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Drugs and devices Gastrointestinal Infections and infestations

Diarrhoea - antibiotic associated

Last revised in May 2025

Diarrhoea is a common consequence of treatment with antibiotics, occurring in 225% of people taking antibiotics

Diarrhoea - antibiotic associated: Summary

  • Diarrhoea is a common consequence of treatment with antibiotics, occurring in 2–25% of people taking antibiotics, depending on the antibiotic prescribed.
  • Around 20% to 30% of cases of antibiotic-associated diarrhoea are due to Clostridioides difficile. Antibiotics frequently associated with C. difficile infection (CDI) include clindamycin, cephalosporins (especially third and fourth-generation), fluoroquinolones, and broad-spectrum penicillins. 
  • Factors that increase the risk of CDI include increased age, frailty, previous history of CDI, exposure to other cases, concomitant use of a proton pump inhibitor or other acid-suppressing drugs, and underlying co-morbidity (such as abdominal surgery, chronic renal disease, inflammatory bowel disease, and immunosuppression).
  • The complications of CDI can be severe and include pseudomembranous colitis, toxic megacolon, perforation of the colon, sepsis, and death.
  • The severity of symptoms should be assessed and the need for hospital admission considered.
  • If C. difficile is suspected, assess whether this is a first or further episode (relapse or recurrence). 
  • If infection with C. difficile is suspected, a stool sample should be taken.
  • If infection with C. difficile is not suspected or testing for C. difficile is negative:
    • The antibiotic should be stopped, if this is appropriate.
    • Fluid loss and symptoms should be managed as for acute gastroenteritis.
  • If CDI is suspected or confirmed:
    • Suspected and non-severe infection is managed with antibiotics after advice from a microbiologist or infectious diseases specialist.
    • Risk of a C. difficile outbreak should be assessed — for example, among other elderly residents in a care or nursing home.
    • Any antibiotics not being used to treat CDI should be stopped, if appropriate.
    • Fluid loss and symptoms should be managed.
    • Antimotility drugs (such as loperamide) should be avoided.
    • Advice should be given on hygiene measures to minimize the spread of C. difficile.
  • Diarrhoea due to C. difficile infection should resolve in 1–2 weeks. The person will remain infectious whilst they still have symptoms, and they should stay away from work or school until they have been free from diarrhoea for 48 hours.
  • Severe and fulminant CDI should be managed in hospital and referral should be considered in individuals at high risk of complications or recurrence, or if they have a recurrent infection after experiencing two previous CDI episodes.

Have I got the right topic?

From age 18 years onwards.

This CKS topic covers the diagnosis and management of antibiotic-associated diarrhoea, including Clostridioides difficile infection.

This CKS topic does not cover the management of acute gastroenteritis (including presumed infectious gastroenteritis) in adults and children, diarrhoea due to food poisoning, or traveller's diarrhoea. These are covered in the CKS topics on Gastroenteritis and Diarrhoea - prevention and advice for travellers.

There are separate CKS topics on Diarrhoea - adult's assessment Gastrointestinal tract (lower) cancers - recognition and referral, Gastrointestinal tract (upper) cancers - recognition and referral, Irritable bowel syndrome, Nausea/vomiting in pregnancy, and Palliative care - nausea and vomiting.

The target audience for this CKS topic is healthcare professionals working within the NHS in the UK, and providing first contact or primary healthcare.

How up-to-date is this topic?

Changes

May 2025 — minor update. Revised wording on recurrent C. difficile infection to improve clarity of the definition. 

Previous changes

February 2025 — minor update. The wording has been updated to clarify treatment options for subsequent C. difficile infection episodes after initial symptom resolution.  

June 2023 — reviewed. A literature search was conducted in June 2023 to identify evidence-based guidelines, UK policy, systematic reviews, and key randomized controlled trials published since the last revision of the topic. Structural changes have been made to the topic. Recommendations on when to consider referral to secondary care have been added.

July 2021 — minor update. Treatment of C. difficile updated to align with Clostridiodes difficile infection: antimicrobial prescribing NICE guideline [NG199]. This has meant removing the recommendation to use metronidazole as the first-line treatment for mild to moderation infection. The most recent recommendation advises vancomycin after consultation with local microbiologists or infectious disease specialists. 

November 2020 — minor update. Broken URL link updated.

February to March 2019 — reviewed. A literature search was conducted in January 2019 to identify evidence-based guidelines, UK policy, systematic reviews, and key RCTs published since the last revision of the topic. There are no major changes to the recommendations in this topic.

October 2018 — minor update. Adverse effects updated within prescribing information - metronidazole. 

March 2018 — minor update. Advice on the use of probiotics as an adjunct to the management of Clostridium difficile - associated diarrhoea was added. 

March to June 2013 — reviewed. A literature search was conducted in February 2013 to identify evidence-based guidelines, UK policy, systematic reviews, and key RCTs published since the last revision of the topic. There are no major changes to the recommendations in this topic.

February 2013 — minor update. The 2013 QIPP options for local implementation have been added to this topic.

October 2012 — minor update. The 2012 QIPP options for local implementation have been added to this topic.

June 2011 — minor update. Recommendations from the Department of Health letter, Diagnostic testing for Clostridium difficile infection, have been included in this topic. The 2010/2011 QIPP options for local implementation have been added to this topic. 

July to September 2009 — this is a new CKS topic. Together with the updated CKS topics on Diarrhoea - prevention and advice for travellers and Gastroenteritis, this CKS topic replaces the former topic on Gastroenteritis.

December 2008 — minor update to the text to amend advice regarding the assessment and investigation of pregnant women with gastroenteritis.

July to September 2006 — reviewed. Validated in December 2006 and issued in January 2007.

July 2007 — minor update to the text to include advice regarding the assessment and investigation of pregnant women with gastroenteritis.

February 2006 — minor update. Nalidixic acid tablets discontinued and prescriptions have been removed. 

June 2003 — reviewed. Validated in September 2003 and issued in October 2003.

January 2000 — rewritten. Validated in March 2000 and issued in May 2000.

October 1998 — written.

Update

New evidence

Evidence-based guidelines

  • UKHSA (2026) Clostridioides difficile infection: how to deal with the problem. UK Health Security Agency. www.gov.uk [Free Full-text]

HTAs (Health Technology Assessments)

No new economic appraisals relevant to England since 1 June 2023.

Economic appraisals

No new economic appraisals relevant to England since 1 June 2023.

Systematic reviews and meta-analyses

No new systematic reviews or meta-analysis which reach the CKS threshold for inclusion since 1 June 2023.

