C. difficile resolution 4 weeks after FMT predicts 8-week cure
LAS VEGAS — Resolution of Clostridium difficile infection symptoms after fecal microbiota transplantation at week 4 is predictive of cure at week 8, according to research presented at ACG 2016. This suggests that clinical cure may be evaluated at week 4 instead of the standard 8-week cure endpoint.
“Current post-FMT assessment occurs 8 weeks after fecal transplant, and this practice is actually derived from current C. diff guidelines,” Jessica R. Allegretti, MD, MPH, from Brigham and Women’s Hospital, said during her presentation. “We ... aimed to evaluate if clinical assessment and C. diff testing at earlier time points are predictive of the standard 8-week cure post-FMT, and secondly, to characterize the asymptomatic C. diff carriage rates post FMT.”
Jessica R. Allegretti
Allegretti and colleagues performed a multicenter prospective cohort study of 185 patients who underwent FMT for recurrent CDI, all of whom were evaluated clinically and by PCR at weeks 1, 4 and 8. At each time point, they evaluated the independent performance of absence of symptoms or negative PCR testing in predicting CDI cure. They also performed a subgroup analysis of patients with IBD.
Overall, 154 (83.2%) patients achieved CDI resolution while FMT failed for 31 (16.7%) by week 8.
Univariate analysis showed week 1 and week 4 clinical and PCR assessment did predict 8-week CDI cure. Further, multivariable analysis showed the absence of symptoms at week 4 was the strongest predictor of 8-week CDI cure.
“We then looked at the individual tests to see which performed the best, and ... again, the absence of symptoms at 4 weeks was the most accurate test at predicting cure, with a sensitivity of 91% and specificity of 87%,” Allegretti said. “What this tells us is that when patients are asymptomatic at 4 weeks post FMT [we can] feel fairly confident that they have achieved cure.”
Week 4 symptom assessment performed better than week 1 symptom assessment, and while the addition of PCR to symptom assessment did slightly increase the accuracy of the model, it did not reach statistical significance, “suggesting that the addition of PCR, knowing its cost and time commitment, ... does not add much when symptom assessment seems to be adequate,” she noted.
Subanalysis of patients with IBD (n = 44) again showed that week 1 and week 4 clinical and PCR assessment predicted CDI cure in patients with IBD, and negative PCR at 4 weeks performed the best with a sensitivity of 100% and a specificity of 80%.
“So in your patients with IBD, if you have a negative PCR at 4 weeks after FMT you can feel very confident that they have achieved cure,” Allegretti said. “While symptoms did perform well in both groups, PCR performed better in patients with IBD.”
Regarding the asymptomatic carriage rate post-FMT, 120 patients were asymptomatic at week 1, and only one was PCR positive, resulting in a 0.8% asymptomatic carriage rate. Furthermore 130 patients were asymptomatic at week 4, and only two were PCR positive, resulting in a 1.5% asymptomatic carriage rate. “So again, the asymptomatic carriage rate post-FMT is very low,” she said.
Allegretti concluded that “symptom resolution at 4 weeks post-FMT accurately predicts 8-week cure, and therefore full 8-week follow up may not be necessary. Negative stool PCR at 4 weeks accurately predicted cure in patients with IBD, and lastly, low asymptomatic C. diff carriage rates post-FMT suggests that FMT is a potent treatment for de-colonization.” – by Adam Leitenberger
Allegretti JR, et al. Abstract #7. Presented at: American College of Gastroenterology Annual Scientific Meeting; Oct. 17-19, 2016; Las Vegas, NV.
Disclosures: The researchers report no relevant financial disclosures.