Comorbid status and the faecal microbial transplantation failure in treatment of recurrent Clostridioides difficile infection – pilot prospective observational cohort study

Abstract

Background Faecal microbial transplantation (FMT) is currently the most effective treatment of recurrent Clostridioides difficile infection (CDI). However, up to 20% of patients experience further recurrences after single FMT. The mechanisms that lead to FMT failure and its risk factors are poorly understood. Comorbidity is one of the risk factors of the failure of standard antibiotic therapy of recurrent CDI. It is not known if comorbidity is also associated with the risk of FMT failure. Methods We conducted a prospective observational cohort study in order to elucidate if comorbid status is associated with FMT failure. Patients with microbiologically proven recurrent CDI were recruited and underwent FMT via retention enema. Patients were followed up for 12 weeks after FMT for signs and symptoms of CDI recurrence. Single FMT failure was defined as recurrence of diarrhoea and a positive stool test for the presence of C. difficile antigen or toxin at any time point during the 12 weeks of follow-up. We assessed the association of single FMT failure with possible manageable and unmanageable risk factors. As a surrogate of comorbid status, we used Charlson Comorbidity Index (CCI) ≥ 7. Results A total of 60 patients that underwent single FMT (34 women, 26 men) were included in the study. Overall, 15 patients (25%) experienced single FMT failure. 24 patients (40%) had CCI ≥ 7, and 45.0% patients with CCI ≥ 7 experienced failure of single FMT. Patients who experienced single FMT failure had a significantly higher CCI and significantly lower albumin concentration as compared to patients who experienced single FMT success. There was no difference in age, C-reactive protein concentration, leukocyte count and time from FMT to first defecation. In multivariate analysis, CCI ≥ 7 was positively associated with the failure of single FMT. Analysis was controlled for sex, age, time from FMT to first defecation, concomitant PPI therapy, severe CDI, hospital-acquired infection and albumin concentration. Conclusions Comorbid status surrogated by CCI is positively associated with the failure of single FMT in the treatment of recurrent CDI.

Faecal microbiota transplantation for Clostridioides difficile infection: Four years’ experience of the Netherlands Donor Feces Bank

“…Our observation is similar to a previous report from an FMT‐expert centre, which showed that 25% of patients referred for FMT did not have confirmed rCDI 18 . In particular, new onset or persistent activity of IBD appears to be a diagnostic pitfall 18 , 19 . In addition, non‐responsiveness to anti‐CDI antibiotics seems to point to an alternative diagnosis rather than therapy‐refractory CDI in most patients.…”

“… 18 In particular, new onset or persistent activity of IBD appears to be a diagnostic pitfall. 18 , 19 In addition, non-responsiveness to anti-CDI antibiotics seems to point to an alternative diagnosis rather than therapy-refractory CDI in most patients. In fact, only four of our 129 patients were deemed to suffer from therapy-refractory CDI by the expert-panel.…”

“…The majority (61%) of early relapses were not preceded by antibiotics, indicating that other factors also contribute to FMT failures, such as an immunocompetence. Other studies have identified Charlson Comorbidity Index, 20 the severity of CDI, 21 , 22 previous (CDI) hospitalisation, 22 , 23 inpatient status, 22 surgery, 23 female sex 23 and older age 24 to predict recurrence after FMT. We did not recognize donor-related factors contributing to FMT outcome, confirming previous reports.…”

A framework to trace microbial engraftment at the strain level during fecal microbiota transplantation

“…For the CDI dataset we used, the original data publishers had defined the FMT success as no relapse of diarrhea after eight weeks from FMT. However, other works did not have such an explicit time limitation [41][42][43][44]. If we collected FMT failure samples from other projects and merged them, the detected determinant strains would be affected.…”

Association Between Charlson Comorbidity Index and Community-Acquired Pressure Injury in Older Acute Inpatients in a Chinese Tertiary Hospital

“…The CCI is a well-established surrogate marker of comorbidity. 10 With further study of the etiology of PI, it has been found that internal factors characterized by comorbidity play an important role in the pathogenesis of PI. 11 Although researchers have recognized that contributing comorbidities are associated with the development of PI, the effects of the combination, number, and severity of comorbid conditions on PI are unknown, and there have been few studies examining the correlation between multiple comorbidities as the main exposure factor and PI.…”