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How should I assess someone presenting with suspected antibiotic-associated diarrhoea?
For people presenting with diarrhoea during, or up to 8 weeks after, a course of antibiotic treatment:
- Assess the severity of the symptoms and consider whether hospital admission is appropriate.
- For further information on assessing symptoms (including the risk of dehydration) and when to admit, see the sections on hospital admission for children and adults in the CKS topic on Gastroenteritis.
- Exclude other potential causes of diarrhoea or contributing factors.
- Ask about recent contact with anyone with acute diarrhoea and/or vomiting, exposure to a known source of enteric infection (possibly contaminated water or food), and recent travel abroad.
- Check for drugs (other than antibiotics) known to cause diarrhoea (for example proton pump inhibitors — also a risk factor for Clostridium difficile infection) or exacerbate diarrhoea (for example laxatives).
- Check which antibiotics were prescribed and the duration of treatment.
- C. difficile infection is more common with certain antibiotics (see Risk factors).
- Consider the possibility of C. difficile infection.
- There are no clinical symptoms that are specific for C. difficile infection.
- However, suspect the possibility of C. difficile infection (particularly if the person is elderly) if risk factors are present.
- Check for any history of C. difficile infection — as the rate of recurrence is high.
- Send a stool sample to test for C. difficile toxin (for further information, see Testing).
- Check whether other cases of C. difficile infection 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.
Additional information
Severity of Clostridium difficile infection can be defined as [DH and HPA, 2008]:
- Mild: not associated with an increased white cell count (WCC). It is typically associated with less than three episodes of loose stools (defined as loose enough to take the shape of the container used to sample it) per day.
- Moderate: associated with an increased WCC (but less than 15 x 109/L) and typically associated with 3–5 loose stools per day.
- Severe: associated with a WCC greater than 15 x 109/L, or an acutely increased serum creatinine concentration (that is, greater than 50% increase above baseline), or a temperature higher than 38.5°C, or evidence of severe colitis (abdominal or radiological signs). The number of stools may be a less reliable indicator of severity.
- Life-threatening: signs and symptoms include hypotension, partial or complete ileus, or toxic megacolon.
Basis for recommendation
These recommendations are extrapolated from guidance issued by the Department of Health and the Health Protection Agency (HPA), and expert opinion on assessing people with acute diarrhoea and clinical features of Clostridium difficile infection [Bartlett, 2002; Starr, 2005; Bartlett and Gerding, 2008; DH and HPA, 2008; World Gastroenterology Organisation, 2008; Rupnik et al, 2009; Williams and Spencer, 2009].
Exclusion of other causes of diarrhoea and assessment for C. difficile infection
- The recommendations to exclude other causes of diarrhoea and to assess for C. difficile infection are consistent with guidance on C. difficile infection issued by the Department of Health and the HPA when managing suspected potentially infectious diarrhoea [DH and HPA, 2008].
- There are no specific clinical features for C. difficile infection and a number of disorders may have similar clinical presentation (for example infections by other enteric pathogens — see the section on Causes in the CKS topic on Gastroenteritis) [Bartlett and Gerding, 2008]. Diarrhoea with a foul-smelling odour is not sufficiently specific for a definitive diagnosis of C. difficile [Rupnik et al, 2009].
- Consequently, people with diarrhoea and appropriate risk factors should be assessed for C. difficile infection.
What test should I perform if a Clostridium difficile infection is suspected?
For adults and children 2 years of age and older with suspected Clostridium difficile infection:
- Send a stool sample to test for C. difficile toxin if:
- A clinical diagnosis of C. difficile infection is suspected, and
- The person is symptomatic with liquid/loose stools (with a consistency that takes the shape of the container).
- Ensure the following details are stated on the request form:
- Clinical features (for example: systemic illness; fever; bloody stool; abdominal pain; immunosuppression; and onset, duration and recurrence of symptoms).
- Recent antibiotic or proton pump inhibitor, or hospital admission.
- Contact with other affected individuals or outbreak.
- State whether the test was requested by the Health Protection Unit or a Consultant in Communicable Disease Control.
- Re-test after 24 hours only if the first test is negative and there is a strong clinical suspicion of C. difficile infection.
- Do not re-test people with positive C. difficile infection if the person is still symptomatic within a period of 28 days.
- Only re-test to confirm recurrent C. difficile infection if the symptoms resolve and then recur.
- 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 Gastroenteritis.
Basis for recommendation
These recommendations are based on guidelines issued by the Department of Health and the Health Protection Agency (HPA) [HPA, 2007a; DH and HPA, 2008].
Laboratory confirmation of Clostridium difficile toxin
- Laboratory diagnosis of C. difficile infection is based on detection of C. difficile toxins (A and B) in the stool sample.
- Laboratory confirmation is required because there are no specific clinical features for C. difficile infection and a number of disorders may have similar clinical presentation (for example infections by other enteric pathogens, see the section on Causes in the CKS topic on Gastroenteritis) [Bartlett and Gerding, 2008].
Repeat testing
- Repeated stool testing is recommended if the first sample tests negative and there is a strong suspicion of C. difficile [DH and HPA, 2008].
