infections (CDI) have been a growing source of concern in healthcare as rates of recurrent infections are increasing in elderly populations and widespread antibiotic usage continues. The Centers for Disease Control and Prevention (CDC) estimates
that there are over half a million cases and 29,000 deaths annually in the US due to CDI’s. More concerning is that these deaths occur within 30 days of initial diagnosis. Antibiotic usage and hospitalization are the biggest risk factors for infection. Not only have CDI’s caused countless infections and deaths, they are a challenge to healthcare infection control efforts given their specialized needs for environmental cleaning and hand hygiene.
published in The Journal of Infectious Diseases
takes a new approach to treatment for recurrent CDI. By looking at the microbiome (the variety of microbes that live in the human body), researchers are playing upon the body’s naturally healthy state to reduce recurrence of infection. Fecal microbiota transplantation (FMT) is one treatment approach that has shown 81-90% success in recurrent CDI patient, however, the invasiveness and donor screening practices can leave room for error and disease transmission (especially of emerging infectious diseases).
The new SER-109 approach, “is composed of approximately 50 species of Firmicutes spores derived from stool specimens from healthy donors. After demonstrating the preclinical efficacy of SER-109 in rodent CDI models, we formulated it for oral delivery in humans based on the hypothesis that spore-forming organisms would compete metabolically with C. difficile
for essential nutrients and/or bile acids.”
Donors were screened for blood-borne and fecal pathogens and were excluded for several criteria including a BMI >25, history of gastrointestinal disorders, smoking, the use of antibiotics within the past six months, or the presence of immunosuppressive/antineoplastic agents. Spore concentrations were determined by dipicolonic acid (DPA) ratios and the “known numbers of spores representing three commensal species” as well as ridding the samples of residual gram-negative bacteria.
After donor stool specimens were provided and formulated into the SER-109 treatment, patients within the clinical study began treatment.
Patients within the study had their antibiotics discontinued two days prior to SER-109 treatment, followed by a bowel preparation and overnight fasting the day before. There were two cohorts. All 15 Cohort 1 members received 30 capsules of SER-109 (between 3x107
spores), and all 15 Cohort 2 members received SER-109 capsules with a lower fixed dose (1 x 108
Patients were followed for 8-weeks post-treatment, after which stool studies were collected to determine the SER-109 impact on gut microbiota. The median age for all cohorts was 66.5 years and the median time from initial CDI diagnosis to the most recent recurrence was 23.1 weeks for Cohort 1 and 34.3 weeks for Cohort 2.
A total of 26 patients out of 30 achieved the endpoint of no C.difficile
-positive diarrhea within the eight weeks following treatment. Interestingly, 4 patients that did not meet the endpoint happened to experience symptoms early on after treatment administration (between days 3-9). While one patient left the study, the other 3 patients had self-limiting diarrheal events, avoided antibiotic usage, and were C.difficile
-negative at eight weeks.
During the “safety phase” (weeks 8-24), 1 patient left the protocol, 2 patients were lost to follow-up, and 3 patients relapsed. Of the 3 patients that had relapse infections, 1 patient received antibiotics, however, 4 other patients from the overall study had antibiotic exposure and failed to relapse.
Based on the results of the study, the SER-109 treatment involving novel microbiome therapeutics shows promise, with 96.7% (29/30) of those patients that were treated achieving C.difficile
resolution at 8-weeks. While this study was limited in its use of an open-label, single-armed evaluation, it shows definite promise in the future of CDI treatment using microbiome therapeutics.