{"id":441,"date":"2023-09-16T22:07:20","date_gmt":"2023-09-16T21:07:20","guid":{"rendered":"https:\/\/microregistrar.com\/?p=441"},"modified":"2023-09-16T22:07:20","modified_gmt":"2023-09-16T21:07:20","slug":"candida-auris-an-emerging-multi-resistant-fungus","status":"publish","type":"post","link":"https:\/\/microregistrar.com\/?p=441","title":{"rendered":"Candida auris: an emerging multi-resistant fungus"},"content":{"rendered":"\n<h4 class=\"wp-block-heading\">Introduction<\/h4>\n\n\n\n<p>Candida auris is a pathogen that has emerged as a global threat in recent years. It is the first human pathogenic fungus subject to international health alerts. The reason behind these concerns are \u2013<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>It is multi-resistant<\/li>\n\n\n\n<li>It isn&#8217;t easy to identify \u2013 often misidentified in standard laboratories<\/li>\n\n\n\n<li>It has been known to cause outbreaks in healthcare settings<\/li>\n\n\n\n<li>It colonises the skin and the hospital environment<\/li>\n<\/ul>\n\n\n\n<figure class=\"wp-block-image\"><img decoding=\"async\" src=\"https:\/\/microregistrar.com\/wp-content\/uploads\/2021\/08\/Capture-2-1024x531.jpg\" alt=\"\" class=\"wp-image-7024\"\/><\/figure>\n\n\n\n<p>Public Health England reported in 2017 that almost all the C auris in the UK are fluconazole-resistant. There is also cross-resistance with other azoles like voriconazole.<br><br>The resistance to echinocandins is about 10%, and polyenes (amphotericin B), 20%.<\/p>\n\n\n\n<p>There have been reports where C auris was resistant to all three classes of antifungal \u2013 pan-resistant.<\/p>\n\n\n\n<h4 class=\"wp-block-heading\">Epidemiology<\/h4>\n\n\n\n<p>Candida auris was first reported in 2009 in Japan from the external ear canal of a patient. However, a retrospective review of microbiology cases in South Korea identified Candida auris from a case dating back to 1996.<\/p>\n\n\n\n<p>Following this, many countries reported cases of C auris. As per CDC, up till February 2021, 49 countries have reported cases of C auris.<\/p>\n\n\n\n<p>Here is a video showing when a country first reported a case of C auris [Forsberg 2019,&nbsp; Hu 2021]<video controls=\"\" src=\"https:\/\/microregistrar.com\/wp-content\/uploads\/2021\/08\/Spread-of-Candida-auris.mp4\"><\/video><\/p>\n\n\n\n<p>UK National Mycology Reference Laboratory (MRL) found evidence of&nbsp;<em>C<\/em>.&nbsp;<em>auris<\/em>&nbsp;in the UK in 2013. It was first identified as the cause of a hospital outbreak in England in 2015. Borman reported that by mid-2019, PHE had recorded approximately 270 cases of&nbsp;<em>C<\/em>.&nbsp;<em>auris<\/em>&nbsp;in England, including at least 35 cases of candidemia. PHE reported in 2017 that over 35 additional hospitals in the United Kingdom had received patients with a known C. auris detection.<\/p>\n\n\n\n<figure class=\"wp-block-image\"><img decoding=\"async\" src=\"https:\/\/microregistrar.com\/wp-content\/uploads\/2021\/08\/image-3-1024x629.png\" alt=\"\" class=\"wp-image-7029\"\/><\/figure>\n\n\n\n<p>Whole-genome sequencing (WGS) identified Candida auris have 4 different clades:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>C<strong>lade I (Southern Asia),<\/strong><\/li>\n\n\n\n<li>C<strong>lade II (East Asia),<\/strong><\/li>\n\n\n\n<li>C<strong>lade III (South Africa), and<\/strong><\/li>\n\n\n\n<li>C<strong>lade IV (South America).<\/strong><\/li>\n<\/ul>\n\n\n\n<p>A potential fifth clade has been reported from Iran [Chow 2019].<\/p>\n\n\n\n<p>There is very little difference between the strains in each clade, but vast differences exist between the clades \u2013 suggesting they emerged independently of each other.<\/p>\n\n\n\n<p>Of these, three clades have been reported in the UK.