Preliminary study results showed that Fecal donor-unrelated donor mix for initial Clostridium difficile infection is associated with specific bacterial communities that do not resemble the donors’ sample.
Adrian Camacho Ortiz, MD, PhD
Fecal donor-unrelated donor mix (FMT-FURM) transplantation for initial Clostridium difficile infection (CDI) typically feature specific bacterial communities that are foreign to donors’ samples and are different than those found among CDI patients receiving vancomycin, according to findings from an open, 2-arm pilot study reported in PLoS One.1
“Our results revealed that the microbiome in the healthy donors´ pool was different from the microbial composition of all the patient samples, regardless of treatment, age, [and] the number of transplants,” said study author Adrian Camacho Ortiz, MD, PhD, and the investigators. “The microbial composition over time in the vancomycin group was different from the microbiome in the FMT-FURM group, which seems to reflect that oral antibiotics have a profound effect on the gut microbiota as has been reported before.”
In this study, investigators randomized hospitalized adult patients with CDI to receive either 250 mg oral vancomycin 6 hours for 10—14 days (n= 9) or FMT-FURM (n= 7) as an intervention for the first CDI episode. The patients did not have a CDI history or history of CDI treatment. Feces donors were included if they were >18 years old, not pregnant and had a body mass index of 20–25 kg/m2.
A reduction on the Bristol stool scale of ≥2 points as well as a ≥50% reduction in bowel movements comprised the determination of CDI resolution. Additional criteria for CDI resolution included absence of fever and no abdominal pain. The investigators obtained a fecal sample from each patient at 0, 3 and 7 days post-treatment. Then, CDI was isolated and characterized by polymerase chain reaction, and the fecal and FMT-FURM samples were evaluated using 16S rRNA sequencing.
A greater proportion of patients in the vancomycin arm experienced resolution of symptoms compared with patients receiving their first and second FMT-FURM dose; however, these differences were not considered significant (88.9% versus 57.1% and 71.4%, respectively; P =.26). Patients randomized to FMT-FURM experienced adverse effects, a finding that appeared to demonstrate the safety of the intervention in this patient population.
The isolates that were recovered (n= 12) in this sample mostly carried tcdB, tcdA, cdtA, and cdtB, with an 18-bp deletion in tcdC, and all isolates were found to be resistant to moxifloxacin and ciprofloxacin yet vulnerable to fidaxomicin, linezolid, metronidazole and tetracycline. Bacteroidetes, Firmicutes and Proteobacteria were the dominant bacteria types among the participants receiving FMT-FURM.
When investigators compared the vancomycin and FMT-FURM groups over time, they found a noticeable difference in microbial composition patterns for those receiving the antibiotic. Overall, Bacteroides spp. represented the most affected bacteria in this sample. An average 29% decrease in Bacteroidetes on day 0 to 15% on day 3 were observed. Conversely, investigators noticed an increase of Proteobacteria of 13% on day 0 to 47% on day 7, an increase potentially attributable to Enterobacteriaceae members.
“Given that the baseline and modifying factors are so different between the traditional FMT patients and our population, treatment response rates and microbiome changes should be carefully evaluated,” added the investigators. “We speculate that the exposure to antibiotics before and/or after FMT-FURM treatment negatively influenced the resolution of CDI even after re-transplantation.”
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