Assessment

1.1.1.

For people with suspected or confirmed C. difficile infection, see Public Health England’s guidance on diagnosis and reporting.

1.1.2.

For people with suspected or confirmed C. difficile infection, assess:

• whether it is a first or further episode (relapse or recurrence) of C. difficile infection
• the severity of C. difficile infection
• individual factors such as age, frailty or comorbidities that may affect the risk of complications or recurrence.

1.1.3.

For people with suspected or confirmed C. difficile infection, review existing antibiotic treatment and stop it unless essential. If an antibiotic is still essential, consider changing to one with a lower risk of causing C. difficile infection.

1.1.4.

For people with suspected or confirmed C. difficile infection, review the need to continue any treatment with:

• proton pump inhibitors
• other medicines with gastrointestinal activity or adverse effects, such as laxatives
• medicines that may cause problems if people are dehydrated, such as non-steroidal anti-inflammatory drugs, angiotensin-converting enzyme inhibitors, angiotensin-2 receptor antagonists and diuretics.

Treating suspected or confirmed C. difficile infection

1.1.5.

For adults, offer an oral antibiotic to treat suspected or confirmed C. difficile infection (see the recommendations on choice of antibiotic). In the community, consider seeking prompt specialist advice from a microbiologist or infectious diseases specialist before starting treatment.

1.1.6.

For children and young people under 18 years, offer an oral antibiotic to treat suspected or confirmed C. difficile infection. Treatment should be started by, or after advice from, a microbiologist, paediatric infectious diseases specialist or paediatric gastroenterologist.

1.1.7.

For people with suspected or confirmed C. difficile infection who cannot take oral medicines, seek specialist advice from a gastroenterologist or pharmacist about alternative enteral routes for antibiotics, such as a nasogastric tube or rectal catheter.

1.1.8.

Manage fluid loss and symptoms associated with suspected or confirmed C. difficile infection as for acute gastroenteritis. Do not offer antimotility medicines such as loperamide.

1.1.9.

Do not offer bezlotoxumab to prevent recurrence of C. difficile infection because it is not cost effective.

1.1.10.

Consider a faecal microbiota transplant for a recurrent episode of C. difficile infection in adults who have had 2 or more previous episodes (see NICE’s interventional procedures guidance on faecal microbiota transplant for recurrent C. difficile infection).

Advice

1.1.11.

Advise people with suspected or confirmed C. difficile infection about:

• drinking enough fluids to avoid dehydration
• preventing the spread of infection (see recommendation 1.3.1)
• seeking medical help if symptoms worsen rapidly or significantly at any time.

Reassessment

1.1.12.

Reassess people with suspected or confirmed C. difficile infection if symptoms or signs do not improve as expected, or worsen rapidly or significantly at any time. Daily review may be needed, for example, if the person is in hospital.

1.1.13.

If antibiotics have been started for suspected C. difficile infection, and subsequent stool sample tests do not confirm C. difficile infection, consider stopping these antibiotics (see Public Health England’s guidance on diagnosis and reporting for recommendations on stool sample tests).

Referral

1.1.14.

Refer people in the community with suspected or confirmed C. difficile infection to hospital if they are severely unwell, or their symptoms or signs worsen rapidly or significantly at any time. Refer urgently if the person has a life-threatening infection.

1.1.15.

Consider referring people in the community to hospital if they could be at high risk of complications or recurrence because of individual factors such as age, frailty or comorbidities.

1.1.16.

Ensure that people in hospital with suspected or confirmed C. difficile infection have care from a multidisciplinary team that may include a microbiologist, infectious diseases specialist, gastroenterologist, surgeon, pharmacist or dietitian, as needed.

Why the committee made the recommendations

Recommendations 1.1.1 to 1.1.4

The committee agreed that although diagnostics and reporting were out-of-scope for this guideline, a recommendation should be included on where to find such information. They concluded, from experience, that people should see Public Health England’s updated guidance on the diagnosis and reporting of Clostridioides difficile.

