Vancomycin followed by fecal microbiota transplant (FMT) was associated with reduced Clostridioides difficile (C. diff)-related mortality in patients hospitalized with refractory severe or fulminant C. diff infection (CDI) at a single center. The improvements came after Indiana University implemented an FMT option in 2013.
About 8% of C. diff patients develop severe or fulminant CDI (SFCDI), which can lead to toxic colon and multiorgan failure. Surgery is the current recommended treatment for these patients if they are refractory to vancomycin, but 30-day mortality is above 40%. FMT is recommended for recurrent CDI, and it achieves cure rates greater than 80%, along with fewer relapses compared with anti-CDI antibiotic therapy.
FMT has been shown to be effective for SFCDI, with a 91% cure rate for serious CDI and 66% for fulminant CDI.
In the study published in the September issue of Clinical Gastroenterology and Hepatology, researchers led by Yao-Wen Cheng, MD, and Monika Fischer, MD, of Indiana University, assessed the effect of FMT on SFCDI after their institution adopted it as a treatment protocol for SFCDI. Patients could receive FMT if there was evidence that their SFCDI was refractory, or if they had two or more CDI recurrences. The treatment includes oral vancomycin and pseudomembrane-driven sequential FMT.
Two hundred five patients were admitted before FMT implementation, 225 after. Fifty patients received FMT because of refractory SFCDI. A median of two FMTs was conducted per patient. 21 other patients received FMT for nonrefractory SFCDI or other conditions, including 18 patients with multiple recurrent CDI.
Thirty-day CDI-related mortality dropped after FMT implementation (4.4% versus 10.2%; P =.02). This was true in both the fulminant subset (9.1% versus 21.3%; P =.015) and the refractory group (12.1% versus 43.2%; P < .001).
The researchers used segmented logistic regression to determine if the improved outcomes could be due to nontreatment factors that varied over time, and found that the difference in CDI-related mortality was eliminated except for refractory SFCDI patients (odds of mortality after FMT implementation, 0.09; P =.023). There was no significant difference between those receiving non-CDI antibiotics (4.8%) and those who did not (6.9%; P =.75).
FMT was associated with lower frequency of CDI-related colectomy overall (2.7% versus 6.8%; P =.041), as well as in the fulminant (5.5% versus 15.7%; P =.017) and refractory subgroups (7.6% versus 31.8%; P =.001).
The findings follow another study that showed improved 3-month mortality for FMT among patients hospitalized with severe CDI (12.1% versus 42.2%; P < .003).
The results underscore the utility of FMT for SFCDI, and suggest it might have the most benefit in refractory SFCDI. The authors believe that FMT should be an alternative to colectomy when first-line anti-CDI antibiotics are partially or completely ineffective. In the absence of FMT, patients who go on to fail vancomycin or fidaxomicin will likely continue to be managed medically, with up to 80% mortality, or through salvage colectomy, with postsurgical morality rates of 30-40%.
Although a randomized trial could answer the question of FMT efficacy more definitively, it is unlikely to be conducted for ethical reasons.
“Further investigation is required to clearly define FMT’s role and timing in the clinical course of severe and fulminant CDI. However, our study suggests that FMT should be offered to patients with severe and fulminant CDI who do not respond to a 5-day course of anti-CDI antibiotics and may be considered in lieu of or before colectomy,” the researchers wrote.
No source of funding was disclosed.
SOURCE: Cheng YW et al. Clin Gastroenterol Hepatol. 2020;18:2234-43. doi: 10.1016/j.cgh.2019.12.029.
