{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T18:59:36Z","timestamp":1792004376627,"version":"4.4.0"},"reference-count":39,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2021,3,24]],"date-time":"2021-03-24T00:00:00Z","timestamp":1616544000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100015512","name":"Wockhardt Ltd","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100015512","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,5,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Triple-action diazabicyclooctanes, e.g. zidebactam, combine \u03b2-lactamase inhibition, antibacterial activity, and \u2018enhancement\u2019 of PBP3-targeted \u03b2-lactams.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>To examine the activity of cefepime\/zidebactam against consecutive \u2018problem\u2019 Gram-negative bacteria referred to the UK national reference laboratory.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>MICs were determined by BSAC agar dilution for 1632 Enterobacterales, 745 Pseudomonas aeruginosa and 450 other non-fermenters, categorized by carbapenemase detection and interpretive reading.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Universal susceptibility to cefepime\/zidebactam 8\u200a+\u200a8\u2009mg\/L was seen for otherwise multidrug-resistant Enterobacterales with AmpC, extended-spectrum, K1, KPC and OXA-48-like \u03b2-lactamases, or with impermeability and \u2018unassigned\u2019 mechanisms. Unlike ceftazidime\/avibactam and all other comparators, cefepime\/zidebactam 8\u200a+\u200a8\u2009mg\/L also inhibited most (190\/210, 90.5%) Enterobacterales with MBLs. Resistance in the remaining minority of MBL producers, and in 13\/24 with both NDM MBLs and OXA-48-like enzymes, was associated with Klebsiella pneumoniae ST14. For Pseudomonas aeruginosa, MICs of cefepime\/zidebactam rose with efflux grade, but exceeded 8\u200a+\u200a8\u2009mg\/L for only 11\/85 isolates even in the highly-raised efflux group. Among 103 P. aeruginosa with ESBLs or MBLs, 97 (94.5%) were inhibited by cefepime\/zidebactam 8\u200a+\u200a8\u2009mg\/L whereas fewer than 15% were susceptible to any comparator. MICs for Acinetobacter baumannii with acquired OXA carbapenemases clustered around 8\u200a+\u200a8 to 32\u200a+\u200a32\u2009mg\/L, with higher values for MBL producers. A strong enhancer effect augmented activity against many isolates that were highly resistant to cefepime and zidebactam alone and which had mechanisms not inhibited by zidebactam.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Assuming successful clinical trials, cefepime\/zidebactam has scope to widely overcome critical resistances in both Enterobacterales and non-fermenters.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/jac\/dkab067","type":"journal-article","created":{"date-parts":[[2021,2,18]],"date-time":"2021-02-18T20:47:44Z","timestamp":1613681264000},"page":"1511-1522","source":"Crossref","is-referenced-by-count":47,"title":["Activity of cefepime\/zidebactam (WCK 5222) against \u2018problem\u2019 antibiotic-resistant Gram-negative bacteria sent to a national reference 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and Healthcare-Associated Infections Reference Unit, Public Health England, 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, Public Health England, 61 Colindale Avenue, London NW9 5EQ, UK"},{"name":"Norwich Medical School, University of East Anglia, Norwich NR4 7TJ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,3,24]]},"reference":[{"key":"2021070808213878900_dkab067-B1","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1021\/acsinfecdis.7b00243","article-title":"Game changers: new \u03b2-lactamase inhibitor combinations targeting antibiotic resistance in Gram-negative bacteria","volume":"4","author":"Bush","year":"2018","journal-title":"ACS Infect 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