{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,23]],"date-time":"2026-02-23T11:20:01Z","timestamp":1771845601471,"version":"3.50.1"},"reference-count":14,"publisher":"American Society for Microbiology","issue":"12","license":[{"start":{"date-parts":[[2017,12,1]],"date-time":"2017-12-01T00:00:00Z","timestamp":1512086400000},"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":[[2017,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            We previously demonstrated that for tazobactam administered in combination with ceftolozane, the pharmacokinetic-pharmacodynamic (PK-PD) index that best described tazobactam efficacy was the percentage of the dosing interval that tazobactam concentrations were above a threshold (%\n            <jats:italic>T<\/jats:italic>\n            &gt;threshold). Using data from studies of\n            <jats:named-content content-type=\"genus-species\">Enterobacteriaceae<\/jats:named-content>\n            producing extended-spectrum \u03b2-lactamases (ESBLs), a relationship between tazobactam %\n            <jats:italic>T<\/jats:italic>\n            &gt;threshold and reduction in log\n            <jats:sub>10<\/jats:sub>\n            CFU\/ml from baseline, for which the tazobactam threshold concentration was the product of the isolate's ceftolozane-tazobactam MIC value and 0.5, was identified. However, since the kinetics of cephalosporin hydrolysis vary among ESBLs and compounds, it is likely that the translational relationship used to derive the tazobactam threshold concentration varies among enzymes and compounds. Using a one-compartment\n            <jats:italic>in vitro<\/jats:italic>\n            infection model, the PK-PD of tazobactam administered in combination with cefepime was characterized, and a translational relationship across ESBL-producing\n            <jats:named-content content-type=\"genus-species\">Enterobacteriaceae<\/jats:named-content>\n            was developed. Four clinical isolates, two\n            <jats:named-content content-type=\"genus-species\">Escherichia coli<\/jats:named-content>\n            and two\n            <jats:named-content content-type=\"genus-species\">Klebsiella pneumoniae<\/jats:named-content>\n            isolates, known to produce CTX-M-15 \u03b2-lactamase enzymes and displaying cefepime MIC values of 2 to 4 mg\/liter in the presence of 4 mg\/liter tazobactam, were evaluated. Tazobactam threshold concentrations from 0.0625\u00d7 to 1\u00d7 the tazobactam-potentiated cefepime MIC value were considered. The threshold that best described the relationship between tazobactam %\n            <jats:italic>T<\/jats:italic>\n            &gt;threshold and change in log\n            <jats:sub>10<\/jats:sub>\n            CFU\/ml from the baseline at 24 h was the product of 0.125 and the cefepime-tazobactam MIC (\n            <jats:italic>R<\/jats:italic>\n            <jats:sup>2<\/jats:sup>\n            = 0.813). The magnitudes of %\n            <jats:italic>T<\/jats:italic>\n            &gt;threshold associated with net bacterial stasis and a 1-log\n            <jats:sub>10<\/jats:sub>\n            CFU\/ml reduction from baseline at 24 h were 21.9% and 52.8%, respectively. These data will be useful in supporting the identification of tazobactam dosing regimens in combination with cefepime for evaluation in future clinical studies.\n          <\/jats:p>","DOI":"10.1128\/aac.01052-17","type":"journal-article","created":{"date-parts":[[2017,9,26]],"date-time":"2017-09-26T00:40:22Z","timestamp":1506386422000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":15,"title":["Pharmacokinetics-Pharmacodynamics of Tazobactam in Combination with Cefepime in an\n            <i>In Vitro<\/i>\n            Infection Model"],"prefix":"10.1128","volume":"61","author":[{"given":"Brian D.","family":"VanScoy","sequence":"first","affiliation":[{"name":"Institute for Clinical Pharmacodynamics, Schenectady, New York, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Tenero","sequence":"additional","affiliation":[{"name":"GlaxoSmithKline, Collegeville, Pennsylvania, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simon","family":"Turner","sequence":"additional","affiliation":[{"name":"GlaxoSmithKline, Middlesex, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David M.","family":"Livermore","sequence":"additional","affiliation":[{"name":"University of East Anglia, Norwich, Norfolk, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jennifer","family":"McCauley","sequence":"additional","affiliation":[{"name":"Institute for Clinical Pharmacodynamics, Schenectady, New York, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haley","family":"Conde","sequence":"additional","affiliation":[{"name":"Institute for Clinical Pharmacodynamics, Schenectady, New York, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sujata M.","family":"Bhavnani","sequence":"additional","affiliation":[{"name":"Institute for Clinical Pharmacodynamics, Schenectady, New York, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christopher M.","family":"Rubino","sequence":"additional","affiliation":[{"name":"Institute for Clinical Pharmacodynamics, Schenectady, New York, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul G.","family":"Ambrose","sequence":"additional","affiliation":[{"name":"Institute for Clinical Pharmacodynamics, Schenectady, New York, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","first-page":"187","article-title":"Piperacillin\/tazobactam in the treatment of serious acute soft tissue infection","volume":"17","author":"Gould IM","year":"1991","unstructured":"Gould IM AnsariAHarveyGDouglasJGSmithCCReidTM. 1991. Piperacillin\/tazobactam in the treatment of serious acute soft tissue infection. Drugs Exp Clin17:187\u2013190.","journal-title":"Drugs Exp Clin"},{"key":"e_1_3_2_3_2","volume-title":"Zerbaxa for injection package insert","author":"Merck & Co, Inc","year":"2016","unstructured":"Merck & Co, Inc. 2016. Zerbaxa for injection package insert. Merck & Co, Inc,Whitehouse Station, NJ."},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.5799\/ahinjs.02.2012.03.0049"},{"key":"e_1_3_2_5_2","first-page":"7","article-title":"The chemistry and structure-activity relationships of C3-quartenary ammonium cephem antibiotics","volume":"8","author":"Laws A","year":"1996","unstructured":"Laws A PageM. 1996. The chemistry and structure-activity relationships of C3-quartenary ammonium cephem antibiotics. J Chemother8:7\u201322.","journal-title":"J Chemother"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.4103\/0974-2727.129083"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/ja.2014.45"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02513-12"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00656-13"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1002\/jps.2600651104"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.34.2.337"},{"key":"e_1_3_2_12_2","volume-title":"Standard M100-S25","author":"Clinical and Laboratory Standards Institute","year":"2015","unstructured":"Clinical and Laboratory Standards Institute. 2015. Performance standards for antimicrobial susceptibility testing. Standard M100-S25,25th supplement. Clinical and Laboratory Standards Institute,Wayne, PA."},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.34.10.1925"},{"key":"e_1_3_2_14_2","volume-title":"Maxipime package insert","author":"Hospira, Inc","year":"2012","unstructured":"Hospira, Inc. 2012. Maxipime package insert. Hospira, Inc,Lake Forest, IL."},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.06349-11"}],"container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.01052-17","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.01052-17","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,21]],"date-time":"2022-02-21T20:45:47Z","timestamp":1645476347000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/AAC.01052-17"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,12]]},"references-count":14,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2017,12]]}},"alternative-id":["10.1128\/AAC.01052-17"],"URL":"https:\/\/doi.org\/10.1128\/aac.01052-17","relation":{},"ISSN":["0066-4804","1098-6596"],"issn-type":[{"value":"0066-4804","type":"print"},{"value":"1098-6596","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,12]]},"assertion":[{"value":"2017-05-30","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2017-07-31","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2017-11-22","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e01052-17"}}