• C. difficile inhabits the microflora of the intestines of humans. Around 3% of healthy adults and up to 70% of babies have a number of C. difficile bacteria living in their gut.

• However, the number of C. difficile bacteria is kept very low and controlled by the millions of harmless bacteria in the intestines that aid digestion.

• C. difficile can grow in large populations in people that are treated with antibiotics, especially broad-spectrum antibiotics.

• This is because the antibiotics kill off the intestines’ normal flora, leaving C. difficile to freely grow and colonize the intestine Ideal condition for growth is around 37ºC (98.6 ºF).

• This explains why the human body plays the perfect host for C. difficile

• When under extreme conditions such as the low pH environment of the stomach.

• High heat or under attack by antibiotics, C. difficile can form spores that can survive for up to two years and withstand extreme conditions.

• The spores can then convert to the active form of C. difficile when conditions are favourable and allow the bacteria to grow^{. (9)}

• In addition, when C. difficile undergoes stress (i.e. osmotic, acid and heat shock).

• Its ability to adhere increased (by increasing expression of surface proteins) allowing it to attach to human tissue cells more easily facilitating its colonization. ⁽¹⁰⁾

• difficile exists in two states—the vegetative (growth) form or the spore state.
• In the vegetative state, the bacterium is able to use nutrients to grow and divide. However, when conditions become unfavourable, C. difficile is able to enter a dormant state and form a highly resistant spore.
• Unfavorable conditions include deprivation of nutrients, exposure to a very acidic environment, or exposure to high temperatures.
• These spores are very resistant to heat, radiation, drying, chemicals, and even oxygen (for up to two years).  
• The spore is dormant, and a thick spore coat protects its genetic material.
• When conditions become favourable again, the C. difficile spore is able to return to its vegetative state.
• The bacteria’s ability to form spores enables its survival through the human digestive system.
• In addition to out into the oxygenated environment until it returns to its human host and back into the vegetative state. ⁽⁹⁾

• Clostridium Difficle enters a person’s body via ingestion of the spores via the faecal-oral route.
• After ingestion, spores travel unchanged through the stomach’s acidic environment and germinate into the vegetative form.
• Pathogenic C. difficile strains produce multiple toxins.
• The best characterized are enterotoxin (Clostridium difficile toxin A) and cytotoxin (Clostridium difficile toxin B).
• Both may produce diarrhoea and inflammation in infected patients (Clostridium difficile colitis), although their relative contributions have been debated. 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, is also described, but its role in disease is not fully understood.
• Additional virulence factors include an adhesin factor which mediates the binding to human colonic cells and a hyaluronidase.
• also C. difficile acquired nosocomially (acquired secondary to a primary hospitalization).
• Because, in the hospital, patients are often on broad-spectrum antibiotic therapy to prevent any infection.
• Nevertheless, these antibiotics can cause pathogenic strains of C. difficile to grow out of control and cause C. difficile- associated disease or CDAD^.(13,14)

Host Range

• The 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. ⁽¹⁵⁾
• A 2015 CDC study estimated that C. difficile afflicted almost half a million Americans and caused 29,000 deaths in 2011.
• The study estimated that 40 per cent of cases began in nursing homes or community health care settings, while 24 per cent occurred in hospitals. ⁽¹⁾

Signs And Symptoms

Diagnosis

• immunoassays (including enzyme immunoassays, enzyme-linked immunosorbent assays, and immunochromatography assay)
• tests for C. difficile toxins,
• amplification of C. difficile DNA, through means such as PCR and loop-mediated isothermal amplification (LAMP) ⁽¹⁵⁾

• Carrying C. difficile without symptoms is common.
• Treatment in those without symptoms is controversial.
• In general, mild cases do not require specific treatment.
• Oral rehydration therapy is useful in treating dehydration associated with diarrhoea ⁽⁵⁾
• Several different antibiotics are used for C. difficile, with the available agents being more or less equally effective.
• Metronidazole typically is the initial drug of choice for mild to moderate disease, it is taken three times a day for ten days.
• Vancomycin by mouth is preferred for severe diseases. Additionally, vancomycin is used to treat mild-to-moderate disease if diarrhoea persists after a course of metronidazole. 
• Since metronidazole has the potential to cause congenital disabilities.
• Pregnant women with Clostridium difficile infection treated with vancomycin regardless of disease severity. 
• Typical vancomycin dosage is taken four times daily for ten days. 
• Given rectally if the person develops an ileus and cannot take medications by mouth^{. (17)}
• Fidaxomicin was found to be as effective as vancomycin in those with mild to moderate disease and may be better in those with severe disease.
• They are tolerated as well as vancomycin and may have a lower risk of recurrence.
• Used in those who have recurrent infections and have not responded to other antibiotics.
• Medications used to slow or stop diarrhoea, such as loperamide, may worsen C. difficile disease, so not recommended.
• Cholestyramine, an ion exchange resin, is effective in binding both toxin A and B, slowing bowel motility, and helping prevent dehydration.
• The Cholestyramine is recommended with vancomycin. A last-resort treatment in those who are immunosuppressed is intravenous immunoglobulin⁽¹⁸⁾
• The fidaxomicin: in 2011, the FDA approved a new agent, fidaxomicin, for the treatment of CDI.

Treatment for relapsed or recurrent CDI

• Not all people who acquire C. difficile develop CDI; thus prevention measures can target reducing both the spread of the bacteria or spores and patient susceptibility to infection.
• One study statistically modelled CDI within the hospital setting and suggested that reducing patient susceptibility to infection is more effective in reducing CDI cases than lowering transmission rates.
• Recent prevention efforts have included antimicrobial stewardship and using environmental and infection control strategies.
• As well as seeking to improve the patient’s immune defences through healthy digestive function and gut flora and improved nutrition

• failure of the immune defences,
• use of antibiotics, particularly broad-spectrum or multiple antibiotics, and changes to the intestinal microbiota.
• older age,
• comorbidities
• use of gastric acid suppressant medications.