Understanding C. difficile
The bacterium Clostridium difficile (C. difficile) is a spore-forming, anaerobic, gram-positive, and toxin-producing organism. C. difficile colonises 5% of adults and 15% to 70% of babies on average, with colonisation being several times greater in hospital patients or nursing home residents. Toxins produced by the bacteria result in inflammation, diarrhoea, and the formation of a "pseudomembrane" in the large bowel.1
Germinant receptors play a crucial role in helping the bacterium make decisions about when to transition from a dormant state to an active, growing state based on their environmental conditions. The germinant receptor CspC is necessary for detecting primary bile acids from the liver. While secondary bile acids from the colon hinder spore germination. Glycine can also function as a germinant through an unknown method.2
The host microbiota (good gut bacteria) and its accompanying metabolome significantly affect the spores' capacity to overrun and colonise the gut. However, changes in the microbiota brought on by antibiotics may create an environment favourable to C. difficile infection, allowing spores to adhere to colonic cells before germinating into vegetative cells.1 2 3
Clostridium difficile Toxin A (CDTA) is a harmful substance created by the bacteria C. difficile. This toxin is closely related to Clostridium difficile Toxin B (CDTB) , and these toxins are the primary factors that make Clostridium difficile bacteria dangerous. Although the effects of CDTA and CDTB on affected cells is well understood, its function in disease pathogenesis has yet to be evident. According to experimental evidence, CDT’s cause protrusions made of microtubules to develop on epithelial cells, which might improve C. difficile colonisation and adhesion.
The gold standard for diagnosing toxic C. difficile in stools is toxigenic culture (TC). First, stool samples are grown anaerobically (without oxygen) on a particular medium for 24 to 48 hours. Then, after identifying a colony and classifying the organisms (typically using an antigen detection technique), isolates are grown for 48 hours before testing using a cell cytotoxicity assay.2
Despite being a reference standard, TC is time-consuming and requires specialised equipment and expert technicians. Delays in diagnosis affect treatment decisions and infection control. Rapid testing helps to reduce these limits. One method is based on recognising a C. difficile product called glutamate dehydrogenase (GDH). GDH is detected in both toxigenic and non-toxigenic strains of C. difficile, and asymptomatic colonisation studies suggest that up to 46% of C. difficile isolates are non-toxigenic. Hence GDH testing must be paired with a toxin detection test.2
CCA, which is conducted directly on the stool or as part of TC, is the gold standard for identifying toxins A and/or B. Filtrates of stool suspensions or culture supernatants are injected into cell culture. The cytopathic impact is measured after 24 or 48 hours.2
Ways to prevent C. difficile when taking antibiotics
Healthcare professionals should implement prevention methods in all suspected instances of an C. difficile infection (CDI), not just those diagnosed. Strategies include:1
- The patient's room must be cleaned entirely after discharge
- Medical personnel and visitors should use gloves and disposable gowns throughout the whole diarrheal episode
- After direct contact with a CDI patient, everyone should wash their hands with soap and water
- Each CDI patient should be separated into a single room. If this is not possible, patients should avoid engaging with one another (for example, reading the same books or magazines or using the same phone) and have separate furniture
- The best way to balance the natural bacterial population in your intestines is with probiotic tablets. These helpful bacterial flora can become scarce as a result of poor diet and antibiotic use, but probiotics can help replenish them4
C difficile: symptoms, causes and treatment
Symptoms of C. difficile
Infection can present as a wide range of clinical illnesses, from asymptomatic colonisation or minor diarrhoea to severe disease. The following are the most common CDI symptoms and warning signs: 2 3
- Watery bloody diarrhoea
- Abdominal Cramps
- Signs of dehydration (a racing heart, increased pulse rate, decreased urine output, dry mouth and sunken eyes, and nausea)
- Weight loss and appetite loss
- Fever
- Confusion
Causes of C. difficile
Common causes of C. difficile include:2 3
- Use of general antibiotics like Penicillins
- Being greater than 65 years old
- Having spent a significant amount of time in a healthcare facility, such as a hospital or nursing home
- Having certain underlying illnesses, such as cancer, renal disease, or inflammatory bowel disease (IBD)
- Use of antibiotics like Clindamycin, Ciprofloxacin, Cephalosporins
- A weakened immune system as a result of illnesses like diabetes, HIV or as a side effect of drugs like steroids or chemotherapy
- Using a proton pump inhibitor (PPI)
Treatment for C. difficile
A course of Vancomycin orally together with supportive care is the first line of therapy for infections that have been shown to be mild to moderate. In cases of severe infection, oral Vancomycin may be given in addition to metronidazole in a drip. A faecal transplant could be an effective treatment for recurring infections. A decrease in the intestinal motility may cause toxin entrapment in the digestive tract, which in turn might lead to toxic megacolon. Thus, anti-diarrheal medications should be avoided and drug usage should be minimised. Replacing fluid and electrolyte losses is also necessary.
Summary
The bacterium Clostridium difficile (C. difficile) is a spore-forming, anaerobic, Gram-positive, and toxin-producing organism. Toxins produced by the bacteria result in inflammation, diarrhoea, and the formation of a "pseudomembrane" in the large bowel. C. difficile requires a variety of factors to promote spore germination.
There are plenty of preventive measures that can be taken, but it is imperative that healthcare professionals should implement prevention methods in all suspected instances, not just those diagnosed.
References
- Czepiel J, Dróżdż M, Pituch H, Kuijper EJ, Perucki W, Mielimonka A, et al. Clostridium difficile infection: review. Eur J Clin Microbiol Infect Dis [Internet]. 2019 Jul 1 [cited 2022 Dec 12];38(7):1211–21. Available from: https://link.springer.com/article/10.1007/s10096-019-03539-6
- Bagdasarian N, Rao K, Malani PN. Diagnosis and treatment of clostridium difficile in adults: a systematic review. JAMA [Internet]. 2015 Jan 27 [cited 2022 Dec 12];313(4):398–408. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6561347/
- Smits WK, Lyras D, Lacy DB, Wilcox MH, Kuijper EJ. Clostridium difficile infection. Nat Rev Dis Primers [Internet]. 2016 Apr 7 [cited 2022 Dec 12];2:16020. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5453186/
- Valdés-Varela L, Gueimonde M, Ruas-Madiedo P. Probiotics for prevention and treatment of clostridium difficile infection. In: Mastrantonio P, Rupnik M, editors. Updates on Clostridium difficile in Europe [Internet]. Cham: Springer International Publishing; 2018 [cited 2023 Sep 5]. p. 161–76. Available from: http://link.springer.com/10.1007/978-3-319-72799-8_10