The information below is largely based on NICE NG199 Clostridioides difficile infection: antimicrobial prescribing (July 2021), but has been refined with local specialist input.

Please see Public Health England's guidance on the diagnosis and reporting of C. difficile

Ensure prompt submission of stool sample for testing if C. difficile infection is suspected. Note any history of antibiotic treatment on request form, and specifically request C. difficile testing as this is not routinely done on community specimens from patients under 65 years of age.

Treating suspected or confirmed C. difficile infection

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

Review existing antibiotic treatment and stop it unless essential. If an antibiotic is still essential, seek advice from a microbiologist for an alternative with a lower risk of causing 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 (NSAIDs), angiotensin-converting enzyme inhibitors, angiotensin 2 receptor antagonists and diuretics

For all patients, local specialists suggest seeking prompt advice from a microbiologist regarding management, especially if the patient still requires antibiotic treatment for another indication. Do not delay initiation of treatment for C. difficile.

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

• drinking enough fluids to avoid dehydration
• preventing the spread of infection
• seeking medical help if symptoms worsen rapidly or significantly at any time
• avoiding the use of antimotility drugs (such as loperamide) to treat diarrhoeal symptoms

First episode of mild, moderate, or severe C. difficile infection

Patients with severe or life-threatening infection should be urgently referred to hospital (see reassessment and referral below)

When considering antibiotic treatment with vancomycin or fidaxomicin in primary care, it may be appropriate to contact community pharmacy to ensure supply is available within an adequate timeframe. Vancomycin 125mg capsules are included in the 2020/21 NHS England South West Enhanced Service for the Availability of Specialist Medicines and should be available from participating community pharmacies. Please note this is an enhanced service that is not available from all community pharmacies. A list of the pharmacies signed up to this service is available here.

1st line antibiotic

For all patients, prompt advice regarding management should be sought from a microbiologist or infectious diseases specialist, however treatment initiation should not be delayed whilst awaiting specialist advice

Vancomycin is the preferred choice as it has superior efficacy to metronidazole in the treatment of C. difficile infection

Vancomycin

• Adults (aged ≥ 18 years): 125mg orally four times a day for 10 days
• Children (aged <18 years): refer to BNFC
• For those unable to swallow capsules, alternative oral formulations may be available (do not use the parenteral route), seek specialist advice

OR

Metronidazole

• Vancomycin is the preferred choice as it has superior efficacy to metronidazole in the treatment of C. difficile infection. Metronidazole may be considered for mild cases (unless considered to be at high risk of relapse*), when other treatment options are not readily available
• Adults (aged ≥ 18 years): 400mg orally three times a day for 10-14 days
• Children (aged <18 years): refer to BNFC
• Metronidazole oral suspension is not recommended for C. difficile infection (theoretical risk that efficacy of metronidazole benzoate may be compromised because of reduced exposure to gastric enzymes).

2nd line antibiotic

Fidaxomicin

• Adults and children with body-weight ≥ 12.5kg: 200mg orally twice a day for 10 days
• Individuals with swallowing difficulties or body-weight <12.5kg: oral suspension given twice a day for 10 days (dose dependent on weight – refer to drug entry)
• Use of fidaxomicin should be discussed with a microbiologist, infectious diseases specialist or gastroenterologist. It should be considered for patients at high risk of relapse*.

* Patients considered to be at high risk of relapse are those who require ongoing antibiotic therapy for other indications and those with historic episodes of C. difficile infection. If in doubt, seek advice from microbiology

Further episodes of C. difficile infection (relapses or recurrent episodes)

Patients with severe or life-threatening infection should be urgently referred to hospital (see reassessment and referral below)

NICE NG199 defines a relapse as occurring within 12 weeks of previous symptom resolution and recurrence as occurring more than 12 weeks after previous symptom resolution.

When considering antibiotic treatment with vancomycin or fidaxomicin in primary care, it may be appropriate to contact community pharmacy to ensure supply is available within an adequate timeframe. Vancomycin 125mg capsules are included in the 2020/21 NHS England South West Enhanced Service for the Availability of Specialist Medicines and should be available from participating community pharmacies. Please note this is an enhanced service that is not available from all community pharmacies. A list of the pharmacies signed up to this service is available here.

Relapse

Fidaxomicin

• Adults and children with body-weight ≥ 12.5kg: 200mg orally twice a day for 10 days
• Individuals with swallowing difficulties or body-weight <12.5kg: oral suspension given twice a day for 10 days (dose dependent on weight – refer to drug entry)
• Use of fidaxomicin should be discussed with a microbiologist, infectious diseases specialist or gastroenterologist.

Recurrence

Seek specialist advice regarding appropriate choice of antibiotic for all patients with recurrent episodes of C. difficile infection.

For recurrent episodes of C. difficile infection in adults who have had 2 or more previous episodes, refer to specialists for consideration of alternative treatments including faecal microbiota transplant.

Fidaxomicin

• Adults and children with body-weight ≥ 12.5kg: 200mg orally twice a day for 10 days
• Individuals with swallowing difficulties or body-weight <12.5kg: oral suspension given twice a day for 10 days (dose dependent on weight – refer to drug entry)

OR

Vancomycin

• Adults (aged ≥ 18 years):
  • 125mg orally four times a day for 10 days
  • A tapering course of vancomycin may be recommended to prevent further relapses or recurrences (seek specialist advice):
    • 125mg every 6 hours for 14 days, then every twelve hours for one week, then once daily for one week, then every other day for one week, then every three days for 2 weeks

• Children (aged <18 years):
  • refer to BNFC
  • A tapering course of vancomycin may be recommended to prevent further relapses or recurrences (seek specialist advice):
    • 10mg/kg (max 125mg) every 6 hours for 10 to 14 days, then every 12 hours for one week, then once daily for one week, then every other day for two to three weeks
• For those unable to swallow capsules, alternative oral formulations may be available (do not use the parenteral route), seek specialist advice

See 5.1.7 Some other antibacterials and 5.1.11 Metronidazole

Reassessment and referral

Reassess people with suspected or confirmed C. difficile infection if symptoms or signs do not improve as expected, and refer to hospital if they are severely unwell, or their symptoms or signs worsen rapidly or significantly at any time.

Use clinical judgement to determine whether antibiotic treatment for C. difficile is ineffective. It is not usually possible to determine this until day 7 because diarrhoea may take 1 to 2 weeks to resolve.

Patients with severe or life-threatening infection should be urgently referred to hospital. Signs include:

• white cell count (WCC) greater than 15 × 10⁹ per litre
• acutely increased serum creatinine concentration (greater than 50% increase above baseline)
• a temperature higher than 38.5^oC
• abdominal signs suggesting evidence of severe colitis
• hypotension
• signs or symptoms suggesting partial or complete ileus
• signs or symptoms suggesting toxic megacolon

Refer adults with 2 or more previous episodes of C. difficile infection to specialists for consideration of alternative treatments including faecal microbiota transplant.

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