{"markup":"\u003C?xml version=\u00221.0\u0022 encoding=\u0022UTF-8\u0022 ?\u003E\n    \u003Chtml version=\u0022HTML+RDFa+MathML 1.1\u0022\n    xmlns:content=\u0022http:\/\/purl.org\/rss\/1.0\/modules\/content\/\u0022\n    xmlns:dc=\u0022http:\/\/purl.org\/dc\/terms\/\u0022\n    xmlns:foaf=\u0022http:\/\/xmlns.com\/foaf\/0.1\/\u0022\n    xmlns:og=\u0022http:\/\/ogp.me\/ns#\u0022\n    xmlns:rdfs=\u0022http:\/\/www.w3.org\/2000\/01\/rdf-schema#\u0022\n    xmlns:sioc=\u0022http:\/\/rdfs.org\/sioc\/ns#\u0022\n    xmlns:sioct=\u0022http:\/\/rdfs.org\/sioc\/types#\u0022\n    xmlns:skos=\u0022http:\/\/www.w3.org\/2004\/02\/skos\/core#\u0022\n    xmlns:xsd=\u0022http:\/\/www.w3.org\/2001\/XMLSchema#\u0022\n    xmlns:mml=\u0022http:\/\/www.w3.org\/1998\/Math\/MathML\u0022\u003E\n  \u003Chead\u003E\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/sites\/default\/files\/js\/js_itu2PgFdrjV-docKmLK8Jn5oXe_05RgvQh73eOhI_mE.js\u0022\u003E\u003C\/script\u003E\n\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_at_symbol.js?nzlm5q\u0022\u003E\u003C\/script\u003E\n\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_article_reference_popup.js?nzlm5q\u0022\u003E\u003C\/script\u003E\n\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/sites\/default\/files\/js\/js_I8yX6RYPZb7AtMcDUA3QKDZqVkvEn35ED11_1i7vVpc.js\u0022\u003E\u003C\/script\u003E\n\u003Cscript type=\u0022text\/javascript\u0022\u003E\n\u003C!--\/\/--\u003E\u003C![CDATA[\/\/\u003E\u003C!--\n(function(i,s,o,g,r,a,m){i[\u0022GoogleAnalyticsObject\u0022]=r;i[r]=i[r]||function(){(i[r].q=i[r].q||[]).push(arguments)},i[r].l=1*new Date();a=s.createElement(o),m=s.getElementsByTagName(o)[0];a.async=1;a.src=g;m.parentNode.insertBefore(a,m)})(window,document,\u0022script\u0022,\u0022\/\/www.google-analytics.com\/analytics.js\u0022,\u0022ga\u0022);ga(\u0022create\u0022, \u0022UA-15605596-27\u0022, {\u0022cookieDomain\u0022:\u0022auto\u0022});ga(\u0022set\u0022, \u0022page\u0022, location.pathname + location.search + location.hash);ga(\u0022send\u0022, \u0022pageview\u0022);ga(\u0027create\u0027, \u0027UA-189672-26\u0027, \u0027auto\u0027, {\u0027name\u0027: \u0027hwTracker\u0027});\r\nga(\u0027hwTracker.send\u0027, \u0027pageview\u0027);\n\/\/--\u003E\u003C!]]\u003E\n\u003C\/script\u003E\n\u003Cscript type=\u0022text\/javascript\u0022\u003E\n\u003C!--\/\/--\u003E\u003C![CDATA[\/\/\u003E\u003C!--\njQuery.extend(Drupal.settings, {\u0022basePath\u0022:\u0022\\\/\u0022,\u0022pathPrefix\u0022:\u0022\u0022,\u0022highwire\u0022:{\u0022markup\u0022:[{\u0022requested\u0022:\u0022full-text\u0022,\u0022variant\u0022:\u0022full-text\u0022,\u0022view\u0022:\u0022full\u0022,\u0022pisa\u0022:\u0022spmdc;15\\\/48\\\/17\u0022},{\u0022requested\u0022:\u0022long\u0022,\u0022variant\u0022:\u0022full-text\u0022,\u0022view\u0022:\u0022full\u0022,\u0022pisa\u0022:\u0022spmdc;15\\\/48\\\/17\u0022}],\u0022ac\u0022:{\u0022spmdc;15\\\/48\\\/17\u0022:{\u0022access\u0022:{\u0022reprint\u0022:true,\u0022full\u0022:true},\u0022pisa_id\u0022:\u0022spmdc;15\\\/48\\\/17\u0022,\u0022atom_uri\u0022:\u0022\u0022,\u0022jcode\u0022:\u0022spmdc\u0022}}},\u0022googleanalytics\u0022:{\u0022trackOutbound\u0022:1,\u0022trackMailto\u0022:1,\u0022trackDownload\u0022:1,\u0022trackDownloadExtensions\u0022:\u00227z|aac|arc|arj|asf|asx|avi|bin|csv|doc(x|m)?|dot(x|m)?|exe|flv|gif|gz|gzip|hqx|jar|jpe?g|js|mp(2|3|4|e?g)|mov(ie)?|msi|msp|pdf|phps|png|ppt(x|m)?|pot(x|m)?|pps(x|m)?|ppam|sld(x|m)?|thmx|qtm?|ra(m|r)?|sea|sit|tar|tgz|torrent|txt|wav|wma|wmv|wpd|xls(x|m|b)?