{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,1]],"date-time":"2025-11-01T13:45:00Z","timestamp":1762004700479,"version":"3.40.5"},"reference-count":27,"publisher":"American Society for Microbiology","issue":"8","license":[{"start":{"date-parts":[[2015,8,1]],"date-time":"2015-08-01T00:00:00Z","timestamp":1438387200000},"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":[[2015,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Ceftolozane, formally CXA-101, is a new antipseudomonal cephalosporin that is also active\n            <jats:italic>in vitro<\/jats:italic>\n            against\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Enterobacteriaceae<\/jats:named-content>\n            but is vulnerable to extended-spectrum \u03b2-lactamases (ESBLs). The addition of tazobactam is intended to broaden coverage to most ESBL-producing\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Escherichia coli<\/jats:named-content>\n            and\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Klebsiella pneumonia<\/jats:named-content>\n            as well as other\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Enterobacteriaceae<\/jats:named-content>\n            . The\n            <jats:italic>in vitro<\/jats:italic>\n            activities of ceftolozane-tazobactam combinations against 67 clinically and molecularly characterized ESBL-producing isolates were examined by checkerboard MIC testing to evaluate their potential clinical feasibility and to assess the optimal tazobactam concentrations to be used in MIC determinations of ceftolozane. Isolates included those from\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">E. coli<\/jats:named-content>\n            (\n            <jats:italic>n<\/jats:italic>\n            = 32),\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">K. pneumoniae<\/jats:named-content>\n            (\n            <jats:italic>n<\/jats:italic>\n            = 19),\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Enterobacter cloacae<\/jats:named-content>\n            (\n            <jats:italic>n<\/jats:italic>\n            = 15), and\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Citrobacter freundii<\/jats:named-content>\n            (\n            <jats:italic>n<\/jats:italic>\n            = 1). Checkerboard experiments were performed to study interactions over the range of 0.008 to 64 mg\/liter ceftolozane and 0.063 to 32 mg\/liter tazobactam using 2-fold-dilution series. The MIC\n            <jats:sub>50<\/jats:sub>\n            and MIC\n            <jats:sub>90<\/jats:sub>\n            of ceftolozane alone for all isolates were 16 and \u226564 mg\/liter, respectively. Increasing concentrations of tazobactam resulted in decreasing MICs of ceftolozane. The 50th and 90th percentile concentrations of tazobactam required to reduce the MIC of ceftolozane to 8 mg\/liter for all organisms in this ESBL collection were 0.5 and 4 mg\/liter, respectively. For\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">E. coli<\/jats:named-content>\n            ,\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">K. pneumoniae<\/jats:named-content>\n            , and\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">E. cloacae<\/jats:named-content>\n            , these values were 0.5 and 2, 1 and 16, and 0.5 and 4 mg\/liter, respectively. When combined with a fixed amount of 4 mg\/liter tazobactam (current CLSI concentration used for susceptibility testing), 90% of the isolates would have an MIC of \u22644 mg\/liter. The combination ceftolozane-tazobactam is a promising alternative option for treating infections due to ESBL-harboring isolates.\n          <\/jats:p>","DOI":"10.1128\/aac.04498-14","type":"journal-article","created":{"date-parts":[[2015,5,19]],"date-time":"2015-05-19T02:31:37Z","timestamp":1432002697000},"page":"4521-4525","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":17,"title":["<i>In Vitro<\/i>\n            Activity of Ceftolozane Alone and in Combination with Tazobactam against Extended-Spectrum-\u03b2-Lactamase-Harboring Enterobacteriaceae"],"prefix":"10.1128","volume":"59","author":[{"given":"Maria J. B.","family":"Melchers","sequence":"first","affiliation":[{"name":"Radboud University Medical Center, Nijmegen, Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anita C. H. A. M.","family":"van Mil","sequence":"additional","affiliation":[{"name":"Canisius Wilhelmina Hospital, Nijmegen, Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6736-4149","authenticated-orcid":false,"given":"Johan W.","family":"Mouton","sequence":"additional","affiliation":[{"name":"Radboud University Medical Center, Nijmegen, Netherlands"},{"name":"Erasmus University Medical Center, Rotterdam, Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.14.4.933-951.2001"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF01641355"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.18.4.657-686.2005"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01009-09"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.00037-09"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.4155\/cli.10.31"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.4065\/mcp.2010.0674"},{"key":"e_1_3_3_9_2","first-page":"284","volume-title":"Abstr 48th Intersci Conf Antimicrob Agents Chemother-Infect Dis Soc Am 46th Annu Mee. 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Clinical and Laboratory Standards Institute, Wayne, PA."},{"key":"e_1_3_3_17_2","volume-title":"ISO 20776-1:2006","author":"International Organization for Standardization","year":"2006","unstructured":"International Organization for Standardization. 2006. Clinical laboratory testing and in vitro diagnostic test systems: susceptibility testing of infectious agents and evaluation of performance of antimicrobial susceptibility test devices. Part 1: reference method for testing the in vitro activity of antimicrobial agents against rapidly growing aerobic bacteria involved in infectious diseases. ISO 20776-1:2006. International Organization for Standardization, Geneva, Switzerland."},{"key":"e_1_3_3_18_2","unstructured":"EUCAST. 2014. Breakpoint tables for interpretation of MICs and zone diameters version 4.0. http:\/\/www.eucast.org\/clinical_breakpoints\/."},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.33.8.1268"},{"key":"e_1_3_3_20_2","volume-title":"American Society for Microbiology","author":"Sader HS","year":"2012","unstructured":"Sader HS, Flamm RK, Streit JM, Jones RN. 2012. Activity of novel antimicrobial ceftolozane\/tazobactam tested against contemporary clinical strains from USA hospitals (2011). Abstr 52nd Intersci Conf Antimicrob Agents Chemother. 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