Primary evidence

  • UKSHA (2025) Increase in Clostridioides difficile infections (CDI): current epidemiology, data and investigations – Technical report. UK Health Security Agency [Free Full-text]

New policies

No new policies since 1 June 2023.

New safety alerts

No new safety alerts since 1 June 2023.

Changes in product availability

No changes in product availability since 1 June 2023.

Goals and outcome measures

Goals

To support primary health care professionals to:

  • Assess the person presenting with antibiotic-associated diarrhoea.
  • Diagnose suspected Clostridioides difficile infection.
  • Manage antibiotic-associated diarrhoea without C. difficile infection.
  • Manage C. difficile infection.

Outcome measures

No outcome measures were found during the review of this topic.

Audit criteria

No audit criteria were found during the review of this topic.

QOF indicators

No QOF indicators were found during the review of this topic.

QIPP - Options for local implementation

No QIPP indicators were found during the review of this topic.

NICE quality standards

No NICE quality standards were found during the review of this topic.

Background information

What is it?

  • Antibiotics can cause diarrhoea via one of the following mechanisms [Bartlett, 2002; Aronson, 2006; NICE, 2015; CADTH, 2018]: 
    • Disruption of the bowel microbiota and mucosal integrity.
    • As a direct effect of the antibiotic (independent of its antimicrobial effect) — for example, erythromycin can increase the rate of gastric emptying by acting as a motilin receptor agonist.
    • Overgrowth of toxin-producing strains of Clostridioides difficile (previously Clostridium difficile) a Gram-positive, spore-forming, anaerobic bacillus, due to disruption of harmless bacteria in the gut.
      • Overgrowth of C. difficile alone does not cause diarrhoea. C. difficile diarrhoea is caused by toxins produced by certain strains of C. difficile that damage the lining of the colon [Smits, 2016]. 
    • An allergic response to the antibiotic (rare).

What are the risk factors for Clostridioides difficile infection?

  • The risk factors for Clostridioides difficile infection (CDI) include: 
    • Increased age (more than 65 years old) [BMJ Best Practice, 2022].
    • Antibiotic treatment — this disrupts the microbiota of the gut, allowing the proliferation of C. difficile. Almost all drugs with antibacterial activity have been implicated with antibiotic-associated diarrhoea [NICE, 2015].
      • Lincosamides (for example clindamycin) are most commonly associated with CDI, followed by monobactams, penicillin combinations, carbapenems, cephalosporins, macrolides, fluoroquinolones, and trimethoprim/sulfamethoxazole [BMJ Best Practice, 2022].
      • The risk of CDI is also increased with longer durations of antibiotic treatment, multiple antibiotics prescribed concurrently, or multiple courses of antibiotics [Smits, 2016; McDonald, 2018]. 
    • History of CDI — reported recurrence rates are inconsistent, being reported between 5 to 50% of cases, although it is accepted to be around 20%. After the first recurrence has improved, this risk of repeated recurrences increases to 40-65% [Song, 2019; BMJ Best Practice, 2022].
    • Exposure to other infected people — the incidence of CDI is 13 times higher among people exposed to an infected family member. Exposure to those already infected can also lead to outbreaks of disease [Sams, 2017; BMJ Best Practice, 2022].
    • Current use of a proton pump inhibitor or other acid-suppressive drugs (such as H2-receptor antagonists) [Cao, 2018; BMJ Best Practice, 2022].
    • Underlying morbidities such as abdominal surgery, chronic renal disease, inflammatory bowel disease, immunosuppression (such as solid organ or haematopoietic stem cell transplant recipients, people with HIV infection, people undergoing cancer chemotherapy), and vitamin D deficiency [McDonald, 2018; Hassoun, 2018; BMJ Best Practice, 2022].
    • Prolonged hospitalization or residence in a nursing home — the presence of asymptomatic carriers in these settings increases the risk of infection [BMJ Best Practice, 2022].

How common is it?

  • Antibiotic-associated diarrhoea is estimated to occur in 2–25% of people taking antibiotics, depending on the antibiotic prescribed [Bartlett, 2002].
    • The rates of diarrhoea are similar for parenteral and oral antibiotic administration [Bartlett, 2002].
  • Around 20–30% of cases of antibiotic-associated diarrhoea are due to Clostridioides difficile [Steele, 2015].
  • The number of C. difficile infections (CDIs) are falling across the NHS.
    • The number of CDIs in the NHS in England decreased substantially from 2007/08 to 2013/14, falling from 107.6 cases per 100,000 population to 24.8 cases per 100,000 population. This has been attributed to surveillance programmes, measures to control antibiotic prescribing, and implementation of and compliance with isolation and hygiene protocols. However, since 2013/2014, the decline in CDI incidence rate has had a more gradual decrease, with a slight increase to 25.2 cases per 100,000 population in 2021/2022 [NICE, 2015; UKHSA, 2022].
  • Asymptomatic carriage of C. difficile:
    • Children under 8 years old — in healthy newborn babies and infants, asymptomatic colonisation of C. difficile is very common. 25-35% of infants will be asymptomatically colonised with C. difficile in their first year of life, dropping to 15% in infants aged 1-8 years [Smits, 2016].
    • Adults — asymptomatic colonisation of C. difficile occurs in less than 2% of adults without recent healthcare contact, 5–7% of residents of long-term care facilities, and 3–26% of adult inpatients in acute care hospitals [McDonald, 2018].

What is the prognosis?

  • Most people with antibiotic-associated diarrhoea experience mild, self-limiting symptoms and recover completely with supportive measures and antibiotic withdrawal [Pimentel, 2010].
  • However, in cases of diarrhoea caused by Clostridioides difficile, some people may develop severe and sometimes fatal disease. Risk factors for mortality from C. difficile infection (CDI) include higher age (greater than 65 years old), comorbidities, acute renal failure, infection with ribotype 027, leukocytosis, hypoalbuminaemia, and recurrent rather than non-recurrent CDI [McDonald, 2018; Enoch, 2020]. 
    •  From 2021 to 2022 the case fatality rate of CDI in England was 13.7% and was highest amongst men aged 85 years and over (26.1%), and women aged 85 and over (19.1%) [UKHSA, 2023a].
  • The recurrence rate for CDI is high after the initial episode: around 20% for the first episode and 40–65% after the second episode in hospitalised patients [BMJ Best Practice, 2022; Song, 2019].
    • Factors associated with an increased risk of recurrent CDI include higher age (greater than 65 years old), previous recurrence of CDI, prior hospitalization, and the start of proton pump inhibitors during or after CDI diagnosis [van Rossen, 2021].

What are the complications?

