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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\u003EResistance of multidrug resistant Gram-negative pathogens to carbapenems is increasing. The value of ceftazidime and avibactam as an alternative to carbapenems was explored in the REPRISE trial. The results indicate that the combination of ceftazidime and avibactam is tolerable and effective, with clinical success similar best available therapy (typically carbapenem monotherapy).\u003C\/p\u003E\u003C\/div\u003E\u003Cul class=\u0022kwd-group\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003EREPRISE\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003ENCT01644643\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Eceftazidime\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Eavibactam\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Eurinary tract infection\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Ecarbapenem\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Ecomplicated intra-abdominal infection\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Ebacterial infections\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Einfectious diseases clinical trials\u003C\/li\u003E\u003C\/ul\u003E\u003Cdiv class=\u0022section\u0022 id=\u0022sec-1\u0022\u003E\u003Cp id=\u0022p-2\u0022\u003EUrinary tract infections (UTIs) due to multidrug-resistant gram-negative bacteria (including ceftazidime resistant) respond to treatment via a combination of ceftazidime and avibactam. The results of REPRISE [\u003Ca class=\u0022external-ref external-ref-type-clintrialgov\u0022 href=\u0022\/lookup\/external-ref?link_type=CLINTRIALGOV\u0026amp;access_num=NCT01644643\u0026amp;atom=%2Fspmdc%2F15%2F48%2F13.atom\u0022\u003ENCT01644643\u003C\/a\u003E], a prospective open-label phase 3 trial, were presented by Yehuda Carmeli, MD, MPH, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.\u003C\/p\u003E\u003Cp id=\u0022p-3\u0022\u003EThe burgeoning prevalence of multidrug-resistant gram-negative pathogens spurred the use of carbapenems, but resistance to carbapenems is also spreading. Ceftazidime-avibactam (CAZ-AVI) may have merit as an alternative, and it was the focus of the REPRISE trial.\u003C\/p\u003E\u003Cp id=\u0022p-4\u0022\u003EPatients aged \u2265\u200518 years who were hospitalized with complicated intra-abdominal infection (cIAI) or complicated urinary tract infection (cUTI) due to ceftazidime-resistant gram-negative bacteria were randomized 1:1 for 5 to 21 days of intravenous therapy involving either best available therapy (BAT; carbapenem antibiotic monotherapy in 97% of cases) or CAZ-AVI (followed by metronidazole in the case of cIAI that could involve anaerobes), with dose reduction for patients with renal impairment. Treatment outcome (test of cure [TOC]) was ascertained 7 to 10 days after the last treatment in the microbiologically modified intention-to-treat (mMITT) population (\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\/13\/F1.large.jpg?width=800\u0026amp;height=600\u0026amp;carousel=1\u0022 title=\u0022Study DesigncIAI, complicated intra-abdominal infection; cUTI, complicated urinary tract infection; IV, intravenous; TOC, test of cure.Reproduced with permission from Y Carmeli, MD, MPH.\u0022 class=\u0022fragment-images colorbox-load\u0022 rel=\u0022gallery-fragment-images-730839507\u0022 data-figure-caption=\u0022Study DesigncIAI, complicated intra-abdominal infection; cUTI, complicated urinary tract infection; IV, intravenous; TOC, test of cure.Reproduced with permission from Y Carmeli, MD, MPH.\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\/13\/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\/13\/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\/13\/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\/16611\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-5\u0022 class=\u0022first-child\u0022\u003EStudy Design\u003C\/p\u003E\u003Cp id=\u0022p-6\u0022\u003EcIAI, complicated intra-abdominal infection; cUTI, complicated urinary tract infection; IV, intravenous; TOC, test of cure.\u003C\/p\u003E\u003Cp id=\u0022p-7\u0022\u003EReproduced with permission from Y Carmeli, MD, MPH.\u003C\/p\u003E\u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cp id=\u0022p-8\u0022\u003ECeftazidime-resistant Enterobacteriaceae and \u003Cem\u003EPseudomonas aeruginosa\u003C\/em\u003E were defined as having a ceftazidime minimal inhibitory concentration of \u2265\u20058 and \u2265\u200516 mg\/L, respectively. The primary end point was the clinical response to treatment. Secondary end points included favorable microbiological response in the mMITT population and safety, as determined by emergent adverse events (AEs) and laboratory testing.\u003C\/p\u003E\u003Cp id=\u0022p-9\u0022\u003EThe 53-center, 16-country trial involved 333 patients randomized to CAZ-AVI (n\u2005=\u2005165; cUTI, n\u2005=\u2005153) or BAT (n\u2005=\u2005168; cUTI, n\u2005=\u2005153). The mMITT population comprised 302 patients (CAZ-AVI, n\u2005=\u2005154; BAT, n\u2005=\u2005148). At baseline, the characteristics were generally similar in the cUTI patients in both groups. Patients with cIAI were broadly similar, considering the small number of patients (\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\/16612\/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\/16612\/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\/16612\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-10\u0022 class=\u0022first-child\u0022\u003EBaseline Characteristics of the Study Groups\u003C\/p\u003E\u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cp id=\u0022p-16\u0022\u003EThe majority of patients were infected with Enterobacteriaceae, most commonly \u003Cem\u003EEscherichia coli\u003C\/em\u003E and \u003Cem\u003EKlebsiella pneumoniae\u003C\/em\u003E. The overall clinical cure rate (cUTI and cIAI) at TOC in the mMITT population was 140 of 154 (90.9%; 95% CI, 85.6% to 94.7%) for CAZ-AVI and 135 of 148 (91.2%; 95% CI, 85.9% to 95.0%) for BAT. For patients with cUTI, the clinical cure rate at TOC in the mMITT population was 132 of 144 (91.7%; 95% CI, 86.3% to 95.4%) for CAZ-AVI and 129 of 137 (94.2%; 95% CI, 89.3% to 97.2%) for BAT. The per-patient favorable microbiological response rate in patients with cUTI treated with CAZ-AVI (n\u2005=\u2005118 of 144, 81.9%; 95% CI, 75.1% to 87.6%) was higher than that with BAT (n\u2005=\u200588 of 137, 64.2%; 95% CI, 56.0% to 71.9%). Rates of clinical cure declined with time but remained \u2265\u200585% for the CAZ-AVI arm.\u003C\/p\u003E\u003Cp id=\u0022p-17\u0022\u003EAEs occurred in 51 of 164 (31.1%) and 66 of 168 (39.3%) patients in the CAZ-AVI and BAT arms, respectively, with serious AEs in 5.5% and 6.0% of patients, respectively. The most frequent AEs were gastrointestinal disorders (12.8% and 17.9%, respectively). Seven deaths (3 in the CAZ-AVI arm and 4 in the BAT arm) were not considered related to the therapy.\u003C\/p\u003E\u003Cp id=\u0022p-18\u0022\u003EThe results indicate the potential value of CAZ-AVI in the treatment of cUTI caused by ceftazidime-resistant gram-negative bacteria. The small numbers of cIAI patients preclude any definitive conclusion about the efficacy of CAZ-AVI in treating this sort of infection.\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\/13.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?nzllxf\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?nzllxf\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?nzllxf\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}