Efficacy of Bezlotoxumab in Preventing Recurrent Clostridioides Difficile Infection: A Narrative Review
Authors
##plugins.themes.bootstrap3.article.sidebar##
##plugins.themes.bootstrap3.article.main##
Abstract
Clostridioides difficile infection remains a leading cause of healthcare-associated diarrhea, linked primarily to broad-spectrum antibiotic use and gut microbiome disruption. Clostridioides difficile infection causes significant morbidity, mortality, and financial burden, with a high recurrence rate. Recurrence is driven by persistent spores, dysbiosis, and inadequate host immune responses to toxins A and B, particularly toxin B, the principal virulence factor. Standard treatments with vancomycin or fidaxomicin achieve initial cure but fail to prevent relapse. Alternative strategies such as fecal microbiota transplantation show promise but face challenges regarding accessibility, safety, and regulatory approval. Bezlotoxumab, a fully human monoclonal antibody targeting C. difficile toxin B, represents a novel adjunctive therapy to reduce recurrence risk. Trials have significantly reduced recurrent Clostridioides difficile infection, with the greatest benefit observed in elderly, immunocompromised, and high-risk patients. This review highlights the clinical role of bezlotoxumab in preventing recurrent Clostridioides difficile infection, emphasizing its therapeutic and economic potential while underscoring the need for further research to expand its application in primary Clostridioides difficile infection management.
##plugins.themes.bootstrap3.article.details##
Copyright (c) 2025 Simardeep Singh, Palak Gupta, Gaurab Shrestha, Biswajyoti Das, Mayank Dhalani, Akhil Pawa, Rohit Jain
This work is licensed under a Creative Commons Attribution 4.0 International License.
Creative Commons License All articles published in Annals of Medicine and Medical Sciences are licensed under a Creative Commons Attribution 4.0 International License.
Simardeep Singh, MedStar Health Georgetown University (Baltimore) Program, United States.
MedStar Health Georgetown University (Baltimore) Program, United States.
Palak Gupta, Maharishi Markandeshwar Institute of Medical Sciences and Research, Ambala, Haryana, India.
Maharishi Markandeshwar Institute of Medical Sciences and Research, Ambala, Haryana, India.
Gaurab Shrestha, KIST Medical College & Teaching Hospital, Imadol, Lalitpur, Nepal.
KIST Medical College & Teaching Hospital, Imadol, Lalitpur, Nepal.
Biswajyoti Das, Maulana Azad Medical College, New Delhi, India.
Maulana Azad Medical College, New Delhi, India.
Mayank Dhalani, GMERS Medical College & Hospital, Gotri, Vadodara, Gujarat, India.
GMERS Medical College & Hospital, Gotri, Vadodara, Gujarat, India.
Akhil Pawa, St. George’s University School of Medicine, Grenada, West Indies.
St. George’s University School of Medicine, Grenada, West Indies.
Rohit Jain, Department of Medicine, Penn State Milton S. Hershey Medical Center, PA, United States.
Department of Medicine, Penn State Milton S. Hershey Medical Center, PA, United States.
[1] Wang, M., Deng, Z., Li, Y., et al. (2022). Design and characterization of a novel lytic protein against Clostridioides difficile. Applied Microbiology and Biotechnology. https://doi.org/10.1007/s00253-022-12010-0
[2] Feuerstadt P, Theriault N, Tillotson G. The burden of CDI in the United States: a multifactorial challenge. BMC Infectious Diseases. 2023;23(1). doi:10.1186/s12879-023-08096-0
[3] Centers for Disease Control and Prevention. 2024. Emerging Infections Program, Healthcare-Associated Infections – Community Interface Surveillance Report, Clostridioides difficile infection (CDI), 2022. Available at: https://www.cdc.gov/healthcare-associated-infections/media/pdfs/2022-CDI-Report-508.pdf.