  • The complications of Clostridioides difficile infection can be severe and include [Winslow, 2014; Steele, 2015; Hassoun, 2018]:  
    • Pseudomembranous colitis.
    • Toxic megacolon.
    • Perforation of the colon.
    • Peritonitis.
    • Sepsis.
    • Death.
  • Rarely, diarrhoea may be absent in severe cases due to the infection causing paralytic ileus and abdominal distension [Burke, 2014].  
  • Risk factors for complicated C. difficile-associated disease include older age, leukocytosis, renal failure, recurrent rather than non-recurrent CDI, and comorbidities [McDonald, 2018; Enoch, 2020].

Diagnosis

When should I suspect antibiotic-associated diarrhoea?

  • Suspect Clostridioides difficile infection (CDI) if risk factors are present (especially if the person is elderly). 
  • There are no clinical symptoms that are specific to CDI, and diagnosis is dependent on the results of appropriate tests. However, symptoms of CDI include:
    • Diarrhoea (common) — can range from loose stool to severe diarrhoea, often mucoid with minimal blood. The absence of diarrhoea may be linked to more severe CDI complications (for example toxic megacolon).
    • Abdominal pain (common) — may be absent or range from mild to severe. 
    • Fever (common).
    • Abdominal tenderness (common) — especially in the lower abdomen.
    • Nausea and vomiting (uncommon).
    • Abdominal distension (uncommon).
    • Symptoms of shock (uncommon) — symptoms of fulminant CDI include systemic symptoms (such as tachycardia and hypotension) combined with severe abdominal pain and tenderness.

Basis for recommendation

These recommendations are based on the British Medical Journal (BMJ) Best Practice guide Clostridioides difficile-associated disease [BMJ Best Practice, 2022] and expert opinion in narrative reviews Treatment of Clostridioides (Clostridium) difficile infection [Jarmo, 2020] and Clostridioides difficile Infection: Update on Management [Mounsey, 2020].

How should I assess someone presenting with suspected antibiotic-associated diarrhoea?

  • Assess the severity of the symptoms and consider whether hospital admission is appropriate.
    • For more information on assessing symptoms (including the risk of dehydration) and when to admit, see the CKS topic on Diarrhoea - adult's assessment.
  • Exclude other potential causes of diarrhoea or contributing factors.
  • Consider the possibility of CDI if Risk factors are present.
    • Check which antibiotics were prescribed and the duration of treatment.
      • Clostridioides difficile infection (CDI) is more common with certain antibiotics (for more information, see Risk factors).
    • There are no clinical symptoms that are specific to CDI, and physical examination may show anything from little or no abdominal pain to signs of an acute abdomen.
    • Check for any history of previous CDI — as the rate of recurrence is high.
    • Send a stool sample to test for C. difficile (for further information, see Investigations).
    • Check whether other cases of CDI have been reported recently — for example, within the care home or in the hospital ward from which the individual has been recently discharged. C. difficile-associated disease can occur in outbreaks.

Basis for recommendation

These recommendations are based on the British Medical Journal (BMJ) Best Practice guide Clostridioides difficile associated disease [BMJ Best Practice, 2022], the National Institute for Health and Care Excellence (NICE) guidelines Clostridioides difficile infection: antimicrobial prescribing [NICE, 2021] and Clostridium difficile infection: risk with broad-spectrum antibiotics [NICE, 2015], the Health Protection Scotland guide Guidance on prevention and control of Clostridium difficile Infection (CDI) in health and social care settings in Scotland [Health Protection Scotland, 2017], and expert opinion in the narrative reviews Clostridium difficile colitis: A clinical review [Ong, 2017], Clostridioides difficile infection [Guh, 2018], and Clostridioides difficile Infection: Update on Management [Mounsey, 2020].

How should I investigate suspected Clostridioides difficile infection?

For adults with suspected Clostridioides difficile infection (CDI):

  • Take stool samples from all symptomatic people where CDI is suspected and the symptoms cannot be attributed to an underlying condition (such as inflammatory colitis) or therapy (such as laxatives).
    • The stool sample must take on the shape of the container and ideally be at least one-quarter filled (to indicate the patient has diarrhoea) before it is sent to the laboratory for testing. 
    • Do not wait to initiate sampling or testing as any delay may increase the severity of the disease and the risk of C. difficile transmission.
    • Ensure the following details are stated on the request form:
      • Clinical features (for example, nature and duration of symptoms).
      • Recent antibiotic or proton pump inhibitor, or hospital admission.  
      • Contact with other affected individuals or outbreak. 
      • Underlying illness. 
  • Check the full blood count and serum creatinine in order to help assess the severity of CDI. 
  • Consider re-testing if the first test is negative and there is a strong clinical suspicion of CDI — seek advice from a microbiologist or infection control specialist. 
  • Do not re-test people with a positive CDI if they are still symptomatic within the same episode. 
  • Only re-test to confirm recurrent CDI if the symptoms resolve and then recur.
  • Do not test to confirm cure as people can remain C. difficile positive even after successful treatment.
  • For more information on how to advise the person to take a stool sample, see the section on Collection of stool samples in the CKS topic on Diarrhoea - adult's assessment.

Severity of Clostridioides difficile infection

The severity of Clostridioides difficile infection (CDI) can be defined as:

  • Non-severe — white cell count lower than 15 x 109/L, a rise in serum creatinine of 50% or less above the person's baseline level, and a core body temperature of 38.5°C (or lower) at presentation.
  • Severe — defined by: 
    • One of the following features at presentation:
      • White cell count of 15 x 109/L  or higher.
      • A rise in serum creatinine levels greater than 50% above baseline.
      • Core body temperature above 38.5°C.
  • Fulminant (previously known as life-threatening or severe-complicated) — defined by any of the following features attributed to CDI:
    • Hypotension.
    • Evidence of septic shock.
    • Evidence of ileus, toxic megacolon or bowel perforation.
    • Rapid deterioration in clinical condition.

