"ranging in genome size from about 30 to about 60 kb. Both environmentally and clinically derived ""C. difficile"" strains carry a diverse and prevalent set of prophages. Clostridioides difficile (bacteria) Clostridioides difficile (syn. ""Clostridium difficile""), also known as C. difficile, C. diff (), or sometimes CDF/cdf, is a species of Gram-positive spore-forming bacterium. ""Clostridioides"" are anaerobic, motile bacteria, ubiquitous in nature, and especially prevalent in soil. Its vegetative cells are rod shaped, pleomorphic, and occur in pairs or short chains. Under the microscope, they appear as long, irregular (often drumstick- or spindle-shaped) cells with a bulge at their terminal ends"
"""C. difficile"" is catalase and superoxide dismutase negative, and produces two types of toxins: enterotoxin A and cytotoxin B, which disrupts cytoskeleton signal transductions in the host. When stressed, the bacteria produce spores that are able to tolerate extreme conditions that the active bacteria cannot tolerate. ""C. difficile"" may become established in the human colon; it is present in 2–5% of the adult population. Sometimes antibiotic therapy for various infections has the adverse effect of disrupting the normal balance of the gut microbiota, in which case ""C. difficile"" may opportunistically dominate, causing ""C. difficile"" infection. The species was transferred from"
"(compare classical Latin /difˈfi.ki.leː/), although spelling pronunciations such as and are commonly heard. The latter two are approximately comparable to the pronunciations of the obsolete English adjective ""difficile"" and the French adjective ""difficile"". Pathogenic ""C. difficile"" strains produce multiple toxins. The best-characterized are enterotoxin (""C. difficile"" toxin A) and cytotoxin (""C. difficile"" toxin B), both of which may produce diarrhea and inflammation in infected patients (""C. difficile"" colitis), although their relative contributions have been debated. The diarrhea may range from a few days of intestinal fluid loss to life-threatening pseudomembranous colitis. Pseudomembranous colitis is associated with intense inflammation of the"
"of one or even both toxins is not always sufficient for producing symptoms. Symptoms of ""C. difficile"" include: diarrhea (at least three loose bowel movements a day), dehydration, abdominal pain that can be severe, loss of appetite and nausea. Patients being treated with antibiotics when symptoms begin should stop taking them, if possible. This break in antibiotic therapy can sometimes lead to spontaneous resolution of symptoms. Patients that don't respond to the cessation of broad-spectrum antibiotics will need to be treated with antibiotics capable of killing C. difficile spores. Primary infections are typically treated with metronidazole. This medication is normally"
"difficile"" that is resistant to fluoroquinolone antibiotics such as ciprofloxacin and levofloxacin, said to be causing geographically dispersed outbreaks in North America, was reported in 2005. The U.S. Centers for Disease Control and Prevention in Atlanta warned of the emergence of an epidemic strain with increased virulence, antibiotic resistance, or both. ""C. difficile"" is transmitted from person to person by the fecal-oral route. The organism forms heat-resistant spores that are not killed by alcohol-based hand cleansers or routine surface cleaning. Thus, these spores survive in clinical environments for long periods. Because of this, the bacteria may be cultured from almost"
"the use of soap in addition to alcohol solutions in order to limit the spread of the spores. ""C. difficile"" infects pigs, calves, and humans, and inhabits a natural reservoir of soil, faeces of domestic animals and humans, sewage, the human intestinal tract, and retail meat. A 2015 CDC study estimated that ""C. diff"" afflicted almost half a million Americans and caused 29,000 deaths in 2011. The study estimated that 40 percent of cases began in nursing homes or community health care settings, while 24 percent occurred in hospitals. ""C. difficile"" is common in the human digestive system. However, ""C."
