Clostridioides difficile, previously known as Clostridium difficile and sometimes referred to as ‘C.diff’, is a Gram-positive bacillus that is also anaerobic, toxin-producing, and spore-producing. The spores are commonly transmitted via the faecal-oral route, making it one of the most widely present pathogens in the physical environment, particularly where hand hygiene practices are not correctly applied, or where the cleaning products used are ineffective, leading to the spread of C.difficile. This is compounded by figures that suggest 3% of adults and up to 66% of children are carrying C.difficile at any one time, with this figure rising among care home residents and hospitalised patients (UK Health Security Agency, 2022). Typical sources of C.difficile infection tend to be asymptomatic carriers, those who are infected, the environment, and the animal intestinal tract (Czepiel et al, 2019).
C.difficile infection tends to manifest itself in patients through watery diarrhoea, fever, reduced appetite, nausea, and abdominal pain/tenderness. Where C.difficile infection is suspected, it is vital that a stool sample is sent for further testing as soon as possible (National Institute for Health and Care Excellence (NICE), 2021); however, to reduce any potential false positive results, it is recommended that C.difficile infection testing should not be conducted on any patient who has received laxatives in the past 48 hours, or in any patient that has not experienced at least three unformed stools (types 5-7 on the Bristol stool chart) in the past 24 hours.
Currently, the guideline from NICE (2021) recommends treating suspected or confirmed C.difficile infection in adults with an oral antibiotic, most commonly vancomycin (with or without metronidazole), and fidaxomicin depending on the suspected severity of the infection. However, the use of metronidazole in the treatment of C.difficile infection has been contested by some, with critics pointing to its seemingly increasing role in treatment failure numbers (Bagdasarian et al, 2015).
The antibiotic conundrum
Antibiotic therapy has been the cornerstone of treatment approaches for most infectious cases for half a century. Coupled with improved sanitation and increasing health literacy, antibiotics have played a significant role in increasing lifespans and recovery from infections across the globe (Mohr, 2016). However, as Leffler et al (2015) observed, antibiotics, particularly broad-spectrum penicillins, cephalosporins, and fluoroquinolones, are associated with a higher rate of development of, more so than any other type. Therefore, in most cases where C.difficile infection is identified, immediately stopping the use of broad-spectrum antibiotics can prevent the infection from worsening (Smits et al, 2016).
One of the core reasons that prolonged antibiotic use can lead to the development of a C.difficile infection, is the antibiotic disturbing the normal colonic microbiota. Prolonged antibiotic use can contribute to the reduction of crucial colonic bacteria, leading to a reduction in the diversity of colonic microbiota (Ross et al, 2016; Theriot et al, 2016). This, coupled with patient exposure to either the bacteria or the spores simultaneously, heightens the chances of developing C.difficile infection and increases the chances of recurring bouts (Zilberburg et al, 2017).
Why is the gut microbiota important?
In the interests of clarity, the gut refers to the gastrointestinal tract, where over a trillion, mostly beneficial, microbes reside, making it the largest colonised organ in the human body (Sidhu and van der Poorten, 2017). These microbes make up approximately 150-400 microbial species, including commensal/pathogenic bacteria, viruses, fungi, and protozoa (Lloyd-Price et al, 2016). They all serve important metabolic, nutritional, and immune functions, ranging from nutrient metabolism and absorption to regulation of the hosts immune system (Shreiner, et al, 2015). The richness and density of the different organisms have been shown to directly affect host functioning through the differential release of cytokines and enzymes (Gao et al, 2020). Ottman et al (2012) went as far to claim that most disease states can be typified by changes in microbiota composition and metabolic function.
When addressing the question of why the gut is so diversely populated, there appears to be a type of mutually beneficial arrangement between host and inhabitants playing out in all of us (Box 1). This unique relationship is likely to have evolved over millions of years and involved a biological compromise, where the human body provided an ideal home for microbes in exchange for certain health benefits (Davenport et al, 2017).
