First recurrence of C. difficile infection in adults

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

Recurrence of C. difficile infection is common. Recurrent disease is defined as C. difficile infection occurring within 2 months of the previous episode, after resolution of symptoms. The risk of recurrence is greater in patientsvan Prehn, 2021:

older than 65 years
with healthcare-associated C. difficile infection
hospitalised in the preceding 3 months
currently or previously receiving concomitant antibiotics
who have started proton pump inhibitors (PPIs) during or after diagnosis of C. difficile infection
who have had a previous episode of C. difficile infection.

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

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).

Treatment choice for a first recurrence in adults depends on whether there was a clear trigger for the recurrence (eg a course of antibiotics) and the drug that initially resolved the first episode – see Treatment choice for first recurrence of Clostridioides difficile infection in adults. Identifying whether a recurrent episode is associated with a clear trigger requires clinical judgement. There is evidence that fidaxomicin is associated with lower rates of recurrence compared to vancomycin. However, the cost of fidaxomicin may be prohibitive and may not be accessible outside of hospital settings. Therefore, in community settings, fidaxomicin should be reserved for adults whose first episode initially resolved with vancomycin and there is no clear trigger for the recurrent episode.Cornely, 2012 Cornely, 2013 Guery, 2018 Louie, 2011 Mikamo, 2018

Table 1. Treatment choice for first recurrence of Clostridioides difficile infection in adults
Drug that initially resolved the first episode	Clear trigger identified	No clear trigger identified
metronidazole	use vancomycin	use vancomycin
vancomycin	use vancomycin	use fidaxomicin
fidaxomicin	use fidaxomicin	consider faecal microbiota transplantation

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

If vancomycin is indicated for first recurrence of C. difficile infection in adults (see Treatment choice for first recurrence of Clostridioides difficile infection in adults), use:

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

If fidaxomicin is indicated for first recurrence of C. difficile infection in adults (see Treatment choice for first recurrence of Clostridioides difficile infection in adults), use:

fidaxomicin 200 mg orally, 12-hourly for 10 days ⁴. fidaxomicin fidaxomicin fidaxomicin

If faecal microbiota transplantation (FMT) is considered for first recurrence of C. difficile infection in adults, 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.

Diarrhoea may take several days to respond to appropriate treatment. Data suggest that the median time to resolution of diarrhoea is 2 to 3 days, with most patients responding by 5 daysLouie, 2006.

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.

For adults who have not clinically improved after 5 days of therapy, see Treatment of refractory Clostridioides difficile infection.

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