- The HPA warns that results from studies indicate that currently-available kits may miss about 1 in 10, to 1 in 5, cases of C. difficile and generally have suboptimal positive predictive values (that is, positive results may sometimes be false positives) [Wilcox et al, 2009].
- This is based on findings of a study undertaken by the National Health Service Centre for Evidence-based Purchasing which found none of the C. difficile-toxin detection assays tested had a particularly high sensitivity [Wilcox and Eastwood, 2009]. In this study (of 600 faecal samples), the sensitivities of the nine commercial assays ranged between 67–92% when compared with the cytotoxin assay (the gold standard). Specificities ranged between 91–99%. The positive predictive values (PPVs) ranged between 49–87%, and the report warned that 'the poor PPVs of toxin detection kits, especially in the context of widespread testing, raises doubts about their appropriateness when used as single tests for the laboratory detection of C. difficile toxins'.
- Consequently, the HPA recommends that toxin detection results should be interpreted cautiously, particularly if the test result is not consistent with the clinical details [Wilcox et al, 2009].
28 day rule
- The Department of Health and the HPA do not recommend re-testing people with positive C. difficile infection if the person is still symptomatic within a period of 28 days [DH and HPA, 2008].
- Based on Department of Health guidance on mandatory healthcare associated infection surveillance system for C. difficile infection, positive results on the same individual within 28 days of the first specimen should be regarded as a single episode [Chief Medical Officer and Chief Nursing Officer, 2008].
- Separate episodes should be reported if positive results on the same individual was reported more than 28 days apart, irrespective of the number of specimens taken in the intervening period, or where they were taken. If a new episode is reported under the 28 day rule, this rule is reset for the new episode.
- The 28 day rule was recommended by the National Clostridium difficile Standards Group, with the intention to avoid bias caused by the difficulties in distinguishing relapse from re-infection and to permit consistency of interpretation [National Clostridium difficile Standards Group, 2003]. This recommendation was based on expert opinion rather than published evidence.
Children younger than 2 years of age
- In healthy newborn babies and infants, asymptomatic colonization of C. difficile is very common, ranging from 15–80%, and is rarely associated with overt disease (possibly due to a lack of toxin receptor expression in the immature gut) [Kelly, 2009; Williams and Spencer, 2009]. By around 2 years of age, the colonization rate drops to levels comparable with those of healthy adults (less than 4%).
- Consequently, the Department of Health and the HPA recommend that testing is generally not advisable in children less than 2 years of age as toxigenic strains of C. difficile, and toxins A and B, may be present in the absence of symptoms [DH and HPA, 2008].
How should I manage antibiotic-associated diarrhoea if C. difficile infection is not suspected or while awaiting the result of C. difficile toxin testing?
For people in whom Clostridium difficile infection is not suspected, or while awaiting a C. difficile toxin test result:
- Assess the severity of the condition and consider whether hospital admission is appropriate (for further information, see the CKS topic on Gastroenteritis).
- 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.
- If highly suspicious that the person has C. difficile infection, consider seeking specialist advice on whether empirical antibiotic treatment should be offered.
- Manage fluid loss and symptoms 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 while awaiting C. difficile results.
- Give advice on hygiene measures to minimize the spread of possible infection (for further information, see the section on Preventing spread of infection in the CKS topic on Gastroenteritis).
Basis for recommendation
These recommendations are based on guidance issued by the Department of Health and Health Protection Agency (HPA) on managing Clostridium difficile infection, and from expert reviews on managing antibiotic-associated diarrhoea [Bartlett, 2002; Tonna and Welsby, 2005; Aronson, 2006; DH and HPA, 2008; Williams and Spencer, 2009].
Stopping the antibiotic
- The Department of Health and HPA recommend that, if possible, antibiotic treatment should be stopped for people with suspected C. difficile infection to allow normal intestinal flora to be re-established [DH and HPA, 2008].
- Antibiotic-associated diarrhoea without C. difficile infection will resolve on discontinuation of the antibiotic [Bartlett, 2002; Tonna and Welsby, 2005; Aronson, 2006].
Antimotility drugs
- CKS does not recommend the use of antimotility drugs in people with suspected C. difficile infection because there is a lack of evidence to support their use and there are concerns about possible adverse effects (for example toxic megacolon). For further information, see Known C. difficile test result.
How should I manage antibiotic-associated diarrhoea once results of C. difficile toxin test are known?
If the Clostridium difficile toxin test result is negative:
- Continue management as outlined in C. difficile not suspected or awaiting result.
- Consider re-testing for C. difficile toxin (24 hours after testing the first sample) only if there is strong clinical suspicion of C. difficile infection (see Testing). Consider seeking specialist advice if in doubt.
If the C. difficile toxin test result is positive:
- Reassess the person's clinical condition.
- For information on assessing severity of C. difficile infection, see Additional information in the section on Assessment.
- If they have features of severe or life-threatening C. difficile infection, or their condition is rapidly deteriorating, admit to hospital.