"to 25% of people. Some tentative evidence indicates fecal microbiota transplantation and probiotics may decrease the risk of recurrence. ""C. difficile"" infections occur in all areas of the world. About 453,000 cases occurred in the United States in 2011, resulting in 29,000 deaths. Rates of disease globally have increased between 2001 and 2016. Women are more often affected than men. The bacterium was discovered in 1935 and found to be disease-causing in 1978. In the United States, healthcare-associated infections increase the cost of care by US$1.5 billion each year. Signs and symptoms of CDI range from mild diarrhea to severe"
"difficile"" infection. The use of systemic antibiotics, including any penicillin-based antibiotic such as ampicillin, cephalosporins, and clindamycin, causes the normal microbiota of the bowel to be altered. In particular, when the antibiotic kills off other competing bacteria in the intestine, any bacteria remaining will have less competition for space and nutrients. The net effect is to permit more extensive growth than normal of certain bacteria. ""C. difficile"" is one such type of bacterium. In addition to proliferating in the bowel, ""C. difficile"" also produces toxins. Without either toxin A or toxin B, ""C. difficile"" may colonize the gut, but is"
"the negative predictive value was 94%. In children, the most prevalent symptom of a CDI is watery diarrhea with at least three bowel movements a day for two or more days, which may be accompanied by fever, loss of appetite, nausea, and/or abdominal pain. Those with a severe infection also may develop serious inflammation of the colon and have little or no diarrhea. Infection with ""C. difficile"" bacteria are responsible for ""C. difficile"" diarrhea. Clostridia are anaerobic motile bacteria, ubiquitous in nature, and especially prevalent in soil. Under the microscope, they appear as long, irregular (often drumstick- or spindle-shaped) cells"
"Clostridial Cytotoxin family The Clostridial Cytotoxin (CCT) Family (TC# 1.C.57) is a member of the RTX-toxin superfamily. There are currently 13 classified members belonging to the CCT family. A representative list of these proteins is available in the Transporter Classification Database. Homologues are found in a variety of Gram-positive and Gram-negative bacteria. ""Clostridium difficile"", the causative agent of nosocomial antibiotic-associated diarrhea and pseudomembranous colitis, possesses two main virulence factors: the large clostridial cytotoxins A (TcdA; TC# 1.C.57.1.2) and B (TcdB, TC# 1.C.57.1.1). Action by large clostridial toxins (LCTs) from Clostridium difficile includes four steps: (1) receptor-mediated endocytosis, (2) translocation of"
"vicinity and allows it to outcompete normal human gut flora. Antibiotic treatment of ""C. diff"" infections may be difficult, due both to antibiotic resistance and physiological factors of the bacterium (spore formation, protective effects of the pseudomembrane). The emergence of a new, highly toxic strain of ""C. difficile"", resistant to fluoroquinolone antibiotics, such as ciprofloxacin and levofloxacin, said to be causing geographically dispersed outbreaks in North America, was reported in 2005. The U.S. Centers for Disease Control (CDC) in Atlanta warned of the emergence of an epidemic strain with increased virulence, antibiotic resistance, or both. Resistance to other antibiotics such"
"diarrhea. Several different antibiotics are used for ""C. difficile"", with the available agents being more or less equally effective. Medications used to slow or stop diarrhea, such as loperamide, have been thought to have the potential to worsen ""C. difficile"" disease, so are not generally recommended. Evidence to support worse outcomes with use however is poor. Cholestyramine, an ion exchange resin, is effective in binding both toxin A and B, slowing bowel motility, and helping prevent dehydration. Cholestyramine is recommended with vancomycin. A last-resort treatment in those who are immunosuppressed is intravenous immunoglobulin. Evidence to support the use of probiotics"
"who are admitted to hospital, it occurs in between four and eight people per 1,000. In 2011, it resulted in about half a million infections and 29,000 deaths in the United States. Due in part to the emergence of a fluoroquinolone-resistant strain, ""C. difficile""-related deaths increased 400% between 2000 and 2007 in the United States. According to the CDC, """"C. difficile"" has become the most common microbial cause of healthcare-associated infections in U.S. hospitals and costs up to $4.8 billion each year in excess health care costs for acute care facilities alone."" Initially named ""Bacillus difficilis"" by Hall and O'Toole"