<\/p>\n\n\n\n<figure class=\"wp-block-image\"><img decoding=\"async\" src=\"https:\/\/journals.plos.org\/plospathogens\/article\/figure\/image?size=large&amp;id=info:doi\/10.1371\/journal.ppat.1008563.g001\" alt=\"\"\/><\/figure>\n\n\n\n<p><em>Ref: Borman AM, Johnson EM (2020) Candida auris in the UK: Introduction, dissemination, and control. PLoS Pathog 16(7): e1008563. https:\/\/doi.org\/10.1371\/journal.ppat.1008563<\/em><\/p>\n\n\n\n<h4 class=\"wp-block-heading\">Clinical features<\/h4>\n\n\n\n<p>C auris was first reported from an ear sample, and many early cases were from chronic otitis media. It received its name from this association. Since then, it has been isolated from various other infections.<\/p>\n\n\n\n<figure class=\"wp-block-image\"><img decoding=\"async\" src=\"https:\/\/microregistrar.com\/wp-content\/uploads\/2021\/08\/image-2-1024x579.png\" alt=\"\" class=\"wp-image-7027\"\/><\/figure>\n\n\n\n<p><em>C auris<\/em>&nbsp;bloodstream infection is associated with 30\u201360% mortality rates.<\/p>\n\n\n\n<p><strong>The risk factors associated with Candida auris infections are<\/strong>:<\/p>\n\n\n\n<figure class=\"wp-block-table\"><table><tbody><tr><td><strong>Risk factors<\/strong><\/td><td><strong>Risk factors<\/strong><\/td><td><strong>Risk factors<\/strong><\/td><\/tr><tr><td>Urinary catheters<\/td><td>Mechanical ventilation<\/td><td>Diabetes mellitus<\/td><\/tr><tr><td>Arterial line, central venous access<\/td><td>Hospital and intensive care unit (ICU) stays<\/td><td>HIV<\/td><\/tr><tr><td>Parenteral nutrition<\/td><td>Prior or continual exposure to broad-spectrum antifungal or antibiotic therapy, especially tetracycline, minocycline and tigecycline.<\/td><td>Elderly age<\/td><\/tr><tr><td>Invasive medical procedures (surgeries) and devices<\/td><td>Chronic renal disease<\/td><td>Immunosuppressed state. Neutropenia<\/td><\/tr><\/tbody><\/table><\/figure>\n\n\n\n<p>[Sekiyere 2018; Han Du, PLOS, 2020 ]<\/p>\n\n\n\n<p><strong>Colonisation:<\/strong><\/p>\n\n\n\n<p>Isolation of Candida auris from a non-sterile site does not always suggest infection. It is known to colonise the skin and, in rare instances, the gut, oral, and oesophagal mucosa. A salivary antimicrobial peptide histatin 5 has a potent antifungal effect on&nbsp;<em>C<\/em>.&nbsp;<em>auris<\/em>, making it difficult for this organism to colonise this area. [Han Du, PLOS, 2020]<\/p>\n\n\n\n<h4 class=\"wp-block-heading\"><strong>Virulence factors:<\/strong><\/h4>\n\n\n\n<ul class=\"wp-block-list\">\n<li>Tolerance to high temp (42 degrees C), high salt concentration and osmotolerance \u2013 able to colonise and persist in various environments.<\/li>\n\n\n\n<li>Ability to form biofilms.<\/li>\n\n\n\n<li>Lipases to degrade and invade host tissues<\/li>\n\n\n\n<li>Morphological transformation may form an aggregate of cells, which are less susceptible to antifungals (however, they are also less virulent).<\/li>\n\n\n\n<li>Resistance to multiple antifungal classes \u2013<\/li>\n<\/ul>\n\n\n\n<figure class=\"wp-block-table\"><table><tbody><tr><td><strong>Class<\/strong><\/td><td><strong>Mechanism<\/strong><\/td><\/tr><tr><td>Azoles<\/td><td>Mutation in&nbsp;<em>ERG11<\/em>&nbsp;(<em>ERG11<\/em>&nbsp;encodes for the lanosterol demethylase \u2013 the target of azole class)<br>MFS efflux pump.<br>Upregulated ABC efflux pump.<\/td><\/tr><tr><td>Echinocandin<\/td><td>Mutation in Fks1 (<em>FKS1<\/em>&nbsp;encodes the catalytic subunit of 1,3-beta-D-glucan synthase that is critical for cell wall synthesis. 1,3-beta-D-glucan synthase is the target of echinocandins)<\/td><\/tr><tr><td>Polyenes<\/td><td>single nucleotide polymorphisms in multiple loci<\/td><\/tr><\/tbody><\/table><\/figure>\n\n\n\n<p>[Chabaane 2019]<\/p>\n\n\n\n<h4 class=\"wp-block-heading\">Diagnosis<\/h4>\n\n\n\n<p>Candida auris is often misidentified as another organism by commercial systems.<\/p>\n\n\n\n<p><strong>As per PHE, any Candida spp. isolates associated with invasive infections and isolates from superficial sites in patients from high-intensity\/augmented care settings and those transferred from an affected hospital (the UK or abroad) should be analysed to species level.<\/strong><\/p>\n\n\n\n<p><strong>Microscopy:<\/strong><\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>C auris is indistinguishable from most other Candida species.