|xlt(x|m)|xlam|xml|z|zip\u0022,\u0022trackUrlFragments\u0022:1},\u0022ajaxPageState\u0022:{\u0022js\u0022:{\u0022sites\\\/all\\\/libraries\\\/cluetip\\\/jquery.cluetip.js\u0022:1,\u0022sites\\\/all\\\/libraries\\\/cluetip\\\/lib\\\/jquery.hoverIntent.js\u0022:1,\u0022sites\\\/all\\\/libraries\\\/cluetip\\\/lib\\\/jquery.bgiframe.min.js\u0022:1,\u0022sites\\\/all\\\/modules\\\/highwire\\\/highwire\\\/plugins\\\/highwire_markup_process\\\/js\\\/highwire_at_symbol.js\u0022:1,\u0022sites\\\/all\\\/modules\\\/highwire\\\/highwire\\\/plugins\\\/highwire_markup_process\\\/js\\\/highwire_article_reference_popup.js\u0022:1,\u0022sites\\\/all\\\/modules\\\/contrib\\\/google_analytics\\\/googleanalytics.js\u0022:1,\u00220\u0022:1}}});\n\/\/--\u003E\u003C!]]\u003E\n\u003C\/script\u003E\n\u003Clink type=\u0022text\/css\u0022 rel=\u0022stylesheet\u0022 href=\u0022\/\/d282kpwvnogo5m.cloudfront.net\/sites\/default\/files\/cdn\/css\/http\/css_Xg7z6oCTVgud_Q0huYz9x9iiD5H_2YPSJ5z2ZViSWdY.css\u0022 media=\u0022all\u0022 \/\u003E\n\u003Clink rel=\u0027stylesheet\u0027 type=\u0027text\/css\u0027 href=\u0027\/sites\/all\/modules\/contrib\/panels\/plugins\/layouts\/onecol\/onecol.css\u0027 \/\u003E\u003C\/head\u003E\u003Cbody\u003E\u003Cdiv class=\u0022panels-ajax-tab-panel panels-ajax-tab-panel-sageoa-tab-art\u0022\u003E\u003Cdiv class=\u0022panel-display panel-1col clearfix\u0022 \u003E\n  \u003Cdiv class=\u0022panel-panel panel-col\u0022\u003E\n    \u003Cdiv\u003E\u003Cdiv class=\u0022panel-pane pane-highwire-markup\u0022 \u003E\n  \n      \n  \n  \u003Cdiv class=\u0022pane-content\u0022\u003E\n    \u003Cdiv class=\u0022highwire-markup\u0022\u003E\u003Cdiv xmlns=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022 id=\u0022content-block-markup\u0022 xmlns:xhtml=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022\u003E\u003Cdiv class=\u0022article fulltext-view \u0022\u003E\u003Cspan class=\u0022highwire-journal-article-marker-start\u0022\u003E\u003C\/span\u003E\u003Cdiv class=\u0022section abstract\u0022 id=\u0022abstract-1\u0022\u003E\u003Ch2\u003ESummary\u003C\/h2\u003E\u003Cp id=\u0022p-1\u0022\u003EA novel antibacterial agent, ceftolozane\/tazobactam, compared with levofloxacin had higher rates of microbiological eradication in patients with hospital-acquired complicated urinary tract infections, including pyelonephritis, with a good safety profile, according to results of a European substudy of the ASPECT-cUTI study. The novel agent was more effective against 4 of the 5 most frequent pathogens and against drug-resistant pathogens.\u003C\/p\u003E\u003C\/div\u003E\u003Cul class=\u0022kwd-group\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003Eceftolozane\/tazobactam\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Ecomplicated urinary tract infections\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EASPECT-cUTI\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003ENCT01345929\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Emicrobial pathogens\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Emicrobiological eradication, infectious diseases clinical trials\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Ebacterial infections\u003C\/li\u003E\u003C\/ul\u003E\u003Cdiv class=\u0022section\u0022 id=\u0022sec-1\u0022\u003E\u003Cp id=\u0022p-2\u0022\u003EAntimicrobial resistance to gram-negative pathogens is increasing. Hospital-acquired urinary tract infections (UTIs) are increasingly resistant to the antibiotics used to treat them, including the fluoroquinolones [Tandogdu Z et al. \u003Cem\u003EWorld J Urol\u003C\/em\u003E. 2014]. Nonetheless, fluoroquinolones, including high-dose levofloxacin, are recommended as first-line therapy in clinical guidelines and remain the most widely used antibacterials to treat complicated urinary tract infection (cUTI) and pyelonephritis.