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16-01-2025 | Clostridioides Difficile | Narrative review Free for a limited time

The evolving landscape of live biotherapeutics in the treatment of Clostridioides difficile infection

Authors: Parul Berry, Sahil Khanna

Published in: Indian Journal of Gastroenterology

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Abstract

Clostridioides difficile (C. difficile) infection (CDI) is common after antibiotic exposure and presents significant morbidity, mortality and healthcare costs worldwide. The rising incidence of recurrent CDI, driven by hypervirulent strains, widespread antibiotic use and increased community transmission, has led to an urgent need for novel therapeutic strategies. Conventional antibiotic treatments, although effective, face limitations due to rising antibiotic resistance and high recurrence rates, which can reach up to 60% after multiple infections. This has prompted exploration of alternative therapies such as fecal microbiota-based therapies, including fecal microbiota transplantation (FMT) and live biotherapeutics (LBPs), which demonstrate superior efficacy in preventing recurrence. They are aimed at restoring the gut microbiota. Fecal microbiota, live-jslm and fecal microbiota spores, live-brpk have been approved by the U.S. Food and Drug Administration in individuals aged 18 years or older for recurrent CDI after standard antimicrobial treatment. They have demonstrated high efficacy and a favorable safety profile in clinical trials. Another LBP under study includes VE-303, which is not derived from human donor stool. This review provides a comprehensive overview of the current therapeutic landscape for CDI, including its epidemiology, pathophysiology, risk factors, diagnostic modalities and treatment strategies. The review delves into the emerging role of live biotherapeutics, with a particular focus on fecal microbiota-based therapies. We explore their development, mechanisms of action, clinical applications and potential to revolutionize CDI management.
Literature
9.
go back to reference Monaghan T, Biswas R, Satav A, Ambalkar S, Wilcox M, Kashyap RS. PTH-90 prevalence of Clostridioides difficile infection in Central India: a prospective observational cohort study. BMJ Publishing Group; 2021. Monaghan T, Biswas R, Satav A, Ambalkar S, Wilcox M, Kashyap RS. PTH-90 prevalence of Clostridioides difficile infection in Central India: a prospective observational cohort study. BMJ Publishing Group; 2021.
16.
25.
go back to reference Miller JM, Binnicker MJ, Campbell S, et al. A guide to utilization of the microbiology laboratory for diagnosis of infectious diseases: 2018 update by the Infectious Diseases Society of America and the American Society for Microbiology. Clin Infect Dis. 2018;67:e1–94. https://doi.org/10.1093/cid/ciy381.CrossRefPubMed Miller JM, Binnicker MJ, Campbell S, et al. A guide to utilization of the microbiology laboratory for diagnosis of infectious diseases: 2018 update by the Infectious Diseases Society of America and the American Society for Microbiology. Clin Infect Dis. 2018;67:e1–94. https://​doi.​org/​10.​1093/​cid/​ciy381.CrossRefPubMed
30.
go back to reference Johnson S, Lavergne V, Skinner AM, et al. Clinical practice guideline by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA): 2021 focused update guidelines on management of Clostridioides difficile infection in adults. Clin Infect Dis. 2021;73:e1029–44. https://doi.org/10.1093/cid/ciab549.CrossRefPubMed Johnson S, Lavergne V, Skinner AM, et al. Clinical practice guideline by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA): 2021 focused update guidelines on management of Clostridioides difficile infection in adults. Clin Infect Dis. 2021;73:e1029–44. https://​doi.​org/​10.​1093/​cid/​ciab549.CrossRefPubMed
36.
go back to reference Fischer A, Sipe BW, Rogers NA, et al. Faecal microbiota transplantation plus selected use of vancomycin for severe-complicated Clostridium difficile infection: description of a protocol with high success rate. Alim Pharmacol Ther. 2015;42:470–6.CrossRef Fischer A, Sipe BW, Rogers NA, et al. Faecal microbiota transplantation plus selected use of vancomycin for severe-complicated Clostridium difficile infection: description of a protocol with high success rate. Alim Pharmacol Ther. 2015;42:470–6.CrossRef
50.
go back to reference Lee P-C, Chang T-E, Wang Y-P, et al. Alteration of gut microbial composition associated with the therapeutic efficacy of fecal microbiota transplantation in Clostridium difficile infection. J Form Med Assocn. 2022;121:1636–46.CrossRef Lee P-C, Chang T-E, Wang Y-P, et al. Alteration of gut microbial composition associated with the therapeutic efficacy of fecal microbiota transplantation in Clostridium difficile infection. J Form Med Assocn. 2022;121:1636–46.CrossRef
59.
go back to reference Khanna S, Pardi DS, Jones C, Shannon WD, Gonzalez C, Blount K. RBX7455, a non-frozen, orally administered investigational live biotherapeutic, is safe, effective, and shifts patients’ microbiomes in a phase 1 study for recurrent Clostridioides difficile infections. Clin Infect Dis. 2021;73:e1613–20. https://doi.org/10.1093/cid/ciaa1430.CrossRefPubMed Khanna S, Pardi DS, Jones C, Shannon WD, Gonzalez C, Blount K. RBX7455, a non-frozen, orally administered investigational live biotherapeutic, is safe, effective, and shifts patients’ microbiomes in a phase 1 study for recurrent Clostridioides difficile infections. Clin Infect Dis. 2021;73:e1613–20. https://​doi.​org/​10.​1093/​cid/​ciaa1430.CrossRefPubMed