"an infection caused by the probiotic supplements. ""Clostridium difficile"", also known more commonly as ""C. diff"", is known to account for 10 to 20 percent of antibiotic-associated diarrhea cases. The reasoning for this, is that the antibiotics administered for the treatment of certain diseases processes such as inflammatory colitis also inadvertently kills a large portion of the gut flora, the normal flora that is usually present within the bowel. With this lower amount of ""healthy"" bacteria present, the overgrowth of ""C. diff"" is then responsible ""for elaborating the enterotoxin"". Antibiotic-associated diarrhea Antibiotic-associated diarrhea (AAD) results from an imbalance in the"
"not occurring with all isolates of ""C. difficile"". Many early studies have suggested that toxin A (also known as TcdA) is the major toxin protein causing antibiotic-associated diarrhea (AAD); however, research scientists within last decade or so have shown that Toxin B (or TcdB) plays a more important role in disease than anyone had forecasted. With this knowledge, Toxin B has been identified as the major virulence factor that causes the opening of tight junctions of intestinal epithelial cells, which enables toxin to increase vascular permeability and induce hemorrhaging. Hence, this leads to tumor necrosis factor α (TNF α) and"
"proinflammatory interleukins being established as the major causative agents of pseudomembranous colitis (PMC) and antibiotic-associated diarrhea (AAD). The involvement of toxin A and—most importantly—toxin B is the key element that determines the disease caused by ""C. difficile"". Clinical laboratories have identified these toxins in patients' stool based on antibody and cytotoxicity assays. These bacterial toxins have been shown to be associated with ""Clostridium sordellii"" hemorrhagic toxin (TcsH), lethal toxin (TcsL), and ""Clostridium novyi"" alpha toxin (Tcn α), thus, making this cohort to be the large family of toxin clostridial. Because of similarities of these toxins with others, researchers have classified"
"difficile"" is a poor competitor, and is often out competed by other bacteria for nutrients in the digestive system. As a result, ""C. difficile"" is kept to a manageable amount. If the sudden introduction of antibiotic disrupts the microbiome, ""C. difficile"" may be able to grow as a result of many of its competitors being killed off. The incubation period is 5–10 days, with a range of 1 day to weeks following antibiotic treatment for AAD (antibiotic associated diarrhea). Additionally, carriage of C. difficile with high levels of toxins are common in young children while disease is rare. The production"
"region, displacing the originally more common and recognizable NAP1 bacteria. Two strains, ribotypes RT078 and RT027, can live on low concentrations of the sugar trehalose; both strains became more common after trehalose was introduced as a food additive in the early 2000s and thus increasing dietary trehalose intake. The first complete genome sequence of a ""C. difficile"" strain was first published in 2005 by Sanger Institute in the UK. This was of the strain 630, a virulent and multiple drug-resistant strain isolated in Switzerland in 1982. Scientists at Sanger Institute have sequenced genomes of about 30 ""C. difficile"" isolates using"
"become resistant to the body's natural immune defenses and/or to outside intervention like drugs. For instance, Clostridium difficile is the most frequent cause of nosocomial diarrhea worldwide, and reports in the early 2000s indicated the advent of a hypervirulent strain in North America and Europe. In study by Stabler et al 2006, comparative phylogenomics (whole-genome comparisons using DNA microarrays combined with Bayesian phylogenies) were used to model the phylogeny of C. difficile. Phylogenetic analysis identified four distinct statistically significant 'clusters' making a hypervirulent clade, a toxin A− B+ clade, and two clades with human and animal isolates. Genetic differences between"
"cephalosporins, and clindamycin. Some research suggests the routine use of antibiotics in the raising of livestock is contributing to outbreaks of bacterial infections such as ""C. difficile"". People are most often infected in hospitals, nursing homes, or other medical institutions, although infection outside medical settings is increasing. Individuals can develop the infection if they touch objects or surfaces that are contaminated with feces and then touch their mouth or mucous membranes. Healthcare workers could possibly spread the bacteria to patients or contaminate surfaces through hand contact. The rate of ""C. difficile"" acquisition is estimated to be 13% in patients with"
