Clostridioides Difficile (Antimicrobial)

• NICE (published July 2021)
• Public Health Scotland (2024)
• Antimicrobial management of Clostridioides Difficile (C. Diff) infection (CDI) in adults 18 years and over (updated April 2025)
• Antimicrobial management of Clostridioides Difficile (C. Diff) infection (CDI) in children (updated June 2024)

Complete Severity Assessment

• Review current antibiotic therapy and stop where possible.
• Cephalosporins, clindamycin, broad-spectrum penicillins (co-amoxiclav) and quinolones (ciprofloxacin) are high-risk but ALL antibiotics (including cefalexin) have the potential to alter the gut microbiome and precipitate C.difficile infection.
• Stop proton pump inhibitors (see algorithm) and anti-motility agents whilst symptomatic, if possible.
• Doses given are for adults; see the SAPG Antimicrobial management of Clostridioides Difficile (C. Diff) injfection (CDI) in children along with a decision tool and current edition of the BNF for Children for drug dosing recommendations in children.
• For administration advice in swallowing difficulties or enteral feeding tubes, see section below.
• Recommend coding GDH positive and/or toxin positive status as Priority 1 in the patient’s medical record. All subsequent antibiotic therapy may provoke a recurrent episode. If further advice on antibiotic therapy is required, contact Microbiology.

Severity Assessment

Mild to moderate CDI

• WCC <15 x 10⁹
• <5 stools of type 5 to 7 on the Bristol Stool chart

Severe CDI is associated with at least one of the following

• Temperature  above 38·5°C
• Suspicion or confirmation of pseudomembranous colitis, toxic megacolon, ileus
• Evidence of severe colitis on CT scan or abdominal X-ray examination
• WBC above 15 cells x 10⁹L
• Acute rising serum creatinine higher than 1·5 x baseline
• NICE includes statement: the number of stools may be a less reliable indicator of severity

Life-threatening CDI is when a patient has any of the following attributable to CDI:

• admission to intensive care unit
• hypotension with or without need for vasopressors
• ileus or significant abdominal distension
• mental status changes
• white blood cells (WBC) higher than 35 x 10⁹/L or less than 2 x 10⁹/L
• serum lactate greater than 2.2mmol/L
• end organ failure (mechanical ventilation, renal failure)

Antibiotic Treatment

Discuss each case with Microbiology to agree optimal treatment, including availability of vancomycin and fidaxomicin.  Note: due to infrequent use, most community pharmacies will not hold stock of vancomycin capsules or fidaxomicin tablets.  Before prescribing, please discuss availability and timescales for obtaining stock to ensure timely initiation of treatment.

Administration in swallowing difficulties or enteral feeding tubes

Vancomycin capsules contain a gel-like matrix that cannot be extracted to add to soft food or administer via an enteral feeding tube.  Oral solutions of vancomycin are not readily available in a timely manner to treat this infection.  Vancomycin injection is licensed by most (but not all) manufacturers for oral and nasogastric tube administration for treatment of C. difficile infection.  Check the brand for specific information and contact Pharmacy with any concerns.

Preparation of a vancomycin solution for oral administration:

• Add 10 mL of Water for Injections to vials containing 500 mg vancomycin powder.  This gives solution strength of 50 mg/mL. 
• For a dose of 125mg vancomycin, draw up 2.5 mL of solution.
• Each dose should then be diluted with 30 mL of sterile water (to minimise GI side effects). 
• A suitable flavouring should be used for oral administration as the injection solution has an unpleasant taste.

After administration via an enteral feeding tube, flush the tube with 10mL of water.  As feed does not interact with vancomycin, there is no requirement for feed breaks around administration times.

Although the vials state 'for single use only', this is for intravenous administration. For enteral administration, the reconstituted solution is chemically stable for 24 hours when stored in the fridge at 2 to 8 °C. It MUST be clearly labelled “For enteral administration only”. 

Make up a new solution each day.