Box 1.Gut microbiota: key bacterial functions
- Provide an effective barrier from pathogen invasion through providing direct competition for nutritional substrate
- Produce antimicrobial substances
- Contribute to immune system maturation
- Develop immune tolerance mechanism
- Help to maintain epithelial barrier
- Provide selected metabolic enzymes that allow for fermentation of dietary compounds
- Generate metabolites that help systemically
The medical community's interest in the transformative and healing properties of healthy gut microbiota seems to be accelerating. Areas of interest include the role of gut microbiota in non-alcoholic fatty liver disease, brain functioning, cardiovascular disease, and gastrointestinal tract disease (D'Argenio and Salvatore, 2015).
Faecal microbiota transplant and C.difficile infection
Transfusion of healthy donor stool to sick patients has existed for centuries; however, the recent use as a legitimate treatment option can be traced back to the 1950s, when an enema of healthy donor stool was transfused into the colon of a patient with fulminant pseudo-membranous colitis (Eiseman et al, 1958). Over the next few decades, research intensified into this area of treatment with administration techniques developing along the way. In 2013 the first randomised controlled trial of faecal microbiota transplant (FMT) demonstrated a sustained clinical cure rate of 90% of patients treated for C.difficile infection with FMT via duodenal infusions (van Nood et al, 2013).
Although the first-line of treatment for suspected C.difficile infection involves targeted antibiotic therapy, a different approach may be considered for recurrent episodes. The current NICE (2021) guideline recommends considering FMT in patients who have experienced two or more previous episodes of C.difficile infection.
What does FMT involve in the treatment of recurrent C.difficile infection?
The primary aim of FMT here is to restore a healthy balance of bacteria in the gut of patients who experience recurrent episodes of C.difficile infection. This is achieved by introducing enteric bacteria taken from the faeces of a healthy donor (Mullish et al, 2018). Qualifying donors could include family members; however, current guidelines advocate, where possible, that FMT is best sourced from a healthy unrelated donor via a centralised stool bank, and that the sample is frozen rather than fresh (Mullish et al, 2018). What is crucial is that the donor is subjected to a rigorous screening process before a sample is successfully used for FMT (Mehta et al, 2022). There is some debate surrounding the efficacy of screening tools used to assess donor eligibility, with some studies identifying a range of 2–32% in eligibility rates, despite the use of similar screening tools (Costello et al, 2016; Craven et al, 2017). However, based on current guidelines and best practice, several exclusionary criteria have been forwarded when it comes to assessing donor eligibility criteria (Box 2).
Box 2.Key exclusionary criteria for faecal microbiota transplant donors
- Increased risk factors for transmittable diseases
- Known history of tropical infection
- Use of antibiotics 3 months prior to donation
- Diarrhoea (>3 loose or watery stools per day for 2 consecutive days; >8 loose stools in past 48 hours)
- Any gastrointestinal illness
- History of autoimmune disease
- BMI >30
- Receipt of chemotherapy
It is recommended that for FMT production, 0.9% saline is used to dilute the sample; for frozen FMT, it is recommended that a cryoprotectant such as glycerol should be added (Mullish et al, 2018). Typically, the amount of stool used for an FMT sample should be at least 50 g with a 1:5 composition of stool to diluent, although the evidence base for this composition is considered weak (Mullish et al, 2018). Once a sufficient homogenisation and filtration process has been applied to the FMT, it is then prepared for its chosen route of administration. Typical routes of administration include:
- Nasogastric tube
- Nasoduodenal tube
- Rectal enema
- Biopsy channel of a colonoscope.
Additionally, encapsulated FMT as a viable treatment option appears to be growing as a safe and efficient method of delivering FMT to recipients (Youngster et al, 2014). This provides the added benefit of being generally less invasive, palatable, and flexible, contributing to an increase in patient consent for the procedure (Kao et al, 2017).
Sometimes, it may be necessary for the recipient to undergo a bowel lavage before the procedure to reduce the presence of C.difficile in the intestines (Mullish et al, 2018). Following the procedure, it may also be necessary for the patient to receive loperamide, or a similar drug, to aid with the retention of the donor stool (Patel et al, 2013; Mullish et al, 2018). In terms of follow-up post procedure, many studies have adopted markedly different follow-up periods, ranging from 2 months to 8 years (Yoon and Brandt, 2010; Rubin et al, 2013). However, current best practice is for the clinician to follow-up with recipients for a minimum of 8 weeks and long enough to assess efficacy and any adverse events (Mullish et al, 2018). Even where the patient might not have initially responded positively to initial FMT, there is good evidence to suggest that where the patient has been unresponsive to the initial treatment of FMT, repeating the treatment can lead to high success rates (van Nood et al, 2013; Youngster et al, 2014).