\u003C\/p\u003E\u003Cp id=\u0022p-3\u0022\u003ECeftolozane\/tazobactam (TOL\/TAZ) is a novel cephalosporin combined with a \u03b2-lactamase inhibitor, and it has been shown to have in vitro activity against \u003Cem\u003EPseudomonas aeruginosa\u003C\/em\u003E and gram-negative pathogens, including most extended-spectrum \u03b2-lactamase (ESBL)\u2013positive strains. This fixed-dose combination (in a 2:1 ratio) has been approved by the FDA to treat complicated intraabdominal infections and cUTIs, including pyelonephritis; an application has been submitted to the European Medicines Agency for these indications.\u003C\/p\u003E\u003Cp id=\u0022p-4\u0022\u003EFlorian M. Wagenlehner, MD, PhD, Justus-Liebig University, Giessen, Germany, presented findings from a European subgroup analysis of the ASPECT-cUTI trial [Wagenlehner FM et al. \u003Cem\u003ELancet\u003C\/em\u003E. 2015] that indicated that TOL\/TAZ vs levofloxacin was safe and effective for the treatment of cUTIs, including pyelonephritis.\u003C\/p\u003E\u003Cp id=\u0022p-5\u0022\u003EThe ASPECT-cUTI trial was a double-blind phase 3 noninferiority trial conducted in 209 centers in 25 countries, and the results of the main study have been reported [Wagenlehner FM et al. \u003Cem\u003ELancet\u003C\/em\u003E. 2015]. The trial randomized men and women aged \u2265\u200518 years who were hospital inpatients between July 2011 and September 2013 in a 1:1 ratio to receive intravenous TOL\/TAZ 1.5 g every 8 hours (n\u2005=\u2005543) or intravenous high-dose levofloxacin 750 mg QD (n\u2005=\u2005540) for 7 days.\u003C\/p\u003E\u003Cp id=\u0022p-6\u0022\u003EThe inclusion criteria included presence of pyuria, \u2265\u20052 clinical signs or symptoms of pyelonephritis or cUTI, and a pretreatment baseline urine culture specimen obtained within 36 hours of the first dose of the study drug. Patients were excluded if they received a nonstudy antibiotic within 48 hours of the baseline urine specimen or had renal impairment (a creatinine clearance \u0026lt;\u200530 mL\/min).\u003C\/p\u003E\u003Cp id=\u0022p-7\u0022\u003EThe primary end point of the ASPECT-cUTI trial was the composite of microbiological eradication (ME) and clinical cure at the test-of-cure visit 5 to 9 days after the end of therapy in the patients who were microbiologically evaluable (modified intention-to-treat population). The main study found that TOL\/TAZ was noninferior to levofloxacin for the primary end point (76.9% vs 68.4%). While the study was not powered to test superiority, the results indicated that TOL\/TAZ was also superior to levofloxacin. The mean age of the patients was 47 years; 72% were women; and about 82% had pyelonephritis at study entry.\u003C\/p\u003E\u003Cp id=\u0022p-8\u0022\u003EThe European subgroup analysis was conducted to evaluate the primary end point, outcomes in patients with drug-resistant pathogens, and the safety of TOL\/TAZ in the patients enrolled in Europe. Of the 812 patients, 544 qualified for the microbiologically evaluable population; 269 had been randomized to TOL\/TAZ and 275 to levofloxacin. Demographic and baseline characteristics for the microbiologically evaluable population were similar between the 2 treatment groups.