{"id":189,"date":"2023-06-25T10:25:08","date_gmt":"2023-06-25T09:25:08","guid":{"rendered":"https:\/\/microregistrar.com\/?p=189"},"modified":"2023-06-25T10:25:08","modified_gmt":"2023-06-25T09:25:08","slug":"ceftolozane-tazobactam","status":"publish","type":"post","link":"https:\/\/microregistrar.com\/?p=189","title":{"rendered":"Ceftolozane-tazobactam"},"content":{"rendered":"\n<p><strong>Class:<\/strong>&nbsp;5th generation cephalosporin.<br>Available as ceftolozane-tazobactam, a beta lactam-beta lactamase inhibitor (BLBLI) combination.<\/p>\n\n\n\n<h3 class=\"wp-block-heading\"><strong>Mechanism of Action:<\/strong><\/h3>\n\n\n\n<p>Similar to other beta-lactam antibiotics. It binds to the penicillin-binding protein (PBP) to inhibit the biosynthesis of the cell wall.<br>It binds with the PBP3 of E coli and PBP3, PBP1a, and PBP1b of Pseudomonas aeruginosa.<\/p>\n\n\n\n<h3 class=\"wp-block-heading\"><strong>Mechanism of resistance:<\/strong><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li>Beta-lactamases,<\/li>\n\n\n\n<li>Modification of PBP binding sites by gene acquisition or target alteration,<\/li>\n\n\n\n<li>Up-regulation of efflux pumps, and<\/li>\n\n\n\n<li>Loss of outer membrane porin channels.<\/li>\n<\/ul>\n\n\n\n<p>It is active against ESBL-producing Enterobacterales but not carbapenemase.<br>It also has some activity against Pseudomonas with chromosomal ampC, upregulated efflux pump or porin loss [Shotridge 2021].<\/p>\n\n\n\n<h3 class=\"wp-block-heading\"><strong>PK\/PD:<\/strong><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li>Important parameter \u2013 Time over MIC (T\/MIC). The concentration needs to be at least 60-70% of the dosing interval for bactericidal activity.<\/li>\n\n\n\n<li>Route \u2013 IV<\/li>\n\n\n\n<li>Plasma protein binding \u2013 20% (approx)<\/li>\n\n\n\n<li>Vd \u2013 13.5L<\/li>\n\n\n\n<li>T1\/2 \u2013 3 to 4hrs<\/li>\n\n\n\n<li>Excretion \u2013 renal, (not metabolised) by glomerular filtration.<\/li>\n\n\n\n<li>Hepatic impairment \u2013 No hepatic metabolism<\/li>\n\n\n\n<li>Renal impairment \u2013 dose adjustment needed in renal impairment<\/li>\n\n\n\n<li>Paediatric population \u2013 not enough data<\/li>\n\n\n\n<li>Augmented renal function (ITU) \u2013 no adjustment needed.<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><strong>Use<\/strong>:<\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li>Complicated intraabdominal infections<\/li>\n\n\n\n<li>Complicated urinary tract infection<\/li>\n\n\n\n<li>Hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP)<\/li>\n\n\n\n<li>Sepsis<\/li>\n\n\n\n<li><a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/31923569\/\">Maraolo (2020)<\/a>&nbsp;reviewed the off-label indications like skin-soft tissue, bone-joint infection and bacteremia and found the&nbsp;overall clinical success rate was 76.2%.<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><strong>Adverse effect:<\/strong><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li>GI adverse effects,\u00a0C difficile associated diarrhoea,\u00a0Increase in AST\/ALT,<\/li>\n\n\n\n<li>Headache,<\/li>\n\n\n\n<li>Renal impairment,<\/li>\n\n\n\n<li>Candidiasis,<\/li>\n\n\n\n<li>Allergy\/hypersensitivity reaction,<\/li>\n\n\n\n<li>Leucopenia, thrombocytopenia<\/li>\n\n\n\n<li>Hypoprothrominaemia (esp in renal\/hepatic impairment, poor nutrition or long antibiotic course),<\/li>\n\n\n\n<li>Haemolytic anaemia (+ve Coomb\u2019s test), hypokalemia.<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><strong>Interaction:<\/strong><\/h3>\n\n\n\n<p>Oral contraceptive, loop diuretics, Warfarin.<\/p>\n\n\n\n<h3 class=\"wp-block-heading\"><strong>Contraindication\/caution:<\/strong><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li>Penicillin hypersensitivity<\/li>\n\n\n\n<li>Pregnancy and breastfeeding \u2013 limited data<\/li>\n\n\n\n<li>C difficile associated diarrhoea\/Pseudomembranous colitis<\/li>\n<\/ul>\n\n\n\n<p>[Ref: NICE&nbsp;Evidence summary]<\/p>\n\n\n\n<h3 class=\"wp-block-heading\"><strong>Spectrum:<\/strong><\/h3>\n\n\n\n<p>Activity is similar to ceftazidime but increased activity against Pseudomonas.<br>It has limited activity against gram-positive bacteria.<\/p>\n\n\n\n<p><strong><em>Cefotolozane-tazobactam<\/em><\/strong><em>&nbsp;is active against \u2013<\/em><\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>Enterobacterales \u2013&nbsp;Including ESBL, but not carbapenemase) \u2013<br><em>E coli,<\/em>&nbsp;<em>Klebsiella spp, Enterobacter cloacae, Serratia spp. Citrobacter spp.<\/em>&nbsp;(KESC)<br><em>Proteus spp, Providencia spp,&nbsp;Morganella morganii<\/em>&nbsp;(PPM).<\/li>\n\n\n\n<li><em>Pseudomonas aeruginosa<\/em>&nbsp;\u2013 including ampC producers, those with oprD porin loss or upregulated efflux pump.<\/li>\n\n\n\n<li><em>Haemophilus influenzae&nbsp;(including if beta-lactamase positive strains)<\/em>.<\/li>\n\n\n\n<li><em>Gram-positive bacteria: Group B Streptococcus,&nbsp;Streptococcus anginosus group,&nbsp;Streptococcus salivarius<\/em>.<\/li>\n\n\n\n<li><em>Anaerobes: B fragilis, Propinibacterium, Fusobacterim, Prevotella.