New and emerging therapies for Clostridium difficile infection

Abstract

(max 200 words)Purpose of review: Clostridium difficile infection has attained high prominence given its prevalence and impacts on patients and healthcare institutions. Multiple new approaches to the prevention and treatment of CDI are undergoing clinical trials. Recent findings:Bezlotoxumab is a monoclonal antibody against toxin B that has successfully completed phase three studies, demonstrating a significant reduction in recurrent CDI when given with standard of care antibiotics. Antibiotics under development include cadazolid and ridinilazole, while surotomycin has had disappointing phase 3 results. Multiple live biotherapeutics are being developed, including freeze thawed and encapsulated versions of faecal microbiota transplantation to improve the practicality of treating patients with recurrent CDI. Alternatives to faecal microbiota transplantation, that aim to improve safety, including a microbial suspension, RBX2660, and a complex spore formulation, SER-109, have progressed to phase 2 studies. A non-toxigenic C. difficile strain has also shown promise to prevent recurrent CDI. In addition, three C. difficile vaccines have progressed to phase 2/3 clinical trials. Summary:The diverse approaches to treating and preventing CDI offer substantial promise that new treatment options will soon emerge, particular ones that reduce the risk of recurrences.3

Immunization with Recombinant TcdB-Encapsulated Nanocomplex Induces Protection against Clostridium difficile Challenge in a Mouse Model

“…Vaccine development has been considered by many to be one way to control the morbidity and relapses due to CDI (Martin and Wilcox, 2016). Most studies on the development of vaccines against CDI focused on the major pathogenic determinants of C. difficile , toxin A and B (Martin and Wilcox, 2016).…”

“…Vaccine development has been considered by many to be one way to control the morbidity and relapses due to CDI (Martin and Wilcox, 2016). Most studies on the development of vaccines against CDI focused on the major pathogenic determinants of C. difficile , toxin A and B (Martin and Wilcox, 2016). Production of anti-toxin antibodies are considered to be the most effective defense mechanism in mediating systemic and mucosal protection against CDI in both animal models and patients (Pechine and Collignon, 2016).…”

The use of faecal microbiota transplant as treatment for recurrent or refractoryClostridium difficileinfection and other potential indications: joint British Society of Gastroenterology (BSG) and Healthcare Infection Society (HIS) guidelines

“…Previous research has demonstrated that commensal bacteria cultured from the stool of healthy donors,22 sterile faecal filtrate23 and/or spores of Firmicutes derived from ethanol-treated stool from healthy donors24 may have similar efficacy to conventional FMT in treating CDI, although results of the latter approach produced disappointing outcome data when extended to a phase II clinical trial 25. For the purposes of this guideline, the BSG/HIS working group considered only studies that used the administration of manipulated whole stool (including encapsulated faeces).…”

Novel therapies and preventative strategies for primary and recurrent Clostridium difficile infections

“…Results from the phase II (ECOSPOR) trial indicate that SER‐109 did not meet the primary endpoint for reducing CDI recurrence overall. However, in high‐risk populations (in this case, those 65 years or older), SER‐109 treatment showed reduced recurrence rates (45% versus 80% recurrence risk) . Two phase III trials (ECOSPOR III–NCT03183128 and ECOSPOR IV–NCT03183141) are currently recruiting.…”