SER-109 Reduces Rates of Recurrent C Difficile Infections

Colleen S. Kraft, MD

In data presented during the American Society of Microbiology (ASM) 2021 World Microbe Forum, researchers found an investigational Clostridium difficile infection (CDI) treatment resulted in a low recurrence rate when compared to placebo.

A team led by Colleen S. Kraft, MD, Emory University School of Medicine, evaluated the distribution of C difficile ribotypes and whether CDI recurrence was related to relapse or reinfection in patients with multiply rCDI.

Background

The researchers previously tested an investigational microbiome therapeutic consisting of purified Firmicutes spores called SER-109 in an attempt to identify the typing of strains from infections to learn more about CDI disease and epidemiology.

“SER-109 may represent a paradigm shift in the clinical management of patients with recurrent CDI,” the authors wrote.

C difficile infections are generally caused by the disruption of the microbiome coupled with exposure to C difficile spores. The leading risk for infections is the exposure of broad spectrum antibiotics, which can cause collateral damage to beneficial microbes that normally reside in the gastrointestinal microbiome.

In addition, there is a current lack of antibiotics that target C difficile due to a lack of effect on C difficile spores that germinate within a disrupted microbiome, preventing a sustained response in the majority of patients.

The researchers previously found SER-109 was superior to placebo in reducing the recurrence of CDI during an 8 week phase 3 study (12.4% vs 39.8%; RR, 0.32; 95% CI, 0.18-0.58; P <0.001 for RR <1.0; P <0.001 for RR <0.833).

Strain Typing

Strain typing data is generally not available to assess whether recurrence is due to relapse or reinfection.

In the ECOSPOR III study, the researchers used selective media to isolate C difficile from baseline stool samples and stool samples from unscheduled visits for recurrence of diarrhea during a 24 week follow-up period. Each participant’s baseline stool sample was taken before randomization without regard to whether the patient had started or completed the standard-of-care antibiotic treatment.

The team also isolated C difficile from ethanol treated stool using C difficile selective agar—Cycloserine-cefoxitin-fructose agar with and without horse blood—as well as enrichment culture—Cycloserine Cefoxitin Mannitol Broth with Taurocholic Acid Lysozyme and Cysteine.

In addition, the investigators saved 1 C difficile isolate per stool sample and typed strains by PCR ribotyping.

Results

In a post-hoc analysis, the researchers evaluated the distribution and prevalence of ribotypes in patients and determined whether the ribotype at recurrence was indicative of relapse or reinfection for up to 24 weeks.

In total, 122 patients (67%) yielded positive cultures at baseline, while 10 (5.5%) yielded no growth. In addition, 50 (27.5%) subjects did not contribute a sample. Overall, there were 33 different ribotypes at baseline with 020/014 the most common ribotype, which was identified in 18.9% of baseline patients.

Hypervirulent ribotypes 027 and 078 (0787/126) were also identified in 15.6% (n = 19) of the patient population at baseline.

A total of 47 recurrences were observed, 11 in the SER-109 arm and 36 in the placebo group. Of those, paired ribotypes were available for 32 recurrence events, including 9 in the treatment group and 23 in the placebo group.

Relapses were also more common in the study (n = 24; 75%).

However, relapse events were lower in patients treated with SER-109 (5 vs. 19). Reinfection events were comparable, but low (4 vs. 4).

“SER-109 significantly reduced CDI recurrence compared to placebo at 8 weeks after dosing with an observed safety profile comparable to placebo,” the authors wrote. “Multiple ribotypes were isolated, which is consistent with typically observed epidemiological studies. Low rates of recurrence with SER-109 observed in ECOSPOR III limit the ability to assess the impact of relapse versus reinfection; however, numerically, SER-109 demonstrated reduced rates of recurrence compared with placebo across ribotypes and protected against the dominant mode of recurrence (relapse) in patients with a history of multiply recurrent CDI.”

The researchers are currently enrolling patients with at least 1 episode of CDI for an open-label study.

The study, “Characterization of Ribotypes Among Study Participants in a Phase 3 Trial of Investigational Microbiome Therapeutic SER-109 to Reduce Recurrent Clostridioides difficile infection (rCDI),”was published online in ASM.