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type=\u0022text\/css\u0022 rel=\u0022stylesheet\u0022 href=\u0022\/\/d282kpwvnogo5m.cloudfront.net\/sites\/default\/files\/advagg_css\/css__ce2QY63WIanKyr8eSq7eavr1XQRRmFD6ZSmwpyJi8lM__zXwFqpqmxrZOXXcd_TpBQpjuELbmIP9wBR5UuTDWAO4__YJWWMMdfCJuAFm5cUEp88OsodhO3ZA-2lzRfoBsSlk4.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\n            \u003Cp id=\u0022p-1\u0022\u003EUsing a pharmacokinetic\/pharmacodynamic (PK\/PD) target algorithm, the \u003Cem\u003Ein vitro\u003C\/em\u003E potency of CXA-201 (CXA101\/tazobactam), a novel cephalosporin and b-lactamase inhibitor combination that is being developed to treat serious bacterial infections, was reported to be lower in isolates from the intensive care unit (ICU) compared with non-ICU isolates.\u003C\/p\u003E\n         \u003C\/div\u003E\u003Cul class=\u0022kwd-group\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003EInfectious Disease Clinical Trials\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EBacterial Infections\u003C\/li\u003E\u003C\/ul\u003E\u003Cp id=\u0022p-2\u0022\u003EUsing a pharmacokinetic\/pharmacodynamic (PK\/PD) target algorithm, the \u003Cem\u003Ein vitro\u003C\/em\u003E potency of CXA-201 (CXA101\/tazobactam), a novel cephalosporin and \u03b2-lactamase inhibitor combination that is being developed to treat serious bacterial infections, was reported to be lower in isolates from the intensive care unit (ICU) compared with non-ICU isolates. This is largely driven by the differences in pathogen incidence in the two environments. Judith Steenbergen, PhD, Cubist Pharmaceuticals, Lexington, Massachusetts, USA, presented data from a study that evaluated the CXA-201 potency for pathogens that were isolated from ICU and non-ICU patients. In addition, the potency of CXA-201 against isolates from different sources of infection was evaluated.\u003C\/p\u003E\u003Cp id=\u0022p-3\u0022\u003ECXA-201 is active against gram-negative pathogens, including \u003Cem\u003EPseudomonas aeruginosa\u003C\/em\u003E and \u003Cem\u003EEnterobacteriaceae\u003C\/em\u003E, and select gram-positive organisms. The PK\/PD parameter that was used in this study to predict efficacy was the time that was necessary to maintain concentrations of CXA-201 above the minimum inhibitory concentration (MIC) for approximately 40% to 50% of the time between dose administrations (T\u0026gt;MIC).\u003C\/p\u003E\u003Cp id=\u0022p-4\u0022\u003ECXA-201 was tested by broth microdilution against 4134 isolates that were collected in 2008 from both ICU (n=1093) and non-ICU (n=3041) patients. A population PK model that was derived from healthy volunteers and infected patients was used to perform the Monte Carlo simulations (taking into account variability between subjects, residual variability, demographic covariates, and MIC). Target attainment rates were obtained for 1-hour infusion of 1500 mg CXA-201 every 8 hours. For pathogens with an MIC of 8 \u03bcg\/mL (cutoff target), the target attainment rate was 98.2% for 40% T\u0026gt;MIC.\u003C\/p\u003E\u003Cp id=\u0022p-5\u0022\u003EMIC\u003Csub\u003E90\u003C\/sub\u003E was higher for isolates from the ICU (MIC\u003Csub\u003E90\u003C\/sub\u003E =8 \u03bcg\/mL) than non-ICU isolates (MIC\u003Csub\u003E90\u003C\/sub\u003E =2 \u03bcg\/mL). This was largely driven by differences in the percentage of \u003Cem\u003EStreptococcus pneumoniae, Acinetobacter spp.\u003C\/em\u003E, and \u003Cem\u003EEscherichia coli\u003C\/em\u003E isolates in the ICU versus non-ICU patients (\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\/11\/12\/10\/F1.large.jpg?width=800\u0026amp;height=600\u0026amp;carousel=1\u0022 title=\u0022Potency of CXA-201 for ICU and Non-ICU Isolates.\u0022 class=\u0022fragment-images colorbox-load\u0022 rel=\u0022gallery-fragment-images-596570243\u0022 data-figure-caption=\u0022Potency of CXA-201 for ICU and Non-ICU Isolates.\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\/11\/12\/10\/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\/11\/12\/10\/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\/11\/12\/10\/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\/12432\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 attrib\u0022\u003E\u003Cspan class=\u0022fig-label\u0022\u003EFigure 1.\u003C\/span\u003E \n            \u003Cp id=\u0022p-6\u0022 class=\u0022first-child\u0022\u003EPotency of CXA-201 for ICU and Non-ICU Isolates.\u003C\/p\u003E\n         \u003Cq class=\u0022attrib\u0022 id=\u0022attrib-1\u0022\u003EReproduced with permission from J. Steenbergen, PhD.\u003C\/q\u003E\u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cp id=\u0022p-7\u0022\u003EMore than 95% of all isolates had an MIC \u22648 \u03bcg\/mL (8 \u03bcg\/mL being the provisional breakpoint), with a range of 68% (\u003Cem\u003EAcinetobacter spp.\u003C\/em\u003E) to 100% (\u003Cem\u003EHaemophilus influenzae\u003C\/em\u003E). When CXA-201 potency was analyzed by site of infection, approximately 95% of all isolates had an MIC \u22648 \u03bcg\/mL, with a range of 94% (blood) to 96.9% (urine).\u003C\/p\u003E\u003Cp id=\u0022p-8\u0022\u003EWhether sorted by site or source, approximately 95% of isolates had an MIC value \u0026lt;8 \u03bcg\/mL. All pathogens had an MIC\u003Csub\u003E90\u003C\/sub\u003E \u22648 \u03bcg\/mL except \u003Cem\u003EEnterobacter cloacae\u003C\/em\u003E (88% inhibited at \u22648 \u03bcg\/mL) and \u003Cem\u003EAcinetobacter spp.\u003C\/em\u003E (68.5% inhibited at \u22648 \u03bcg\/mL). Thus, CXA-201 is predicted to achieve excellent target attainment of 40% T\u0026gt;MIC against common ICU pathogens and multidrug-resistant gram-negative pathogens, including \u003Cem\u003EP. aeruginosa\u003C\/em\u003E (99.3% inhibited at \u22648 \u03bcg\/mL).\u003C\/p\u003E\u003Cul class=\u0022copyright-statement\u0022\u003E\u003Cli class=\u0022fn\u0022 id=\u0022copyright-statement-1\u0022\u003E\u00a9 2011 MD Conference Express\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\/11\/12\/10.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?nzmx5d\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?nzmx5d\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}