UDCA for recurrent C.difficile!

Clin Infect Dis. 2019 Jan 18;68(3):498-500

Contributed by Dr Abi Manesh

Image source: Nature Med. 2014 Mar;20(3):246-7

It is always interesting when the pathophysiological basis of diseases form the basis for their treatments. Clostridium difficile associated pseudomembranous colitis is a serious disease especially among hospitalized immunocompromised individuals receiving broad-spectrum antibiotics. C.difficile, a spore former is rare in a healthy gut except among infants. Primary bile salts produced from the liver induce germination of these spores resulting in vegetative forms – the first step in the pathogenesis. However, secondary bile salts, the deoxycholated primary bile salts inhibit the growth of these vegetative forms – thereby protecting the body from developing C.difficile disease. For formation of secondary bile salts we need the normal microbiota. When you have a patient on broad spectrum antibiotics this second step is lost resulting the continued proliferation of the C.difficile vegetative forms resulting in clinical disease.

Addition of ursodeoxycholic acid (UDCA), a pharmaceutical secondary bile acid should then reverse the second step. In this study, the authors describe the off-label use of UDCA as salvage therapy to prevent CDI recurrence in 16 patients with contraindications for fecal microbiota transplant. All but one patient had multiple prior CDI episodes (median 3.5; IQI, 2.3–5). UDCA was prescribed as adjunctive therapy following a CDI episode in 11 patients (68.8%) and as prophylaxis in the setting of ongoing need for systemic antibiotics in 5 patients (31.2%). Fifteen patients (93.8%) ultimately received systemic antibiotics while on UDCA. In sum, 14 of the 16 (87.5%) patients remained free of recurrent CDI at a median follow-up of 264 days (IQI, 152–406) from UDCA prescription.

Acknowledging the limitations like small sample size and absence of control group, these results represent proof of concept that UDCA may be effective in preventing CDI in patients with high probability of recurrence and merit further evaluation to determine if they are reproducible.