{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T01:27:29Z","timestamp":1789954049468,"version":"4.0.1"},"reference-count":23,"publisher":"American Society for Microbiology","issue":"1","license":[{"start":{"date-parts":[[2012,1,1]],"date-time":"2012-01-01T00:00:00Z","timestamp":1325376000000},"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":[[2012,1]]},"abstract":"ABSTRACT<\/jats:title>\n \n CXA-101 is a novel antipseudomonal cephalosporin with enhanced activity against Gram-negative organisms displaying various resistance mechanisms. This study evaluates the efficacy of exposures approximating human percent free time above the MIC (%fT > MIC) of CXA-101 with or without tazobactam and piperacillin-tazobactam (TZP) against target Gram-negative organisms, including those expressing extended-spectrum \u03b2-lactamases (ESBLs). Sixteen clinical Gram-negative isolates (6\n Pseudomonas aeruginosa<\/jats:named-content>\n isolates [piperacillin-tazobactam MIC range, 8 to 64 \u03bcg\/ml], 4\n Escherichia coli<\/jats:named-content>\n isolates (2 ESBL and 2 non-ESBL expressing), and 4\n Klebsiella pneumoniae<\/jats:named-content>\n isolates (3 ESBL and 1 non-ESBL expressing) were used in an immunocompetent murine thigh infection model. After infection, groups of mice were administered doses of CXA-101 with or without tazobactam (2:1) designed to approximate the %fT > MIC observed in humans given 1 g of CXA-101 with or without tazobactam every 8 h as a 1-h infusion. As a comparison, groups of mice were administered piperacillin-tazobactam doses designed to approximate the %fT > MIC observed in humans given 4.5 g piperacillin-tazobactam every 6 h as a 30-min infusion. Predicted piperacillin-tazobactam %fT > MIC exposures of greater than 40% resulted in static to >1 log decreases in CFU in non-ESBL-expressing organisms with MICs of \u226432 \u03bcg\/ml after 24 h of therapy. Predicted CXA-101 with or without tazobactam %fT > MIC exposures of \u226537.5% resulted in 1- to 3-log-unit decreases in CFU in non-ESBL-expressing organisms, with MICs of \u226416 \u03bcg\/ml after 24 h of therapy. With regard to the ESBL-expressing organisms, the inhibitor combinations showed enhanced CFU decreases versus CXA-101 alone. Due to enhanced\n in vitro<\/jats:italic>\n potency and resultant increased\n in vivo<\/jats:italic>\n exposure, CXA-101 produced statistically significant reductions in CFU in 9 isolates compared with piperacillin-tazobactam. The addition of tazobactam to CXA-101 produced significant reductions in CFU for 7 isolates compared with piperacillin-tazobactam. Overall, human simulated exposures of CXA-101 with or without tazobactam demonstrated improved efficacy versus piperacillin-tazobactam.\n <\/jats:p>","DOI":"10.1128\/aac.01752-10","type":"journal-article","created":{"date-parts":[[2011,11,8]],"date-time":"2011-11-08T08:47:43Z","timestamp":1320742063000},"page":"544-549","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":47,"title":["In Vivo<\/i>\n Comparison of CXA-101 (FR264205) with and without Tazobactam versus Piperacillin-Tazobactam Using Human Simulated Exposures against Phenotypically Diverse Gram-Negative Organisms"],"prefix":"10.1128","volume":"56","author":[{"given":"Catharine C.","family":"Bulik","sequence":"first","affiliation":[{"name":"Center for Anti-Infective Research and Development, Hartford Hospital, Hartford, Connecticut, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pamela R.","family":"Tessier","sequence":"additional","affiliation":[{"name":"Center for Anti-Infective Research and Development, Hartford Hospital, Hartford, Connecticut, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca A.","family":"Keel","sequence":"additional","affiliation":[{"name":"Center for Anti-Infective Research and Development, Hartford Hospital, Hartford, Connecticut, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina A.","family":"Sutherland","sequence":"additional","affiliation":[{"name":"Center for Anti-Infective Research and Development, Hartford Hospital, Hartford, Connecticut, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David P.","family":"Nicolau","sequence":"additional","affiliation":[{"name":"Center for Anti-Infective Research and Development, Hartford Hospital, Hartford, Connecticut, USA"},{"name":"Division of Infectious Diseases, Hartford Hospital, Hartford, Connecticut, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.47.5.1643-1646.2003"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200405-644ST"},{"key":"e_1_3_2_4_2","first-page":"307","article-title":"Recent developments in antimicrobial therapy with beta-lactam antibiotics","volume":"14","author":"Beam TR","year":"1983","unstructured":"BeamTRJr. 1983. Recent developments in antimicrobial therapy with beta-lactam antibiotics. J. Med. 14:307\u2013336.","journal-title":"J. Med"},{"key":"e_1_3_2_5_2","volume-title":"49th Annu. Meet. Intersci. Conf. Antimicrob. Agents Chemother","author":"Brown NP","year":"2009","unstructured":"BrownNP PillarCM SahmDF GeY. 2009. Activity profile of CXA-101 and CXA-101\/tazobactam against target gram-negative and gram-positive pathogens, abstr F1-1986. Abstr. 49th Annu. Meet. Intersci. Conf. Antimicrob. Agents Chemother."},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00912-09"},{"key":"e_1_3_2_7_2","volume-title":"CLSI document M7-A7 (26)2","author":"Clinical and Laboratory Standards Institute","year":"2007","unstructured":"Clinical and Laboratory Standards Institute. 2007. Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically; approved standard, 7th ed. CLSI document M7-A7 (26)2. 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Comparative assessment of inoculum effects on the antimicrobial activity of amoxicillin-clavulanate and piperacillin-tazobactam with extended-spectrum \u03b2-lactamase-producing and extended-spectrum \u03b2-lactamase-non-producing Escherichia coli isolates. Clin. Microbiol. Infect. 16:132\u2013136.","journal-title":"Clin. Microbiol. Infect"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1159\/000057663"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01104-09"},{"key":"e_1_3_2_18_2","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1592\/phco.28.2.235","article-title":"The current state of multidrug resistant Gram-negative bacilli in North America","volume":"28","author":"Nicasio AM","year":"2008","unstructured":"NicasioAM KutiJL NicolauDP. 2008. The current state of multidrug resistant Gram-negative bacilli in North America. 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