Basis for recommendation

These recommendations are based on the Department of Health and Social Care guideline Updated guidance on the diagnosis and reporting of Clostridium difficile [DH, 2012], the British Medical Journal (BMJ) Best Practice guide Clostridioides difficile associated disease [BMJ Best Practice, 2022], the Health Protection Scotland guide Guidance on prevention and control of Clostridium difficile Infection (CDI) in health and social care settings in Scotland [Health Protection Scotland, 2017], the Irish Department of Health guideline Surveillance, diagnosis and management of Clostridium difficile infection in Ireland [An Roinn Slainte, 2014], the European Society of Clinical Microbiology and Infectious Diseases guidelines Update of the diagnostic guidance document for Clostridium difficile infection [Crobach, 2016] and 2021 update on the treatment guidance document for Clostridioides difficile infection in adults [van Prehn, 2021], the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA) guideline Clinical Practice Guidelines for Clostridium difficile infection in adults and children: 2017 update [McDonald, 2018], the British Society of Gastroenterology guideline Guidelines for the investigation of chronic diarrhoea in adults: British Society of Gastroenterology, 3rd edition [Arasaradnam, 2018], the National Institute for Health and Care Excellence (NICE) guideline Clostridioides difficile infection: antimicrobial prescribing [NICE, 2021], and expert opinion in the narrative reviews Clostridium difficile colitis: A clinical review [Ong, 2017], Clostridioides difficile infection [Guh, 2018], Clostridioides difficile Infection: Update on Management [Mounsey, 2020], and Management of Clostridioides difficile infection in adults and challenges in clinical practice: review and comparison of current IDSA/SHEA, ESCMID and ASID guidelines [Bishop, 2022].

Laboratory confirmation of CDI

  • British Society of Gastroenterology and Department of Health guidelines state that when testing for CDI, a standardised two-stage approach is recommended. This identifies the organism with glutamate dehydrogenase enzyme immunoassay (EIA), nucleic acid amplification testing, or PCR; then toxin EIA is performed to identify active C. difficile toxin production. This combination of a sensitive test followed by a specific test produces high negative and positive predictive values when the test results agree [DH, 2012; Arasaradnam, 2018; Mounsey, 2020].
  • When interpreting the laboratory results [DH, 2012]:
    • If GDH EIA (or NAAT) is positive, and toxin EIA is positive (positive predictive value [PPV] = 91.4%), then C. difficile is most likely to be present.
    • If GDH EIA is negative, and toxin EIA is negative (negative predictive value [NPV] = 98.9%) then C. difficile is very unlikely to be present.
    • If GDH EIA (or NAAT) is positive, and toxin EIA is negative, then C. difficile could be present (potential C. difficile excretors).
  • It is important to only send stool samples from people with new, unexplained diarrhoea, as asymptomatic carriage is common and can lead to false positives. Several guidelines recommend only sending a stool sample after the person has 3 or more unformed stools in 24 hours [BMJ Best Practice, 2022]. However, this is based on low quality evidence, and testing stool from symptomatic patients as soon as possible, because the results may be used to reduce the risk of transmission of C. difficile, is recommended [DH, 2012; An Roinn Slainte, 2014].
  • The recommendation to describe the clinical features is pragmatic and based on information in a Health Protection Scotland guideline [Health Protection Scotland, 2017].

Re-testing

  • Re-test only if the first test is negative and there is a strong clinical suspicion of CDI — seek specialist advice.
    • CKS recommends seeking advice from a microbiologist on whether retesting is indicated, based on opinion from experts:
      • Health Protection Scotland guidance on obtaining stool specimens notes that a negative test result does not necessarily exclude infection, particularly if clinical symptoms are highly indicative, and advises discussion with a consultant medical microbiologist or infection control doctor [Health Protection Scotland, 2017].
      • European diagnostic guidance for C. difficile and North American clinical practice guidelines for CDI also discuss the potential value of repeated testing after a negative sample if there is a high clinical suspicion [Crobach, 2016; McDonald, 2018]. 
  • Do not re-test people with a positive CDI if they are still symptomatic during the same episode.
    • If there has been a positive sample, repeated testing during the same episode of diarrhoea is not recommended by Health Protection Scotland guidelines on prevention and treatment of CDI [Health Protection Scotland, 2017]. This is consistent with Irish Department of Health guidelines that advise against retesting when a person is on treatment for CDI [An Roinn Slainte, 2014], and North American guidelines that do not recommend repeat testing (within 7 days) during the same episode of diarrhoea [McDonald, 2018].
  • Only re-test to confirm recurrent CDI if the symptoms resolve and then recur.
    • North American guidelines advise testing (including toxin detection) if recurrent CDI is suspected after diarrhoea has stopped with successful treatment  [McDonald, 2018]. This is consistent with Health Protection Scotland and the Irish Department of Health who recommend repeat testing if recurrent diarrhoea occurs after a symptom-free interval in a person with recent CDI [An Roinn Slainte, 2014; Health Protection Scotland, 2017].

Severity of CDI

  • There is currently no consensus on the classification of CDI severity [NICE, 2021]. Previous guidelines have suggested that severity should be defined as mild, moderate, severe, or life threatening. It is now believed that severe and non-severe are more helpful as definitions, and the term fulminant brings the classification closer in line with current American and European guidelines [Bishop, 2022; NICE, 2021]. Although the only universally agreed on biomarker for assessing severity is white cell count, other markers for severity are based on the European Society of Clinical Microbiology and Infectious Diseases guidelines [van Prehn, 2021].

Management

Scenario: Management of antibiotic associated diarrhoea

From age 18 years onwards.

How should I manage antibiotic-associated diarrhoea if Clostridioides difficile infection is not suspected, or the C. difficile test result is negative?

For people in whom Clostridioides difficile infection is not suspected, or the C. difficile test result is negative:

  • Assess the severity of the condition and consider whether hospital admission is appropriate (for further information, see the section on Admission or referral in the CKS topic on Diarrhoea - adult's assessment). 
  • If hospital admission is not required:
    • Stop the antibiotic, if this is appropriate.
      • Seek specialist advice if it is not appropriate to stop the antibiotic and the diarrhoea is severe.
    • Manage fluid loss and symptoms as for acute gastroenteritis (for further information, see the CKS topic on Gastroenteritis).
  • If the C. difficile toxin test result is negative, consider seeking specialist advice and retesting if there is a strong clinical suspicion of C. difficile infection or if in doubt.

Basis for recommendation

These recommendations are based on the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA) guideline Clinical Practice Guidelines for Clostridium difficile infection in adults and children: 2017 update [McDonald, 2018], the European Society of Clinical Microbiology and Infectious Diseases guidelines Update of the diagnostic guidance document for Clostridium difficile infection [Crobach, 2016], the Public Health England (PHE) guideline SMI B10: processing of faeces for Clostridium difficile [PHE, 2018], expert opinion in the narrative review Probiotics for antibiotic-associated diarrhea and Clostridium difficile infection: A review of clinical effectiveness [CADTH, 2018], and is pragmatic based on what CKS considers to be good clinical practice.

Consider whether hospital admission is appropriate

This recommendation is pragmatic and based on what CKS considers to be good clinical practice.