The committee discussed that, in practice, there has been a change in the definition of the severity of C. difficile from the 4 categories (mild, moderate, severe and life threatening) used by Public Health England to 3 categories (non-severe, severe and life threatening). However, the Public Health England categories still apply because this is current national guidance.

The committee discussed the findings of the economic model, which took into account severity by adjusting for older age, increased risk of recurrence, increased hospitalisation and a higher risk of fulminant colitis (see the economic analysis in the evidence review for full details; there was a lack of useful direct evidence for severity that could be used in the economic model). The economic model found that severity did not cause a substantial change in which antibiotic was the most cost effective. Therefore, the committee agreed that the main reason to assess severity was to identify the appropriate place of care, overall management, and any subsequent improvement or worsening. They also agreed that an assessment of whether the current infection was a first or further episode (relapse or recurrence) of C. difficile infection should be included. This was because recurrence was a driver in the economic model and determines antibiotic choice (see also the rationale on choice of antibiotic).

The committee recognised that C. difficile infection most commonly affects people who are taking or have recently taken antibiotics. They discussed that, even though antibiotics being taken may be associated with the C. difficile infection, the person may still need antibiotics for the original infection. They agreed that, in line with good antimicrobial stewardship, prescribers should review existing antibiotic treatment and:

• stop it unless essential, or
• if an antibiotic is still essential, consider changing to one with a lower risk of causing C. difficile infection.

The committee agreed that it is good prescribing practice to review the continuing need for existing proton pump inhibitor (PPI) treatment in people with suspected or confirmed C. difficile infection, in line with NICE’s guideline on medicines optimisation. They were aware that, although some associations have been made between PPI use and the risk of C. difficile infection or recurrence, there is no definitive evidence of a causal or exacerbator effect. Also, no evidence from systematic reviews or randomised controlled trials was found to support stopping current PPI treatment. The committee agreed that suddenly stopping a PPI during an acute episode of infection may cause additional gastric symptoms. Additionally, some people will need ongoing gastroprotection for a clinical indication. However, they were aware that many people may be taking a PPI without a clear indication, so concluded that the use and need for a PPI should be reviewed.

The committee agreed that, when people present with suspected or confirmed C. difficile infection, it is good prescribing practice to review other medicines with gastrointestinal activity or adverse effects (such as laxatives) being taken. They also agreed that it is good practice to review other medicines being taken that may have detrimental effects if people are acutely ill and dehydrated. These include non-steroidal anti-inflammatory drugs, angiotensin-converting enzyme inhibitors, angiotensin-2 receptor antagonists and diuretics.

Return to the recommendations

Why the committee made the recommendations

Recommendations 1.1.5 to 1.1.10

The committee agreed that an oral antibiotic should be offered for suspected or confirmed C. difficile infection in adults, young people and children.

For adults presenting in the community, the committee agreed that GPs may be unfamiliar with diagnosing and treating C. difficile infection, so may want to seek prompt specialist advice from a microbiologist or infectious diseases specialist before starting treatment. The committee noted that, for people in hospital, once diagnosed, they would be under the care of a multidisciplinary team, which would ensure appropriate review and care.

The committee discussed the lack of evidence on treating C. difficile infection in children and young people. They were aware that, in practice, very few children have C. difficile infection. The committee agreed that a positive test for C. difficile in children 2 years and under is often because of high carriage rates of the bacteria rather than because of actual infection. They considered that this may lead to overprescribing of antibiotics. The committee concluded that treatment for C. difficile infection in children and young people should only be started by a microbiologist, paediatric infectious diseases specialist or paediatric gastroenterologist, or after advice from such a specialist.

The committee discussed the most appropriate route of administration of antibiotics for C. difficile infection. They agreed that the enteral route is best because sufficient concentrations within the intestinal lumen need to be reached. The committee concluded that it is preferable to take antibiotics orally or, if this is not possible, enterally in some other way (such as a nasogastric or enteral feeding tube, or rectally). They advised seeking specialist advice on administration from a specialist gastroenterologist or pharmacist if the oral route is not available.