\u003C\/p\u003E\u003Cp id=\u0022p-9\u0022\u003EThe ME rate for the main study was 84.7% with TOL\/TAZ and 75.4% with levofloxacin (9.4% difference; 99% CI, 1.5% to 17.1%). In the European analysis, the ME rates for the overall cohort and for patients with pyelonephritis were similar to that in the main study and were slightly lower in the patients with cUTI (\u003Ca id=\u0022xref-fig-1-1\u0022 class=\u0022xref-fig\u0022 href=\u0022#F1\u0022\u003EFigure 1\u003C\/a\u003E).\u003C\/p\u003E\u003Cdiv id=\u0022F1\u0022 class=\u0022fig pos-float  odd\u0022\u003E\u003Cdiv class=\u0022highwire-figure\u0022\u003E\u003Cdiv class=\u0022fig-inline-img-wrapper\u0022\u003E\u003Cdiv class=\u0022fig-inline-img\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/15\/48\/17\/F1.large.jpg?width=800\u0026amp;height=600\u0026amp;carousel=1\u0022 title=\u0022Microbiological Response by Diagnosis in European AnalysiscLUTI, complicated lower-urinary tract infection.Reproduced with permission from FM Wagenlehner, MD, PhD.\u0022 class=\u0022fragment-images colorbox-load\u0022 rel=\u0022gallery-fragment-images-190631324\u0022 data-figure-caption=\u0022Microbiological Response by Diagnosis in European AnalysiscLUTI, complicated lower-urinary tract infection.Reproduced with permission from FM Wagenlehner, MD, PhD.\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003E\u003Cimg class=\u0022fragment-image\u0022 alt=\u0022Figure 1.\u0022 src=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/15\/48\/17\/F1.medium.gif\u0022\/\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cul class=\u0022highwire-figure-links inline\u0022\u003E\u003Cli class=\u00220 first\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/15\/48\/17\/F1.large.jpg?download=true\u0022 class=\u0022highwire-figure-link highwire-figure-link-download\u0022 title=\u0022Download Figure 1.\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload figure\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00221\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/15\/48\/17\/F1.large.jpg\u0022 class=\u0022highwire-figure-link highwire-figure-link-newtab\u0022 target=\u0022_blank\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EOpen in new tab\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00222 last\u0022\u003E\u003Ca href=\u0022\/highwire\/powerpoint\/16617\u0022 class=\u0022highwire-figure-link highwire-figure-link-ppt\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload powerpoint\u003C\/a\u003E\u003C\/li\u003E\u003C\/ul\u003E\u003C\/div\u003E\u003Cdiv class=\u0022fig-caption\u0022 xmlns:xhtml=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022\u003E\u003Cspan class=\u0022fig-label\u0022\u003EFigure 1.\u003C\/span\u003E \u003Cp id=\u0022p-10\u0022 class=\u0022first-child\u0022\u003EMicrobiological Response by Diagnosis in European Analysis\u003C\/p\u003E\u003Cp id=\u0022p-11\u0022\u003EcLUTI, complicated lower-urinary tract infection.\u003C\/p\u003E\u003Cp id=\u0022p-12\u0022\u003EReproduced with permission from FM Wagenlehner, MD, PhD.\u003C\/p\u003E\u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cp id=\u0022p-13\u0022\u003EAt baseline, the most frequent organism was \u003Cem\u003EEscherichia coli\u003C\/em\u003E, in 78.6% of patients in the main study and 76.5% in the European subgroup; of these patients, 13% and 10%, respectively, were considered to be \u003Cem\u003EE coli\u003C\/em\u003E ESBL producers. TOL\/TAZ compared with levofloxacin had higher rates of ME against \u003Cem\u003EE coli\u003C\/em\u003E (90% vs 78.6%), \u003Cem\u003EKlebsiella pneumoniae\u003C\/em\u003E (81% vs 55%), \u003Cem\u003EProteus mirabilis\u003C\/em\u003E (100% vs 72.7%), and \u003Cem\u003EPseudomonas aeruginosa\u003C\/em\u003E (83.3% vs 45%), while it was the opposite for \u003Cem\u003EEnterobacter cloacae\u003C\/em\u003E (33.3% vs 100%). TOL\/TAZ had substantial rates of ME against drug-resistant pathogens compared with levofloxacin (\u003Ca id=\u0022xref-table-wrap-1-1\u0022 class=\u0022xref-table\u0022 href=\u0022#T1\u0022\u003ETable 1\u003C\/a\u003E).