Repeat testing people with a negative result

North American clinical practice guidelines for CDI from the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA) advise considering repeat testing in symptomatic people with a negative test for whom there is a high clinical suspicion of CDI [McDonald, 2018]. This is consistent with advice in a diagnostic guidance document for CDI from the European Society of Clinical Microbiology and Infectious Diseases [Crobach, 2016] and Public Health England, who note that one-off negative results can occur [PHE, 2018].

How should I manage a confirmed or suspected Clostridioides difficile infection?

  • Assess the severity of the condition and consider whether hospital admission is appropriate.
    • People with features of severe Clostridioides difficile infection (CDI) should be admitted to hospital.
  • For people who have confirmed or suspected non-severe CDI:
    • If awaiting a C. difficile test result and it is highly suspicious that the person has CDI, assess the severity and consider seeking specialist advice on whether an empirical antibiotic should be offered.  
    • If CDI is confirmed, consider seeking prompt specialist advice from a microbiologist or infectious disease specialist before prescribing an antibiotic. As a guide, NICE recommends: 
      • For the initial episode of non-severe: vancomycin 125 mg orally four times a day for 10 days. 
      • Second-line antibiotic advice for a first episode of non-severe CDI: fidaxomicin 200 mg orally twice a day for 10 days. 
      • A repeat course of antibiotics is necessary for further disease episodes:
        • Fidaxomicin 200 mg orally twice a day for 10 days, if the new episode is within 12 weeks of initial symptom resolution (relapse).
        • Vancomycin 125 mg orally four times a day for 10 days or fidaxomicin 200 mg orally twice a day for 10 days, if the new episode is more than 12 weeks of initial symptom resolution (recurrence).
      • For people with CDI who cannot take oral medicines, seek specialist advice about alternative antibiotics.  
      • Use clinical judgement to determine whether antibiotic treatment for CDI is ineffective. It is not usually possible to determine this until day 7 as diarrhoea may take 1 to 2 weeks to resolve.
    • Assess whether there is a risk of a C. difficile outbreak — for example, among other elderly residents in a care or nursing home.
    • Stop any antibiotics not being used for treating CDI, if this is appropriate. Seek specialist advice if this is not possible and the diarrhoea is severe.
    • Manage fluid loss as for acute gastroenteritis (for further information, see the CKS topic on Gastroenteritis).
    • Avoid the use of antimotility drugs (such as loperamide) to treat diarrhoeal symptoms. If possible, avoid other drugs with anti-peristaltic effects (such as opioids).
    • Review the need to continue with any of the following treatments:
      • Proton pump inhibitors.
      • Medicines with gastrointestinal activity such as laxatives.
      • Medicines which may cause problems if people are dehydrated, such as nonsteroidal anti-inflammatory drugs, angiotensin-converting enzyme inhibitors, angiotensin-2 receptor antagonists, and diuretics.
    • If the person's condition has improved considerably or has resolved without treatment, consider the possibility of a false-positive test result.
    • If antibiotics have been started for suspected CDI, and subsequent stool sample tests do not confirm CDI, consider stopping these antibiotics. 

What information and advice can I give someone with a suspected or confirmed Clostridioides difficile infection?

  • Give advice on hygiene measures to minimize the spread of Clostridioides difficile (see the CKS topic on Gastroenteritis).
    • Note that alcohol-based hand rubs are not effective in removing C. difficile spores.
  • Advise people that:
    • The diarrhoea should resolve in 1–2 weeks. It is not usually possible to determine whether antibiotic treatment is effective until day 7. 
    • They should seek immediate medical help if symptoms worsen rapidly or significantly at any time.
    • They remain infectious while they are still ill and have symptoms.
    • They should not return to work or school until they have been free from diarrhoea for 48 hours. If medication is prescribed, they should ensure that the full course is completed and there is no further diarrhoea or vomiting for 48 hours afterwards.
    • Once recovered, they should seek medical advice if they develop unexplained diarrhoea, as there is a high rate of recurrence with C. difficile infection.
  • Offer written information, such as NHS information on Clostridium difficile infection, available at www.nhs.uk.

When should I refer someone with Clostridioides difficile infection?

  • Refer people with suspected or confirmed Clostridioides difficile infection (CDI) 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 fulminant infection.
  • Consider referring people to hospital if they could be at high risk of complications or recurrence because of individual factors such as age, frailty, or comorbidities. 
  • Consider referral of people with recurrent CDI, who have had at least two previous episodes of CDI, to a gastroenterologist. 

Basis for recommendation

These recommendations are based on the National Institute for Health and Care Excellence guidelines Clostridioides difficile infection: antimicrobial prescribing [NICE, 2021] and Faecal microbiota transplant for recurrent Clostridioides difficile infection [NICE, 2022], the British Medical Journal (BMJ) Best Practice guide Clostridioides difficile associated disease [BMJ Best Practice, 2022], the Health Protection Scotland guide Guidance on prevention and control of Clostridium difficile Infection (CDI) in health and social care settings in Scotland [Health Protection Scotland, 2017], the Irish Department of Health guideline Surveillance, diagnosis and management of Clostridium difficile infection in Ireland [An Roinn Slainte, 2014], the European Society of Clinical Microbiology and Infectious Diseases guidelines  2021 update on the treatment guidance document for Clostridioides difficile infection in adults [van Prehn, 2021], the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA) guideline Clinical Practice Guidelines for Clostridium difficile infection in adults and children: 2017 update [McDonald, 2018], the Public Health England (PHE) guideline SMI B10: processing of faeces for Clostridium difficile [PHE, 2018], and expert opinion in the narrative reviews Practice parameters for the management of Clostridium difficile infection [Steele, 2015], Common questions about Clostridium difficile infection [Winslow, 2014], Recognition and management of Clostridium difficile in older adults [Sams, 2017], Clostridium difficile colitis: A clinical review [Ong, 2017], Clostridioides difficile infection [Guh, 2018], Clostridioides difficile Infection: Update on Management [Mounsey, 2020], and Management of Clostridioides difficile infection in adults and challenges in clinical practice: review and comparison of current IDSA/SHEA, ESCMID and ASID guidelines [Bishop, 2022].