- If the person's condition has improved considerably or has resolved without treatment, consider the possibility of a false-positive test result.
- If hospital admission is not required:
- Consult local policy or seek specialist advice on further management (including antibiotic treatment — see Additional information).
- 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 C. difficile infection, if this is appropriate. Seek specialist advice if this is not possible and the diarrhoea is severe.
- Manage fluid loss and symptoms 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).
- Do not recommend the use of probiotics for the treatment and prevention of C. difficile infection.
- Give advice on hygiene measures to minimize the spread of C. difficile (see the section on Preventing spread of infection in the CKS topic on Gastroenteritis).
- Review the person daily and monitor for signs of increasing severity of disease, as they may deteriorate very rapidly.
- Advise people that:
- The diarrhoea should resolve in 1–2 weeks.
- 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.
Additional information
Antibiotic treatment for C. difficile infection
- People with features of severe infection should be managed in secondary care.
- Mild-to-moderate C. difficile infection may be managed in primary care.
- Consult local policy or seek specialist advice if in doubt.
- People with mild disease may not require specific C. difficile antibiotic treatment [DH and HPA, 2008].
- For mild-to-moderate C. difficile infection, metronidazole is recommended first-line because it is as effective as oral vancomycin and is less expensive [DH and HPA, 2008]. As a guide, the Department of Health and Health Protection Agency recommend [DH and HPA, 2008]:
- For the initial episode of C. difficile infection: oral metronidazole 400 mg to 500 mg three times a day for 10–14 days.
- For the first recurrence: repeat the same antibiotic used to treat the initial episode (unless the first episode was treated with metronidazole and the recurrence is severe, in which case vancomycin should be used).
- Vancomycin is reserved for severe C. difficile infection or for subsequent recurrences.
Basis for recommendation
These recommendations are based on guidance issued by the Department of Health and Health Protection Agency (HPA) [DH and HPA, 2008], and expert opinion [Bartlett, 2002; Hurley and Nguyen, 2002; Starr, 2005; Tonna and Welsby, 2005; Kelly and LaMont, 2008; Williams and Spencer, 2009].
Positive test result for Clostridium difficile infection in people whose symptoms have improved
- The recommendation to consider an alternative diagnosis in these people is in line with the HPA recommendation that caution should be applied when interpreting toxin detection results, particularly if the clinical symptoms and signs are not consistent with the test result [Wilcox et al, 2009]. This is due to the poor positive predictive values associated with C. difficile toxin detection kits (for further information, see Testing).
Stopping the antibiotic causing the diarrhoea (apart from any being use to treat the C. difficile infection)
- The Department of Health and HPA recommend that, if possible, antibiotic treatment should be stopped for people with C. difficile infection to allow normal intestinal flora to be re-established [DH and HPA, 2008].
Antimotility drugs and drugs with anti-peristaltic effects
- There is no good evidence to support the use of antimotility drugs (such as loperamide) for treating C. difficile infection.
- Antimotility drugs and other drugs with anti-peristaltic effects (for example, opioids) should be avoided in people with acute C. difficile infection because of the theoretical risk of precipitating toxic megacolon by slowing the clearance of C. difficile toxin from the intestine [Mylonakis et al, 2001; DH and HPA, 2008; Gerding et al, 2008].
- This is in line with the recommendations from the manufacturer of loperamide, which state that loperamide is contraindicated in people where inhibition of peristalsis should be avoided due to the possible risk of significant sequelae including ileus, megacolon, and toxic megacolon (including people with pseudomembranous colitis associated with the use of broad-spectrum antibiotics) [ABPI Medicines Compendium, 2008].
Probiotics
- The use of probiotics is not recommended by the HPA and Department of Health as there is insufficient evidence to demonstrate their efficacy for treating or preventing C. difficile infection [DH and HPA, 2008].
Hygiene measures to minimize the spread of C. difficile
- 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 [DH and HPA, 2008].
What follow-up should I consider for people with antibiotic-associated diarrhoea?
Antibiotic-associated diarrhoea without Clostridium difficile infection
- No follow-up is necessary, as symptoms will resolve after cessation of the antibiotic.
- However, advise the person to seek medical advice if they develop unexplained diarrhoea within 8 weeks of stopping the antibiotic, as there is a possibility they might subsequently develop C. difficile infection.
People with C. difficile infection
- Review the person daily and monitor for signs of increasing severity of disease as they may deteriorate very rapidly (see Known C. difficile test result). Consider hospital admission if appropriate.
- Consider the possibility of post-infective bowel syndrome if the diarrhoea persists despite 20 days of treatment, and the following features are present:
- The person is stable, and
- The daily number of loose/liquid stools has decreased, and
- The white cell count is normal, and
- There is no abdominal pain or distension.
- Once recovered, advise the person to seek medical advice if they develop unexplained diarrhoea, as there is a high rate of recurrence with C. difficile infection (see Prognosis).
Basis for recommendation
These recommendations are based on guidance issued by the Department of Health (DH) and Health Protection Agency (HPA) [DH and HPA, 2008], and published expert opinion [Bartlett, 2002].