<\/em>&nbsp;<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\"><strong>Trials<\/strong><\/h3>\n\n\n\n<p>ASPECT-NP \u2013&nbsp;multicentre randomised controlled, double-blind, non-inferiority trial. A high&nbsp;dose of ceftolozane with tazobactam was non-inferior to meropenem for treating seriously ill people with VAP or ventilated HAP&nbsp;caused by Gram-negative pathogens such as&nbsp;<em>Pseudomonas aeruginosa<\/em>&nbsp;(including multidrug-resistant strains) and Enterobacterales including ESBL producers.<\/p>\n\n\n\n<p>This study did not include less severe HAP patients, immunosuppressed patients, cystic fibrosis patients, dialysis patients, and children.<\/p>\n\n\n\n<p>ASPECT-cUTI:\u00a0RCT\u00a0 in adults with complicated urinary tract infections or acute pyelonephritis IV ceftolozane\/ tazobactam was non\u2011inferior to IV levofloxacin clinical cure and statistically superior for microbiological eradication. This trial did not have enough data on\u00a0men, older people, children, pregnant patients\/breastfeeding women, immunocompromised, septic shock, complicated lower urinary tract infections or people with moderate to severe renal impairment.<\/p>\n\n\n\n<p>ASPECT-cIAI:\u00a0RCT in adults with complicated intra\u2011abdominal infections, intravenous ceftolozane\/tazobactam plus metronidazole, was non\u2011inferior to intravenous meropenem plus saline (placebo) in terms of clinical cure rates 24\u201332\u00a0days after starting treatment. This result may not be generalisable to older people, those with severe renal failure, rapidly progressing disease (septic shock), children, and immunocompromised patients.<\/p>\n\n\n\n<figure class=\"wp-block-image size-large\"><img loading=\"lazy\" decoding=\"async\" width=\"1024\" height=\"594\" src=\"https:\/\/microregistrar.com\/wp-content\/uploads\/2023\/06\/image-5-1024x594.jpeg\" alt=\"\" class=\"wp-image-190\" srcset=\"https:\/\/microregistrar.com\/wp-content\/uploads\/2023\/06\/image-5-1024x594.jpeg 1024w, https:\/\/microregistrar.com\/wp-content\/uploads\/2023\/06\/image-5-300x174.jpeg 300w, https:\/\/microregistrar.com\/wp-content\/uploads\/2023\/06\/image-5-768x445.jpeg 768w, https:\/\/microregistrar.com\/wp-content\/uploads\/2023\/06\/image-5.jpeg 1080w\" sizes=\"auto, (max-width: 1024px) 100vw, 1024px\" \/><\/figure>\n","protected":false},"excerpt":{"rendered":"<p>Class:&nbsp;5th generation cephalosporin.Available as ceftolozane-tazobactam, a beta lactam-beta lactamase inhibitor (BLBLI) combination. Mechanism of Action: Similar to other beta-lactam antibiotics. [&hellip;]<\/p>\n","protected":false},"author":1,"featured_media":191,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"site-sidebar-layout":"default","site-content-layout":"","ast-site-content-layout":"default","site-content-style":"default","site-sidebar-style":"default","ast-global-header-display":"","ast-banner-title-visibility":"","ast-main-header-display":"","ast-hfb-above-header-display":"","ast-hfb-below-header-display":"","ast-hfb-mobile-header-display":"","site-post-title":"","ast-breadcrumbs-content":"","ast-featured-img":"","footer-sml-layout":"","ast-disable-related-posts":"","theme-transparent-header-meta":"","adv-header-id-meta":"","stick-header-meta":"","header-above-stick-meta":"","header-main-stick-meta":"","header-below-stick-meta":"","astra-migrate-meta-layouts":"default","ast-page-background-enabled":"default","ast-page-background-meta":{"desktop":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"tablet":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"mobile":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""}},"ast-content-background-meta":{"desktop":{"background-color":"var(--ast-global-color-4)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"tablet":{"background-color":"var(--ast-global-color-4)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"mobile":{"background-color":"var(--ast-global-color-4)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""}},"ngg_post_thumbnail":0,"footnotes":""},"categories":[9],"tags":[28,42,30],"class_list":["post-189","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-antibiotic","tag-antibiotic","tag-ceftolozane-tazobactam","tag-cephalosporin"],"_links":{"self":[{"href":"https:\/\/microregistrar.com\/index.php?rest_route=\/wp\/v2\/posts\/189","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/microregistrar.com\/index.php?rest_route=\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/microregistrar.com\/index.php?rest_route=\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/microregistrar.com\/index.php?rest_route=\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/microregistrar.com\/index.php?rest_route=%2Fwp%2Fv2%2Fcomments&post=189"}],"version-history":[{"count":1,"href":"https:\/\/microregistrar.com\/index.php?rest_route=\/wp\/v2\/posts\/189\/revisions"}],"predecessor-version":[{"id":192,"href":"https:\/\/microregistrar.com\/index.php?rest_route=\/wp\/v2\/posts\/189\/revisions\/192"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/microregistrar.com\/index.php?rest_route=\/wp\/v2\/media\/191"}],"wp:attachment":[{"href":"https:\/\/microregistrar.com\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=189"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/microregistrar.com\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=189"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/microregistrar.com\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=189"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}