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Clostridioides Difficileinfections bioMérieux In vitro diagnostics serving CLOSTRIDIOIDES public health DIFFICILE INFECTIONS A major player in in vitro diagnostics for more than 50 years, From Diagnosis to bioMérieux has always been driven by a pioneering spirit and unrelenting commitment to improve public health worldwide. Outbreak Management Our diagnostic solutions bring high medical value to healthcare professionals, providing them with the most relevant and reliable information, as quickly as possible, to support treatment decisions and better patient care. bioMérieux’s mission entails a commitment to support medical education, by promoting access to diagnostic knowledge for as many people as possible. Focusing on the medical value of diagnostics, our collection of educational booklets aims to raise awareness of the essential role that diagnostic test results play in healthcare decisions. Other educational booklets are available. Consult your local bioMérieux representative. The information in this booklet is for educational purposes only and is not intended to be exhaustive. It is not intended to be a substitute for professional medical advice. Always consult a medical director, physician, or other qualified health provider regarding processes and/or protocols for diagnosis and treatment of a medical condition. bioMérieux assumes no responsibility or liability for any diagnosis established or treatment prescribed by the physician. bioMérieux, Inc. • 100 Rodolphe Street • Durham, NC 27712 • USA • Tel: (800) 682 2666 • Fax: (800) 968 9494 © 2019 bioMérieux, Inc. • BIOMERIEUX and the BIOMERIEUX logo, are used pending and/or registered trademarks belonging to bioMérieux, or one of its subsidiaries, or one of its companies. companies. its or one of subsidiaries, its or one of bioMérieux, belonging to trademarks registered pending and/or used are logo, and the BIOMERIEUX • BIOMERIEUX Inc. bioMérieux, © 2019 owner respective its of is the property name or trademark other Any www.biomerieux-usa.com INTRODUCTION INTRODUCTION Clostridioides difficile infection (CDI) is now established as a worldwide As a high proportion of hospitalized patients receive antibiotics, this threat, with major consequences for morbidity, mortality and healthcare means that there are large numbers of potentially susceptible hosts who costs. This educational booklet concentrates on the key information needed may acquire, be colonized by, transmit and/or become infected by C. difficile. to understand, diagnose, control and treat CDI, taking into account the large expansion of knowledge that has occurred in response to the emergence In short, C. difficile is a nosocomial pathogen that has found and exploited of C. difficile in the first decade of this millennium as a global threat. ‘weaknesses’ in our healthcare systems. C. difficile infection can be considered as a healthcare quality indicator, potentially reflecting This transformation of C. difficile was likely driven by four main factors: infection control and antimicrobial prescribing practice, as is already the case in some countries. firstly, the spread of epidemic strains and, in particular, a so-called ‘hypervirulent’ clone, variably referred to as C. difficile ribotype 027/ Improved control of C. difficile requires a greater understanding of the NAP1/BI, which is associated with increased morbidity and mortality, pathogen, the at-risk hosts and how transmission occurs, improved use of especially in the elderly; detection and diagnosis methods, and optimized treatment options. secondly, sub-optimal infection control precautions in many different healthcare settings likely contributed to the transmission of C. difficile strains, in particular those with epidemic potential; thirdly, sub-optimal antimicrobial stewardship, which provided a se- lective pressure for some antibiotic-resistant C. difficile strains, Professor Mark H. Wilcox particularly the C. difficile ribotype 027/ fluoroquinolone-resistant B Med Sci, BM, BS, MD, FRCPath. NAP1/BI clone; and lastly, confusion about when, where and how best to test for Consultant / Head of Microbiology Research & Development, evidence of C. difficile infection has contributed to under-detection/ and Infection Lead of the Leeds NIHR Diagnostic Technologies, under-reporting of cases which has fueled the spread of this opportunistic Medical Technology and In Vitro Diagnostic Co-operative, pathogen. Leeds Teaching Hospitals NHS Trust, UK Clostridioides difficile is the new taxonomic classification for Clostridium difficile. For easy reading and reference, look for the colored boxes This booklet provides essential information on the diagnosis, treatment highlighting the key points in each chapter. and prevention of C. difficile infections. Although not exhaustive, it is intended as a succinct and practical reminder for laboratory professionals and clinicians. CONTENTS 1 WHAT IS CLOSTRIDIOIDES DIFFICILE p. 4 AND C. DIFFICILE INFECTION (CDI)? 