Second and subsequent recurrences of C. difficile infection in adults

For an overview of managing C. difficile infection in adults, see Overview of managing a new episode of diarrhoea in adults with risk factors for Clostridioides difficile infection

Seek expert advice for severe, complicated or fulminant disease (for definitions, see Severity assessment of C. difficile infection in adults). See Severe, complicated or fulminant Clostridioides difficile infection for recommendations.

In addition to starting antibiotics for C. difficile infection, management includes:

  • starting rehydration strategies
  • stopping any implicated antibiotics unless there is a strong rationale for continuing them. In up to 25% of patients in whom antibiotics are stopped, symptoms resolve and the risk of relapse is reduced. If antibiotics cannot be stopped, seek expert advice
  • avoiding proton pump inhibitors (PPIs) and antimotility drugs
  • considering whether any of the following may be contributing to ongoing symptoms and addressing these, if possible:
    • other factors (eg diet, caffeine, lactose) or medications (eg lactulose) that may exacerbate diarrhoea
    • concomitant conditions that can cause similar symptoms (eg inflammatory bowel disease).

Faecal microbiota transplantation (FMT) or ‘stool transplant’ is an effective therapy for C. difficile infection, and is the preferred treatment for adults with second and subsequent recurrences. Because of the logistical delays with obtaining faecal microbiota transplantation, most hospital protocols suggest starting interim treatment with vancomycin or fidaxomicin, which is stopped 48 hours before administration of faecal microbiota transplantation (see dosage below)Cammarota, 2015Kao, 2017.

Several routes of administration for faecal microbiota transplantation are possible, including via oral capsules, nasoduodenal tube, enema and via endoscopy – seek expert advice. Emerging evidence suggests that administration via colonoscopy is associated with optimal outcomes, but consider the procedural risk associated with this route of administrationBaunwall, 2020.

Several formulations of faecal microbiota transplantation have been approved by the Australian Therapeutic Goods Administration (TGA). TGA-approved formulations are preferred, if possible, because this removes the logistical issues of donor screening. However, at the time of writing, there are no long-term safety data for TGA-approved formulations. Seek expert advice.

Note: In adults, faecal microbiota transplantation is the preferred treatment for second and subsequent recurrences.

For a second or subsequent recurrence of C. difficile infection in adults, useCornely, 2012Cornely, 2013Guery, 2018Johnson, 2021Louie, 2011Mikamo, 2018van Prehn, 2021:

1faecal microbiota transplantation, administered according to local hospital protocols

OR

2fidaxomicin 200 mg orally, 12-hourly for 10 days1 fidaxomicin fidaxomicin fidaxomicin

OR

3vancomycin 125 mg orally or enterally, 6-hourly for 14 days. Consider tapering the dose before stopping; for example: after the initial 14 days of therapy, use 125 mg orally, 12-hourly for 1 week; then 125 mg orally, daily for 1 week; then 125 mg orally every 2 or 3 days for 2 to 8 weeks234. vancomycin vancomycin vancomycin

Note: Do not give vancomycin intravenously to treat C. difficile infection.

Emerging evidence suggests that extended-pulsed fidaxomicin regimens may be associated with lower recurrence rates, but this has not formally been compared to standard regimens of fidaxomicinGuery, 2018.

Bezlotoxumab has been shown to reduce recurrence of C. difficile infection in a trial where most patients were treated with oral vancomycin; however, bezlotoxumab is no longer registered for use in Australia.

For information about follow-up testing and patient education, see Follow-up for patients with Clostridioides difficile infection.

1 At the time of writing, fidaxomicin is not available on the Pharmaceutical Benefits Scheme (PBS) for this indication. See the PBS website for current information.Return
2 Injectable vancomycin can be given orally or enterally, as an alternative to oral capsules. Dissolve 500 mg of vancomycin powder in 10 mL of water, measure the appropriate dose (eg 125 mg = 2.5 mL), and give orally or enterally. Flavouring syrups can be added before administration to improve palatability.Return
3 Intravenous vancomycin is not effective against C. difficile infection because of inadequate penetration of the drug into the lumen of the colon.Return
4 Systemic absorption of vancomycin can occur with oral or enteral administration. If toxicity is suspected, consider measuring vancomycin plasma concentrations; otherwise, therapeutic drug monitoring is not required.Return