Clostridium difficile is a Gram-positive, rod-shaped, obligately anaerobic bacterium belonging to the division Firmicutes. The endospore-forming bacterium is considered one of the most important nosocomial pathogens and can lead to the occurrence of antibiotic-associated colitis, especially in the clinical setting.
What is Clostridium difficile?
Clostridium difficile is a rod-shaped, gram-positive bacterium and belongs to the Clostridiaceae family. C. difficile is considered a facultative pathogen that can lead to life-threatening inflammation of the colon (pseudomembranous colitis), especially after antibiotic use. This makes it one of the most relevant nosocomial pathogens (“hospital germs“), since broad-spectrum antibiotics are frequently used in hospitals and therapy times with antibiotic drugs are usually longer. C. difficile belongs to the obligate anaerobic bacteria and therefore has no possibility of active metabolism in an oxygenated (oxic) environment. Even small amounts of oxygen can have a toxic effect on the bacterium. In addition, this Clostridia species has the ability to form endospores, which are very resistant to various environmental influences. If the cell perceives a strong stress, the strictly regulated process of spore formation is initiated (sporulation). During sporulation, the vegetative cell forms an additional cell compartment, which, among other things, protects the DNA and important proteins in the mature spore by a very stable cell envelope. The spore is released after the mother cell dies, thus ensuring the cell’s survival. This metabolically inactive form of survival allows it to tolerate stress factors such as heat, oxygen, drought, or even many alcohol-based disinfectants until the spore can revert to a vegetative state under more favorable environmental conditions.
Occurrence, distribution, and characteristics
Clostridium difficile is basically distributed throughout the world (ubiquitous) and is found in the environment primarily in soils, dust, or surface waters. C. difficile can also be found in the intestines of humans or animals. Thus, slightly less than 5% of all adults carry the bacterium mostly unnoticed. In contrast, the germ has been found in about 80% of all infants, which probably makes it one of the first bacteria to colonize the intestine of a newborn. A serious problem is the high prevalence in hospitals. The bacterium can be detected in 20%-40% of all patients, and many patients also experience recolonization with C. difficile there, but without developing symptoms immediately. It is reported that the frequency and severity of C. difficile infections has increased over the past few years. The very resistant spores, which are even resistant to many common alcohol-based disinfectants, have a high persistence in dirt, dust, on clothing or floors. This, together with the sometimes inadequate hygiene in hospitals, contributes to a rapid spread among patients. This high rate of spread becomes problematic when the conditions for acute infection with C. difficile are considered. In healthy individuals, a natural colonization of the (large) intestine with apathogenic bacteria (intestinal microbiota) provides protection against other, harmful bacterial species. By adapting and interacting with the human host, this microbiota can limit the growth of undesirable germs to a certain extent. Our normal intestinal microbiota includes bacteria of the genera Bacteroides, Faecalibacterium or Escherichia, and Clostridium species, but not Clostridium difficile. If this microbiota is partially or completely killed by antibiotic use, C. difficile spores can germinate in the anoxic environment of the colon and proliferate rapidly. Although multiplication after antibiotic use is the most common cause of acute infection, elderly or immunocompromised patients are also at risk. In addition, patients taking proton pump inhibitors to regulate gastric acid are at risk of the bacterium not being killed by gastric acid and entering the intestine. Usually, infection with C. difficile leads to severe diarrhea and inflammation of the colon. If the bacterium re-enters an oxygen-containing environment via the stool, sporulation starts immediately due to the oxygen stress.After excretion and sporulation, the spores can thus be easily transmitted by the patient to other patients, staff or various surfaces. During this acute phase of illness, there is the highest risk of infection and spread.
Diseases and symptoms
Clostridium difficile can cause a specific form of intestinal inflammation (pseudomembranous or antibiotic-associated colitis) under certain circumstances described previously. Typical symptoms include abrupt onset of diarrhea, fever, lower abdominal pain, and dehydration and electrolyte deficiency associated with diarrhea. In mild forms of progression, mushy, liquid diarrhea occurs; in more severe cases, life-threatening inflammation and swelling of the entire colon (toxic megacolon), intestinal perforation or blood poisoning (sepsis) can occur. It is important for the physician to differentiate Clostridium difficile from other potential pathogens. Risk factors such as age, immunosuppression, and the use of antibiotics, proton pump inhibitors, or anti-inflammatory drugs serve as important indicators. Together with microbiological examinations and the detection of specific toxins produced by C. difficile, they can confirm a diagnosis. The toxins are two of the main virulence factors of C. difficile: TcdA (toxin A) and TcdB (toxin B). These are largely responsible for damage to intestinal tissue, although there are strains that do not produce toxin A and can still lead to severe disease. In addition, studies have shown that toxin B is the more relevant factor and is supported in its action by toxin A. Both toxins can penetrate the epithelial cells of the intestine, where they alter both important structural proteins (actins) and signaling pathways within the cell (various GTPases involved in the organization of the actin skeleton). As a result, the cells lose their original shape (change in cell morphology) and important intercellular connections (tight junctions) can be destroyed. This leads to cell death (apoptosis), leakage of fluid, and allows toxins or pathogens to penetrate deeper tissue layers and further damage the mucosa. The damaged cells, together with cells of the immune system and fibrins, form the typical pseudomembrane, which can be considered a sufficiently definitive identification of a C. difficile infection in endoscopic diagnostics.
