clavulanate with\/without other antibiotics. We used Cox regression to analyse 30\u2005day all-cause mortality by in vitro amoxicillin\/clavulanate susceptibility (activity) using the EUCAST resistance breakpoint (&amp;gt;8\/2\u2005mg\/L), categorical MIC, and a higher resistance breakpoint (&amp;gt;32\/2\u2005mg\/L), adjusting for other antibiotic activity and confounders including comorbidities, vital signs and blood tests.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>A total of 1720 E. coli bacteraemias (1626 patients) were treated with empirical amoxicillin\/clavulanate. Thirty-day mortality was 193\/1400 (14%) for any active baseline therapy and 52\/320 (16%) for inactive baseline therapy (P\u200a=\u200a0.17). With EUCAST breakpoints, there was no evidence that mortality differed for inactive versus active amoxicillin\/clavulanate [adjusted HR (aHR)\u200a=\u200a1.27 (95% CI 0.83\u20131.93); P\u200a=\u200a0.28], nor of an association with active aminoglycoside (P\u200a=\u200a0.93) or other active antibiotics (P\u200a=\u200a0.18). Considering categorical amoxicillin\/clavulanate MIC, MICs\u200a&amp;gt;\u200a32\/2\u2005mg\/L were associated with mortality [aHR\u200a=\u200a1.85 versus MIC\u200a=\u200a2\/2\u2005mg\/L (95% CI 0.99\u20133.73); P\u200a=\u200a0.054]. A higher resistance breakpoint (&amp;gt;32\/2\u2005mg\/L) was independently associated with higher mortality [aHR\u200a=\u200a1.82 (95% CI 1.07\u20133.10); P\u200a=\u200a0.027], as were MICs\u200a&amp;gt;\u200a32\/2\u2005mg\/L with active empirical aminoglycosides [aHR\u200a=\u200a2.34 (95% CI 1.40\u20133.89); P\u200a=\u200a0.001], but not MICs\u200a&amp;gt;\u200a32\/2\u2005mg\/L with active non-aminoglycoside antibiotic(s) [aHR\u200a=\u200a0.87 (95% CI 0.40\u20131.89); P\u200a=\u200a0.72].<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>We found no evidence that EUCAST-defined amoxicillin\/clavulanate resistance was associated with increased mortality, but a higher resistance breakpoint (MIC\u200a&amp;gt;\u200a32\/2\u2005mg\/L) was. Additional active baseline non-aminoglycoside antibiotics attenuated amoxicillin\/clavulanate resistance-associated mortality, but aminoglycosides did not. Granular phenotyping and comparison with clinical outcomes may improve AMR breakpoints.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/jac\/dkac189","type":"journal-article","created":{"date-parts":[[2022,6,20]],"date-time":"2022-06-20T12:42:17Z","timestamp":1655728937000},"page":"2536-2545","source":"Crossref","is-referenced-by-count":14,"title":["Mortality risks associated with empirical antibiotic activity in\n                    <i>Escherichia coli<\/i>\n                    bacteraemia: an analysis of electronic health records"],"prefix":"10.1093","volume":"77","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1356-0392","authenticated-orcid":false,"given":"Chang Ho","family":"Yoon","sequence":"first","affiliation":[{"name":"Big Data Institute, Nuffield Department of Population Health, University of Oxford , UK"},{"name":"Nuffield Department of Medicine, University of Oxford , UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sean","family":"Bartlett","sequence":"additional","affiliation":[{"name":"Nuffield Department of Medicine, University of Oxford , UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4508-7969","authenticated-orcid":false,"given":"Nicole","family":"Stoesser","sequence":"additional","affiliation":[{"name":"Nuffield Department of Medicine, University of Oxford , UK"},{"name":"Department of Infectious Diseases and Microbiology, Oxford University Hospitals NHS Foundation Trust, John Radcliffe Hospital , Oxford , UK"},{"name":"The National Institute for Health Research Oxford Biomedical Research Centre, University of Oxford , Oxford , UK"},{"name":"Health Protection Research Unit in Healthcare Associated Infections and Antimicrobial Resistance, University of Oxford , UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7097-8950","authenticated-orcid":false,"given":"Koen B","family":"Pouwels","sequence":"additional","affiliation":[{"name":"Health Protection Research Unit in Healthcare Associated Infections and Antimicrobial Resistance, University of Oxford , UK"},{"name":"Health Economics Research Centre, Nuffield Department of Population Health, University of Oxford , Oxford , UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicola","family":"Jones","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases and Microbiology, Oxford University Hospitals NHS Foundation Trust, John Radcliffe Hospital , Oxford , UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Derrick W","family":"Crook","sequence":"additional","affiliation":[{"name":"Nuffield Department of Medicine, University of Oxford , UK"},{"name":"Department of Infectious Diseases and Microbiology, Oxford University Hospitals NHS Foundation Trust, John Radcliffe Hospital , Oxford , UK"},{"name":"The National Institute for Health Research Oxford Biomedical Research Centre, University of Oxford , Oxford , UK"},{"name":"Health Protection Research Unit in Healthcare Associated Infections and Antimicrobial Resistance, University of Oxford , UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tim E A","family":"Peto","sequence":"additional","affiliation":[{"name":"Nuffield Department of Medicine, University of Oxford , UK"},{"name":"Department of Infectious Diseases and Microbiology, Oxford University Hospitals NHS Foundation Trust, John Radcliffe Hospital , Oxford , UK"},{"name":"The National Institute for Health Research Oxford Biomedical Research Centre, University of Oxford , Oxford , UK"},{"name":"Health Protection Research Unit in Healthcare Associated Infections and Antimicrobial Resistance, University of Oxford , UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A Sarah","family":"Walker","sequence":"additional","affiliation":[{"name":"Nuffield Department of Medicine, University of Oxford , UK"},{"name":"The National Institute for Health Research Oxford Biomedical Research Centre, University of Oxford , Oxford , UK"},{"name":"Health Protection Research Unit in Healthcare Associated Infections and Antimicrobial Resistance, University of Oxford , UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David W","family":"Eyre","sequence":"additional","affiliation":[{"name":"Big Data Institute, Nuffield Department of Population Health, University of Oxford , UK"},{"name":"Department of Infectious Diseases and Microbiology, Oxford University Hospitals NHS Foundation Trust, John Radcliffe Hospital , Oxford , UK"},{"name":"The National Institute for Health Research Oxford Biomedical Research Centre, University of Oxford , Oxford , UK"},{"name":"Health Protection Research 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