The committee agreed that, in line with the general management of gastroenteritis (see the NICE clinical knowledge summary on adult gastroenteritis and NICE’s guideline on diarrhoea and vomiting caused by gastroenteritis in under 5s), prescribers and other care staff should monitor and manage fluid loss and gastroenteritis symptoms. Antimotility drugs such as loperamide should be avoided because they slow down the action of the gut. This can lead to C. difficile toxins being retained for longer, which may make a person more unwell.

Bezlotoxumab was not recommended as adjunctive therapy to antibiotics to prevent recurrent C. difficile infection. The committee discussed the clinical evidence, which showed that bezlotoxumab was more effective than placebo at preventing recurrence. However, they also reviewed the economic analysis and agreed that adding bezlotoxumab to either vancomycin or fidaxomicin was not a cost-effective option (there is a 0% probability of it being cost effective at £30,000 per quality-adjusted life year [QALY] gained). The committee agreed that this finding was robust, even in people with a higher risk of recurrence, and were confident in making a recommendation for bezlotoxumab not to be used.

The committee noted that faecal microbiota transplantation (FMT; a procedure done in a small number of specialist centres) was not effective as a first-line treatment for C. difficile infection compared with vancomycin. They were aware that long-term safety data on, and regulations about the use of, FMT are minimal compared with medicines. They were aware of variation in mortality rates associated with FMT use, and that there is almost no evidence for its use in children. NICE’s interventional procedures guidance on FMT for recurrent C. difficile infection states that ‘current evidence on the efficacy and safety of FMT for recurrent Clostridium difficile infection is adequate to support the use of this procedure provided that normal arrangements are in place for clinical governance, consent and audit’. In the economic model, FMT was placed as a third-line treatment (for people with continuing symptoms after first- and second-line antibiotics) that may help prevent serious complications. The committee agreed that FMT may be useful in adults who have had 2 or more previous episodes of C. difficile infection in addition to the current episode to prevent recurrence of C. difficile infection. They were aware of ongoing developments around the screening of faecal microbiota donors to identify multidrug-resistant organisms.

For more details, see the summary of the evidence on treating initial or first recurrent C. difficile infection.

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Why the committee made the recommendation

Recommendation 1.1.11

The committee discussed what advice on self-care people with a C. difficile infection would need and agreed that, from their experience, 3 key areas of advice were needed:

• maintaining fluid intake to avoid dehydration (and on the symptoms or signs of dehydration that people should be aware of)
• the need to help reduce the spread of C. difficile infection, which is contagious (that is, people should follow the advice in the NICE clinical knowledge summary on adult gastroenteritis and in NICE’s guideline on diarrhoea and vomiting caused by gastroenteritis in under 5s)
• when to seek medical help.

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Why the committee made the recommendations

Recommendations 1.1.12 to 1.1.13

The committee were aware that C. difficile infection should be managed as a diagnosis in its own right. They agreed that the management and progress of suspected or confirmed C. difficile infection should be monitored during treatment. This could include assessing the severity of the infection and symptoms, and the need for hydration. The committee concluded that, from their experience, it would be good practice to reassess people if symptoms or signs of infection do not improve as expected or worsen rapidly or significantly at any time. They agreed that daily review is usual in hospital and that, in the community, people should be given appropriate safety netting advice to ensure that they return for reassessment if needed.

The committee also agreed that clinicians should consider stopping antibiotics for C. difficile infection if they have been started for clinically suspected C. difficile infection before stool sample test results are available and subsequent results do not confirm infection.

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Why the committee made the recommendations

Recommendations 1.1.14 to 1.1.16

The committee agreed that people with suspected or confirmed C. difficile infection in the community should be referred to hospital if they are severely unwell, or their symptoms or signs worsen rapidly or significantly at any time. For life-threatening infection, an urgent referral is needed. The committee recognised that there are some individual factors (such as age, frailty and comorbidities) for which it may also be appropriate to consider referral to hospital. This is because they are associated with a higher risk of complications or recurrence.