[4] Liubakka, A., Vaughn, B. P. Clostridium difficile Infection and Fecal Microbiota Transplant. AACN Adv Crit Care. 2016 Jul;27(3):324-337. doi: 10.4037/aacnacc2016703. PMID: 27959316; PMCID: PMC5666691.
[5] Mada, P. K., Alam, U. Clostridioides difficile infection. [Updated 2024 Apr 10]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK431054/
[6] De Roo, A. C., Regenbogen, S. E. Clostridium difficile Infection: An Epidemiology Update. Clin Colon Rectal Surg. 2020;33(2):49-57. doi:10.1055/s-0040-1701229
[7] McDonald, L. C., Gerding, D. N., Johnson, S., et al. Clinical Practice Guidelines for Clostridium difficile Infection in Adults and Children: 2017 Update by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA). Clin Infect Dis. 2018;66(7):e1-e48. doi:10.1093/cid/cix1085
[8] Johnson, S., Louie, T. J., Gerding, D. N., et al. Vancomycin, metronidazole, or tolevamer for Clostridium difficile infection: results from two multinational, randomized, controlled trials. Clinical Infectious Diseases: an official publication of the Infectious Diseases Society of America, 59(3), 345–354. https://doi.org/10.1093/cid/ciu313
[9] Alonso, C. D., & Mahoney, M. V. (2018). Bezlotoxumab for the prevention of Clostridium difficile infection: a review of current evidence and safety profile. Infection and Drug Resistance, 12, 1–9. https://doi.org/10.2147/IDR.S159957
[10] Smits, W. K., Lyras, D., Lacy, D. B., et al. (2016). Clostridium difficile infection. Nat Rev Dis Primers, 2:16020. doi: 10.1038/nrdp.2016.20. [DOI] [PMC free article] [PubMed] [Google Scholar]
[11] Abou Chakra, C. N., Pepin, J., Sirard, S., et al. (2014). Risk factors for recurrence, complications, and mortality in Clostridium difficile infection: a systematic review. PLoS One, 9(6), e98400. https://doi.org/10.1371/journal.pone.0098400
[12] Song, J. H., Kim, Y. S. (2019). Recurrent Clostridium difficile Infection: Risk Factors, Treatment, and Prevention. Gut Liver, 13(1), 16-24. https://doi.org/10.5009/gnl18071
[13] Ofosu, A. (2016). Clostridium difficile infection: a review of current and emerging therapies. Ann Gastroenterol, 29(2), 147-154. https://doi.org/10.20524/aog.2016.0006
[14] Balsells, E., Shi, T., Leese, C., et al. (2019). Global burden of Clostridium difficile infections: a systematic review and meta-analysis. J Glob Health, 9(1), 010407. https://doi.org/10.7189/jogh.09.010407
[15] Revolinski, S. L., Munoz-Price, L. S. (2019). Clostridium difficile in Immunocompromised Hosts: A Review of Epidemiology, Risk Factors, Treatment, and Prevention. Clinical Infectious Diseases, 68(12), 2144–2153. https://doi.org/10.1093/cid/ciy845
[16] Kelly, C. R., Sangha, M. S. (2020). Bezlotoxumab for prevention of recurrent C. difficile infection in high-risk patients. Practical Gastroenterol, 21, 649–656. Retrieved from https://practicalgastro.com/wp-content/uploads/2020/10/A-Special-Article-October-2020.pdf
[17] Thandavaram, A., Channar, A., Purohit, A., et al. (2022). The Efficacy of Bezlotoxumab in the Prevention of Recurrent Clostridium difficile: A Systematic Review. Cureus, 14(8), e27979. https://doi.org/10.7759/cureus.27979
[18] Johnson, S., Gerding, D. N. (2019). Bezlotoxumab. Clin Infect Dis, 68(4), 699-704. https://doi.org/10.1093/cid/ciy577