Side-effects
Although a recognised and clinically recommended intervention, FMT can present the recipient with some side effects. The main side effects include:
- Abdominal discomfort
- Cramps
- Bloating
- Diarrhoea
- Constipation.
In some extremely rare cases, there can also be transmission of diseases not detected through screening (Gupta and Khanna, 2017).
The nurse's role
Infection prevention and control
Perhaps unsurprisingly, the most effective role a nurse can play in the management of C.difficile infection is one based on prevention – even before the need for FMT. Adherence to standard infection prevention and control procedures is key in preventing the spread of C.difficile. These standard infection prevention and control measures include, but are not limited to, following the World Health Organization's ‘five moments of hand hygiene’ (with soap and water as alcohol hand gel is ineffective at removing C.difficile spores), encouraging appropriate cough hygiene, and safe management of linen (NHS England, 2023). Although the application of standard infection prevention and control measures to prevent the spread of C.difficile might seem obvious, research has underlined how many nurses do not adhere to these basic precautions in the UK (Ward, 2012; van Buijtene and Foster, 2019). More worryingly, poor adherence to standard infection prevention and control measures may develop before the nurse has even qualified, with some research identifying the transmission of poor practice from mentor to student in placement areas (Ward, 2012).
It is also vital, from an infection prevention and control perspective, that any patient suspected of being positive for C.difficile infection is moved to a side-room with en-suite facilities (if available). Before any patient contact, the nurse is required to don the appropriate personal protective equipment (PPE) (gloves and apron) and dispose of it according to local/national guidelines. Finally, all patient equipment and environmental surfaces should be thoroughly decontaminated with daily cleaning (Public Health England and Department of Health and Social Care, 2019).
Communication and information
It is possible that nurses will come into contact with a patient awaiting FMT in a range of settings, whether primary, secondary, or tertiary care environments. Despite careful consultation with clinicians and specific teams, the patient might still lack knowledge or even harbour reservations related to the procedure. This is to be expected, given the nature of the procedure, with the patient potentially reluctant to discuss this with anyone outside of their immediate circle for fear of being judged as ‘abnormal’ (Chauhan et al, 2020). It is important for the nurse to address any concerns the patient might have surrounding FMT. Asking open, probing questions allows the nurse to identify what specifically the patient is concerned about in relation to FMT (Delves-Yates, 2022).
There is limited qualitative research concerning patient opinions and thoughts on FMT; however, studies have highlighted that some patients do express reservations when first offered the procedure, with the most common barriers including aesthetics, infection concerns, and the procedure involved in the administration of the donor sample (Pakyz et al, 2016; Gill et al, 2020).
Conclusion
C.difficile infection has the potential to significantly harm the patient, with the worst outcome possible being death. Antibiotics, although beneficial and normally effective in treating initial cases of C.difficile infection, might not prove as effective in treating recurrent episodes. FMT is a safe and proven intervention that is underused in the treatment of recurring C.difficile infection. It should be considered due to its remarkable success rate, coupled with the fact that antibiotics are not a primary, or even supplementary treatment approach used, which has positive implications for initiatives such as antimicrobial stewardship.
By adhering to standard infection prevention and control precautions, the spread of C.difficile can be limited – this requires a united effort as well as vigilance from nurses to achieve this. The nurse who possesses the relevant knowledge of FMT needs to use their effective communication skills to allay any reservations the patient might have about the treatment to work towards a safe, successful intervention.
KEY POINTS
- Clostridiodes difficile infection can cause diarrhoea, sepsis, toxic megacolon, and in severe cases, death
- As nurses spend the most time of any of the healthcare team with the patient, it is vital that they have a basic understanding of conditions such as C. difficile, and the treatment protocols involved
- FMT administration is rapidly developing, with encapsulated administration holding great promise in increasing acceptability amongst eligible recipients
CPD reflective questions
- What are some of the symptoms of C.difficile infection and why is it problematic?
- What are the benefits of receiving a faecal microbiota transplant? What are the risks and how are these managed?
- Consider some of the reservations patients might have about undergoing an FMT procedure