The committee agreed that people who develop C. difficile infection while in hospital are unlikely to be having care from a microbiologist or infectious diseases specialist at diagnosis. However, once diagnosed they should be under the care of a multidisciplinary team to ensure appropriate review and care. The team could include, as needed, a microbiologist, infectious diseases specialist, gastroenterologist, surgeon, pharmacist and dietitian. This would depend, for example, on the severity of illness and need for surgery.

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Why the committee made the recommendations

The committee discussed the evidence for the effectiveness and cost effectiveness of the different antibiotic options for treating C. difficile infection. They were aware that antibiotic resistance is not a major concern when treating C. difficile infection.

Why the committee made the recommendations

Recommendations 1.3.1 to 1.3.4

The committee agreed that, although preventing C. difficile infection through good antimicrobial stewardship, infection control and environmental hygiene were out-of-scope for this guideline, a recommendation should be included on where to find such information. They concluded, from experience, that people should see Public Health England’s guidance on C. difficile infection: how to deal with the problem, and NICE’s guidance on healthcare-associated infections and antimicrobial stewardship.

The committee also discussed the importance of ensuring that a diagnosis of C. difficile infection is recorded in a person’s medical records. This is particularly important when transferring from one care setting to another, so that it can be taken into account before prescribing any future antibiotics, to help minimise the risk of recurrent episodes.

The committee noted the lack of evidence of clinical or cost effectiveness to prevent C. difficile infection with antibiotics. They recognised that there was some evidence for rifaximin preventing further recurrences from a single study in people who already had recurrent infection. However, the intensive way in which antibiotics were used in the study has raised concerns about the possible emergence of rifamycin resistance, which has been reported in C. difficile infection cases, and prolonged flora disturbance.

The committee also recognised the limited evidence of benefit for:

• fidaxomicin in preventing C. difficile infection in people having a haematopoietic stem cell transplant who had fluoroquinolone prophylaxis
• vancomycin in preventing C. difficile infection in people who are in hospital.

The economic model only included treatment options, including adjunctive treatment with bezlotoxumab (which is used to prevent recurrent infection) and FMT to determine sequencing of treatments. It did not include comparisons for preventing a first episode of C. difficile infection with antibiotics, prebiotics or probiotics. The committee concluded that, because of the lack of evidence and concerns about antimicrobial resistance, antibiotics should not be offered for preventing C. difficile infection.

The committee noted the lack of convincing evidence of effect for prebiotics (oligofructose), which showed little difference in preventing C. difficile-associated outcomes in the included studies. They concluded that prebiotics conferred no benefit and that people taking antibiotics should not be advised to take prebiotics to prevent C. difficile infection.

The committee agreed that there is some evidence of a small effect with probiotics in preventing C. difficile infection. However, there were many limitations in the evidence, including:

• a high number needed to treat
• aggregation of the results of different types of probiotics in meta-analyses
• the lack of effectiveness when using confirmed cases only (in everyone, but particularly in children).

The committee also noted concerns from expert testimony about the high prevalence of C. difficile infection in the placebo arms of some studies, which does not reflect clinical practice in the UK. The single study done in a UK setting found no evidence of effect for probiotics in people aged over 65 years. They further noted that NHS England’s guidance on conditions for which over the counter items should not routinely be prescribed in primary care states that probiotics should not routinely be prescribed.

The committee concluded that, because of concerns about the evidence base (including cost effectiveness), people taking antibiotics should not be advised to take probiotics to prevent C. difficile infection.

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Antibiotics

FMT for treating initial C. difficile infection

There were no statistically significant differences in clinical effectiveness (resolution of C. difficile infection, treatment failure, all-cause and C. difficile infection attributable mortality or length of stay) of:

• the first dose of FMT compared with vancomycin
• the second dose of FMT compared with vancomycin (Camacho-Ortiz et al. 2017).

