{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T05:25:10Z","timestamp":1791523510113,"version":"4.3.4"},"reference-count":18,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2022,8,16]],"date-time":"2022-08-16T00:00:00Z","timestamp":1660608000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100015512","name":"Wockhardt","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100015512","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,9,30]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Secondary healthcare will remain pressured for some years, both because SARS-CoV-2 will circulate as a nosocomial pathogen, and owing to backlogs of patients awaiting delayed elective procedures. These stresses will drive the use of Outpatient Parenteral Antibiotic Therapy (OPAT), which will need to cover increasingly resistant Gram-negative opportunists. We evaluated the activity of ertapenem\/zidebactam, proposed for 2\u200a+\u200a2\u2005g q24h administration.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Materials and methods<\/jats:title>\n                  <jats:p>MICs were determined, by BSAC agar dilution, for 1632 Enterobacterales submitted to the UK national reference laboratory for investigation of antimicrobial resistance.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Over 90% of Escherichia coli with AmpC, ESBLs, KPC, metallo- or OXA-48 carbapenemases were inhibited by ertapenem\/zidebactam 1:1 at ertapenem\u2019s current 0.5\u2005mg\/L breakpoint. For other major Enterobacterales, the proportions inhibited by ertapenem\/zidebactam 1:1 at 0.5\u2005mg\/L were mostly 65% to 90% but were lower for Klebsiella pneumoniae\/oxytoca with metallo- or OXA-48 \u03b2-lactamases. However, animal studies support an 8\u2005mg\/L breakpoint for ertapenem\/zidebactam, based on a shortened T&amp;gt;MIC being needed compared with ertapenem alone. On this basis ertapenem\/zidebactam would count as active against 90%\u2013100% of isolates in all groups except K. pneumoniae\/oxytoca with MBLs (\u00b1OXA-48), where MICs and percent susceptibility vary substantially even with inocula within the BSAC acceptable range.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Ertapenem\/zidebactam has a proposed once-daily regimen well suited to OPAT. Even on highly conservative breakpoint projections, it has potential against MDR E. coli, including metallo-carbapenemase producers. If trial data sustain the 8\u2005mg\/L breakpoint indicated by animal experiments, its potential will extend widely across infections due to ESBL-, AmpC- and carbapenemase-producing Enterobacterales.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/jac\/dkac280","type":"journal-article","created":{"date-parts":[[2022,8,16]],"date-time":"2022-08-16T14:19:45Z","timestamp":1660659585000},"page":"2772-2778","source":"Crossref","is-referenced-by-count":14,"title":["Activity of ertapenem\/zidebactam (WCK 6777) against problem Enterobacterales"],"prefix":"10.1093","volume":"77","author":[{"given":"Shazad","family":"Mushtaq","sequence":"first","affiliation":[{"name":"Antimicrobial Resistance and Healthcare Associated Infections Reference Unit, Reference Services Division, United Kingdom Health Security Agency , 61 Colindale Avenue, London NW9 5EQ , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Garello","sequence":"additional","affiliation":[{"name":"Antimicrobial Resistance and Healthcare Associated Infections Reference Unit, Reference Services Division, United Kingdom Health Security Agency , 61 Colindale Avenue, London NW9 5EQ , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Vickers","sequence":"additional","affiliation":[{"name":"Antimicrobial Resistance and Healthcare Associated Infections Reference Unit, Reference Services Division, United Kingdom Health Security Agency , 61 Colindale Avenue, London NW9 5EQ , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neil","family":"Woodford","sequence":"additional","affiliation":[{"name":"Antimicrobial Resistance and Healthcare Associated Infections Reference Unit, Reference Services Division, United Kingdom Health Security Agency , 61 Colindale Avenue, London NW9 5EQ , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David M","family":"Livermore","sequence":"additional","affiliation":[{"name":"Antimicrobial