Dataset Information

Application of Antibody-Mediated Therapy for Treatment and Prevention of Clostridium difficile Infection.

ABSTRACT: Clostridium difficile causes antibiotic- and healthcare-associated diarrhea, which is characterized by a high mortality rate (5-15%) and high recurrence rate of 20% or more. Therapeutic alternatives to antibiotics are urgently needed to improve the overall cure rate. Among these, therapeutic antibodies have shown promising results in clinical studies. Herein, the authors review current monoclonal and polyclonal anti- C. difficile antibodies that have entered the clinical development stage, either for systemic administration or by the oral route. The antibodies can be applied as monotherapy or in combination with standard-of-care to treat an infection with C. difficile or to protect from a recurrence. Bezlotoxumab is the first antibody for secondary prevention of recurrence of C. difficile infection approved by the regulatory agencies in US and Europe. The human monoclonal antibody is administered systemically to patients receiving oral standard-of-care antibiotics. Other antibodies are currently in the clinical pipeline, and some are intended for oral use. They show a good safety profile, high efficacy and low production costs, and can be considered promising therapies of the future. The most promising orally administered drug candidate is a bovine antibody from hyperimmune colostral milk, which is in an advanced clinical development stage. Which antibody will enter the market is dependent on its bioavailability at the site of infection as well as its activity against C. difficile toxins, protection against colonization and possible action on spore formation. The antibody must demonstrate a clear benefit in comparison with other available treatment options to be considered for use by clinicians.

SUBMITTER: Forster B

PROVIDER: S-EPMC6027166 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Application of Antibody-Mediated Therapy for Treatment and Prevention of Clostridium difficile Infection.

Förster Beatrix B Chung Pui Khi PK Crobach Monique J T MJT Kuijper Ed J EJ

Frontiers in microbiology 20180625

Clostridium difficile causes antibiotic- and healthcare-associated diarrhea, which is characterized by a high mortality rate (5-15%) and high recurrence rate of 20% or more. Therapeutic alternatives to antibiotics are urgently needed to improve the overall cure rate. Among these, therapeutic antibodies have shown promising results in clinical studies. Herein, the authors review current monoclonal and polyclonal anti- C. difficile antibodies that have entered the clinical developmen ...[more]

PMID: 29988597

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Project description:The current picture of Clostridium difficile infection (CDI) is alarming with a mortality rate ranging between 3% and 15% and a CDI recurrence rate ranging from 12% to 40%. Despite the great efforts made over the past 10?years to face the CDI burden, there are still gray areas in our knowledge on CDI management. The traditional anti-CDI antimicrobials are not always adequate in addressing the current needs in CDI management. The aim of our review is to give an update on novel antimicrobials for the treatment of CDI, considering the currently available evidences on their efficacy, safety, molecular mechanism of action, and their probability to be successfully introduced into the clinical practice in the near future. We identified, through a PubMed search, 16 novel antimicrobial molecules under study for CDI treatment: cadazolid, surotomycin, ridinilazole, LFF571, ramoplanin, CRS3123, fusidic acid, nitazoxanide, rifampin, rifaximin, tigecycline, auranofin, NVB302, thuricin CD, lacticin 3147, and acyldepsipeptide antimicrobials. In comparison with the traditional anti-CDI antimicrobial treatment, some of the novel antimicrobials reviewed in this study offer several advantages, i.e., the favorable pharmacokinetic and pharmacodynamic profile, the narrow-spectrum activity against CD that implicates a low impact on the gut microbiota composition, the inhibitory activity on CD sporulation and toxins production. Among these novel antimicrobials, the most active compounds in reducing spore production are cadazolid, ridinilazole, CRS3123, ramoplanin and, potentially, the acyldepsipeptide antimicrobials. These antimicrobials may potentially reduce CD environment spread and persistence, thus reducing CDI healthcare-associated acquisition. However, some of them, i.e., surotomycin, fusidic acid, etc., will not be available due to lack of superiority versus standard of treatment. The most CD narrow-spectrum novel antimicrobials that allow to preserve microbiota integrity are cadazolid, ridinilazole, auranofin, and thuricin CD. In conclusion, the novel antimicrobial molecules under development for CDI have promising key features and advancements in comparison to the traditional anti-CDI antimicrobials. In the near future, some of these new molecules might be effective alternatives to fight CDI.

Dataset Information

Application of Antibody-Mediated Therapy for Treatment and Prevention of Clostridium difficile Infection.

Publications

Application of Antibody-Mediated Therapy for Treatment and Prevention of <i>Clostridium difficile</i> Infection.

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