FMT for treating recurrent C. difficile infection

There were statistically significant increases in clinical effectiveness (resolution of symptoms, resolution of diarrhoea, relapse of diarrhoea) with:

• a 4- to 10-day course of vancomycin followed by FMT compared with 10 days of vancomycin at 1- and 8-week follow up (Hvas et al. 2019)
• a 4- to 10-day course of vancomycin followed by FMT compared with 10 days of fidaxomicin at 8-week follow up (Hvas et al. 2019)
• a 4- to 5-day course of vancomycin plus bowel lavage followed by FMT compared with either 14 days of vancomycin (with or without bowel lavage) at 10-week follow up, and at 5-week follow up for relapse (van Nood et al. 2013)
• a 3-day course of vancomycin followed by FMT compared with a standard then a pulsed course of vancomycin at 10-week follow up (Cammarota et al. 2015).

There were no statistically significant differences in all-cause or C. difficile infection-related mortality for a short course of vancomycin plus bowel lavage followed by FMT compared with 14 days of vancomycin or 14 days of vancomycin plus bowel lavage (van Nood et al. 2013).

There were no statistically significant differences in adverse events for:

• a short course of oral vancomycin followed by FMT compared with either 10 days of vancomycin or fidaxomicin (Hvas et al. 2019)
• a short course of vancomycin followed by FMT compared with vancomycin, either with or without bowel lavage (van Nood et al. 2013).

There was a statistically significant lower mean number of days of diarrhoea compared with a course of vancomycin followed by FMT compared with tapered vancomycin (Hota et al. 2017). However, a short course of vancomycin followed by FMT or bowel lavage plus FMT statistically significantly increased treatment-related diarrhoea, bloating or cramping (Cammarota et al. 2015; van Nood et al. 2013).

Serious adverse events were reported in 2 RCTs. In 1 RCT, a sepsis-like response occurred (possibly related to FMT) but resolved without admission or treatment (Hvas et al. 2019). In the other RCT, 3 serious adverse events were noted but none were thought to be treatment related (Hota et al. 2017).

Antibiotics

In adults who had an initial or first recurrent episode of C. difficile infection treated with vancomycin or metronidazole, immediate rifaximin for 20 days was statistically significantly more effective than placebo at reducing recurrence of both C. difficile infection-confirmed diarrhoea and self-reported diarrhoea. However, when the outcomes of recurrent C. difficile infection-confirmed diarrhoea and recurrent self-reported diarrhoea were analysed separately, there was no statistically significant difference between rifaximin and placebo in either group (Garey et al. 2011).

In adults who had an initial, first recurrent, or second or later recurrent episode of C. difficile infection treated with vancomycin or metronidazole, there was no statistically significant difference between immediate rifaximin for 28 days and placebo for recurrent C. difficile infection at 12 weeks or 6 months, or for rehospitalisation for C. difficile infection within 6 months. When subgroup analysis was done for standard care antibiotic treatment with metronidazole or vancomycin, there was no statistically significant difference between rifaximin and placebo for C. difficile infection recurrence. There was also no statistically significant difference in effect between rifaximin and placebo on C. difficile infection recurrence when post-hoc analyses were done for C. difficile infection history (Major et al. 2019).

A Kaplan–Meier analysis showed that rifaximin led to a statistically significant increased time to both recurrent C. difficile infection-confirmed diarrhoea and recurrent self-reported diarrhoea compared with placebo (Garey et al. 2011). However, when the time to C. difficile infection-confirmed diarrhoea and time to self-reported diarrhoea were analysed separately, there was no statistically significant difference between rifaximin and placebo.

There were no statistically significant differences between rifaximin and placebo for mortality, serious and non-serious adverse events (Major et al. 2019).

Monoclonal antibodies

In adults with an initial or recurrent episode of C. difficile infection treated with standard care antibiotic treatment (that is, metronidazole, vancomycin or fidaxomicin), bezlotoxumab was statistically significantly more effective than placebo for recurrent C. difficile infection, 12 weeks of sustained cure and recurrence of diarrhoea (regardless of whether it was associated with a positive toxin test; Wilcox et al. 2017). A Kaplan–Meier analysis suggested that bezlotoxumab increased time to recurrence of C. difficile infection compared with placebo, but it was unclear if the differences were statistically significant.

