Enteral Vancomycin as Primary Prophylaxis Against Clostridioides Difficile Infection in Critically Ill Patients

Summary

The goal of this clinical trial is to determine if oral vancomycin can prevent C.diff infection in adults who are critically ill and are at high risk of C.diff infection due to their medical conditions and being in the hospital. It will also help us learn about the safety of the drug in this setting. The main questions the trial aims to answer are: * Does oral vancomycin lower the rate of C.diff infection in high-risk patients? * Does C.diff carrier status change the C.diff infection rate as well as clearance of carrier status when vancomycin is used as primary prophylaxis? Researchers will compare the oral, active drug vancomycin to a placebo (a look-alike substance that contains no drug) to determine if vancomycin works to prevent C.diff infection in the hospital. Participants will: * Take oral vancomycin or a placebo while they receive systemic antibiotic(s) for up to five days after the last dose of said systemic antibiotic(s). The treatment of said systemic antibiotic(s) is not to exceed 21 days. * When discharged from the hospital, participants will continue to take the study medication in the event he/she did not complete the intended course of the study medication while in the hospital. * Participants will provide stool sample or rectal swabs for to assess their C.diff carrier status as well as any change in stool microbiome status, including VRE (vancomycin resistant Enterococcus) * After completion of the intervention period, participants will be contacted via telephone to assess if they developed diarrhea or any untoward effects of study medication.

Timeline

Start

2024-10-21

Primary completion

2026-12-31

Completion

2026-12-31

Publications

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• Background Bobo LD, Dubberke ER, Kollef M. Clostridium difficile in the ICU: the struggle continues. Chest. 2011 Dec;140(6):1643-1653. doi: 10.1378/chest.11-0556.
• Background Rineh A, Kelso MJ, Vatansever F, Tegos GP, Hamblin MR. Clostridium difficile infection: molecular pathogenesis and novel therapeutics. Expert Rev Anti Infect Ther. 2014 Jan;12(1):131-50. doi: 10.1586/14787210.2014.866515.
• Background Zhang S, Palazuelos-Munoz S, Balsells EM, Nair H, Chit A, Kyaw MH. Cost of hospital management of Clostridium difficile infection in United States-a meta-analysis and modelling study. BMC Infect Dis. 2016 Aug 25;16(1):447. doi: 10.1186/s12879-016-1786-6.
• Background Vedantam G, Clark A, Chu M, McQuade R, Mallozzi M, Viswanathan VK. Clostridium difficile infection: toxins and non-toxin virulence factors, and their contributions to disease establishment and host response. Gut Microbes. 2012 Mar-Apr;3(2):121-34. doi: 10.4161/gmic.19399. Epub 2012 Mar 1.
• Background Lemiech-Mirowska E, Michalkiewicz M, Sierocka A, Gaszynska E, Marczak M. The Hospital Environment as a Potential Source for Clostridioides difficile Transmission Based on Spore Detection Surveys Conducted at Paediatric Oncology and Gastroenterology Units. Int J Environ Res Public Health. 2023 Jan 15;20(2):1590. doi: 10.3390/ijerph20021590.
• Background Kochan TJ, Foley MH, Shoshiev MS, Somers MJ, Carlson PE, Hanna PC. Updates to Clostridium difficile Spore Germination. J Bacteriol. 2018 Jul 25;200(16):e00218-18. doi: 10.1128/JB.00218-18. Print 2018 Aug 15.
• Background Gil F, Lagos-Moraga S, Calderon-Romero P, Pizarro-Guajardo M, Paredes-Sabja D. Updates on Clostridium difficile spore biology. Anaerobe. 2017 Jun;45:3-9. doi: 10.1016/j.anaerobe.2017.02.018. Epub 2017 Feb 22.
• Background Paredes-Sabja D, Shen A, Sorg JA. Clostridium difficile spore biology: sporulation, germination, and spore structural proteins. Trends Microbiol. 2014 Jul;22(7):406-16. doi: 10.1016/j.tim.2014.04.003. Epub 2014 May 7.
• Background Martinez-Melendez A, Cruz-Lopez F, Morfin-Otero R, Maldonado-Garza HJ, Garza-Gonzalez E. An Update on Clostridioides difficile Binary Toxin. Toxins (Basel). 2022 Apr 27;14(5):305. doi: 10.3390/toxins14050305.
• 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 Papic N, Maric LS, Vince A. Efficacy of oral vancomycin in primary prevention of Clostridium Difficile infection in elderly patients treated with systemic antibiotic therapy. Infect Dis (Lond). 2018 Jun;50(6):483-486. doi: 10.1080/23744235.2018.1425551. Epub 2018 Jan 11. No abstract available.
• Background DailyMed - FIRVANQ- vancomycin hydrochloride kit. Accessed September 7, 2023. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=5aca5508-b577-446c-9980-ab4c7582b4b9
• Background Fishbein SRS, Hink T, Reske KA, Cass C, Struttmann E, Iqbal ZH, Seiler S, Kwon JH, Burnham CA, Dantas G, Dubberke ER. Randomized Controlled Trial of Oral Vancomycin Treatment in Clostridioides difficile-Colonized Patients. mSphere. 2021 Jan 13;6(1):e00936-20. doi: 10.1128/mSphere.00936-20.
• Background Ganetsky A, Han JH, Hughes ME, Babushok DV, Frey NV, Gill SI, Hexner EO, Loren AW, Luger SM, Mangan JK, Martin ME, Smith J, Freyer CW, Gilmar C, Schuster M, Stadtmauer EA, Porter DL. Oral Vancomycin Prophylaxis Is Highly Effective in Preventing Clostridium difficile Infection in Allogeneic Hematopoietic Cell Transplant Recipients. Clin Infect Dis. 2019 May 30;68(12):2003-2009. doi: 10.1093/cid/ciy822.
• 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.

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