How should I manage a patient with a confirmed C. difficile infection who is not responding to initial treatment?

If a patient with confirmed Clostridioides difficile infection (CDI) is not responding to initial treatment, first assess the severity of the infection and consider whether hospital admission is appropriate, especially if symptoms worsen or are severe.

Initial treatment for a first episode of non-severe CDI is oral vancomycin 125 mg four times daily for 10 days. If there is no improvement by day 7, consider that diarrhoea may take 1 to 2 weeks to resolve, but if treatment failure is suspected, seek prompt specialist advice from a microbiologist or infectious disease specialist before changing antibiotics.

For patients not responding to initial vancomycin, second-line treatment with fidaxomicin 200 mg orally twice daily for 10 days is recommended.

If the patient has recurrent CDI (a new episode within 12 weeks of symptom resolution), a repeat course of fidaxomicin or vancomycin is advised.

Stop any non-CDI antibiotics if possible, manage fluid loss as for acute gastroenteritis, and avoid antimotility drugs such as loperamide.

For patients unable to take oral medications or with severe disease not responding to oral therapy, seek specialist advice urgently for alternative antibiotic options or hospital management.

Consider referral to a gastroenterologist if the patient has had at least two previous episodes of CDI, as faecal microbiota transplantation may be indicated.

Advise on strict hygiene measures to prevent spread, including hand washing with soap and water, as alcohol-based hand rubs do not kill C. difficile spores.