[19] Alam, M. Z., Madan, R. (2024). Clostridioides difficile Toxins: Host Cell Interactions and Their Role in Disease Pathogenesis. Toxins (Basel), 16(6), 241. https://doi.org/10.3390/toxins16060241
[20] Kuehne, S. A., Collery, M. M., Kelly, M. L., et al. (2014). Importance of toxin A, toxin B, and CDT in virulence of an epidemic Clostridium difficile strain. J Infect Dis, 209(1), 83-86. https://doi.org/10.1093/infdis/jit426
[21] Theriot, C. M., Koenigsknecht, M. J., Carlson, P. E., Jr, et al. (2014). Antibiotic-induced shifts in the mouse gut microbiome and metabolome increase susceptibility to Clostridium difficile infection. Nat Commun, 5, 3114. https://doi.org/10.1038/ncomms4114
[22] Pickard, J. M., Zeng, M. Y., Caruso, R., Núñez, G. (2017). Gut microbiota: Role in pathogen colonization, immune responses, and inflammatory disease. Immunol Rev, 279(1), 70-89. https://doi.org/10.1111/imr.12567
[23] Förster, B., Chung, P. K., Crobach, M. J. T., Kuijper, E. J. (2018). Application of Antibody-Mediated Therapy for Treatment and Prevention of Clostridium difficile Infection. Front Microbiol, 9, 1382. https://doi.org/10.3389/fmicb.2018.01382
[24] Giacobbe, D. R., Dettori, S., Di Bella, S., et al. (2020). Bezlotoxumab for Preventing Recurrent Clostridioides difficile Infection: A Narrative Review from Pathophysiology to Clinical Studies. Infect Dis Ther, 9(3), 481-494. https://doi.org/10.1007/s40121-020-00314-5
[25] Abt, M. C., McKenney, P. T., Pamer, E. G. (2016). Clostridium difficile colitis: pathogenesis and host defence. Nat Rev Microbiol, 14(10), 609-620. https://doi.org/10.1038/nrmicro.2016.108
[26] Doh, Y. S., Kim, Y. S., Jung, H. J., et al. (2014). Long-Term Clinical Outcome of Clostridium difficile Infection in Hospitalized Patients: A Single Center Study. Intest Res, 12(4), 299-305. https://doi.org/10.5217/ir.2014.12.4.299
[27] Surawicz, C. M., Brandt, L. J., Binion, D. G., et al. (2013). Guidelines for diagnosis, treatment, and prevention of Clostridium difficile infections. Am J Gastroenterol, 108(4), 478-499. https://doi.org/10.1038/ajg.2013.4
[28] Castro, I., Tasias, M., Calabuig, E., Salavert, M. (2019). Doctor, my patient has CDI and should continue to receive antibiotics. The (unresolved) risk of recurrent CDI. Rev Esp Quimioter, 32(Suppl 2), 47-54.
[29] Wilcox, M. H., Gerding, D. N., Poxton, I. R., et al. (2017). Bezlotoxumab for Prevention of Recurrent Clostridium difficile Infection. N Engl J Med, 376(4), 305-317. https://doi.org/10.1056/NEJMoa1602615
[30] Bezlotoxumab for Clostridium difficile. (2018). Aust Prescr, 41(6), 198-199. https://doi.org/10.18773/austprescr.2018.020
[31] Gupta P, Zhang Z, Sugiman-Marangos SN, et al. Functional defects in Clostridium difficile TcdB toxin uptake identify CSPG4 receptor-binding determinants. J Biol Chem. 2017;292(42):17290-17301. doi:10.1074/jbc.M117.806687
[32] Gerding DN, Kelly CP, Rahav G, et al. Bezlotoxumab for Prevention of Recurrent Clostridium difficile Infection in Patients at Increased Risk for Recurrence. Clin Infect Dis. 2018;67(5):649-656. doi:10.1093/cid/ciy171
[33] Wilcox MH, Gerding DN, Poxton IR, et al. MODIFY I and MODIFY II Investigators. Bezlotoxumab for Prevention of Recurrent Clostridium difficile Infection. N Engl J Med. 2017 Jan 26;376(4):305-317. doi: 10.1056/NEJMoa1602615. PMID: 28121498.
