Refractory C. difficile infection in adults

If the patient has developed severe, complicated or fulminant disease (for definitions, see Severity assessment of C. difficile infection in adults), seek expert advice. For treatment recommendations, see Severe, complicated or fulminant Clostridioides difficile infection.

In adults with refractory C. difficile infection, before escalating treatment, consider whether any of the following may be contributing to ongoing symptoms and address these, if possible:

ongoing antibiotics for other indications that may predispose to treatment failure
other factors (eg diet, caffeine, lactose) or medications (eg lactulose) that may exacerbate diarrhoea
a concomitant condition that can cause similar symptoms (eg inflammatory bowel disease).

In addition to antibiotic therapy, continue rehydration strategies.

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

For adults with refractory mild to moderate C. difficile infection who started treatment with metronidazole, change to vancomycin; use:

vancomycin 125 mg orally or enterally, 6-hourly for 10 days¹ ² ³. vancomycin vancomycin vancomycin

For adults with refractory mild to moderate C. difficile who started treatment with vancomycin, change to fidaxomicin; use:

fidaxomicin 200 mg orally, 12-hourly for 10 days⁴ Oliver, 2022. fidaxomicin fidaxomicin fidaxomicin

If fidaxomicin cannot be used or is inaccessible, continue therapy with vancomycin to complete a total duration of 10 days and reassess the clinical progress.

For adults who have clinically improved, complete the course. For information about follow-up testing and patient education, see Follow-up for patients with Clostridioides difficile infection.

Ongoing refractory C. difficile infection is defined as a lack of clinical improvement a further 5 to 7 days after switching therapy.

For adults who have ongoing refractory mild to moderate C. difficile infection who are currently using vancomycin, switch to fidaxomicin (see dosage above).

For adults who have ongoing refractory mild to moderate C. difficile infection who are currently using fidaxomicin, consider faecal microbiota transplantation (FMT) or ‘stool transplant’ – seek expert advice. For more information on faecal microbiota transplantation, see Second and subsequent recurrences of C. difficile infection in adults. Because of the logistical delays with obtaining faecal microbiota transplantation, most hospital protocols suggest starting vancomycin or fidaxomicin while awaiting faecal microbiota transplantation.

¹ 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

² Intravenous vancomycin is not effective against C. difficile infection because of inadequate penetration of the drug into the lumen of the colon.Return

³ 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

⁴ 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