Clostridioides Difficile (CDI) Information pack for general practitioners (Antimicrobial)

• Antibiotic exposure, especially long duration and >1 course in the previous 3 months, in particular the “4-Cs”, ciprofloxacin (quinolones), co-amoxiclav (broad spectrum penicillins), clindamycin and cephalosporins (3rd generation).
• Gastrointestinal surgery/manipulation.
• Prolonged stay in healthcare settings.
• Serious underlying illness.
• Immunocompromised patients.
• Advancing age (>80% are >65yrs).
• Previous diagnosis of CDI.
• Chronic renal disease.
• Patients prescribed proton pump inhibitors or H₂ Antagonists (ie omeprazole and lansoprazole).

Clinical symptoms include:

• Varying degrees of diarrhoea from mild through to severe inflammation of the bowel in the form of pseudo membranous colitis, toxic megacolon, intestinal perforation and sepsis.
• Fever.
• Raised white cell count.
• Poor appetite/nausea.
• Blood in stool.
• Abdominal pain and tenderness.

Diarrhoea is defined as the passage of 3 or more loose or liquid stools per day, or more frequently than is normal for the individual (usually at least 3 times in a 24 hour period) that cannot be attributed to laxatives, enteral feeding, treatments etc, or to underlying conditions such as colitis, overflow etc.

A faecal specimen of a least 2ml should be collected in blue top container with integral spoon. Ensure container is properly closed, and do not overfill. Only samples that take the shape of the container will be tested by the laboratory.

All samples must be accompanied by a microbiology request form with C.difficile as the investigation required. Please indicate whether currently/recently receiving antibiotics and any clinical details. NB if the request form is not completed with the appropriate details, it will be rejected by the microbiology department and not tested.

GDH: Glutamate Dehydrogenase (GDH) is an enzyme produced in large quantities by all toxigenic and NON-toxigenic strains, making it an excellent antigen marker for the organism.  GDH detection is used as a screening test and indicates the possible presence of the C. difficile infection within the gut.  A positive result may indicate C. difficile infection or colonisation.  If the patient is symptomatic please contact microbiologist to discuss case management.

TOXIN A/B: if the GDH test is positive a TOXIN A/B test is then performed.  This detects the presence or absence of the two high molecular weight toxins produced by C.difficile that are responsible for the clinical manifestations and symptoms of C.difficile infection.

C. difficile toxin is a notifiable organism under the Public Health Scotland Act 2008.  Reporting occurs via the testing laboratory.

A negative test result does not necessarily exclude infection especially if clinical symptoms are highly suggestive.  These cases should be discussed with the Consultant Microbiologist or Infection Control Doctor.

Further stool specimens should not be sent following diagnosis of CDI.  Samples sent within 28 days will NOT be tested unless discussed with the Infection Prevention & Control Team or the Consultant Microbiologist first.  There is no requirement to send clearance samples.  Advice on repeat samples should be sought from the Consultant Microbiologist when symptoms have recurred after the initial treatment.

The current NICE guidance statement does not recommend the use of probiotics, (NICE guidance statement 1.3.4) Do not advise people taking antibiotics to take prebiotics or probiotics to prevent C. difficile infection.

The committee also 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.

• Check there are no other medicines prescribed that could cause diarrhoea eg laxatives, anti motility medication and stop if appropriate.
• Check there are no medicines prescribed which may exacerbate the condition eg anti-hypertensives particularly ACEIs, diuretics, metformin and stop if appropriate.
• Check no other medicine changes that could have changed bowel habit eg codeine.
• Check if any medicine that could cause immunosuppression (may be associated with more severe disease) and consider withholding.
• Review the prescription of any antimicrobial and only continue if clinical benefit outweighs risk (discuss with Medical Microbiologist if required).

Review any prescription of a proton pump inhibitor or H2 antagonist with a view to stopping if possible (see PPI review).

• Consider other causes of diarrhoea eg medicines, norovirus, impaction with overflow, chronic disease eg inflammatory bowel disease.
• Consider CDI if any of the following: antibiotic within last 3 months, recent surgical procedure, recent prolonged hospital stay, serious underlying disease, PPI or H₂ antagonist prescription.
• As soon as CDI suspected commence empiric treatment as per local protocol (see CDI treatment) and ensure Infection Prevention and Control measures are in place as per National Infection Prevention and Control Manual: A-Z Pathogens.  Do not wait on microbiology laboratory result.
• Advise to obtain stool sample and next steps – eg treatment and monitoring requirements.
• Determine if hospitalisation is required based on severity markers eg temp>38·5°C, pulse> 100, BP<100systolic, suspicion of ileus or megacolon.
• Advise patient on: drinking enough fluids to avoid dehydration; preventing the spread of infection through optimal hand hygiene and cleaning; seeking medical help if symptoms worsen rapidly or significantly at any time.
• Provide Clostridioides difficile infection (CDI) Information leaflet to patient.

• Review after 3 days to determine response to treatment and be alert to signs of increasing severity (as above).  If patient develops signs of severe C. difficile infection, discuss with Microbiologist and consider referral to hospital.
• If no improvement or deterioration after 7 days treatment, contact Microbiologist.
• Consider checking infection markers (WCC, CRP and renal function).
• In cases of recurrent CDI discuss further treatment with Microbiologist.
• If in any doubt, contact Microbiologist for advice on management.

Guidance on Prevention and Control of Clostridium difficile Infection (CDI) in Care Settings in Scotland, 2017. V3 https://hpspubsrepo.blob.core.windows.net/hps-website/nss/2060/documents/1_shpn-6-cdi-in-scotland%202017.pdf

Guidance on prevention and control of Clostridioides difficile Infection (CDI) in community-based settings in Scotland, 4 November 2024 Scottish Health Protection Network Guidance https://publichealthscotland.scot/publications/guidance-on-prevention-and-control-of-clostridioides-difficile-infection-cdi-in-community-based-settings-in-scotland/guidance-on-prevention-and-control-of-clostridioides-difficile-infection-in-community-based-settings-in-scotland-version-1-new/overview/intended-audience/

National Infection prevention and Control Manual for older people and adult care homeshttps://www.nipcm.scot.nhs.uk/infection-prevention-and-control-manual-for-older-people-and-adult-care-homes/

Updated advice on Clostridioides difficile (C.diff) Infection (CDI), Scottish Antimicrobial Prescribing Group, March2025 Clostridioides difficile (C.diff) infection (CDI)

Clostridioides difficile infection: antimicrobial prescribing, NICE/PHE, July 2021 (last updated July 2024) https://www.nice.org.uk/guidance/ng199

Clostridium difficile infection information for hospital patients and visitors HPS 2020
https://hpspubsrepo.blob.core.windows.net/hps-website/nss/3001/documents/1_c-diff-information-leaflet-2020-03-26.pdf
Print version:
https://hpspubsrepo.blob.core.windows.net/hps-website/nss/3001/documents/2_cdiff-information-leaflet-2020-03-25-print.pdf

Washing clothes at home, information for people in hospitals or care homes and their relatives.  HPS 2019
https://hpspubsrepo.blob.core.windows.net/hps-website/nss/2639/documents/1_washing-clothes-home-english.pdf