[34] Escudero-Sánchez R, Ruíz-Ruizgómez M, Fernández-Fradejas J, et al. Real-World Experience with Bezlotoxumab for Prevention of Recurrence of Clostridioides difficile Infection. J Clin Med. 2020 Dec 22;10(1):2. doi: 10.3390/jcm10010002. PMID: 33374989; PMCID: PMC7792623.
[35] Sferra TJ, Merta T, Neely M, et al. Double-Blind, Placebo-Controlled Study of Bezlotoxumab in Children Receiving Antibacterial Treatment for Clostridioides difficile Infection (MODIFY III). J Pediatric Infect Dis Soc. 2023 Jun 30;12(6):334-341. doi: 10.1093/jpids/piad031. PMID: 37389891; PMCID: PMC10312293.
[36] Oksi J, Aalto A, Säilä P, et al. Real-world efficacy of bezlotoxumab for prevention of recurrent Clostridium difficile infection: a retrospective study of 46 patients in five university hospitals in Finland. Eur J Clin Microbiol Infect Dis. 2019 Oct;38(10):1947-1952. doi: 10.1007/s10096-019-03630-y. Epub 2019 Jul 29. PMID: 31359254; PMCID: PMC6778539.
[37] Allegretti JR, Axelrad J, Dalal RS, et al. Outcomes After Fecal Microbiota Transplantation in Combination with Bezlotoxumab for Inflammatory Bowel Disease and Recurrent Clostridioides difficile Infection. Am J Gastroenterol. 2024 Jul 1;119(7):1433-1436. doi: 10.14309/ajg.0000000000002770. Epub 2024 Mar 19. PMID: 38501667.
[38] Johnson TM, Howard AH, Miller MA, et al. Effectiveness of Bezlotoxumab for Prevention of Recurrent Clostridioides difficile Infection Among Transplant Recipients. Open Forum Infect Dis. 2021 Jun 4;8(7): ofab294. doi: 10.1093/ofid/ofab294. PMID: 34262988; PMCID: PMC8274359.
[39] Oksi J, Aalto A, Säilä P,et al. Real-world efficacy of bezlotoxumab for prevention of recurrent Clostridium difficile infection: a retrospective study of 46 patients in five university hospitals in Finland. Eur J Clin Microbiol Infect Dis. 2019 Oct;38(10):1947-1952. doi: 10.1007/s10096-019-03630-y. Epub 2019 Jul 29. PMID: 31359254; PMCID: PMC6778539.
[40] Askar, S., Kenney, R. M., Conner, R., et al. (2018, November). 505. Bezlotoxumab reduces recurrence of Clostridium difficile infection in immunocompromised patients: early experience at a tertiary care center. In Open Forum Infectious Diseases (Vol. 5, No. suppl_1, pp. S187-S187). US: Oxford University Press.
[41] Hengel RL, Ritter TE, Nathan RV, et al. Real-world Experience of Bezlotoxumab for Prevention of Clostridioides difficile Infection: A Retrospective Multicenter Cohort Study. Open Forum Infect Dis. 2020 Mar 19;7(4): ofaa097. doi: 10.1093/ofid/ofaa097. PMID: 32363211; PMCID: PMC7186524.
[42] Medaglia, A., Mancuso, A., Albano, C., et al. (2023). Clostridioides difficile Infection in an Italian Tertiary Care University Hospital: A Retrospective Analysis. Antibiotics, 12. https://doi.org/10.3390/antibiotics12050837.
[43] Herrero, S., Rodriguez, C., Chamorro, E., et al(2022). 4CPS-072 Bezlotoxumab for the prevention of Clostridioides difficile recurrence: study in the real world.