Assess the risk of a C. difficile outbreak
  • This recommendation is extrapolated from expert opinion in a review article that outlines the need for awareness of the potential for outbreaks of CDI in vulnerable populations [Sams, 2017]. Public Health England notes the association with outbreaks in hospitals and extended care facilities for the elderly [PHE, 2018].  
Monitoring and reassessment 
  • Previous guidelines suggested daily review of people with CDI to monitor for signs of increasing severity of disease. This is usual for hospital settings, but in the community, people should be given appropriate safety netting advice to return for reassessment only if needed. This is based on the NICE guideline [NICE, 2021] and is pragmatic based on what CKS considers good medical practice.
Advise on the time course of the illness
  • The recommendations about the duration of illness are based on the NHS A-Z Clostridium difficile (C. diff) infection [NHS, 2022].
  • Information on infection risk and avoidance of school or work is extrapolated from PHE guidance on health protection in schools and other childcare facilities for diarrhoea and vomiting [UKHSA, 2023b] and patient information on leaving hospital for people who have had C. difficile during admission [DH, 2011]. 
Consider the possibility of a false-positive test result
  • C. difficile may be an incidental finding in stools of people with diarrhoea due to another cause and indiscriminate testing increases the likelihood of a false positive result (examples of inappropriate testing in one study included people without diarrhoea and those who had recently used laxatives). 
Use of probiotics
  • Probiotics are thought to repopulate the gastrointestinal tract and limit the growth of C. difficile [Guh, 2018]. However, they are not recommended by NICE on the grounds of insufficient evidence [NICE, 2021], and a review of guidelines from international organisations found that most did not support the use of probiotics for prevention or treatment of CDI, and that their use may have significant adverse effects or delay microbiome reconstitution after antibiotic treatment [Bishop, 2022]. 
Give advice on hygiene measures
  • Hygiene measures are important because the spores of C. difficile are transmissible and can contaminate the environment, where they survive for a long period of time as they are resistant to heat, acid, and chemicals. The spores can be picked up by contact with a person or contaminated surface and then swallowed. Carers of a person with CDI are easily contaminated and hand washing with liquid soap and water is advised to remove spores and prevent their spread as alcohol hand rubs do not kill spores [Steele, 2015; Health Protection Scotland, 2017]. 
Referral
  • The recommendation to refer people who have had at least 3 episodes of CDI is based on NICE guidelines [NICE, 2021; NICE, 2022], which suggest consideration of faecal transplantation for people with 2 or more recurrent infections, and is pragmatic based on what CKS considers good medical practice.

Prescribing information

Important aspects of prescribing information relevant to primary healthcare are covered in this section specifically for the drugs recommended in this CKS topic. For further information on contraindications, cautions, drug interactions, and adverse effects, see the electronic Medicines Compendium (eMC), or the British National Formulary (BNF).

Vancomycin

What are the cautions and contraindications with vancomycin?

  • Do not prescribe vancomycin in people with:
    • Known vancomycin hypersensitivity.
  • Prescribe vancomycin with caution in people with:
    • Inflammatory disorders of the intestinal mucosa or Clostridioides difficile-induced pseudomembranous colitis — these patients may be at risk for the development of adverse reactions, especially if there is a concomitant renal impairment. The greater the renal impairment, the greater the risk of developing the adverse reactions associated with the parenteral administration of vancomycin. Monitoring of serum vancomycin concentrations of patients with inflammatory disorders of the intestinal mucosa should be performed.
    • Underlying renal dysfunction — serial monitoring of renal function should be performed when treating patients with underlying renal dysfunction or patients receiving concomitant therapy with an aminoglycoside or other nephrotoxic drugs.
    • Underlying hearing loss — serial tests of auditory function may be helpful in order to minimise the risk of ototoxicity in patients with underlying hearing loss, or who are receiving concomitant therapy with an ototoxic agent such as an aminoglycoside.

[EMC, 2022; BNF, 2023]

What are the adverse effects of vancomycin?

  • Blood disorders — reversible neutropenia, agranulocytosis, eosinophilia, thrombocytopenia, and pancytopenia (rare).
  • Immune disorders — hypersensitivity and anaphylactic reactions (rare)
  • Ear disorders — transient loss of hearing (uncommon), vertigo, tinnitus, dizziness (rare).
  • Cardiac disorders — cardiac arrest (very rare).
  • Vascular disorders — decrease in blood pressure (common) and vasculitis (rare).
  • Respiratory disorders — dyspnoea and stridor (common).
  • Gastrointestinal disorders — nausea (rare), pseudomembranous enterocolitis (very rare), vomiting, and diarrhoea.
  • Skin disorders — flushing of the upper body (“red man syndrome”), exanthema, mucosal inflammation, pruritus, urticaria (common), exfoliative dermatitis, Stevens-Johnson syndrome, toxic epidermal necrolysis (TEN), linear IgA bullous dermatosis (very rare), eosinophilia and systemic symptoms (DRESS syndrome), and AGEP (acute generalized exanthematous pustulosis).
  • Renal disorders — renal insufficiency manifested primarily by increased serum creatinine and serum urea (common), interstitial nephritis, acute renal failure (rare), and acute tubular necrosis. 
  • Other adverse effects — phlebitis, redness of the upper body and face (common), drug fever, shivering, and pain and muscle spasm of the chest and back muscles (rare).

[EMC, 2022; BNF, 2023]

What drug interactions are associated with vancomycin?

Potential interactions with vancomycin include:

  • Ototoxic medication — concurrent and/or sequential systemic or topical use of other potentially ototoxic requires careful monitoring.
  • Nephrotoxic medication — concurrent and/or sequential systemic or topical use of other potentially nephrotoxic requires careful monitoring.

[EMC, 2022; BNF, 2023]

Are there issues prescribing vancomycin in pregnancy and breastfeeding?

Pregnancy

  • The manufacturer advises that it should only be used if the benefit outweighs the risk.

Breastfeeding

  • Vancomycin is excreted in human milk and may result in disorders of the intestinal flora with diarrhoea, fungus infection and possibly sensitisation in breastfed infants. In premature and young neonates, risk of systemic effects cannot be excluded. 
  • Vancomycin should only be prescribed to breastfeeding mothers if other antibiotics have failed, and it is recommended that breastfeeding be halted during vancomycin treatment.

[EMC, 2022; BNF, 2023]

Fidaxomicin

What are the cautions and contraindications with fidaxomicin?

  • Do not prescribe fidaxomicin in people with:
    • Known fidaxomicin hypersensitivity.
  • Prescribe fidaxomicin with caution in people with:
    • Renal and hepatic impairment.
    • Known macrolides allergy — some patients with hypersensitivity reactions reported having an allergy to macrolides.
    • Pseudomembranous colitis or fulminant Clostridioides difficile infection.

[BNF, 2023; EMC, 2023]

What are the adverse effects of fidaxomicin?