<\/li>\n\n\n\n<li>Germ tube test &#8211; negative budding yeast; some strains can form rudimentary pseudohyphae on cornmeal agar.<\/li>\n<\/ul>\n\n\n\n<p><strong>Culture:<\/strong><\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>C. auris grows well at 40\u201342\u00ba C. Growth at 42 \u2013 45\u2070C may be useful to help differentiate it from many other Candida species, especially C haemolounii, with which it is frequently confused.<\/li>\n\n\n\n<li>Colonies on CHROMagar may appear white, pink, red, or purple. Although it can be used for screening purposes, it cannot be used as the sole method of identification.<\/li>\n<\/ul>\n\n\n\n<figure class=\"wp-block-image\"><img decoding=\"async\" src=\"https:\/\/microregistrar.com\/wp-content\/uploads\/2021\/08\/image-4-1024x366.png\" alt=\"\" class=\"wp-image-7032\"\/><figcaption class=\"wp-element-caption\"><em>CHROMagar Candida<\/em><\/figcaption><\/figure>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>CHROMagar Candida Plus<\/strong>:<br>Developed specifically to facilitate the detection and identification of&nbsp;<em>C<\/em>.&nbsp;<em>auris<\/em>.<br>Performs well as a primary isolation medium and permits&nbsp;<em>C<\/em>.&nbsp;<em>auris<\/em>&nbsp;to be differentiated from over 50 other yeast species in&nbsp;<em>Candida<\/em>&nbsp;and related genera<\/li>\n<\/ul>\n\n\n\n<figure class=\"wp-block-image\"><img decoding=\"async\" src=\"https:\/\/microregistrar.com\/wp-content\/uploads\/2021\/08\/image-5.png\" alt=\"\" class=\"wp-image-7033\"\/><\/figure>\n\n\n\n<figure class=\"wp-block-image\"><img decoding=\"async\" src=\"https:\/\/microregistrar.com\/wp-content\/uploads\/2021\/08\/image-6.png\" alt=\"\" class=\"wp-image-7034\"\/><figcaption class=\"wp-element-caption\">Ref:&nbsp;<a href=\"http:\/\/www.chromagar.com\/clinical-microbiology-chromagar-candida-plus-focus-on-candida-species-88.html?PHPSESSID=582d48abd0ca28b93f87447862888693\" target=\"_blank\" rel=\"noreferrer noopener\">Chromagar.com<\/a><\/figcaption><\/figure>\n\n\n\n<p><strong>Automated commercial system:<\/strong><\/p>\n\n\n\n<p>Automated commercial systems often misidentify C auris. CDC has presented a list of common misidentifications.<\/p>\n\n\n\n<figure class=\"wp-block-table\"><table><tbody><tr><td><strong>System<\/strong><\/td><td><strong>Misidentification<\/strong><\/td><\/tr><tr><td>Vitek 2 YST<\/td><td><em>Candida haemulonii<\/em><br><em>Candida duobushaemulonii<\/em><\/td><\/tr><tr><td>API 20C<\/td><td><em>Rhodotorula glutinis<\/em>&nbsp;(characteristic red colour not present)<br><em>Candida sake<\/em><\/td><\/tr><tr><td>API ID 32C<\/td><td><em>Candida intermedia<\/em><br><em>Candida sake<\/em><br><em>Saccharomyces kluyveri<\/em><\/td><\/tr><tr><td>BD Phoenix yeast identification system<\/td><td><em>Candida haemulonii<\/em><br><em>Candida catenulata<\/em><\/td><\/tr><tr><td>MicroScan<\/td><td><em>Candida famata<\/em><br><em>Candida guilliermondii<\/em><br><em>Candida lusitaniae<\/em><br><em>Candida parapsilosis<\/em><\/td><\/tr><tr><td>RapID Yeast Plus<\/td><td><em>Candida parapsilosis<\/em><\/td><\/tr><\/tbody><\/table><\/figure>\n\n\n\n<p>So, if these organisms are identified from the respective platform \u2013 the possibility of a C auris should be considered.<\/p>\n\n\n\n<p><strong>MALDI-ToF and molecular tests<\/strong>:<\/p>\n\n\n\n<p>MALDI-ToF and molecular methods are considered the best identification methods.<br><br><strong>MALDI<\/strong>-ToF: Bruker Biotyper and BioM\u00e9rieux VITEK (MALDI-TOF) MS can identify C auris but the lab must ensure that the database is updated and contains C auris in it.