Secondary Prevention of Clostridioides Difficile Using Vancomycin

Summary

Re-exposure to systemic antibiotics (i.e., antibiotics absorbed into the bloodstream) is common after a Clostridioides difficile infection (CDI) and is the strongest risk factor for a recurrent episode. Oral vancomycin to prevent a recurrence during antibiotic re-exposure may reduce this risk but the data supporting this practice are limited. The aim of this trial is: 1\) Does oral vancomycin prophylaxis prevent CDI recurrences in patients with recent CDI (within 120 days) and who are re-exposed to systemic antibiotics? The trial will compare oral vancomycin to placebo. Participants will: * Take the study drug (either vancomycin or placebo) twice daily for the duration of systemic antibiotics plus once daily for 7 days after completion of systemic antibiotics. * Attend an in-person or over the phone follow-up at day 56 * Respond to weekly electronic questionnaires

Timeline

Start

2025-11-01

Primary completion

2028-10-01

Completion

2029-10-01

Publications

• Background van Prehn J, Reigadas E, Vogelzang EH, Bouza E, Hristea A, Guery B, Krutova M, Noren T, Allerberger F, Coia JE, Goorhuis A, van Rossen TM, Ooijevaar RE, Burns K, Scharvik Olesen BR, Tschudin-Sutter S, Wilcox MH, Vehreschild MJGT, Fitzpatrick F, Kuijper EJ; Guideline Committee of the European Study Group on Clostridioides difficile. European Society of Clinical Microbiology and Infectious Diseases: 2021 update on the treatment guidance document for Clostridioides difficile infection in adults. Clin Microbiol Infect. 2021 Dec;27 Suppl 2:S1-S21. doi: 10.1016/j.cmi.2021.09.038. Epub 2021 Oct 20.
• Background Johnson S, Lavergne V, Skinner AM, Gonzales-Luna AJ, Garey KW, Kelly CP, Wilcox MH. 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 Sep 7;73(5):e1029-e1044. doi: 10.1093/cid/ciab549.
• Background McDonald LC, Gerding DN, Johnson S, Bakken JS, Carroll KC, Coffin SE, Dubberke ER, Garey KW, Gould CV, Kelly C, Loo V, Shaklee Sammons J, Sandora TJ, Wilcox MH. 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 Mar 19;66(7):987-994. doi: 10.1093/cid/ciy149.
• Background Kelly CR, Fischer M, Allegretti JR, LaPlante K, Stewart DB, Limketkai BN, Stollman NH. ACG Clinical Guidelines: Prevention, Diagnosis, and Treatment of Clostridioides difficile Infections. Am J Gastroenterol. 2021 Jun 1;116(6):1124-1147. doi: 10.14309/ajg.0000000000001278.
• Background San-Juan R, Origuen J, Campion K, Fernandez-Ruiz M, Diaz-Pollan B, Callejas-Diaz A, Candela G, Orellana MA, Lora D, Llorente Munoz I, Garcia MT, Martinez-Una M, Ferrari JM, Aguado JM. Evaluation of the effectiveness and safety of oral vancomycin versus placebo in the prevention of recurrence of Clostridioides difficile infection in patients under systemic antibiotic therapy: a phase III, randomised, double-blind clinical trial. BMJ Open. 2023 Sep 13;13(9):e072121. doi: 10.1136/bmjopen-2023-072121.
• Background Maraolo AE, Mazzitelli M, Zappulo E, Scotto R, Granata G, Andini R, Durante-Mangoni E, Petrosillo N, Gentile I. Oral Vancomycin Prophylaxis for Primary and Secondary Prevention of Clostridioides difficile Infection in Patients Treated with Systemic Antibiotic Therapy: A Systematic Review, Meta-Analysis and Trial Sequential Analysis. Antibiotics (Basel). 2022 Jan 30;11(2):183. doi: 10.3390/antibiotics11020183.
• Background Johnson SW, Brown SV, Priest DH. Effectiveness of Oral Vancomycin for Prevention of Healthcare Facility-Onset Clostridioides difficile Infection in Targeted Patients During Systemic Antibiotic Exposure. Clin Infect Dis. 2020 Aug 22;71(5):1133-1139. doi: 10.1093/cid/ciz966.
• Background McDonald EG, Prosty C, Hanula R, Bortolussi-Courval E, Albuquerque AM, Tong SYC, Hamilton F, Lee TC. Observational versus randomized controlled trials to inform antibiotic treatment durations: a narrative review. Clin Microbiol Infect. 2023 Feb;29(2):165-170. doi: 10.1016/j.cmi.2022.09.002. Epub 2022 Sep 13.
