Pathogenicity:

 The alteration of the gut microbiome, which is frequently brought on by broad-spectrum antibiotics like cephalosporins, is the first step in Clostridium Difficile’s pathogenicity. Because these antibiotics eliminate protective commensals, they decrease microbial diversity, which facilitates the germination of C. difficile spores. TcdA and TcdB, two important toxins produced by C. difficile, are the main causes of its virulence:

  • Toxin A, or TcdA, increases permeability and induces inflammation, which affects the intestinal mucosa and leads to fluid buildup.

  • Toxin B, or TcdB, is more powerful than TcdA and causes inflammation and cell death by directly harming epithelial cells by upsetting their cytoskeleton.

In extreme situations, the toxins harm the epithelial extensively, which leads to the creation of pseudomembranes, which are collections of fibrin, inflammatory waste, and dead cells. Patients who are in this inflammatory environment are more likely to experience consequences including toxic megacolon, which causes the colon to swell, become paralysed, and become vulnerable to rupture.

Clinical Course:

In this case, the old woman’s microbiota was probably disturbed by her initial antibiotic treatment, which allowed C. difficile to colonise and produce toxins. The development of pseudomembranous colitis after diarrhoea is a sign of high levels of toxin activity. Refractory CDI, which may be linked to hyper virulent strains like ribotype 027, is characterised by symptoms that persist even after receiving normal antibiotic treatment (vancomycin and metronidazole). This strain increases the amount of the toxin and creates another binary toxin that makes the sickness worse.

Treatment Challenges:

Some instances do not respond to the standard therapy of oral vancomycin and fidaxomicin. Restoring microbial variety has been demonstrated to be possible with alternatives such as faecal microbiota transplantation (FMT). However, the patient’s illness worsened to the point that a toxic megacolon was required, requiring an urgent colectomy. Although the damaged colon is removed during this vital procedure, there is a significant chance of complications or death.

Risk factors and Prevention:

In this instance, the risk variables are pre-existing weakness, hospitalisation, senior age and antibiotic exposure. These elements weaken the immune system’s defences against the toxins and colonisation of C. difficile. The following are examples of successful prevention techniques:

  • Antibiotic stewardship: Preserving gut flora by reducing the use of unneeded antibiotics.

  • Infection control: To stop the spread of spores in medical environments, sick patients should be isolated, hands should be cleaned, and the environment should be kept clean.

  • FMT and probiotics are becoming popular preventative measures for people who are at a high risk.

 

 

References:

Apic.org. (2019). Clostridioides difficile Infection and Pseudomembranous Colitis. [online] Available at: https://text.apic.org/toc/healthcare-associated-pathogens-and-diseases/clostridioides-difficile-infection-and-pseudomembranous-colitis.

Cleveland Clinic. (n.d.). Pseudomembranous Colitis: Symptoms, Causes, Treatment & Prevention. [online] Available at: https://my.clevelandclinic.org/health/diseases/17718-pseudomembranous-colitis.

Goudarzi, M., Seyedjavadi, S.S., Goudarzi, H., Mehdizadeh Aghdam, E. and Nazeri, S. (2014). Clostridium difficileInfection: Epidemiology, Pathogenesis, Risk Factors, and Therapeutic Options. Scientifica, 2014, pp.1–9. doi:https://doi.org/10.1155/2014/916826.

Schäffler, H. and Breitrück, A. (2018). Clostridium difficile – From Colonization to Infection. Frontiers in Microbiology, 9(646). doi:https://doi.org/10.3389/fmicb.2018.00646.