60.
go back to reference Inc. FP. REBYOTA[Package insert] 2022. Accessed 01 August 2024. Inc. FP. REBYOTA[Package insert] 2022. Accessed 01 August 2024.
67.
go back to reference Khanna S, Dubberke ER, Knapple WL, et al. S132 An interim analysis of a phase 3, open-label study indicates efficacy and safety of RBX2660 in patients with recurrent Clostridioides difficile infection. Am J Gastroenterol. 2022;117(10S). Khanna S, Dubberke ER, Knapple WL, et al. S132 An interim analysis of a phase 3, open-label study indicates efficacy and safety of RBX2660 in patients with recurrent Clostridioides difficile infection. Am J Gastroenterol. 2022;117(10S).
68.
go back to reference Feuerstadt P, Chopra T, Knapple W, et al. PUNCH CD3-OLS: a phase 3 prospective observational cohort study to evaluate the safety and efficacy of fecal microbiota, live-jslm (REBYOTA) in adults with recurrent Clostridioides difficile infection. Clin Infect Dis. 2024:ciae437. https://doi.org/10.1093/cid/ciae437.CrossRefPubMed Feuerstadt P, Chopra T, Knapple W, et al. PUNCH CD3-OLS: a phase 3 prospective observational cohort study to evaluate the safety and efficacy of fecal microbiota, live-jslm (REBYOTA) in adults with recurrent Clostridioides difficile infection. Clin Infect Dis. 2024:ciae437. https://​doi.​org/​10.​1093/​cid/​ciae437.CrossRefPubMed
75.
go back to reference Sims MD, Khanna S, Feuerstadt P, et al. Safety and tolerability of SER-109 as an investigational microbiome therapeutic in adults with recurrent Clostridioides difficile infection: a phase 3, open-label, single-arm trial. JAMA Network Open. 2023;6:e2255758-e.CrossRef Sims MD, Khanna S, Feuerstadt P, et al. Safety and tolerability of SER-109 as an investigational microbiome therapeutic in adults with recurrent Clostridioides difficile infection: a phase 3, open-label, single-arm trial. JAMA Network Open. 2023;6:e2255758-e.CrossRef
76.
go back to reference Huang ES, Lashner B, Sims M, et al. 694 Durability of the clinical response to SER-109, an investigational oral microbiome therapeutic, in a phase 3 open-label trial (ECOSPOR IV) in patients with recurrent Clostridioides difficile infection. Gastroenterology. 2023;164:S-141.CrossRef Huang ES, Lashner B, Sims M, et al. 694 Durability of the clinical response to SER-109, an investigational oral microbiome therapeutic, in a phase 3 open-label trial (ECOSPOR IV) in patients with recurrent Clostridioides difficile infection. Gastroenterology. 2023;164:S-141.CrossRef
77.
go back to reference Lashner B, von Moltke L, De A, Pardi DS. S77 Safety and efficacy of fecal microbiota spores, live-brpk (formerly SER-109) in older patients with recurrent Clostridioides difficile infection: findings from an integrated analysis of phase 3 trials. Am J Gastroenterol. 2023;118(12S):S21. Lashner B, von Moltke L, De A, Pardi DS. S77 Safety and efficacy of fecal microbiota spores, live-brpk (formerly SER-109) in older patients with recurrent Clostridioides difficile infection: findings from an integrated analysis of phase 3 trials. Am J Gastroenterol. 2023;118(12S):S21.
78.
go back to reference Etifa P, Rodríguez C, Harmanus C, et al. Non-toxigenic Clostridioides difficile strain E4 (NTCD-E4) prevents establishment of primary C. difficile infection by epidemic PCR ribotype 027 in an in vitro human gut model. Antibiotics. 2023;12:435.CrossRefPubMedPubMedCentral Etifa P, Rodríguez C, Harmanus C, et al. Non-toxigenic Clostridioides difficile strain E4 (NTCD-E4) prevents establishment of primary C. difficile infection by epidemic PCR ribotype 027 in an in vitro human gut model. Antibiotics. 2023;12:435.CrossRefPubMedPubMedCentral
79.
go back to reference Gerding DN, Meyer T, Lee C, Cohen SH, Murthy UK, Poirier A, et al. Administration of spores of nontoxigenic Clostridium difficile strain M3 for prevention of recurrent C difficile infection: a randomized clinical trial. JAMA. 2015;313:1719–27. Gerding DN, Meyer T, Lee C, Cohen SH, Murthy UK, Poirier A, et al. Administration of spores of nontoxigenic Clostridium difficile strain M3 for prevention of recurrent C difficile infection: a randomized clinical trial. JAMA. 2015;313:1719–27.
82.
go back to reference Nale JY, Spencer J, Hargreaves KR, et al. Bacteriophage combinations significantly reduce Clostridium difficile growth in vitro and proliferation in vivo. Antimicrobial Agents Chemother. 2016;60:968–81. Nale JY, Spencer J, Hargreaves KR, et al. Bacteriophage combinations significantly reduce Clostridium difficile growth in vitro and proliferation in vivo. Antimicrobial Agents Chemother. 2016;60:968–81.
Metadata
Title
The evolving landscape of live biotherapeutics in the treatment of Clostridioides difficile infection
Authors
Parul Berry
Sahil Khanna
Publication date
16-01-2025
Publisher
Springer India
Published in
Indian Journal of Gastroenterology
Print ISSN: 0254-8860
Electronic ISSN: 0975-0711
DOI
https://doi.org/10.1007/s12664-024-01717-9