{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T11:19:03Z","timestamp":1788779943345,"version":"build-2803163510"},"reference-count":23,"publisher":"American Society for Microbiology","issue":"5","license":[{"start":{"date-parts":[[2017,5,1]],"date-time":"2017-05-01T00:00:00Z","timestamp":1493596800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2017,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    WCK 5222 consists of cefepime combined with zidebactam, a bicyclo-acyl hydrazide \u03b2-lactam enhancer antibiotic with a dual action involving binding to Gram-negative bacterial PBP2 and \u03b2-lactamase inhibition. We evaluated the\n                    <jats:italic>in vitro<\/jats:italic>\n                    activity of cefepime-zidebactam against 7,876 contemporary (2015) clinical isolates of\n                    <jats:named-content content-type=\"genus-species\">Enterobacteriaceae<\/jats:named-content>\n                    (\n                    <jats:italic>n<\/jats:italic>\n                    = 5,946),\n                    <jats:named-content content-type=\"genus-species\">Pseudomonas aeruginosa<\/jats:named-content>\n                    (\n                    <jats:italic>n<\/jats:italic>\n                    = 1,291), and\n                    <jats:named-content content-type=\"genus-species\">Acinetobacter<\/jats:named-content>\n                    spp. (\n                    <jats:italic>n<\/jats:italic>\n                    = 639) from the United States (\n                    <jats:italic>n<\/jats:italic>\n                    = 2,919), Europe (\n                    <jats:italic>n<\/jats:italic>\n                    = 3,004), the Asia-Pacific (\n                    <jats:italic>n<\/jats:italic>\n                    = 1,370), and Latin America (\n                    <jats:italic>n<\/jats:italic>\n                    = 583). The isolates were tested by a reference broth microdilution method for susceptibility against cefepime-zidebactam (1:1 and 2:1 ratios) and comparator agents. Cefepime-zidebactam was the most active compound tested against\n                    <jats:named-content content-type=\"genus-species\">Enterobacteriaceae<\/jats:named-content>\n                    (MIC\n                    <jats:sub>50\/90<\/jats:sub>\n                    , \u22640.03\/0.12 \u03bcg\/ml [1:1] and 0.06\/0.25 \u03bcg\/ml [2:1]; 99.9% of isolates were inhibited at \u22644 [1:1] and \u22648 \u03bcg\/ml [2:1]). Cefepime-zidebactam was active against individual\n                    <jats:named-content content-type=\"genus-species\">Enterobacteriaceae<\/jats:named-content>\n                    species (MIC\n                    <jats:sub>50\/90<\/jats:sub>\n                    , \u22640.03 to 0.06\/\u22640.03 to 0.5 \u03bcg\/ml [1:1]) and retained potent activity against carbapenem-resistant isolates (MIC\n                    <jats:sub>50\/90<\/jats:sub>\n                    , 1\/4 \u03bcg\/ml; 99.3% of isolates were inhibited at \u22648 \u03bcg\/ml [1:1]). Cefepime-zidebactam activity was consistent among geographic regions, and only one isolate showed MIC values of &gt;8 \u03bcg\/ml (1:1). Cefepime-zidebactam was also very active against\n                    <jats:named-content content-type=\"genus-species\">P. aeruginosa<\/jats:named-content>\n                    with MIC\n                    <jats:sub>50\/90<\/jats:sub>\n                    values of 1\/4 \u03bcg\/ml, and 99.5% of isolates were inhibited at \u22648 \u03bcg\/ml (1:1). The MIC values for cefepime-zidebactam at the 1:1 ratio were generally 2-fold lower than those for cefepime-zidebactam at the 2:1 ratio (MIC\n                    <jats:sub>50\/90<\/jats:sub>\n                    , 2\/8 \u03bcg\/ml) and zidebactam alone (MIC\n                    <jats:sub>50\/90<\/jats:sub>\n                    , 4\/8 \u03bcg\/ml). Against\n                    <jats:named-content content-type=\"genus-species\">Acinetobacter<\/jats:named-content>\n                    spp., cefepime-zidebactam at 1:1 and 2:1 ratios (MIC\n                    <jats:sub>50\/90<\/jats:sub>\n                    , 16\/32 \u03bcg\/ml for both) was 4-fold more active than cefepime or ceftazidime. Zidebactam exhibited potent\n                    <jats:italic>in vitro<\/jats:italic>\n                    antimicrobial activity against some organisms. These results support the clinical development of WCK 5222 for the treatment of Gram-negative bacterial infections, including those caused by multidrug-resistant isolates.