• Background Connor KA, Conn KM. Analysis of the impact of secondary prophylaxis on Clostridioides difficile recurrence in critically ill adults. SAGE Open Med. 2020 Jun 12;8:2050312120930898. doi: 10.1177/2050312120930898. eCollection 2020.
• Background Caroff DA, Menchaca JT, Zhang Z, Rhee C, Calderwood MS, Kubiak DW, Yokoe DS, Klompas M. Oral vancomycin prophylaxis during systemic antibiotic exposure to prevent Clostridiodes difficile infection relapses. Infect Control Hosp Epidemiol. 2019 Jun;40(6):662-667. doi: 10.1017/ice.2019.88. Epub 2019 Apr 29.
• Background Najjar-Debbiny R, Barnett-Griness O, Arbel A, Cohen S, Weber G, Amar M, Yassin R, Greenfeld I, Shehadeh S, Saliba W. Secondary prophylaxis for Clostridioides difficile infection for patients on non-C. difficile antibiotics: a retrospective cohort study. Microbes Infect. 2024 Jul-Aug;26(5-6):105349. doi: 10.1016/j.micinf.2024.105349. Epub 2024 May 6.
• Background Van Hise NW, Bryant AM, Hennessey EK, Crannage AJ, Khoury JA, Manian FA. Efficacy of Oral Vancomycin in Preventing Recurrent Clostridium difficile Infection in Patients Treated With Systemic Antimicrobial Agents. Clin Infect Dis. 2016 Sep 1;63(5):651-3. doi: 10.1093/cid/ciw401. Epub 2016 Jun 17.
• Background Carignan A, Poulin S, Martin P, Labbe AC, Valiquette L, Al-Bachari H, Montpetit LP, Pepin J. Efficacy of Secondary Prophylaxis With Vancomycin for Preventing Recurrent Clostridium difficile Infections. Am J Gastroenterol. 2016 Dec;111(12):1834-1840. doi: 10.1038/ajg.2016.417. Epub 2016 Sep 13.
• Background Abujamel T, Cadnum JL, Jury LA, Sunkesula VC, Kundrapu S, Jump RL, Stintzi AC, Donskey CJ. Defining the vulnerable period for re-establishment of Clostridium difficile colonization after treatment of C. difficile infection with oral vancomycin or metronidazole. PLoS One. 2013 Oct 2;8(10):e76269. doi: 10.1371/journal.pone.0076269. eCollection 2013.
• Background Seekatz AM, Rao K, Santhosh K, Young VB; New Collective Author. Dynamics of the fecal microbiome in patients with recurrent and nonrecurrent Clostridium difficile infection. Genome Med. 2016 Apr 27;8(1):47. doi: 10.1186/s13073-016-0298-8.
• Background Sethi AK, Al-Nassir WN, Nerandzic MM, Bobulsky GS, Donskey CJ. Persistence of skin contamination and environmental shedding of Clostridium difficile during and after treatment of C. difficile infection. Infect Control Hosp Epidemiol. 2010 Jan;31(1):21-7. doi: 10.1086/649016.
• Background Kimura T, Snijder R, Sugitani T. Characterization and risk factors for recurrence of Clostridioides (Clostridium) difficile infection in Japan: A nationwide real-world analysis using a large hospital-based administrative dataset. J Infect Chemother. 2019 Aug;25(8):615-620. doi: 10.1016/j.jiac.2019.03.011. Epub 2019 Apr 12.
• Background Zilberberg MD, Reske K, Olsen M, Yan Y, Dubberke ER. Risk factors for recurrent Clostridium difficile infection (CDI) hospitalization among hospitalized patients with an initial CDI episode: a retrospective cohort study. BMC Infect Dis. 2014 Jun 4;14:306. doi: 10.1186/1471-2334-14-306.
• Background Deshpande A, Pasupuleti V, Thota P, Pant C, Rolston DD, Hernandez AV, Donskey CJ, Fraser TG. Risk factors for recurrent Clostridium difficile infection: a systematic review and meta-analysis. Infect Control Hosp Epidemiol. 2015 Apr;36(4):452-60. doi: 10.1017/ice.2014.88. Epub 2015 Jan 28.
• Prosty C, Carignan A, Chan AK, Chen Y, Daley P, Daneman N, Kandel C, Longtin Y, Perez-Patrigeon S, Wuerz T, Cheaveau J, Hota SS, Ogundipe O, Steiner TS, Tsang JLY, Archambault P, Bergevin M, Brophy JM, Girouard G, Kong L, Parkes L, Reinblatt S, MacFadden D, Lee TC, McDonald EG. Secondary Prophylaxis of Recurrent Clostridioides difficile Infections During Systemic Antibiotics with Vancomycin (SPORES-V): study protocol for a randomized controlled trial. Trials. 2026 Jul 9. doi: 10.1186/s13063-026-09883-1. Online ahead of print.

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