  • Immune system disorders — rash, pruritus (uncommon), and hypersensitivity reactions (angioedema and dyspnoea).
  • Metabolism and nutrition disorders — decreased appetite (uncommon).
  • Nervous system disorders — dizziness, headache, and dysgeusia (uncommon).
  • Gastrointestinal disorders — vomiting, nausea, constipation (common), abdominal distention, flatulence, and dry mouth (uncommon).

[BNF, 2023; EMC, 2023]

What drug interactions are associated with fidaxomicin?

Potential interactions with fidaxomicin include:

  • P-glycoprotein inhibitors — co-administration of potent P-glycoprotein inhibitors such as ciclosporin, ketoconazole, erythromycin, clarithromycin, verapamil, dronedarone and amiodarone is not recommended. If co-administered, caution is advised.

[BNF, 2023; EMC, 2023]

Pregnancy and breastfeeding

Pregnancy

  • There are no data on fidaxomicin use in pregnant women, the manufacturer advises that it should be avoided. 

Breastfeeding

  • It is unknown if fidaxomicin is excreted in breast milk. The manufacturer advises that a decision must be made to discontinue breastfeeding or abstain from fidaxomicin therapy taking into account the benefit of breastfeeding for the child and the benefit of therapy for the woman.

[BNF, 2023; EMC, 2023]

Supporting evidence

This CKS topic is largely based on the National Institute for Health and Care Excellence guideline Clostridioides difficile infection: antimicrobial prescribing [NICE, 2021]; the Department of Health and Social Care guideline Updated guidance on the diagnosis and reporting of Clostridium difficile [DH, 2012]; the British Medical Journal (BMJ) Best Practice guide Clostridioides difficile associated disease [BMJ Best Practice, 2022]; and expert opinion in the narrative reviews Practice parameters for the management of Clostridium difficile infection [Steele, 2015], Common questions about Clostridium difficile infection [Winslow, 2014], Recognition and management of Clostridium difficile in older adults [Sams, 2017], Clostridium difficile colitis: A clinical review [Ong, 2017], Clostridioides difficile infection [Guh, 2018], Clostridioides difficile Infection: Update on Management [Mounsey, 2020], and Management of Clostridioides difficile infection in adults and challenges in clinical practice: review and comparison of current IDSA/SHEA, ESCMID and ASID guidelines [Bishop, 2022]. The rationale for the primary care diagnosis and management of antibiotic-associated diarrhoea (including Clostridium difficile infection) is discussed in the relevant basis for recommendation sections.

How this topic was developed

This section briefly describes the processes used in developing and updating this topic. Further details on the full process can be found in the About Us section and on the Clarity Informatics website.

Search strategy

A literature search was conducted for guidelines and systematic reviews on primary care management of antibiotic associated diarrhoea.

Search dates

January 2019 - June 2023

Key search terms

The terms listed below are the core search terms that were used for EBSCOhost MEDLINE (searched 18th January 2019). These were combined with filters to identify guidelines, systematic reviews and primary care relevant literature in EBSCOhost MEDLINE. The strategy was adapted for The Cochrane Library databases. 

S9    S3 OR S4 OR S5 OR S6 OR S7 OR S8 
S8    AB ( (pseudomembranous N2 (colitis or enterocolitis)) ) OR TI ( (pseudomembranous N2 (colitis or enterocolitis)) ) 
S7    (MH "Enterocolitis, Pseudomembranous") 
S6    AB clostridium difficile OR TI clostridium difficile 
S5    (MH "Clostridium difficile") 
S4    AB (diarrh* N3 antibiotic*) OR TI (diarrh* N3 antibiotic*) 
S3    S1 AND S2 
S2    (MH "Diarrhea+") 
S1    (MH "Anti-Bacterial Agents+") 

Sources of guidelines

Sources of systematic reviews and meta-analyses

  • The Cochrane Library:
    • Systematic reviews
    • Protocols
    • Database of Abstracts of Reviews of Effects
  • Medline (with systematic review filter)
  • EMBASE (with systematic review filter)

Sources of health technology assessments and economic appraisals

Sources of randomized controlled trials

  • The Cochrane Library:
    • Central Register of Controlled Trials
  • Medline (with randomized controlled trial filter)
  • EMBASE (with randomized controlled trial filter)

Sources of evidence based reviews and evidence summaries

Sources of national policy

Patient experiences

Sources of medicines information

The following sources are used by CKS pharmacists and are not necessarily searched by CKS information specialists for all topics. Some of these resources are not freely available and require subscriptions to access content.

Stakeholder engagement

Our policy

The external review process is an essential part of CKS topic development. Consultation with a wide range of stakeholders provides quality assurance of the topic in terms of:

  • Clinical accuracy.
  • Consistency with other providers of clinical knowledge for primary care.
  • Accuracy of implementation of national guidance (in particular NICE guidelines).
  • Usability.

Principles of the consultation process

  • The process is inclusive and any individual may participate.
  • To participate, an individual must declare whether they have any competing interests or not. If they do not declare whether or not they have competing interests, their comments will not be considered.
  • Comments received after the deadline will be considered, but they may not be acted upon before the clinical topic is issued onto the website.
  • Comments are accepted in any format that is convenient to the reviewer, although an electronic format is encouraged.
  • External reviewers are not paid for commenting on the draft topics.
  • Discussion with an individual or an organization about the CKS response to their comments is only undertaken in exceptional circumstances (at the discretion of the Clinical Editor or Editorial Steering Group).
  • All reviewers are thanked and offered a letter acknowledging their contribution for the purposes of appraisal/revalidation.
  • All reviewers are invited to be acknowledged on the website. All reviewers are given the opportunity to feedback about the external review process, enabling improvements to be made where appropriate.

Stakeholders

  • Key stakeholders identified by the CKS team are invited to comment on draft CKS topics. Individuals and organizations can also register an interest to feedback on a specific topic, or topics in a particular clinical area, through the Getting involved section of the Clarity Informatics website.
  • Stakeholders identified from the following groups are invited to review draft topics:
    • Experts in the topic area.
    • Professional organizations and societies (for example, Royal Colleges).
    • Patient organizations, Clarity has established close links with groups such as Age UK and the Alzheimer’s Society specifically for their input into new topic development, review of current topic content and advice on relevant areas of expert knowledge.
    • Guideline development groups where the topic is an implementation of a guideline.
    • The British National Formulary team.
    • The editorial team that develop MeReC Publications.
  • Reviewers are provided with clear instructions about what to review, what comments are particularly helpful, how to submit comments, and declaring interests.