Various subgroup analyses for C. difficile infection risk factors and stratification variables were done. Bezlotoxumab was statistically significantly more effective than placebo for recurrence of C. difficile infection for the stratification variables of inpatients and outpatients, and whether people had vancomycin or metronidazole as their standard care antibiotic treatment. However, there was no statistically significant difference between bezlotoxumab and placebo for the outcome of recurrence of C. difficile infection for the stratification variable of people having fidaxomicin as their standard care antibiotic treatment.

There were no statistically significant differences between bezlotoxumab and placebo for the outcomes of initial clinical cure at 2 days and mortality.

There was no statistically significant difference between bezlotoxumab and placebo for infusion-specific adverse events or adverse events leading to treatment being stopped at 24-hour follow up. There was also no statistically significant difference between bezlotoxumab and placebo for drug-related adverse events, other adverse events (most commonly abdominal pain, diarrhoea, nausea, vomiting, fatigue, pyrexia, serious C. difficile, urinary tract infection or headache), serious adverse events or for drug-related serious adverse events, occurring during the 4 weeks after the bezlotoxumab infusion.

FMT for preventing C. difficile infection recurrence

In NICE analyses, there were no statistically significant differences in the clinical effectiveness (recurrence) of the following doses of FMT taken after antibiotic treatment for a current episode of C. difficile infection in adults with multiple recurrent infections:

• a single dose of FMT compared with placebo
• 2 doses of FMT compared with placebo
• 2 doses of FMT compared with a single dose of FMT
• 1 or 2 doses of FMT (pooled) compared with placebo (Dubberke et al. 2018).

There was no statistically significant difference in adverse events. However, 3 severe adverse events were reported and thought to be related to FMT in the ‘2 doses of FMT’ group. There were 6 deaths (3 in the ‘2 doses of FMT’ group and 3 in the ‘1 dose of FMT’ group) in the FMT arms of the trial and none in the placebo group.

Prebiotics for relapse of diarrhoea

There was a statistically significant decrease in relapse of diarrhoea with metronidazole or vancomycin plus the prebiotic oligofructose compared with metronidazole or vancomycin plus placebo for diarrhoea associated with C. difficile infection in adults aged over 65 years (Lewis et al. 2005a). No statistically significant difference was noted for C. difficile culture positivity at 30- or 60-day follow up.

Antibiotics choice

Probiotics for persistent diarrhoea

There was a statistically significant reduction in the mean number of days of diarrhoea with oral rehydration solution plus the probiotic Lactobacillus rhamnosus GG compared with oral rehydration solution alone in children with a positive C. difficile stool culture (Basu et al. 2007). However, there was no statistically significant difference in the mean number of days of vomiting.

Antibiotics

In people without C. difficile infection having a haematopoietic stem cell transplant and fluoroquinolone prophylaxis during neutropenia, there was no statistically significant difference between fidaxomicin and placebo for reducing prophylaxis failure at 30, 60 or 70 days (Mullane et al. 2019). There was also no statistically significant difference between fidaxomicin and placebo for any adverse events reported in the study.

Fidaxomicin was statistically significantly more effective than placebo at reducing confirmed diarrhoea associated with C. difficile infection at 30, 60 and 70 days. A Kaplan–Meier analysis showed a statistically significantly increased time to recurrence of C. difficile infection with fidaxomicin compared with placebo.

In people without C. difficile infection who were hospitalised for up to 30 days before their current hospitalisation, there was no statistically significant difference between oral vancomycin and placebo for:

• healthcare facility-onset (symptomatic infection more than 72 hours after hospital admission) C. difficile infection, or
• community-onset healthcare facility-associated (symptomatic infection up to 3 months after hospital discharge) C. difficile infection after hospital discharge (Johnson et al. 2020).

