Clostridioides difficile

<!DOCTYPE html> <html lang="en" > <head > <meta charset="UTF-8" /> <meta http-equiv="X-UA-Compatible" content="IE=edge" /> <meta name="HandheldFriendly" content="True" /> <meta name="MobileOptimized" content="320" /> <meta name="viewport" content="width=device-width, initial-scale=1.0" /> <link rel="stylesheet" href="/static/assets/style-70b9163a.css" /> <script type="module" crossorigin="" src="/static/assets/base_style-ec2bc71e.js"></script> <link rel="stylesheet" href="/static/assets/style-ef962842.css" /> <link rel="stylesheet" href="/static/assets/style-3ade8b5c.css" /> <script type="module" crossorigin="" src="/static/assets/article_style-d757a0dd.js"></script> <style> @media screen and (min-width: 64em) { div.pmc-wm { background: repeat-y; background-image: url("data:image/svg+xml,%3Csvg xmlns='http://www.w3.org/2000/svg' width='20' height='350' xmlns:xlink='http://www.w3.org/1999/xlink'%3E%3Cdefs%3E%3Cfilter x='-.02' y='0' width='1.05' height='1' id='c'%3E%3CfeFlood flood-color='%23FFF'/%3E%3CfeComposite in='SourceGraphic'/%3E%3C/filter%3E%3Ctext id='b' font-family='Helvetica' font-size='11pt' style='opacity:1;fill:%23005ea2;stroke:none;text-anchor:middle' x='175' y='14'%3EAuthor Manuscript%3C/text%3E%3Cpath id='a' style='fill:%23005ea2' d='M0 8h350v3H0z'/%3E%3C/defs%3E%3Cuse xlink:href='%23a' transform='rotate(90 10 10)'/%3E%3Cuse xlink:href='%23b' transform='rotate(90 10 10)' filter='url(%23c)'/%3E%3C/svg%3E"); padding-left: 3rem; } } </style> <link rel="apple-touch-icon" sizes="180x180" href="/static/img/favicons/apple-touch-icon.png" /> <link rel="icon" type="image/png" sizes="48x48" href="/static/img/favicons/favicon-48x48.png" /> <link rel="icon" type="image/png" sizes="32x32" href="/static/img/favicons/favicon-32x32.png" /> <link rel="icon" type="image/png" sizes="16x16" href="/static/img/favicons/favicon-16x16.png" /> <link rel="manifest" href="/static/img/favicons/site.webmanifest" /> <link rel="mask-icon" href="/static/img/favicons/safari-pinned-tab.svg" color="#0071bc" /> <meta name="msapplication-config" content="/static/img/favicons/browserconfig.xml" /> <meta name="theme-color" content="#ffffff" /> <title> Clostridioides difficile - PMC </title>  <meta name="ncbi_app" content="cloudpmc-viewer" /> <meta name="ncbi_db" content="pmc" /> <meta name="ncbi_phid" content="E5FD9234742212830392340023F623A4.m_1" />  <meta name="ncbi_pdid" content="article" /> <link rel="preconnect" href="https://www.google-analytics.com" /> <link rel="dns-prefetch" href="https://cdn.ncbi.nlm.nih.gov" /> <link rel="preconnect" href="https://code.jquery.com" /> <meta name="ncbi_domain" content="nihpa"> <meta name="ncbi_type" content="fulltext"> <meta name="ncbi_pcid" content="manuscript"> <link rel="canonical" href="https://pmc.ncbi.nlm.nih.gov/articles/PMC6637408/"> <meta name="robots" content="INDEX,NOFOLLOW,NOARCHIVE"> <meta name="citation_journal_title" content="Trends in microbiology"> <meta name="citation_title" content="Clostridioides difficile"> <meta name="citation_author" content="Brindar K Sandhu"> <meta name="citation_author_institution" content="Genetics and Molecular Biology Graduate Program, Emory University, Atlanta, GA USA 30322"> <meta name="citation_author_institution" content="Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA USA 30322"> <meta name="citation_author_institution" content="Emory Antibiotic Resistance Center, Emory University School of Medicine, Atlanta, GA USA 30322"> <meta name="citation_author" content="Shonna M McBride"> <meta name="citation_author_institution" content="Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA USA 30322"> <meta name="citation_author_institution" content="Emory Antibiotic Resistance Center, Emory University School of Medicine, Atlanta, GA USA 30322"> <meta name="citation_publication_date" content="2018 Oct 5"> <meta name="citation_volume" content="26"> <meta