Patient engagement

Clarity Informatics has enlisted the support and involvement of patients and lay persons at all stages in the process of creating the content which include:

  • Topic selection
  • Scoping of topic
  • Selection of clinical scenarios
  • First draft internal review
  • Second draft internal review
  • External review
  • Final draft and pre-publication

Our lay and patient involvement includes membership on the editorial steering group, contacting expert patient groups, organizations and individuals.

Evidence exclusion criteria

Our policy

Scoping a literature search, and reviewing the evidence for CKS is a methodical and systematic process that is carried out by the lead clinical author for each topic. Relevant evidence is gathered in order that the clinical author can make fully informed decisions and recommendations. It is important to note that some evidence may be excluded for a variety of reasons. These reasons may be applied across all CKS topics or may be specific to a given topic.

Studies identified during literature searches are reviewed to identify the most appropriate information to author a CKS topic, ensuring any recommendations are based on the best evidence. We use the principles of the GRADE and PICOT approaches to assess the quality of published research. We use the principles of AGREE II to assess the quality of published guidelines.

Standard exclusions for scoping literature:

  • Animal studies
  • Original research is not written in English

Possible exclusions for reviewed literature:

  • Sample size too small or study underpowered
  • Bias evident or promotional literature
  • Population not relevant
  • Intervention/treatment not relevant
  • Outcomes not relevant
  • Outcomes have no clear evidence of clinical effectiveness
  • Setting not relevant
  • Not relevant to UK
  • Incorrect study type
  • Review article
  • Duplicate reference

Organizational, behavioural and financial barriers

Our policy

The CKS literature searches take into consideration the following concepts, which are discussed at the initial scoping of the topic.

  • Feasibility
    • Studies are selected depending on whether the intervention under investigation is available in the NHS and can be practically and safely undertaken in primary care.
  • Organizational and Financial Impact Analysis
  • Studies are selected and evaluated on whether the intervention under investigations may have an impact on local clinical service provision or national impact on cost for the NHS. The principles of clinical budget impact analysis are adhered to, evaluated and recorded by the author. The following factors are considered when making this assessment and analysis.
    • Eligible population
    • Current interventions
    • Likely uptake of new intervention or recommendation
    • Cost of the current or new intervention mix
    • Impact on other costs
    • Condition-related costs
    • In-direct costs and service impacts
    • Time dependencies
  • Cost-effectiveness or cost-benefit analysis studies are identified where available. 

We also evaluate and include evidence from NICE accredited sources which provide economic evaluations of recommendations, such as NICE guidelines. When a recommended action may not be possible because of resource constraints, this is explicitly indicated to healthcare professionals by the wording of the CKS recommendation.

Declarations of interest

Our policy

Clarity Informatics requests that all those involved in the writing and reviewing of topics, and those involved in the external review process to declare any competing interests. Signed copies are securely held by Clarity Informatics and are available on request with the permission of the individual. A copy of the declaration of interest form which participants are asked to complete annually is also available on request. A brief outline of the declarations of interest policy is described here and full details of the policy is available on the Clarity Informatics website. Declarations of interests of the authors are not routinely published, however competing interests of all those involved in the topic update or development are listed below. Competing interests include:

  • Personal financial interests
  • Personal family interest
  • Personal non-financial interest
  • Non-personal financial gain or benefit

Although particular attention is given to interests that could result in financial gains or losses for the individual, competing interests may also arise from academic competition or for political, personal, religious, and reputational reasons. An individual is not obliged to seek out knowledge of work done for, or on behalf of, the healthcare industry within the departments for which they are responsible if they would not normally expect to be informed.

Who should declare competing interests?

Any individual (or organization) involved in developing, reviewing, or commenting on clinical content, particularly the recommendations should declare competing interests. This includes the authoring team members, expert advisers, external reviewers of draft topics, individuals providing feedback on published topics, and Editorial Steering Group members. Declarations of interest are completed annually for authoring team and editorial steering group members, and are completed at the start of the topic update and development process for external stakeholders.

Competing interests declared for this topic:

None.

References

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  • Health Protection Scotland (2017) Guidance on prevention and control of Clostridium difficile Infection (CDI) in health and social care settings in Scotland. Scottish Health Protection Network. Scottish guidance no 6 2017 edition. Health Protection Scotland. http://www.hps.scot.nhs.uk [Free Full-text]
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  • NICE (2022) Faecal microbiota transplant for recurrent Clostridioides difficile infection. National Institute for Health and Care Excellence. https://www.nice.org.uk [Free Full-text]
  • Ong, G.K., Reidy, T.J., Huk, M.D. and Lane, F.R. (2017) Clostridium difficile colitis: A clinical review. American Journal of Surgery 213(3), 565-571. [Abstract]
  • PHE (2018) Guidance. SMI B10: processing of faeces for Clostridium difficile. Public Health England. http://www.gov.uk [Free Full-text]
  • Pimentel, R. and Choure, A. (2010) Antibiotic-associated diarrhea and Clostridium Difficile. Cleveland Clinic Journal of Medicine. http://www.clevelandclinicmeded.com [Free Full-text]
  • Sams, A.W. and Kennedy-Malone, L. (2017) Recognition and management of Clostridium difficile in older adults. Nurse Practitioner 42(5), 50-55. [Abstract]
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  • Song, J.H. and Kim, Y.S. (2019) Recurrent Clostridium difficile Infection: Risk Factors, Treatment, and Prevention. Gut and Liver 13(1), 16-24. [Free Full-text]
  • Steele, S.R., McCormick, J., Melton, G.B., et al. (2015) Practice parameters for the management of Clostridium difficile infection. Diseases of the Colon and Rectum 58(1), 10-24. [Abstract]
  • UKHSA (2022) Annual epidemiological commentary: Gram-negative, MRSA, MSSA bacteraemia and C. difficile infections, up to and including financial year 2021 to 2022. UK Health Security Agency. https://www.gov.uk [Free Full-text]
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  • van Prehn, J., Reigadas, E., Vogelzang, E.H., et al. (2021) European Society of Clinical Microbiology and Infectious Diseases: 2021 update on the treatment guidance document for Clostridioides difficile infection in adults. Clinical Microbiology and Infection 27(Supp 2), S1-S21. [Abstract] [Free Full-text]
  • van Rossen, T.M., Ooijevaar, R.E., Vandenbroucke-Grauls, C.M.J.E., et al. (2021) Prognostic factors for severe and recurrent Clostridioides difficile infection: a systematic review. Clinical Microbiology and Infection 28(3), 321-331. [Abstract] [Free Full-text]
  • Winslow, B.T., Onysko, M., Thompson, K.A., et al. (2014) Common questions about Clostridium difficile infection. American Family Physician 89(6), 437-442. [Abstract] [Free Full-text]
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