{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T11:59:06Z","timestamp":1789732746492,"version":"4.0.1"},"reference-count":32,"publisher":"American Society for Microbiology","issue":"6","license":[{"start":{"date-parts":[[2009,6,1]],"date-time":"2009-06-01T00:00:00Z","timestamp":1243814400000},"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":[[2009,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Ceftaroline is a novel broad-spectrum cephalosporin that exhibits bactericidal activity against many gram-positive and -negative pathogens. However, the activity of ceftaroline cannot be solely relied upon for eradication of multidrug-resistant gram-negative isolates, such as\n            <jats:italic>Pseudomonas aeruginosa<\/jats:italic>\n            and extended-spectrum \u03b2-lactamase (ESBL)-producing\n            <jats:italic>Enterobacteriaceae<\/jats:italic>\n            , which represent a current clinical concern. As drug combinations might be beneficial by potential synergy, we evaluated the in vitro activity of ceftaroline combined with meropenem, aztreonam, cefepime, tazobactam, amikacin, levofloxacin, and tigecycline. Susceptibility testing was performed for 20 clinical\n            <jats:italic>P. aeruginosa<\/jats:italic>\n            isolates, 10 ESBL-producing\n            <jats:italic>Escherichia coli<\/jats:italic>\n            isolates, 10 ESBL-producing\n            <jats:italic>Klebsiella pneumoniae<\/jats:italic>\n            isolates, and 10 AmpC-derepressed\n            <jats:italic>Enterobacter cloacae<\/jats:italic>\n            isolates. Time-kill experiments were performed for 10 isolates using antimicrobials at one-fourth the MIC. Ceftaroline exhibited a MIC range of 0.125 to 1,024 \u03bcg\/ml and was reduced 2- to 512-fold by combination with tazobactam (4 \u03bcg\/ml) for ESBL-producing strains. In time-kill experiments, ceftaroline plus amikacin was synergistic against 90% of the isolates (and indifferent for one\n            <jats:italic>P. aeruginosa<\/jats:italic>\n            isolate). Ceftaroline plus tazobactam was indifferent for\n            <jats:italic>E. cloacae<\/jats:italic>\n            and\n            <jats:italic>P. aeruginosa<\/jats:italic>\n            strains but synergistic against 100% of\n            <jats:italic>E. coli<\/jats:italic>\n            and\n            <jats:italic>K. pneumoniae<\/jats:italic>\n            isolates. Combinations of ceftaroline plus meropenem or aztreonam were also synergistic for all\n            <jats:italic>E. coli<\/jats:italic>\n            and\n            <jats:italic>E. cloacae<\/jats:italic>\n            isolates, respectively, but indifferent against 90% of the other isolates. Finally, combinations of ceftaroline plus either tigecycline, levofloxacin, or cefepime were indifferent for 100% of the isolates. No antagonism was observed with any combination. Ceftaroline plus amikacin appeared as the most likely synergistic combination. This represents a promising therapeutic option, and further studies are warranted to elucidate the clinical value of ceftaroline combinations against resistant gram-negative pathogens.\n          <\/jats:p>","DOI":"10.1128\/aac.01452-08","type":"journal-article","created":{"date-parts":[[2009,4,7]],"date-time":"2009-04-07T01:07:24Z","timestamp":1239066444000},"page":"2360-2366","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":50,"title":["In Vitro Activity of Ceftaroline Alone and in Combination against Clinical Isolates of Resistant Gram-Negative Pathogens, Including \u03b2-Lactamase-Producing\n            <i>Enterobacteriaceae<\/i>\n            and\n            <i>Pseudomonas aeruginosa<\/i>"],"prefix":"10.1128","volume":"53","author":[{"given":"Ce\u0301line","family":"Vidaillac","sequence":"first","affiliation":[{"name":"Anti-Infective Research Laboratory, Eugene Applebaum College of Pharmacy and Health Sciences"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steve N.","family":"Leonard","sequence":"additional","affiliation":[{"name":"Anti-Infective Research Laboratory, Eugene Applebaum College of Pharmacy and Health Sciences"},{"name":"Detroit Receiving Hospital, Detroit, Michigan 48201"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helio S.","family":"Sader","sequence":"additional","affiliation":[{"name":"JMI Laboratories, Inc., 345 Beaver Kreek Center, Suite A, North Liberty, Iowa 52317"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronald N.","family":"Jones","sequence":"additional","affiliation":[{"name":"JMI Laboratories, Inc., 345 Beaver Kreek Center, Suite A, North Liberty, Iowa 52317"},{"name":"Tufts University School of Medicine, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael J.","family":"Rybak","sequence":"additional","affiliation":[{"name":"Anti-Infective Research Laboratory, Eugene Applebaum College of Pharmacy and Health Sciences"},{"name":"School of Medicine, Wayne State University, Detroit, Michigan 48201"},{"name":"Detroit Receiving Hospital, Detroit, Michigan 48201"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"crossref","unstructured":"Novexel and Forest Laboratories announce license agreement for NXL 104 a novel broad-spectrum beta lactamase inhibitor 2008","DOI":"10.3833\/pdr.v2008i93.210"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200405-644ST"},{"key":"e_1_3_2_4_2","doi-asserted-by":"crossref","first-page":"517","DOI":"10.2174\/092986708783503186","volume":"15","year":"2008","unstructured":"Bassetti, M., E. 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