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Clostridioides difficile
Published in Firza Alexander Gronthoud, Practical Clinical Microbiology and Infectious Diseases, 2020
Bezlotoxumab is a monoclonal antibody which blocks toxin B. In combination with standard antibiotic treatment, it has been shown to significantly reduce the rate of recurrence. Currently more studies are needed to investigate the optimal role and indication for use. Bezlotoxumab may increase risk of congestive heart failure.
Delivery of a therapeutic antibody to the lower gastrointestinal tract for the treatment of Clostridium difficile infection (CDI)
Published in Pharmaceutical Development and Technology, 2023
Bowen Jiang, Dongyue Yu, Yongrong Zhang, Therwa Hamza, Hanping Feng, Stephen W. Hoag
Antibodies that can neutralize TcdA and TcdB present a treatment option for acute and recurrent CDI treatment. Bezlotoxumab (ZINPLAVA™, Merck & Co., Inc.) is an intravenously administrated monoclonal antibody that binds to and neutralizes Tcd B (Orth et al. 2014). In two phase 3 clinical trials, a single infusion of bezlotoxumab to patients receiving standard antibiotics treatment reduced the recurrence rate of CDI by about 10% (Wilcox et al. 2017). Bezlotoxumab is the first antibody therapeutic approved for the treatment of recurrent CDI; other antibodies are being tested in clinics (Hussack and Tanha 2016). The adverse effects of Bezlotoxumab were comparable to the placebo groups. With the limitation of standard antibiotics treatment for recurrent CDI and the cost and inconvenience of fecal transplantation, therapeutic antibodies, like bezlotoxumab, provide promising treatment options with clear mechanisms and efficacy.
Bezlotoxumab prevents extraintestinal organ damage induced by Clostridioides difficile infection
Published in Gut Microbes, 2022
Steven J. Mileto, Melanie L. Hutton, Sarah L. Walton, Antariksh Das, Lisa J. Ioannidis, Don Ketagoda, Kylie M. Quinn, Kate M. Denton, Diana S. Hansen, Dena Lyras
Although progression of CDI into sepsis and septic shock is a rare complication of CDI, this disease profile is a major contributing factor to patient fatality. Detecting sepsis-like serum markers and disease symptoms in mice, and identifying therapeutics that prevent these outcomes, is an important outcome of the work described here as it provides new insights into this poorly characterized aspect of CDI. Administration of bezlotoxumab is already FDA approved, and is used primarily to prevent CDI recurrence. The work presented here shows that bezlotoxumab can prevent systemic disease pathologies and symptoms during acute infection, in particular thymic and kidney injury, and changes in serum glucose, urea and IL-6, and is supported by results published by others.48,58 Bezlotoxumab may therefore be a suitable adjunct therapy for cases of severe primary CDI, and may prevent the onset of systemic disease complications that may worsen patient outcomes. Adjunct therapies such as pooled human intravenous immunoglobulin (IVIG) have shown efficacy in reducing C. difficile disease and aiding in disease resolution (reviewed in70), however they vary in formulation and in TcdA/B antibody levels; thus, bezlotoxumab may be a more suitable treatment alternative. By detecting these changes early in disease, timely intervention can occur, which may help prevent the onset of severe symptoms and improve the current mortality rate of CDI, at roughly 20,000 deaths each year in the U.S.A alone.71
Clinical management of severe, fulminant, and refractory Clostridioides difficile infection
Published in Expert Review of Anti-infective Therapy, 2020
Bezlotoxumab, a fully humanized monoclonal antibody against C. difficile toxin B was shown to be useful in the treatment of CDI. In MODIFY I and MODIFY II, two double-blind, randomized, placebo-controlled, phase III trials, patients were randomized to receive bezlotoxumab (antitoxin B), actoxumab (antitoxin A), or placebo, in addition to standard of care antibiotics (metronidazole, vancomycin, and/or fidaxomicin) [51]. Rates of CDI recurrence within 12 weeks upon comparison of bezlotoxumab versus placebo were 17% vs 28% (p < 0.001) in MODIFY 1% and 15% vs 26% (P < 0.001) in MODIFY 2. In a subgroup analysis of patients with SCDI, rates of recurrence were 10.7% for subjects receiving bezlotoxumab versus 22.4% for placebo.