Latest Evidence and Clinical Guidance to Reduce Clostridioides difficile Infection Recurrence

Clostridium difficile bacteria
Clostridium difficile bacteria
Studies present promising therapeutic options to reduce recurrent CDI, as well as strategies to improve favorable economic outcomes.

Treatment with fidaxomicin decreased recurrence and increased global cure in patients with high-risk Clostridioides difficile infection (CDI), while an oral investigational microbiome drug, SER-262, also reduced recurrent CDI by restoring colonization resistance, according to research presented at IDWeek 2019, held October 2 to 6, in Washington, DC.

CDI is a leading cause of nosocomial infection and the major challenge of current therapeutic options for the management of this infection is recurrence of disease after the completion of treatment. Several explanations for the cause of recurrent CDI have been evaluated, including inadequate antibiotic efficacy or persistent dysbiosis.

Kohinke, et al1 explored the effect of fidaxomicin in a quasi-experimental study comprising 282 adults with either a first episode or first recurrence of CDI at Carilion Roanoke Memorial Hospital in Virginia. Researchers evaluated patients for recurrence of CDI before and after implementation of a directive to treat high-risk patients with fidaxomicin; these periods were defined as May 2017 to November 2017 and May 2018 to November 2018, respectively. Recurrence was defined as re-infection within 4 weeks of treatment. In the pre-implementation group, 39.6% received oral vancomycin, 59.1% metronidazole, and 1.3% fidaxomicin. In the post-implementation group, oral vancomycin was administered to 44.5% of patients and fidaxomicin to 52.3%.

The researchers discovered that the use of fidaxomicin as a first-line agent was associated with decreased recurrence compared with vancomycin (30.2% vs 17.1%, P =.019). Further, secondary endpoints of global cure and infection-related readmission demonstrated similar results (86% vs 75%; P =.44, and 28.6% vs 37.5%; P =.67, respectively). An additional benefit included possible reduction in estimated healthcare costs of $461,176 and up to $1,107,953 in CDI-related expenses per year due to reduction in hospital readmissions.

Study limitations included a single-center design, lack of randomization, and the potential for misclassification bias.

In a separate study, Ford, et al2 evaluated an alternative option for the reduction of recurrent CDI rates. Researchers investigated the safety, tolerability, and efficacy of SER-262, an oral capsule that contains a consortium of 12 bacterial strains in spore form, designed to restore colonization resistance in the microbiome of the gut. The SERES-262-001 phase 1b randomized placebo-controlled dose escalation study enrolled 96 patients with primary CDI in 8 dose cohorts in a 5:1 ratio to evaluate the prevention of recurrent CDI. Patients were administered SER-262 after treatment with either vancomycin (n=39) or metronidazole (n=57). Fecal samples were evaluated for SER-262 engraftment using strain-specific molecular probes. End points included safety and recurrent CDI rates for <8 weeks post-treatment and strain engraftment at 1, 4, 8, 12, and 24 weeks.

Results from post-hoc analysis demonstrated reduced rates of recurrent CDI in the vancomycin plus SER-262 group compared with metronidazole plus SER-262 (6.3 vs 27.1%, respectively, P =.02). A total of 8 of 12 SER-262 strains exhibited significant engraftment compared with placebo. Further, greater SER-262 strain engraftment was observed in patients who received vancomycin compared with those who received metronidazole (P <.001). An investigation of the diversity of patients’ microbiome before antibiotic therapy demonstrated that compared with patients who received metronidazole patients who received vancomycin had lower concentrations of Bacteroidetes and Firmicute spp. Moreover, SER-262 safety was comparable with placebo.

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Thus, the investigators concluded that SER-262 was safe and well-tolerated and “the higher efficacy rates of SER-262 in reducing [recurrent] CDI among [patients who received vancomycin] may be due to low baseline microbial diversity, which creates an ecologic niche for greater engraftment of dose species.”

Both studies present promising therapeutic options to reduce recurrent CDI and strategies to improve favorable economic outcomes.


  1. Kohinke R, McDaniel L, Perhac A, Everson N. First-line fidaxomicin use in high-risk inpatients reduces recurrence rates. Presented at: IDWeek 2019; October-2-6, 2019; Washington, DC. Abstract 2437.
  2. Ford C, Litcofsky B, McGovern B, et al. Engraftment of investigational microbiome drug, SER-262, in subjects receiving vancomycin is associated with reduced rates of recurrence after primary Clostridiumdifficile infection (CDI). Presented at: IDWeek 2019; October-2-6, 2019; Washington, DC. Abstract 1503.