{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T07:23:03Z","timestamp":1791098583331,"version":"4.1.0"},"reference-count":21,"publisher":"American Society for Microbiology","issue":"7","license":[{"start":{"date-parts":[[2011,7,1]],"date-time":"2011-07-01T00:00:00Z","timestamp":1309478400000},"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":[[2011,7]]},"abstract":"ABSTRACT<\/jats:title>\n \n Ceftaroline exhibits\n in vitro<\/jats:named-content>\n activity against extended-spectrum \u03b2-lactamase (ESBL)-, AmpC-, and KPC-producing\n Enterobacteriaceae<\/jats:named-content>\n when combined with the novel \u03b2-lactamase inhibitor NXL104. The purpose of this study was to evaluate the efficacy of a human-simulated regimen of ceftaroline plus NXL104 against\n Enterobacteriaceae<\/jats:named-content>\n in a murine thigh infection model.\n <\/jats:p>\n \n IMPORTANCE<\/jats:bold>\n Twelve\n Enterobacteriaceae<\/jats:named-content>\n isolates were tested with neutropenic ICR mice. Seven of these isolates were also tested with immunocompetent mice. Doses were given to simulate human free-drug exposures of ceftaroline (600 mg) plus NXL104 (600 mg) every 8 h over 24 h by targeting the percentage of time that free drug concentrations remain above the MIC, \u0192\n T<\/jats:italic>\n >MIC. The change in log\n 10<\/jats:sub>\n CFU\/ml compared with 0 h controls was observed after 24 h. Human-simulated exposures were achieved against all isolates (MICs of \u22640.015 to 1 \u03bcg\/ml) in both the neutropenic and the immunocompetent host models, which was equivalent to a \u0192\n T<\/jats:italic>\n >MIC of 100%. A 0.5 to \u22652 log CFU reduction was observed in the neutropenic thigh infection model. Furthermore, significantly greater reductions in bacterial density were observed for five of seven isolates studied in an immunocompetent model than in the neutropenic-host model. Regardless of immune status, ceftaroline (600 mg) combined with NXL104 (600 mg) every 8 h provided predictable efficacy against ESBL-, non-ESBL-, and KPC-producing isolates with an MIC of \u22641 \u03bcg\/ml and could be useful in combating the growing threat of resistant\n Enterobacteriaceae<\/jats:named-content>\n .\n <\/jats:p>","DOI":"10.1128\/aac.00024-11","type":"journal-article","created":{"date-parts":[[2011,4,26]],"date-time":"2011-04-26T03:04:49Z","timestamp":1303787089000},"page":"3220-3225","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":46,"title":["In Vivo<\/i>\n Efficacy of a Human-Simulated Regimen of Ceftaroline Combined with NXL104 against Extended-Spectrum-\u03b2-Lactamase (ESBL)-Producing and Non-ESBL-Producing Enterobacteriaceae"],"prefix":"10.1128","volume":"55","author":[{"given":"Dora E.","family":"Wiskirchen","sequence":"first","affiliation":[{"name":"Center for Anti-Infective Research and Development, Hartford, Connecticut, and Cerexa, Inc., Oakland, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jared L.","family":"Crandon","sequence":"additional","affiliation":[{"name":"Center for Anti-Infective Research and Development, Hartford, Connecticut, and Cerexa, Inc., Oakland, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guilherme H.","family":"Furtado","sequence":"additional","affiliation":[{"name":"Center for Anti-Infective Research and Development, Hartford, Connecticut, and Cerexa, Inc., Oakland, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory","family":"Williams","sequence":"additional","affiliation":[{"name":"Hartford Hospital, Hartford, Connecticut, and Cerexa, Inc., Oakland, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David P.","family":"Nicolau","sequence":"additional","affiliation":[{"name":"Center for Anti-Infective Research and Development, Hartford, Connecticut, and Cerexa, Inc., Oakland, California"},{"name":"Division of Infectious Diseases, Hartford, Connecticut, and Cerexa, Inc., Oakland, California"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1086\/510079"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.42.9.2375"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.50.4.1376-1383.2006"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.2165\/00003495-200666010-00001"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro862"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkq253"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00641-09"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00149-08"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0968-0896(03)00126-3"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.2146\/ajhp070477"},{"key":"e_1_3_2_12_2","unstructured":"LevasseurP.. 2009.\nIn vivo antibacterial efficacy of ceftaroline combined with the \u03b2-lactamase inhibitor NXL 104 in a murine septicemia model abstract B-1339a.\nAbstr. 49th Annu. Meet. Intersci. Conf. Antimicrob. 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