Prebiotics

In inpatients aged over 65 years without C. difficile infection who were prescribed a broad-spectrum antibiotic, the prebiotic oligofructose did not have a statistically significantly different effect to placebo at end of follow up for all-cause mortality or for incidence of diarrhoea, significant diarrhoea (3 loose stools or more in a 24-hour period), non-significant diarrhoea (1 or 2 loose stools in a 24-hour period), C. difficile-associated diarrhoea or C. difficile-associated significant diarrhoea (Lewis et al. 2005b).

In the oligofructose group, the median (interquartile range) length of hospital stay was 17 days (13 to 22) compared with 15 days (11 to 18) in the placebo group.

Probiotics

The evidence for probiotics in the prevention of C. difficile infection in adults comes from 1 systematic review (Goldenberg et al. 2017). The population in the included studies was people aged over 18 years having antibiotic treatment for any reason.

Probiotics statistically significantly reduced the incidence of C. difficile infection compared with any comparator (follow-up time point not reported) in studies in inpatients, but not in studies in outpatients or patients in mixed settings.

Probiotics were not statistically significantly different compared with any comparator for the outcome of incidence of C. difficile infection determined by detection of C. difficile in stools, either overall or in any setting (inpatients, outpatients, or mixed settings; follow-up time points not reported).

Probiotics statistically significantly reduced the number of adverse events compared with any comparator (follow-up time point not reported). Details of the adverse events were not reported.

Probiotics

The evidence for probiotics in preventing C. difficile infection in children and young people comes from 1 systematic review (Goldenberg et al. 2017) and 1 RCT (Kolodziej and Szajewska 2019). The population in the included studies was children and young people aged under 18 years who were having antibiotic treatment for any reason.

Probiotics statistically significantly reduced the incidence of C. difficile infection compared with any comparator (follow-up time point not reported) in the inpatient and mixed settings studies.

Probiotics were not statistically significantly different compared with any comparator in inpatient studies for the outcome of incidence of C. difficile infection determined by detection of C. difficile in stool (follow-up time point not reported).

Probiotics were not statistically significantly different compared with any comparator for adverse events.

Vancomycin

Vancomycin is a glycopeptide that is taken orally to treat Clostridioides difficile infection. With oral use, the company advises monitoring serum vancomycin concentration in people with inflammatory intestinal disorders in which absorption may be enhanced. It also advises that serial auditory function tests may help to minimise the risk of ototoxicity in people with an underlying hearing loss, or who are having concomitant therapy with other ototoxic drugs. In renal impairment or in people having concomitant treatment with an aminoglycoside or other nephrotoxic drug, the manufacturer advises serial monitoring of renal function. The manufacturer advises that vancomycin should be used in pregnancy only if the potential benefit outweighs the risk. Prolonged use of vancomycin may result in the overgrowth of non-susceptible organisms. Acquired resistance to glycopeptides is most common in enterococci, in which multiresistant strains have been seen (see BNF information on vancomycin and vancomycin summary of product characteristics).

Fidaxomicin

Fidaxomicin is a macrocyclic antibacterial that is poorly absorbed from the gastrointestinal tract, so is not used to treat systemic infections. It is taken orally to treat C. difficile infection. Common side effects when taken orally for C. difficile infection include constipation, nausea and vomiting. The manufacturer advises that it is preferable to avoid using fidaxomicin in pregnancy as a precaution (see BNF information on fidaxomicin and fidaxomicin summary of product characteristics).

Faecal microbiota transplant

In NICE’s interventional procedures guidance on faecal microbiota transplant for recurrent C. difficile infection, it states that ‘The US Food and Drug Administration has advised that stool donors for faecal microbiota transplantation should be screened with questions that specifically address risk factors for colonisation with multidrug-resistant organisms (MDROs), and individuals at higher risk of colonisation with MDROs should be excluded as donors. In addition, donor stool should be specifically tested for MDROs and not used if positive’. While short-term safety and adverse events with a faecal microbiota transplant were reported in the included studies for this guidance, the committee identified that longer-term safety of the procedure is not yet known.