<\/p>\n\n\n\n<p><strong>Molecular methods:<\/strong>&nbsp;sequencing the D1-D2 region of the 28s rDNA or the Internal Transcribed Region (ITS) of rDNA \u2013 are some methods that can be used. [Ref:&nbsp;<a href=\"https:\/\/www.cdc.gov\/fungal\/candida-auris\/identification.html\" target=\"_blank\" rel=\"noreferrer noopener\">CDC<\/a>]<\/p>\n\n\n\n<h2 class=\"wp-block-heading\">Susceptibility test<\/h2>\n\n\n\n<p>There are currently no established&nbsp;<em>C. auris<\/em>-specific susceptibility breakpoints. Tentative breakpoint from CDC<\/p>\n\n\n\n<figure class=\"wp-block-table\"><table><tbody><tr><td><strong>Antifungal<\/strong><\/td><td><strong>MIC<\/strong>&nbsp;<strong>\u00b5g\/mL<\/strong><\/td><td><\/td><\/tr><tr><td>Fluconazole<\/td><td>\u226532<\/td><td><\/td><\/tr><tr><td>Voriconazole and other second generation triazoles<\/td><td>NA<\/td><td>Consider using fluconazole susceptibility as a surrogate; however, isolates that are resistant to fluconazole may respond to other triazoles occasionally<\/td><\/tr><tr><td>Amphotericin B<\/td><td>\u22652<\/td><td>a MIC of 1.5 is determined; that value should be rounded up to 2<\/td><\/tr><tr><td>Anidulafungin<\/td><td>\u2265 4<\/td><td><\/td><\/tr><tr><td>Caspofungin<\/td><td>\u2265 2<\/td><td><\/td><\/tr><tr><td>Micafungin<\/td><td>\u2265 4<\/td><td><\/td><\/tr><\/tbody><\/table><\/figure>\n\n\n\n<h2 class=\"wp-block-heading\">Treatment<\/h2>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Echinocandins<\/strong>&nbsp;(caspofungin, anidulafungin, micafungin) are considered as the first line therapy pending susceptibility test.<\/li>\n\n\n\n<li>However, resistance may develop quickly while a patient is receiving therapy and strains resistant to echinocandins have been reported. Clinical monitoring and repeat susceptibility testing from new isolates should be considered.<\/li>\n\n\n\n<li>As per CDC, liposomal amphotericin B (5 mg\/kg daily) could be considered if the patient is clinically unresponsive to echinocandin treatment or has persistent fungemia for &gt;5 days.<\/li>\n\n\n\n<li>Combination therapy has not been evaluated in clinical settings (CDC). PHE suggest if the urinary tract or central nervous system (CNS) is involved, dual therapy may be necessary, and some antifungal classes do not have bio-availability in either urine or CNS.<\/li>\n\n\n\n<li>Terbinafine: Currently, UK strains remain susceptible to the topical agents&#8217; nystatin and terbinafine, and it is possible that for the treatment of any future multi-drug resistant strains, a regimen incorporating oral terbinafine could be considered [<a rel=\"noreferrer noopener\" href=\"https:\/\/assets.publishing.service.gov.uk\/government\/uploads\/system\/uploads\/attachment_data\/file\/637685\/Updated_Candida_auris_Guidance_v2.pdf\" target=\"_blank\">PHE<\/a>].<\/li>\n\n\n\n<li>Multiple new drugs are being evaluated with potential activity against C auris. Novel antifungals&nbsp;<strong>ibrexafungerp<\/strong>&nbsp;have activity against C auris. [de Oliveira 2019, Billamboz 2021]<\/li>\n<\/ul>\n","protected":false},"excerpt":{"rendered":"<p>Introduction Candida auris is a pathogen that has emerged as a global threat in recent years. It is the first [&hellip;]<\/p>\n","protected":false},"author":1,"featured_media":0,"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":[12],"tags":[147,13],"class_list":["post-441","post","type-post","status-publish","format-standard","hentry","category-mycology","tag-candida-auris","tag-mycology"],"_links":{"self":[{"href":"https:\/\/microregistrar.com\/index.php?rest_route=\/wp\/v2\/posts\/441","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=441"}],"version-history":[{"count":2,"href":"https:\/\/microregistrar.com\/index.php?rest_route=\/wp\/v2\/posts\/441\/revisions"}],"predecessor-version":[{"id":628,"href":"https:\/\/microregistrar.com\/index.php?rest_route=\/wp\/v2\/posts\/441\/revisions\/628"}],"wp:attachment":[{"href":"https:\/\/microregistrar.com\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=441"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/microregistrar.com\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=441"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/microregistrar.com\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=441"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}