"A (catalytic domain), and fragment B (transmembrane and receptor binding domain). Fragment A catalyzes the NAD+ -dependent ADP-ribosylation of elongation factor 2, thereby inhibiting protein synthesis in eukaryotic cells. Fragment B binds to the cell surface receptor and facilitates the delivery of fragment A to the cytosol. The bacterium is sensitive to the majority of antibiotics, such as the penicillins, ampicillin, cephalosporins, quinolones, chloramphenicol, tetracyclines, cefuroxime, and trimethoprim. The genome of ""C. diphtheriae"" consists of a single circular chromosome of 2.5 Mbp, with no plasmids. The genome shows an extreme compositional bias, being noticeably higher in G+C near the origin"
"any surface. Once spores are ingested, their acid-resistance allows them to pass through the stomach unscathed. Upon exposure to bile acids, they germinate and multiply into vegetative cells in the colon. In 2005, molecular analysis led to the identification of the ""C. difficile"" strain type characterized as group BI by restriction endonuclease analysis, as North American pulse-field-type NAP1 by pulsed-field gel electrophoresis and as ribotype 027; the differing terminology reflects the predominant techniques used for epidemiological typing. This strain is referred to as ""C. difficile"" BI/NAP1/027. ""C. difficile"" colitis is associated most strongly with the use of these antibiotics: fluoroquinolones,"
"used as markers to diagnose ""C. difficile"" infection. Over 90% of patients infected with ""C. difficile"" were found to have cytotoxic activity in their stool. Glucosylation of Rho GTPases inactivates the GTPase proteins, leading to collapse of the cytoskelton, resulting in cell rounding. A tissue culture assay has been developed to detect ""C. difficile"" toxins in stool samples. A cell rounding assay (cytotoxicity assay) has been developed to diagnose ""C. difficile"" infection. Enzyme-linked immunosorbent assays (ELISAs) have been used to detect TcdA and TcdB with specific antibodies. When used with an ELISA, the cytotoxicity assay is the ""gold standard"" when"
"vasopressors as clinically indicated. ""Clostridium difficile""-associated diarrhea (CDAD) has been reported for nearly all antibacterial agents including ceftaroline, and may range in severity from mild diarrhea to fatal colitis. Careful medical history is necessary because CDAD has been reported to occur more than two months after the administration of antibacterial agents. If CDAD is suspected or confirmed, antibacterials not directed against"" C. difficile"" should be discontinued, if possible. Prescribing ceftaroline in the absence of a proven or strongly suspected bacterial infection is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria. In"
"to vancomycin, trimethoprim-sulfamethoxazole, and ciprofloxacin. Mortality related to ""C."" ""tertium"" bacteremia treated appropriately appears to be quite low. The selection effect of antibiotics on ""C."" ""tertium"" may occur in cases where patients have had prior exposure to β-lactam antibiotics. Clostridium tertium Clostridium tertium is an anaerobic, motile, gram-positive bacterium. Although it can be considered an uncommon pathogen in humans, there has been substantial evidence of septic episodes in human beings. C. ""tertium"" is easily decolorized in Gram-stained smears and can be mistaken for a Gram-negative organism. However, ""C."" ""tertium"" does not grow on selective media for Gram-negative organisms. ""C."" ""tertium"""
"decrease anaerobic fermentation of soluble carbohydrates, resulting in damage to the cecal and colonic mucosa and allowing increased absorption of endotoxins from the lumen of the gut. The causative agent may be ""Clostridium perfringens"", type A, but the bacteria are recoverable only in the preliminary stages of the disease. The suspect toxin could also be a form of ""Clostridium difficile"". In a 2009 study at the University of Arizona, ""C. difficile"" toxins A and B were detected, large numbers of ""C. difficile"" were isolated, and genetic characterization revealed them to be North American pulsed-field gel electrophoresis type 1, polymerase chain"