name="citation_issue" content="12"> <meta name="citation_firstpage" content="1049"> <meta name="citation_doi" content="10.1016/j.tim.2018.09.004"> <meta name="citation_pmid" content="30297117"> <meta name="citation_abstract_html_url" content="https://pmc.ncbi.nlm.nih.gov/articles/PMC6637408/"> <meta name="citation_fulltext_html_url" content="https://pmc.ncbi.nlm.nih.gov/articles/PMC6637408/"> <meta name="citation_pdf_url" content="https://pmc.ncbi.nlm.nih.gov/articles/PMC6637408/pdf/nihms-1031432.pdf"> <meta name="description" content="Clostridioides difficile is a spore-forming, anaerobic, intestinal pathogen that causes severe diarrhea that can lead to death. In 2011, C. difficile infected ~500,000 people in the US and killed ~29,000 people. C. difficile infection (CDI) is the ..."> <meta name="og:title" content="Clostridioides difficile"> <meta name="og:type" content="article"> <meta name="og:site_name" content="PubMed Central (PMC)"> <meta name="og:description" content="Clostridioides difficile is a spore-forming, anaerobic, intestinal pathogen that causes severe diarrhea that can lead to death. In 2011, C. difficile infected ~500,000 people in the US and killed ~29,000 people. 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Author manuscript; available in PMC: 2019 Jul 18.</div> <div> <em>Published in final edited form as: </em>Trends Microbiol. 2018 Oct 5;26(12):1049–1050. doi: <a href="https://doi.org/10.1016/j.tim.2018.09.004" class="usa-link usa-link--external" data-ga-action="click_feat_suppl" target="_blank" rel="noopener noreferrer">10.1016/j.tim.2018.09.004</a> </div> <nav id="journal_context_menu" hidden="hidden"><ul class="menu-list font-family-ui" role="menu"> <li role="presentation"><a href="https://www.ncbi.nlm.nih.gov/pmc/?term=%22Trends%20Microbiol%22%5Bjour%5D" class="usa-link" role="menuitem">Search in PMC</a></li> <li role="presentation"><a href="https://pubmed.ncbi.nlm.nih.gov/?term=%22Trends%20Microbiol%22%5Bjour%5D" lang="en" class="usa-link" role="menuitem">Search in PubMed</a></li> <li role="presentation"><a href="https://www.ncbi.nlm.nih.gov/nlmcatalog?term=%22Trends%20Microbiol%22%5BTitle%20Abbreviation%5D" class="usa-link" role="menuitem">View in NLM Catalog</a></li> <li role="presentation"><a href="?term=%22Trends%20Microbiol%22%5Bjour%5D" class="usa-link" role="menuitem" data-add-to-search="true">Add to search</a></li> </ul></nav></section><section class="front-matter"><div class="ameta p font-secondary font-xs"> <hgroup><h1>Clostridioides difficile</h1></hgroup><div class="cg p"> <a href="https://pubmed.ncbi.nlm.nih.gov/?term=%22Sandhu%20BK%22%5BAuthor%5D" class="usa-link" aria-describedby="id1"><span class="name western">Brindar K Sandhu</span></a><div hidden="hidden" id="id1"> <h3><span class="name western">Brindar K Sandhu</span></h3> <div class="p"> <sup>1</sup>Genetics and Molecular Biology Graduate Program, Emory University, Atlanta, GA USA 30322</div> <div class="p"> <sup>2</sup>Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA USA 30322</div> <div class="p"> <sup>3</sup>Emory Antibiotic Resistance Center, Emory University School of Medicine, Atlanta, GA USA 30322</div> <div class="p">Find articles by <a href="https://pubmed.ncbi.nlm.nih.gov/?term=%22Sandhu%20BK%22%5BAuthor%5D" class="usa-link"><span class="name western">Brindar K Sandhu</span></a> </div> </div> <sup>1,</sup><sup>2,</sup><sup>3</sup>, <a href="https://pubmed.ncbi.nlm.nih.gov/?term=%22McBride%20SM%22%5BAuthor%5D" class="usa-link" aria-describedby="id2"><span class="name western">Shonna M McBride</span></a><div hidden="hidden" id="id2"> <h3><span class="name western">Shonna M McBride</span></h3> <div class="p"> <sup>2</sup>Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA USA 30322</div> <div class="p"> <sup>3</sup>Emory Antibiotic Resistance Center, Emory University School of Medicine, Atlanta, GA