2 EPIDEMIOLOGY AND SURVEILLANCE p. 12 3 LABORATORY DIAGNOSTICS p. 17 4 TREATMENT p. 27 5 PREVENTION & CONTROL OF CDI p. 29 6 CDI AS A HEALTHCARE QUALITY p. 31 INDICATOR 7 CONCLUSIONS AND FUTURE p. 34 PERSPECTIVES REFERENCES p. 36 CDI GUIDELINES p. 41 2 3 WHAT IS CLOSTRIDIOIDES DIFFICILE AND C. DIFFICILE INFECTION (CDI)? By contrast, when the microbiota is damaged (e.g. antibiotic exposure) Enterobacteriaceae, Enterococcaceae and Streptococcaceae increase, alongside an environment enriched with amino acids and primary bile acids, which promotes C. difficile germination, colonization and toxin production (Figure 1 - Dysbiosis). 1 WHAT IS CLOSTRIDIOIDES DIFFICILE AND C. DIFFICILE INFECTION (CDI)? Figure 1: Microbial and metabolite status during health and disease Adapted from Ross CL, et al. Anaerobe 2016;41:37-43 What is Clostridioides difficile? HEALTHY DYSBIOSIS Clostridioides difficile is a naturally-occurring species of Gram-positive bacteria of the genus Clostridioides. It has recently been proposed that the name Clostridium difficile change to Clostridioides difficile; either term is cor- rect, and both abbreviate to C. difficile or “C. diff”. C. difficile is present in the large intestine of 1-3% of healthy adults and the majority of healthy infants (but these normally only remain colonized for 1-2 years at most). Clostridia are motile, anaerobic, spore-forming rods (bacilli). When stressed, the bacteria produce spores that are resistant to extreme conditions of heat, drying, and a wide range of antibiotics and chemicals, including some disinfectants. Only pathogenic (toxigenic) strains of C. difficile cause CDI, due to the production of one or two distinct toxins (A and B), which damage the colonic cells, causing cell breakdown and an inflammatory response. Recent evidence Gram stain of Clostridioides difficile (CDC) highlights a key role for toxin B in humans [Wilcox et al, 2017]. Another toxin, binary toxin is also expressed in some virulent strain groups, and may be How does C. difficile cause CDI? associated with worse outcomes, including mortality [Cartman et al, 2010; Berry et al, 2017]. C. difficile proliferates in the human colon when there is a modification of the Non-toxigenic strains do not cause clinical illness, but may provide protection normal/healthy microbiota (bacterial intestinal flora). against colonization with toxigenic strains and so against CDI [Gerding et al, A ‘healthy colonic’ microbiota contains commensal bacteria, short chain 2015; Crobach et al, 2018]. Some but not all individuals develop a host fatty acids, chenodeoxycholate and deoxycholate (secondary bile acids), antitoxin antibody response, which can provide some protection against CDI which together inhibit germination of C. difficile spores and growth of and/or recurrent CDI [Kyne et al, 2000; Kyne et al, 2001]. vegetative cells (Figure 1 - Healthy). 4 5 WHAT IS CLOSTRIDIOIDES DIFFICILE AND C. DIFFICILE INFECTION (CDI)? What is the clinical presentation of CDI? Clostridioides difficile infection is most often an antibiotic-induced illness, often contracted in hospitals or healthcare institutions, due to the pre- SEVERAL KEY FACTORS INTERACT TO DETERMINE sence of elderly, colonized patients with increased potential for transmission. THE ANTIBIOTIC RISK OF INDUCING CDI: The usual symptoms of CDI may include any or all of the following (but especially the first two): Extent of microbiome dysbiosis (Figure 1) watery diarrhea Antibiotics vary in both the degree and duration of microbiome disturbance they cause, thereby potentially providing a greater/longer lower abdominal cramps opportunity for C. difficile strains to colonize, proliferate and cause abdominal bloating disease. Antibiotics that cause profound dysbiosis of anaerobic components nausea of the microbiome appear to be particularly associated with CDI. fever Mucus or pus (very occasionally blood) may be found in the stools. Leukocytosis, Antibiotic penetration into the colon sometimes extremely high, may also accompany CDI. Broad spectrum antibiotics that are excreted predominantly via the gastrointestinal tract are considered to be high CDI risk. This helps to Symptoms generally start during antibiotic therapy, or up to 1 month after explain the high CDI rates associated, for example, with ceftriaxone completion. (which undergoes biliary excretion), as opposed to some renally-excreted Populations most at risk of CDI include: antibiotics that have lower CDI risk. [Khan et al, 2003; Dancer et al, 2013]. people who take antibiotics C. difficile strain antibiotic susceptibility prolonged stay in healthcare
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