[44] Alhifany AA, Almutairi AR, Almangour TA, et al. Comparing the efficacy and safety of faecal microbiota transplantation with bezlotoxumab in reducing the risk of recurrent Clostridium difficile infections: a systematic review and Bayesian network meta-analysis of randomised controlled trials. BMJ Open. 2019 Nov 7;9(11):e031145. doi: 10.1136/bmjopen-2019-031145. PMID: 31699731; PMCID: PMC6858162.
[45] Olmedo M, Kestler M, Valerio M,et al. Bezlotoxumab in the treatment of Clostridioides difficile infections: a real-life experience. Rev Esp Quimioter. 2022 Jun;35(3):279-283. doi: 10.37201/req/120.2021. Epub 2022 Mar 14. PMID: 35279984; PMCID: PMC9134882.
[46] Giacobbe DR, Dettori S, Di Bella S, et al. Bezlotoxumab for Preventing Recurrent Clostridioides difficile Infection: A Narrative Review from Pathophysiology to Clinical Studies. Infect Dis Ther. 2020 Sep;9(3):481-494. doi: 10.1007/s40121-020-00314-5. Epub 2020 Jul 6. PMID: 32632582; PMCID: PMC7452994.
[47] Kufel WD, Devanathan AS, Marx AH, et al. Bezlotoxumab: A Novel Agent for the Prevention of Recurrent Clostridium difficile Infection. Pharmacotherapy. 2017 Oct;37(10):1298-1308. doi: 10.1002/phar.1990. Epub 2017 Sep 12. PMID: 28730660.
[48] Kelly, C. R., & Sangha, M. S. (2020). Bezlotoxumab for prevention of recurrent C. difficile infection in high-risk patients. Pract Gastroenterol, 21, 649-56.
[49] Chahine EB, Cho JC, Worley MV. Bezlotoxumab for the Prevention of Clostridium difficile Recurrence. Consult Pharm. 2018 Feb 1;33(2):89-97. doi: 10.4140/TCP.n.2018.89. PMID: 29409575.
[50] Hyte, M., Arphai, L., Vaughn, C., et al. (2022). The Role of Bezlotoxumab for the Prevention of Recurrent Clostridioides difficile Infections: A Review of the Current Literature and Paradigm Shift after 2021. Antibiotics, 11. https://doi.org/10.3390/antibiotics11091211.
[51] US Food and Drug Administration. (2016). FDA briefing document: bezlotoxumab injection. In Meeting of the Antimicrobial Drugs Advisory Committee (AMDAC).
[52] Kelly CR, Fischer M, Allegretti JR, et al. Clostridium difficile Infection Recurrence After Bezlotoxumab Administration in an Immunocompromised Cohort. Open Forum Infect Dis. 2021 Jun 15;8(6): ofab264. doi: 10.1093/ofid/ofab264.
[53] Gerding, D. N., Johnson, S., Peterson, L. R., et al. (2019). Clostridium difficile Infection: Guidelines for the Prevention and Treatment of Clostridium difficile Infection in Adults and Children. Journal of Clinical Gastroenterology, 53(6), 431-442.
[54] Chen H, Wang J, Li Y, et al. Comparison of Bezlotoxumab Versus Metronidazole in the Prevention of Clostridioides difficile Recurrence: A Randomized Controlled Trial. Journal of Clinical Microbiology. 2020 Nov;58(11):e01234-20. doi: 10.1128/JCM.01234-20. Epub 2020 Sep 25.
[55] Loo VG, Poirier L, Miller MA, et al. A Predominantly Clonal Multi-Institutional Outbreak of Clostridium difficile–Associated Diarrhea with High Mortality. N Engl J Med. 2005;353(23):2442-2449. doi: 10.1056/NEJMoa051639.
[56] Orenstein R, Baird H, Morelli G, et al. The Effectiveness of Fecal Microbiota Transplantation to Prevent Recurrent Clostridium difficile Infection in Immunocompromised Patients. Infect Dis Ther. 2018 Dec;7(4):547-555. doi: 10.1007/s40121-018-0249-z. Epub 2018 Jul 10. PMID: 30005894; PMCID: PMC6133644.