USA 30322</div> <div class="p">Find articles by <a href="https://pubmed.ncbi.nlm.nih.gov/?term=%22McBride%20SM%22%5BAuthor%5D" class="usa-link"><span class="name western">Shonna M McBride</span></a> </div> </div> <sup>2,</sup><sup>3</sup> </div> <ul class="d-buttons inline-list"> <li><button class="d-button" aria-controls="aip_a" aria-expanded="false">Author information</button></li> <li><button class="d-button" aria-controls="anp_a" aria-expanded="false">Article notes</button></li> <li><button class="d-button" aria-controls="clp_a" aria-expanded="false">Copyright and License information</button></li> </ul> <div class="d-panels font-secondary-light"> <div id="aip_a" class="d-panel p" style="display: none"> <div class="p" id="A1"> <sup>1</sup>Genetics and Molecular Biology Graduate Program, Emory University, Atlanta, GA USA 30322</div> <div id="A2"> <sup>2</sup>Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA USA 30322</div> <div id="A3"> <sup>3</sup>Emory Antibiotic Resistance Center, Emory University School of Medicine, Atlanta, GA USA 30322</div> </div> <div id="anp_a" class="d-panel p" style="display: none"><div class="notes p"><section id="historyarticle-meta1" class="history"><p>Issue date 2018 Dec.</p></section></div></div> <div id="clp_a" class="d-panel p" style="display: none"><div class="p"><a href="/about/copyright/" class="usa-link">PMC Copyright notice</a></div></div> </div> <div>PMCID: PMC6637408 NIHMSID: NIHMS1031432 PMID: <a href="https://pubmed.ncbi.nlm.nih.gov/30297117/" class="usa-link">30297117</a> </div> <div class="ra xbox p" role="complementary" aria-label="Related or updated information about this article"><div>The publisher's version of this article is available at <a href="https://doi.org/10.1016/j.tim.2018.09.004" class="usa-link usa-link--external" data-ga-action="click_feat_suppl" target="_blank" rel="noopener noreferrer">Trends Microbiol</a> </div></div> </div></section></section><section aria-label="Article content"><section class="body main-article-body"><section class="abstract" id="ABS1"><h2>Abstract</h2> <p id="P1"><em>Clostridioides difficile</em> is a spore-forming, anaerobic, intestinal pathogen that causes severe diarrhea that can lead to death. In 2011, <em>C. difficile</em> infected ~500,000 people in the US and killed ~29,000 people. <em>C. difficile</em> infection (CDI) is the most common health care related infection in the US, leading to increased health care costs of $4.8 billion dollars. This pathogen transmits via the oral-fecal route as a highly contagious and resilient spore. Upon exposure to primary bile acids in the intestine, <em>C. difficile</em> germinates, and in the absence of colonization resistance from the normal microbiota, the bacterium colonizes the colon and produces toxins. These toxins inhibit actin polymerization in host cells, leading to cell death. <em>C. difficile</em> cells can then sporulate in the intestine and exit the body via diarrheal shedding. In culture, sporulation is induced at stationary phase in a nutrient-limiting environment, but the intestinal triggers of sporulation are still unknown.</p></section><section id="S1"><h2 class="pmc_sec_title">Key Facts:</h2> <ul id="L2" class="list" style="list-style-type:disc"> <li><p id="P2"><em>C. difficile</em> was first described in 1935, but wasn’t linked to antibiotic-associated diarrhea and pseudomembranous colitis until 1978.</p></li> <li><p id="P3"><em>C. difficile</em> has a single, circular chromosome comprised of approximately 4.3 Mb.</p></li> <li><p id="P4"><em>C. difficile</em> spores are resistant to heat, oxygen, and ethanol-based disinfectants, but can be killed by a 1:10 dilution of sodium hypochlorite (bleach).</p></li> <li><p id="P5">CDI animal models include the hamster, mouse, young hare, infant pig, prairie dog, foal, quail, and, recently, the rat.