Clostridiodes difficile is a pretty big problem, causing quite a bit of morbidity and mortality every year, and it’s becoming more and more common. It can be pretty tricky to treat. C. diff is an anaerobic, spore-forming rod and it makes a toxin that contributes to the severity of the disease. It causes diarrhea and can end up in toxic megacolon/fulminant colitis requiring bowel resection, complete removal of the colon, or causing death. It contributes to tens of thousands of deaths a year.
Risk Factors:
- Exposure to Antibiotics: This is the biggest risk factor. The ones that cause it the most are CLINDAMYCIN, FLUOROQUINOLONES, CARBAPENEMS, and 3RD or 4th GEN CEPHALOSPORINS. Even one dose in the past 8 weeks seems to increase risk. Exposure to more than 1 antibiotic increases risk.
- Hospitalization (especially longer stays)
- Age over 65
- Cancer
- IBD
- Kidney Disease
- Organ transplant
- Liver disease
- Immunodeficiency
- Exposure to proton pump inhibitors
It’s not recommended to test everyone with diarrhea. You should only test patients with unexplained and new-onset ≥3 unformed stools in 24 hours who have risk factors. If you use screening criteria such as this, a nucleic acid amplification test (NAAT) is fine. Otherwise, you want to a multistep algorithm for testing (ie, GDH plus toxin; GDH plus toxin, arbitrated by NAAT; or NAAT plus toxin) rather than a toxin test alone. See the SHEA guidelines for treatment and testing.
C. diff is spread via the fecal oral route. Alcohol based cleaners don’t remove the spores. You need soap and water and a thorough hand cleaning.
Disease Severity:
Non-severe: WBC <= 15,000 and SCr < 1.5
Severe Disease: WBC 15,000-20,000 or more or SCr > 1.5
Fulminant: Presence of shock, hypotension, ileus or megacolon
Treatment Depends on Disease Severity.
It’s important to note that metronidazole used to be first-line therapy. It has fallen out favor in the 2017 guidelines. Vancomycin is considered the drug of choice, with some exceptions, now. Also, treatments used to be recommended for 14 days, however now most are only recommended for 10 days.
- Discontinue therapy with the inciting antibiotic agent(s) as soon as possible.
- First Episode:
- Non-severe
- vancomycin 125 mg PO four times a day for 10 days OR
- fidaxomicin 200 mg PO BID for 10 days OR
- metronidazole 500 mg PO TID for 10 days (only if other two aren’t available)
- Severe
- vancomycin 125 mg PO four times a day for 10 days OR
- fidaxomicin 200 mg PO BID for 10 days
- Fulminant
- vancomycin 500 mg PO four times a day AND 500 mg metronidazole IV every 8 hours for 10-14 days
- Non-severe
- First recurrence
- If previously treated with metronidazole: vancomycin 125 mg PO four times a day for 10 days
- If previously treated with vancomycin:
- vancomycin 125 mg PO four times a day for 10 days THEN taper vancomycin 125 mg BID for 7 days then daily for 7 days, vancomycin once every 2-3 days for 2 to 8 weeks OR
- fidaxomicin 200 mg PO BID for 10 days
- Consider adding bezlotoxumab 10 mg/kg IV one time dose to any of the above (note: as of January 2025, bezlotoxumab has been discontinued by the manufacture and it doesn’t look like it will be picked up by anyone else).
- Second or third recurrence
- vancomycin 125 mg PO four times a day for 10 days THEN taper vancomycin 125 mg BID for 7 days then daily for 7 days, vancomycin once every 2-3 days for 2 to 8 weeks OR
- vancomycin 125 mg PO four times a day for 10 days THEN rifaximin 400 mg BID for 20 days
- Consider fidaxomicin if not already given (fidaxomicin 200 mg PO BID for 10 days)
- Fecal transplant is an option
- Consider adding bezlotoxumab 10 mg/kg IV one time dose to any of the above
Bezlotoxumab is a newer agent. It’s a monoclonal antibody that neutralizes the toxin produced by C. diff. It can prevent damage to the colon, but it should not be used alone as treatment.
Fecal transplants are only recommended for those who have 2 or more recurrences. Enemas are less effective than capsules or NG administration. VOWST (fecal microbiota spores, live-brpk – a capsule to be taken orally) and REBYOTA (a pre-packaged, single-dose 150 mL microbiota suspension for rectal administration) are commercially available fecal transplants, but some facilities make their own and there are commercial stool banks. There is a risk of transferring harmful bacteria or viruses from the donor to the recipient. This has resulted in death, but that’s pretty rare.
Proton Pump Inhibitors: The SHEA guidelines state: “Although there is an epidemiologic association between proton pump inhibitor (PPI) use and CDI, and unnecessary PPIs should always be discontinued, there is insufficient evidence for discontinuation of PPIs as a measure for preventing CDI.” Histamines receptor antagnoists have less association with C. diff.
Prophylaxis with vancomycin has been recommended in past guidelines, but the 2017 guidelines say there is insufficient evidence to recommend routine prophylaxis.