Bezlotoxumab in Patients with a Primary Clostridioides difficile Infection: A Literature Review

Abstract

Background: Nowadays, one of the main issues in the management of Clostridioides difficile infection (CDI) is the high rate of recurrences (rCDI), causing increased mortality and higher health care costs. Objectives: To assess the available evidence on the use of bezlotoxumab for the prevention of rCDI during a first CDI episode. Methods: Published articles on bezlotoxumab during a primary CDI episode were identified through computerized literature searches with the search terms [(bezlotoxumab) AND (CDI) OR (Clostridioides difficile infection)] using PubMed and by reviewing the references of retrieved articles. PubMed was searched until 31 August 2022. Results: Eighty-eight studies were identified as published from December 2014 to June 2022. Five studies were included in this study, one was a phase III clinical trial and four were sub-analyses or extensions of the previous phase III clinical trial. In the phase III clinical trial, the subgroup analysis on the included primary CDI patients showed that 13.5% of patients receiving bezlotoxumab had an rCDI, whilst 20.9% of patients in the placebo group had an rCDI at the twelve weeks follow-up (absolute difference: −7.4). Conclusions: Bezlotoxumab administration during the standard of care antibiotic therapy is effective and safe in reducing the rate of rCDI. Despite its high cost, evidence suggests considering bezlotoxumab in patients with a primary CDI episode. Further studies are needed to assess the benefit in specific subgroups of primary CDI patients and to define the risk factors to guide bezlotoxumab use.

Antibiotics in the clinical pipeline as of December 2022

“…Another mAb that also neutralizes B. anthracis toxins, raxibacumab [52,53], was similarly approved in 2012. The mAb bezlotoxumab, which binds to toxin B produced by C. difficile [54,55], was approved in 2016 to help prevent the recurrence of CDI after successfully completing two phase-III trials [56,57].…”

“…Telacebec ( 31) is an inhibitor of the mycobacterial respiratory cytochrome bc 1 complex [185,186,369]. Inhibition of bacterial respiratory systems is an emerging MoA [369,370] with three bedaquiline analogs, sudapyridine (38), TBAJ-876 (55) and TBAJ-587 (56) that are also in clinical development. GSK2556286 (57) was recently disclosed to be an adenylyl cyclase Rv1625c agonist, which interferes with cholesterol catabolism and reduces the levels of this critical carbon source [304].…”

Foodborne Clostridioides Species: Pathogenicity, Virulence and Biocontrol Options

“…Cure rates of >90% with vancomycin at dosage of >125 mg orally 3-4 times daily for >10 days Oral metronidazole should be limited to the treatment of an initial episode of mild-moderate CDI [5] Severe complicated/fulminant hypotension, septic shock, elevated serum lactate, ileus, toxic megacolon, bowel perforation or any fulminant course of disease (deterioration of the patient) [20] Fidaxomicin or vancomycin 125 mg, 6 hourly for 10 days and consider intravenous tigecycline 100 mg, followed by 50 mg 12 hourly [17] Not using single-use assays for diagnosis [18] ESCMIDrecommended diagnostic algorithm [18] Metronidazole associated with a substantial number of treatment failures (25%), 25% relapsed within 1-2 months [19] Fulminant refractory CDI not responding to recommended CDI antibiotic treatment, i.e., no response after 3-5 days of therapy [17] Fidaxomicin, Vancomycin, Tigecycline considered, surgery recommended [17] Mab bezlotoxumab and antibiotics for treatment of a second or further recurrence of CDI [19] Asymptomatic carriers of C. difficile may disseminate spores in the hospital leading to outbreaks [5] No use of metronidazole for treatment of severe or recurrent CDIs Fidaxomicin is a poorly absorbed macrolide highly active against C.…”

“…In cases of fulminant CDI where hypotension, shock, paralytic ileus, and/or toxic megacolon are present, a high dose of oral vancomycin and IV metronidazole is recommended [20]. The monoclonal antibody, bezlotoxumab, which was approved in 2016, can be used in conjunction with antibiotic therapy for C. difficile toxin B types [19]. The use of faecal transplantation for recurring CDI is recommended where treatment failure is evident, in patients with three or more episodes of CDI post initial treatment [20].…”

Advances in Therapeutic Strategies for the Management of Clostridioides difficile Infection

“…When fidaxomicin is not administrable, oral vancomycin 125 mg four times per day for 10 days is recommended [ 10 ]. In case of an episode of CDI with increased risk of recurrence, bezlotoxumab can be added to the oral standard of care treatment [ 11 ].…”