Clostridium difficile (etymology and pronunciation), also known as C. difficile, C. diff ( ), or sometimes CDF/cdf, is a species of Gram-positive spore-forming bacterium.
Clostridia (members of the genus Clostridium and of the Clostridiaceae family) 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 (forms subterminal spores). Under Gram staining, C. difficile cells are Gram-positive and show optimum growth on blood agar at human body temperatures in the absence of oxygen. 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 flora, in which case C. difficile may opportunistically dominate, causing Clostridium difficile infection.
Video Clostridium difficile (bacteria)
Human pathogen
Pathogenic C. difficile strains produce multiple toxins. The best-characterized are enterotoxin (Clostridium difficile toxin A) and cytotoxin (Clostridium difficile toxin B), both of which may produce diarrhea and inflammation in infected patients (Clostridium 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 colon and formation of pseudomembranes on the intestinal mucosal surface. Toxins A and B are glucosyltransferases that target and inactivate the Rho family of GTPases. Toxin B (cytotoxin) induces actin depolymerization by a mechanism correlated with a decrease in the ADP-ribosylation of the low molecular mass GTP-binding Rho proteins. Another toxin, binary toxin, also has been described, but its role in disease is not fully understood.
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.
Maps Clostridium difficile (bacteria)
Transmission
C. difficile is transmitted from person to person by the fecal-oral route. Clostridium difficile is shed in faeces. Any surface, device, or material (e.g., toilets, bathing tubs, and electronic rectal thermometers) that becomes contaminated with faeces may serve as a reservoir for the Clostridium difficile spores. Clostridium difficile spores are transferred to patients mainly via the hands of healthcare personnel who have touched a contaminated surface or item. Clostridium 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.
Host range
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. 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).
Signs and symptoms
Symptoms of C. difficile include: Watery diarrhea at least a minimum of three times a day and up to 15 times a day. Abdominal cramping and pain that can be severe. Loss of appetite and dehydration. Weight loss and nausea.
Treatment
The primary infection of C. difficile is normally treated with antibiotics such as fidaxomicin, vancomycin and metronidazole. The patient should stop taking any other antibiotics if it is possible, and the diarrhea should stop. Normally, metronidazole is not recommended for treating C. difficile infections by the FDA. Despite this, it is commonly used for very minor cases, but should never be used for severe ones. This medication is normally given orally and should be taken for a minimum of 10 days.
A problem that commonly occurs with antibiotics used as a treatment for C. difficile, is that 20% of the patients will have the infection come back. Also, a fraction of those patients will continuously have reoccurrences of the infection. The first return of a C. difficile infection is usually treated with the same antibiotic used. However, for all future infections, it should be managed with oral vancomycin or fidaxomicin.
Another unique way of treating C. difficile, is transplanting healthy stool. Healthcare providers can transplant stool from a healthy person to the colon of a patient with repeat C. difficile infections. This process has been shown to successfully treat the disease, and it appears to be the most effective method for helping patients with repeat infections. One concern though, is that there is still little known about the long terms effects of this process.
Strains
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.
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.
Genome
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 next-generation sequencing technologies from 454 Life Sciences and Illumina.
Researchers at McGill University in Montreal sequenced the genome of the highly virulent Quebec strain of C. difficile in 2005 using ultra-high-throughput sequencing technology. The tests involved doing 400,000 DNA parallel-sequencing reactions of the bacterium's genome, which had been fragmented for sequencing. These sequences were assembled computationally to form a complete genome sequence.
In 2012, scientists at University of Oxford sequenced C. difficile genomes from 486 cases arising over four years in Oxfordshire using next-generation sequencing technologies from Illumina.
Bacteriophage
At least eight mainly temperate bacteriophages have been isolated from C. difficile, 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.
Naming and pronunciation
The species name is New Latin, from the Greek kloster (???????), "spindle", and Latin difficile, "difficult, obstinate". It is pronounced in medical English (compare classical Latin /dif'fi.ki.le:/), 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.
It has been proposed, in a July 2013 paper from Environmental Microbiology, one of the journals of the Society for Applied Microbiology, to rename the species Peptoclostridium difficile.
Notes
References
- Pathogen Safety Data Sheets: Infectious Substances - Clostridium Difficile, Public Health Agency, Canada, 10 September 2014.
- Type strain of Clostridium difficile, BacDive - the Bacterial Diversity Metadatabase.
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