Resistance and Healthcare Associated Infections Reference Unit, Reference Services Division, United Kingdom Health Security Agency , 61 Colindale Avenue, London NW9 5EQ , UK"},{"name":"Norwich Medical School, University of East Anglia , Norwich, Norfolk NR4 7TJ , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,8,16]]},"reference":[{"key":"2022122101553757000_dkac280-B1","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1080\/14787210.2020.1810566","article-title":"Recent innovations and new applications of outpatient parenteral antimicrobial therapy","volume":"19","author":"Farmer","year":"2021","journal-title":"Expert Rev Anti Infect Ther"},{"key":"2022122101553757000_dkac280-B2","doi-asserted-by":"crossref","first-page":"3125","DOI":"10.1093\/jac\/dkz343","article-title":"Outpatient parenteral antimicrobial therapy: updated recommendations from the UK","volume":"74","author":"Chapman","year":"2019","journal-title":"J Antimicrob Chemother"},{"key":"2022122101553757000_dkac280-B3","doi-asserted-by":"crossref","first-page":"1481","DOI":"10.1093\/jac\/dkac047","article-title":"BSAC OPAT Initiative. Outpatient parenteral antimicrobial therapy (OPAT) in the UK: findings from the BSAC National Outcomes Registry (2015\u201319)","volume":"77","author":"Gilchrist","year":"2022","journal-title":"J Antimicrob Chemother"},{"key":"2022122101553757000_dkac280-B4","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/bs.aambs.2014.09.002","article-title":"Escherichia coli ST131: the quintessential example of an international multiresistant high-risk clone","volume":"90","author":"Mathers","year":"2015","journal-title":"Adv Appl Microbiol"},{"key":"2022122101553757000_dkac280-B5","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1016\/j.idc.2020.08.002","article-title":"Multidrug-resistant bacteria in the community: an update","volume":"34","author":"van Duin","year":"2020","journal-title":"Infect Dis Clin North Am"},{"key":"2022122101553757000_dkac280-B6","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1093\/jac\/dkp029","article-title":"Molecular mechanisms disrupting porin expression in ertapenem-resistant Klebsiella and Enterobacter spp. clinical isolates from the UK","volume":"63","author":"Doumith","year":"2009","journal-title":"J Antimicrob Chemother"},{"key":"2022122101553757000_dkac280-B7","doi-asserted-by":"crossref","first-page":"1931","DOI":"10.1093\/jac\/dkac110","article-title":"In vivo efficacy of WCK 6777 (ertapenem\/zidebactam) against carbapenemase-producing Klebsiella pneumoniae in the neutropenic murine pneumonia model","volume":"77","author":"Gethers","year":"2022","journal-title":"J Antimicrob Chemother"},{"key":"2022122101553757000_dkac280-B8","doi-asserted-by":"crossref","DOI":"10.1016\/j.ijantimicag.2021.106318","article-title":"Cefepime\/tazobactam compared with other tazobactam combinations against problem Gram-negative bacteria","volume":"57","author":"Mushtaq","year":"2021","journal-title":"Int J Antimicrob Agents"},{"key":"2022122101553757000_dkac280-B9","doi-asserted-by":"crossref","first-page":"1511","DOI":"10.1093\/jac\/dkab067","article-title":"Activity of cefepime\/zidebactam (WCK 5222) against \u2018problem\u2019 antibiotic-resistant Gram-negative bacteria sent to a national reference laboratory","volume":"76","author":"Mushtaq","year":"2021","journal-title":"J Antimicrob Chemother"},{"key":"2022122101553757000_dkac280-B10","doi-asserted-by":"crossref","first-page":"2278","DOI":"10.1093\/jac\/dkx136","article-title":"Activity of ceftolozane\/tazobactam against surveillance and \u2018problem\u2019 Enterobacteriaceae, Pseudomonas aeruginosa and non-fermenters from the British Isles","volume":"72","author":"Livermore","year":"2017","journal-title":"J Antimicrob Chemother"},{"key":"2022122101553757000_dkac280-B11","doi-asserted-by":"crossref","first-page":"648","DOI":"10.1093\/jac\/dkx438","article-title":"Activity of ceftazidime\/avibactam against problem Enterobacteriaceae and Pseudomonas aeruginosa in the UK, 2015\u201316","volume":"73","author":"Livermore","year":"2018","journal-title":"J Antimicrob Chemother"},{"key":"2022122101553757000_dkac280-B12","first-page":"1","article-title":"A guide to sensitivity testing. 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