\u003C\/p\u003E\u003Cdiv id=\u0022T1\u0022 class=\u0022table pos-float\u0022\u003E\u003Cdiv class=\u0022table-inline\u0022\u003E\u003Cdiv class=\u0022callout\u0022\u003E\u003Cspan\u003EView this table:\u003C\/span\u003E\u003Cul class=\u0022callout-links\u0022\u003E\u003Cli class=\u00220 first\u0022\u003E\u003Ca href=\u0022\/\u0022 class=\u0022table-expand-inline\u0022 data-table-url=\u0022\/highwire\/markup\/16618\/expansion?postprocessors=highwire_figures%2Chighwire_math%2Chighwire_inline_linked_media%2Chighwire_embed\u0026amp;table-expand-inline=1\u0022 html=\u00221\u0022 fragment=\u0022#\u0022 external=\u00221\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView inline\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00221\u0022\u003E\u003Ca href=\u0022\/highwire\/markup\/16618\/expansion?width=1000\u0026amp;height=500\u0026amp;iframe=true\u0026amp;postprocessors=highwire_figures%2Chighwire_math%2Chighwire_inline_linked_media\u0022 class=\u0022colorbox colorbox-load table-expand-popup\u0022 rel=\u0022gallery-fragment-tables\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView popup\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00222 last\u0022\u003E\u003Ca href=\u0022\/highwire\/powerpoint\/16618\u0022 class=\u0022highwire-figure-link highwire-figure-link-ppt\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload powerpoint\u003C\/a\u003E\u003C\/li\u003E\u003C\/ul\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cdiv class=\u0022table-caption\u0022\u003E\u003Cspan class=\u0022table-label\u0022\u003ETable 1.\u003C\/span\u003E \u003Cp id=\u0022p-14\u0022 class=\u0022first-child\u0022\u003EEfficacy Against Drug-Resistant Pathogens\u003C\/p\u003E\u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cp id=\u0022p-17\u0022\u003EThe incidence of adverse events (AEs) and serious AEs was similar between the TOL\/TAZ group (27.5% and 2.0%) and the levofloxacin group (26.5% and 2.2%, respectively). More patients discontinued the study drug because of an AE in the levofloxacin group (2.0%) vs the TOL\/TAZ group (1.0%).\u003C\/p\u003E\u003C\/div\u003E\u003Cul class=\u0022copyright-statement\u0022\u003E\u003Cli class=\u0022fn\u0022 id=\u0022copyright-statement-1\u0022\u003E\u00a9 2015 SAGE Publications\u003C\/li\u003E\u003C\/ul\u003E\u003Cspan class=\u0022highwire-journal-article-marker-end\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Cspan id=\u0022related-urls\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Ca href=\u0022http:\/\/mdc.sagepub.com\/content\/15\/48\/17.abstract\u0022 class=\u0022hw-link hw-link-article-abstract\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView Summary\u003C\/a\u003E\u003C\/div\u003E  \u003C\/div\u003E\n\n  \n  \u003C\/div\u003E\n\u003C\/div\u003E\n  \u003C\/div\u003E\n\u003C\/div\u003E\n\u003C\/div\u003E\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_figures.js?nzlm5q\u0022\u003E\u003C\/script\u003E\n\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_openurl.js?nzlm5q\u0022\u003E\u003C\/script\u003E\n\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_tables.js?nzlm5q\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}