</p></li> <li><p id="P6"><em>C. difficile</em> toxin action has been characterized in the rat, mouse, hamster, rabbit, guinea pig, infant rhesus monkey, and the zebrafish embryo.</p></li> <li><p id="P7">The two major toxins produced by <em>C. difficile</em> are TcdA and TcdB, which are glucosyltransferases that inhibit Rho, Rac, and Cdc42. A third toxin, Cdt, is found in the ribotype 027 strain.</p></li> </ul></section><section id="S2"><h2 class="pmc_sec_title">Disease Facts:</h2> <ul id="L4" class="list" style="list-style-type:disc"> <li><p id="P8">People most at risk for CDI are the elderly, people in healthcare settings, and those who have received antibiotic treatment.</p></li> <li><p id="P9">The antibiotics that provide the highest risk of CDI are clindamycin, floroquinolones, cephalosporins, monobactams, and carbapenems, with increased risk correlated with greater cumulative dose, number of antibiotics, and duration of exposure.</p></li> <li><p id="P10">The estimated rate of CDI recurrence is 13.5% and death is 1.3%, both within the first 30 days of initial infection.</p></li> </ul></section><section id="S3"><h2 class="pmc_sec_title">Taxonomy and classification:</h2> <p id="P11">Kingdom: Bacteria</p> <p id="P12">Phylum: Firmicutes</p> <p id="P13">Class: Clostridia</p> <p id="P14">Order: Clostridiales</p> <p id="P15">Family: Clostridiaceae</p> <p id="P16">Genus: <em>Clostridioides</em> (formerly <em>Peptoclostridium</em> and <em>Clostridium</em>)</p> <p id="P17">Species: <em>difficile</em></p> <p id="P18">Gram-positive</p></section><section id="floats-group1" class="floats-group"><figure class="fig xbox font-sm" id="F1"><p class="img-box line-height-none margin-x-neg-2 tablet:margin-x-0 text-center"><a class="tileshop" target="_blank" href="https://www.ncbi.nlm.nih.gov/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=Click%20on%20image%20to%20zoom&p=PMC3&id=6637408_nihms-1031432-f0001.jpg"><img class="graphic zoom-in" src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a6ed/6637408/966bb84e0fb0/nihms-1031432-f0001.jpg" loading="lazy" height="687" width="800" alt="graphic file with name nihms-1031432-f0001.jpg"></a></p> <div class="p text-right font-secondary"><a href="figure/F1/" class="usa-link" target="_blank" rel="noopener noreferrer">Open in a new tab</a></div></figure><figure class="fig xbox font-sm" id="F2"><p class="img-box line-height-none margin-x-neg-2 tablet:margin-x-0 text-center"><a class="tileshop" target="_blank" href="https://www.ncbi.nlm.nih.gov/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=Click%20on%20image%20to%20zoom&p=PMC3&id=6637408_nihms-1031432-f0002.jpg"><img class="graphic zoom-in" src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a6ed/6637408/4ba24b51d2f5/nihms-1031432-f0002.jpg" loading="lazy" height="501" width="800" alt="graphic file with name nihms-1031432-f0002.jpg"></a></p> <div class="p text-right font-secondary"><a href="figure/F2/" class="usa-link" target="_blank" rel="noopener noreferrer">Open in a new tab</a></div></figure></section><section id="S4" class="ack"><h2 class="pmc_sec_title">ACKNOWLEDGEMENTS</h2> <p id="P19">Details of toxin effects are adapted from <a href="#R10" class="usa-link" aria-describedby="R10">Abt <em>et al</em>. (2016)</a>. Work in the McBride lab is supported by the U.S. National Institutes of Health through research grants A1121684 and A1116933 to S.M.M. The content of this manuscript is solely the responsibility of the authors and does not necessarily reflect the official views of the National Institutes of Health.</p></section><section id="ref-list1" class="ref-list"><h2 class="pmc_sec_title">literature</h2> <section id="ref-list1_sec2"><ul class="ref-list font-sm" style="list-style-type:none"> <li id="R1"> <span class="label">1.</span><cite>Lessa FC, et al. , Burden of Clostridium difficile Infection in the United States. 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