The Clinical Efficacy, Safety, and Tolerability of Vancomycin for the Treatment of Recurrent Clostridioides difficile Infection – A Systematic Review

Figures & data

Figure 1 Shows the flow chart of inclusion and exclusion of records.

Note: The flow chart is adapted from Page MJ, McKenzie JE, Bossuyt PM, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021:n71. Creative Commons.²¹

Table 1 Shows the results for All Included Studies

Paper	Study Design	Intervention	Study Population	Follow-Up	Dose of Vancomycin	Effect of Vancomycin	Adverse Events
Cammarota et al^Citation3 (2015) Italy	Open-label, randomized and controlled trial with two arms.	1) Feacal microbiota transplantation by colonoscopy. 2) vancomycin.	20 individuals received feacal microbiota transplantation, and 19 individuals received vancomycin. Median number of recurrences in the vancomycin group: 3	10 weeks after end of vancomycin course.	125mg four times a day for 10 days followed by 125–500mg every 2–3 days for at least 3 weeks.	26% (n = 5) of individuals were cured, and 63% (n = 12) individuals had recurrence. Two individuals died from C. difficile related complications.	No adverse events specifically related to vancomycin.
Hota et al^Citation22 (2016) Canada	Open-label, randomized and controlled trial with two arms.	1) Feacal transplantation by enema. 2) vancomycin	16 individuals received feacal transplantation, and 12 individuals received vancomycin. Median number of recurrences in the vancomycin group: 4.4	120 days.	125mg four times a day for 14 days followed by 4 weeks of taper-and-pulse regimen: 125mg twice a day for 1 week, 125mg once a day for 1 week, 125mg every second day for 1 week, and 125mg every third day for 1 week.	41.7% (n = 5) experienced recurrence, resolution of symptoms in 58.3% of individuals.	Early and late adverse events: Fever, nausea or vomiting, abdominal pain/vomiting, abdominal distension, abdominal bloating, feeling generally unwell, mucoid stools, bloody stools, smelly stools, fecal incontinence, anorexia, fatigue, skin rash.
Rode et al^Citation6 (2021) Denmark	Open-label, randomized and controlled trial with three arms.	1) rectal bacteriotherapy (12-strain mixture) by enema. 2) Faecal microbiota transplantation by enema. 3) vancomycin.	34 individuals received faecal microbiota transplantation, 31 individuals received rectal bacteriotherapy and 31 individuals received vancomycin. 42% of participants in the vancomycin group had 2 or more recurrences.	90 days.	125mg four times a day for 14 days. For individuals with two or more recurrences, additional 5 weeks of taper-and pulse regimen was given: 125mg twice a day for 1 week, 125mg once a day for 1 week, 125mg every other day for 1 week, and 125mg every third day for 2 weeks.	Clinical cure rate at day 90 was 45% (n = 14). n = 3 individuals experienced treatment failure during tapering of vancomycin.	None related to vancomycin.
Hvas et al^Citation2 (2019) Denmark	Open-label single-center, randomized clinical trial with three arms.	1) Faecal microbiota transplantation applied by colonoscopy or nasojejunal tube after 4–10 days of vancomycin. 2) Fidaxomycin. 3) vancomycin.	24 individuals received faecal microbiota transplantation, 24 individuals received fidaxomicin, and 16 individuals received vancomycin. Median number of recurrences in the vancomycin group: 3	8 weeks.	125mg four times a day for 10 days.	Clinical resolution and negative C. difficile test in 19% (n = 3) of individuals.	No adverse events related to a specific antibiotic treatment.
Van Nood et al^Citation23 (2013) Holland	Open-label, randomized and controlled trial with three arms.	1) vancomycin, bowel lavage and subsequent infusion of donor faeces through a nasoduodenal tube. 2) Vancomycin 3) Vancomycin with bowel lavage.	16 individuals received vancomycin, bowel lavage and donor faeces, 13 individuals received vancomycin and 13 individuals received vancomycin with bowel lavage. Median number of recurrences in the vancomycin group: 3	10 weeks After initiation of therapy	500mg four times a day for 14 days.	Resolution of infection in 31% of individuals (n = 4). 62% (n = 8) had recurrence after 5 weeks	None related to vancomycin.
Surawicz et al^Citation1 (2000) USA	Part of a double-blind, randomized and placebo-controlled trials.	1) High dose vancomycin in combination with Saccharomyces boulardii (1g/day for 28 days). 2) High dose vancomycin in combination with placebo.	18 individuals received vancomycin and Saccharomyces boularii and 14 individuals received vancomycin and placebo Median number of recurrences in the vancomycin group: 2.4	8 weeks	2g/day for 10 days	50% (n = 7) had recurrence of CDI. 3 individuals had 1 recurrence and 4 individuals had 2 recurrences.	No significant difference between the two groups. Not further specified.

Figure 2 Shows the risk of bias assessment on criteria 1–14 (refer to Supplementary Document 2). For each study, criteria with low risk of bias are colored green, high risk of bias are colored red, and unclear risk of bias are colored yellow.

Page MJ, McKenzie JE, Bossuyt PM, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021:n71. doi:10.1136/bmj.n71

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Cammarota G, Masucci L, Ianiro G, et al. Randomised clinical trial: faecal microbiota transplantation by colonoscopy vs. vancomycin for the treatment of recurrent Clostridium difficile infection. Aliment Pharmacol Ther. 2015;41(9):835–843. doi:10.1111/apt.13144

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Hota SS, Sales V, Tomlinson G, et al. Oral vancomycin followed by fecal transplantation versus tapering oral vancomycin treatment for recurrent clostridium difficile infection: an open-label, randomized controlled trial. Clin Infect Dis. 2017;64(3):265–271. doi:10.1093/cid/ciw731

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Rode AA, Chehri M, Krogsgaard LR, et al. Randomised clinical trial: a 12-strain bacterial mixture versus faecal microbiota transplantation versus vancomycin for recurrent Clostridioides difficile infections. Aliment Pharmacol Ther. 2021;53(9):999–1009. doi:10.1111/APT.16309

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Hvas CL, Dahl Jørgensen SM, Jørgensen SP, et al. Fecal microbiota transplantation is superior to fidaxomicin for treatment of recurrent clostridium difficile infection. Gastroenterology. 2019;156(5):1324–1332.e3. doi:10.1053/j.gastro.2018.12.019

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van Nood E, Vrieze A, Nieuwdorp M, et al. Duodenal infusion of donor feces for recurrent clostridium difficile. N Engl J Med. 2013;368(5):407–415. doi:10.1056/NEJMoa1205037

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Surawicz CM, McFarland LV, Greenberg RN, et al. The search for a better treatment for recurrent clostridium difficile disease: use of high‐dose vancomycin combined with saccharomyces boulardii. Clin Infect Dis. 2000;31(4):1012–1017. doi:10.1086/318130

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