Bezlotoxumab for Preventing Recurrent Clostridioides difficile Infection: A Narrative Review from Pathophysiology to Clinical Studies

Abstract

Clostridioides difficile infection (CDI) and recurrent CDI (rCDI) remain associated with a reduction in the patients' quality of life and with increased healthcare costs. Bezlotoxumab is a monoclonal antibody against toxin B of C. difficile, approved for prevention of rCDI. In this narrative review, we briefly discuss the pathophysiology of CDI and the mechanism of action of bezlotoxumab, as well as the available evidence from investigational and observational studies in terms of efficacy, effectiveness, and safety of bezlotoxumab for the prevention of rCDI. Overall, bezlotoxumab has proved efficacious in reducing the burden of rCDI, thereby providing clinicians with an important novel strategy to achieve sustained cure. Nonetheless, experiences outside randomized controlled trials (RCTs) remain scant, and mostly represented by case series without a control group. Along with the conduction of RCTs to directly compare bezlotoxumab with faecal microbiota transplantation (or to precisely evaluate the role of their combined use), further widening our post-marketing experience remains paramount to firmly guide the use of bezlotoxumab outside RCTs, and to clearly identify those real-life settings where its preventive benefits can be exploited most.

Oral Vancomycin Prophylaxis for Primary and Secondary Prevention of Clostridioides difficile Infection in Patients Treated with Systemic Antibiotic Therapy: A Systematic Review, Meta-Analysis and Trial Sequential Analysis

“…Notwithstanding the lack of head-to-head studies, OVP appears very appealing as opposed to other potential preventive strategies for CDI, such as fecal microbiota transplantation (strategy of dysbiosis restoration) [ 58 ] or passive immunization with bezlotoxumab [ 59 ], in the light of its very low cost and ease of administration [ 60 ].…”

The adaptive immune response toClostridioides difficile: A tricky balance between immunoprotection and immunopathogenesis

“…78,79 Moreover, Bezlotoxumab a monoclonal Ab against toxin B of C. difficile, has been approved for the prevention of recurrent CDI. 80 The most advanced vaccine until October 2017 was a toxoidbased vaccine produced by Sanofi Pasteur. After a large-scale phase III clinical trial, it was concluded that the primary objective, the prevention of primary CDI, was unlikely to be achieved and the entire program of vaccine development was halted.…”

“…Nowadays, immune‐based strategies relying on active vaccination or passive administration targeting TcdA, TcdB, and other antigens of C. difficile are under investigation in clinical trials (Pfizer, Intercell, and Medarex) 78,79 . Moreover, Bezlotoxumab a monoclonal Ab against toxin B of C. difficile , has been approved for the prevention of recurrent CDI 80 . The most advanced vaccine until October 2017 was a toxoid‐based vaccine produced by Sanofi Pasteur.…”

Some Suggestions from PK/PD Principles to Contain Resistance in the Clinical Setting—Focus on ICU Patients and Gram-Negative Strains

“…In the near future, there will possibly be non-pharmacological tools and/or non-antibiotic therapies to fight bacterial diseases. Immunotherapy is the most advanced alternative approach with a number of antibodies, including bezlotuxumab targeting Clostridium difficile , already approved by FDA [ 7 ]. Another strategy is represented by the exploitation of bacteriophages genetically modified that may be engineered to produce bacterial-biofilm-degrading enzymes upon infection, to overexpress genes able to repress bacterial DNA repair systems, to deliver genes able to make pathogens more susceptible to antibiotics or to express antimicrobial peptides and toxins.…”