\n                  <\/jats:p>","DOI":"10.1128\/aac.00072-17","type":"journal-article","created":{"date-parts":[[2017,2,27]],"date-time":"2017-02-27T20:40:27Z","timestamp":1488228027000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":74,"title":["WCK 5222 (Cefepime-Zidebactam) Antimicrobial Activity against Clinical Isolates of Gram-Negative Bacteria Collected Worldwide in 2015"],"prefix":"10.1128","volume":"61","author":[{"given":"Helio S.","family":"Sader","sequence":"first","affiliation":[{"name":"JMI Laboratories, North Liberty, Iowa, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariana","family":"Castanheira","sequence":"additional","affiliation":[{"name":"JMI Laboratories, North Liberty, Iowa, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Huband","sequence":"additional","affiliation":[{"name":"JMI Laboratories, North Liberty, Iowa, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronald N.","family":"Jones","sequence":"additional","affiliation":[{"name":"JMI Laboratories, North Liberty, Iowa, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert K.","family":"Flamm","sequence":"additional","affiliation":[{"name":"JMI Laboratories, North Liberty, Iowa, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/cit152"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1111\/nyas.12023"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-0691.2012.03821.x"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02252-12"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1089\/mdr.2012.0238"},{"key":"e_1_3_2_7_2","first-page":"165","article-title":"Vital signs: carbapenem-resistant enterobacteriaceae","volume":"62","author":"Jacob JT","year":"2013","unstructured":"Jacob JT KleinELaxminarayanRBeldavsZLynfieldRKallenAJRicksPEdwardsJSrinivasanAFridkinSRasheedKJLonswayDBulensSHerreraRMcDonaldLCPatelJLimbagoBBellMCardoD. 2013. Vital signs: carbapenem-resistant enterobacteriaceae. MMWR Morb Mortal Wkly Rep62:165\u2013170.","journal-title":"MMWR Morb Mortal Wkly Rep"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1574-6976.2011.00268.x"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-0691.2011.03570.x"},{"key":"e_1_3_2_10_2","unstructured":"Palwe\nSR\nJoshiPRKhandeHNBiniwaleSSBhagwatSSPatelMV. WCK 5107 (zidebactam ZID): a pan Gram-negative beta-lactam enhancer augmenting beta-lactam pharmacodynamics in wild type and carbapenemase producers (CP) abstr Sunday-438. 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Braun Medical, Inc","year":"2015","unstructured":"B. Braun Medical, Inc. 2015. Maxipime package insert, November 2015. B. Braun Medical, Inc,Bethlehem, PA."},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijantimicag.2015.08.011"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.diagmicrobio.2013.10.008"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01121-13"},{"key":"e_1_3_2_21_2","article-title":"WCK 5222 (cefepime-zidebactam) antimicrobial activity tested against Gram-negative organisms producing clinically relevant \u03b2-lactamases","author":"Sader HS","unstructured":"Sader HS RhombergPRFlammRKJonesRNCastanheiraM. WCK 5222 (cefepime-zidebactam) antimicrobial activity tested against Gram-negative organisms producing clinically relevant \u03b2-lactamases. 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European Committee on Antimicrobial Susceptibility Testing."}],"container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.00072-17","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.00072-17","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,21]],"date-time":"2022-02-21T15:55:29Z","timestamp":1645458929000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/AAC.00072-17"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,5]]},"references-count":23,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2017,5]]}},"alternative-id":["10.1128\/AAC.00072-17"],"URL":"https:\/\/doi.org\/10.1128\/aac.00072-17","relation":{},"ISSN":["0066-4804","1098-6596"],"issn-type":[{"value":"0066-4804","type":"print"},{"value":"1098-6596","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,5]]},"assertion":[{"value":"2017-01-11","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2017-02-19","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2017-04-24","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e00072-17"}}