"colitis. Sustained periods of dysbiosis lead to extended amounts of stress and inflammation in the gut microbiome, which can in turn promote the production of carcinogenic metabolites. ""C. difficile"" is an opportunistic bacteria that commonly infects patients following a disruption in the microbiome, such as treatment with antibiotics. Infection can lead to several different symptoms including watery diarrhea, fever, loss of appetite, nausea, and abdominal pain. Severe or chronic infections of ""C. difficile"" can lead to inflammation of the colon, a condition known as colitis. Periodontitis is an oral infection that can damage the bones supporting teeth and lead to"
"Emerging treatment protocols for C. difficile infections involve fecal microbiota transplantation of donor feces. (see Fecal transplant). Initial reports of treatment describe success rates of 90%, with few side effects. Efficacy is speculated to result from restoring bacterial balances of bacteroides and firmicutes classes of bacteria. Gut flora composition also changes in severe illnesses, due not only to antibiotic use but also to such factors as ischemia of the gut, failure to eat, and immune compromise. Negative effects from this have led to interest in selective digestive tract decontamination (SDD), a treatment to kill only pathogenic bacteria and allow the"
"Clostridial necrotizing enteritis Clostridial necrotizing enteritis (CNE), also called enteritis necroticans and pigbel, is an often fatal type of food poisoning caused by a β-toxin of ""Clostridium perfringens"", Type C. It occurs in some developing countries, but was also documented in Germany following World War II, where it was called ""Darmbrand"" (meaning bowel necrosis). The toxin is normally inactivated by certain proteolytic enzymes and by normal cooking, but when these protections are impeded, and low protein is consumed, the disease emerges. Sporadic and extremely rare cases occur in diabetics. In New Guinea, where people eat a lot of sweet potatoes,"
"Campylobacter concisus Campylobacter concisus is a Gram-negative, highly fastidious, mesophilic bacterium that grows under both anaerobic and microaerobic conditions with the presence of hydrogen significantly aiding growth. Motile, with either unipolar or bipolar flagella, the organisms have a characteristic spiral/corkscrew appearance and are oxidase-positive. Although the human oral cavity is the natural colonization site of the bacterium, ""C. concisus"" may also colonize the intestinal tract of some individuals. In particular, several studies have reported higher intestinal prevalence of ""C. concisus"" in patients with IBD compared to healthy controls, which has led to current speculation of the bacterium's implication in the"
"mainly via the hands of healthcare personnel who have touched a contaminated surface or item. ""C. difficile"" can live for long periods of time on surfaces. The organism forms heat-resistant spores that are not killed by alcohol-based hand cleansers or routine surface cleaning, thus, these spores survive in clinical environments for long periods. Because of this, the bacterium may be cultured from almost any surface. Once spores are ingested, their acid-resistance allows them to pass through the stomach unscathed. They germinate and multiply into vegetative cells in the colon upon exposure to bile acids. Consequently, the World Health Organization advocates"
"Clostridium tertium Clostridium tertium is an anaerobic, motile, gram-positive bacterium. Although it can be considered an uncommon pathogen in humans, there has been substantial evidence of septic episodes in human beings. C. ""tertium"" is easily decolorized in Gram-stained smears and can be mistaken for a Gram-negative organism. However, ""C."" ""tertium"" does not grow on selective media for Gram-negative organisms. ""C."" ""tertium"" was initially isolated from war wounds by Captain Herbert Henry (RAMC) in 1917, but it was not until the first human cases of ""C."" ""tertium"" bacteremia were reported in 1963 that it was recognized as a human pathogen. ""C."""
"albicans"" and ""Oidium albicans"". The current classification is ""nomen conservandum"", which means the name is authorized for use by the International Botanical Congress (IBC). The genus ""Candida"" includes about 150 different species; however, only a few are known to cause human infections. ""C. albicans"" is the most significant pathogenic species. Other species pathogenic in humans include ""C. tropicalis"", ""C. glabrata"", ""C. krusei"", ""C. parapsilosis"", ""C. dubliniensis"", and ""C. lusitaniae"". The name ""Candida"" was proposed by Berkhout. It is from the Latin word ""toga candida"", referring to the white toga (robe) worn by candidates for the Senate of the ancient Roman"