Abstract
Primary sclerosing cholangitis (PSC) is a rare, progressive liver disease characterized by cholestasis and bile duct fibrosis that has no accepted therapy known to delay or arrest its progression. We report a 23-year-old female patient who at age 14 was diagnosed with moderate pancolonic ulcerative colitis (UC) and at age 15 with small-duct PSC unresponsive to conventional therapy. The patient began single drug therapy with the antibiotic oral vancomycin (OVT) and achieved normalization of liver enzymes and resolution of UC symptoms with colonic mucosal healing. These improvements have persisted over 8 years. There has been no colon dysplasia, liver fibrosis or failure, bile duct stricture, or cancer. Of note, the patient’s response was dependent on the brand of oral vancomycin capsule, as well as dose. This raised the questions of possible differences in bioequivalence of different commercial versions of the drug and whether this factor might play into the variability of efficacy seen in published trials. Evidence suggests that oral vancomycin both alters the intestinal microbiome and has immunomodulatory effects. Its striking effectiveness in this and other patients supports further investigation in randomized trials, with careful attention to its bioavailability profile in the gut.
Similar content being viewed by others
References
Lindor KD, Kowdley KV, Harrison ME, et al. ACG clinical guideline: primary sclerosing cholangitis. Am J Gastroenterol. 2015;110:646–59 (quiz 660).
Miloh T, Arnon R, Shneider B, et al. A retrospective single-center review of primary sclerosing cholangitis in children. Clin Gastroenterol Hepatol. 2009;7:239–45.
Feldstein AE, Perrault J, El-Youssif M, et al. Primary sclerosing cholangitis in children: a long-term follow-up study. Hepatology. 2003;38:210–7.
Maroni L, Ninfole E, Pinto C, et al. Gut–liver axis and inflammasome activation in cholangiocyte pathophysiology. Cells. 2020;9:736. https://doi.org/10.3390/cells9030736.
Laborda TJ, Jensen MK, Kavan M, et al. Treatment of primary sclerosing cholangitis in children. World J Hepatol. 2019;11:19–36.
Olsson R, Boberg KM, de Muckadell OS, et al. High-dose ursodeoxycholic acid in primary sclerosing cholangitis: a 5-year multicenter, randomized, controlled study. Gastroenterology. 2005;129:1464–72.
Lindor KD, Kowdley KV, Luketic VA, et al. High-dose ursodeoxycholic acid for the treatment of primary sclerosing cholangitis. Hepatology. 2009;50:808–14.
Tabibian JH, O’Hara SP, Lindor KD. Primary sclerosing cholangitis and the microbiota: current knowledge and perspectives on etiopathogenesis and emerging therapies. Scand J Gastroenterol. 2014;49:901–8.
Shah A, Macdonald GA, Morrison M, et al. Targeting the gut microbiome as a treatment for primary sclerosing cholangitis: a conceptional framework. Am J Gastroenterol. 2020;115:814–22.
Damman JL, Rodriguez EA, Ali AH, et al. Review article: the evidence that vancomycin is a therapeutic option for primary sclerosing cholangitis. Aliment Pharmacol Ther. 2018;47:886–95.
Ali AH, Damman J, Shah SB, et al. Open-label prospective therapeutic clinical trials: oral vancomycin in children and adults with primary sclerosing cholangitis. Scand J Gastroenterol. 2020;55:941–50.
Marcone GL, Binda E, Berini F, et al. Old and new glycopeptide antibiotics: from product to gene and back in the post-genomic era. Biotechnol Adv. 2018;36:534–54.
Vesga O, Agudelo M, Salazar BE, et al. Generic vancomycin products fail in vivo despite being pharmaceutical equivalents of the innovator. Antimicrob Agents Chemother. 2010;54:3271–9.
Louie A, Boyne MT, Patel V, et al. Pharmacodynamic evaluation of the activities of six parenteral vancomycin products available in the United States. Antimicrob Agents Chemother. 2015;59:622–32.
Buness C, Lindor KD, Miloh T. Oral vancomycin therapy in a child with primary sclerosing cholangitis and severe ulcerative colitis. Pediatr Gastroenterol Hepatol Nutr. 2016;19:210–3.
Buness JG, Ali AH, Tabibian JH, et al. Potential association of doxycycline with the onset of primary sclerosing cholangitis: a case series. Am J Ther. 2019. https://doi.org/10.1097/MJT.0000000000001065 ((published ahead of print)).
Bjornsson E, Olsson R, Bergquist A, et al. The natural history of small-duct primary sclerosing cholangitis. Gastroenterology. 2008;134:975–80.
Davies YK, Cox KM, Abdullah BA, et al. Long-term treatment of primary sclerosing cholangitis in children with oral vancomycin: an immunomodulating antibiotic. J Pediatr Gastroenterol Nutr. 2008;47:61–7.
Dean G, Hanauer S, Levitsky J. The role of the intestine in the pathogenesis of primary sclerosing cholangitis: evidence and therapeutic implications. Hepatology. 2020;72:1127–38.
Tabibian JH, Weeding E, Jorgensen RA, et al. Randomised clinical trial: vancomycin or metronidazole in patients with primary sclerosing cholangitis—a pilot study. Aliment Pharmacol Ther. 2013;37:604–12.
Davies YK, Tsay CJ, Caccamo DV, et al. Successful treatment of recurrent primary sclerosing cholangitis after orthotopic liver transplantation with oral vancomycin. Case Rep Transplant. 2013. https://doi.org/10.1155/2013/314292 ((publication ahead of print)).
Deneau MR. Oral vancomycin, ursodeoxycholic acid or no therapy for pediatric primary sclerosing cholangitis: a matched analysis. Hepatology. 2020. https://doi.org/10.1002/hep.31560 ((publication ahead of print)).
Siedlar M, Szczepanik A, Wiȩckiewicz J, et al. Vancomycin down-regulates lipopolysaccharide-induced tumour necrosis factor alpha (TNFα) production and TNFa-mRNA accumulation in human blood monocytes. Immunopharmacology. 1997;35:265–71.
Abarbanel DN, Seki SM, Davies Y, et al. Immunomodulatory effect of vancomycin on Treg in pediatric inflammatory bowel disease and primary sclerosing cholangitis. J Clin Immunol. 2013;33:397–406.
Nakamoto N, Sasaki N, Aoki R, et al. Gut pathobionts underlie intestinal barrier dysfunction and liver T helper 17 cell immune response in primary sclerosing cholangitis. Nat Microbiol. 2019;4:492–503.
Vaughn BP, Kaiser T, Staley C, et al. A pilot study of fecal bile acid and microbiota profiles in inflammatory bowel disease and primary sclerosing cholangitis. Clin Exp Gastroenterol. 2019;12:9–19.
Kim HK, Choi SM, Kang G, et al. Comparison of in vivo pharmacokinetics and pharmacodynamics of vancomycin products available in Korea. Yonsei Med J. 2020;61:301–9.
Sauter M, Uhl P, Meid AD, et al. New insights into the pharmacokinetics of vancomycin after oral and intravenous administration: an investigation in beagle dogs. J Pharm Sci. 2020;109:2090–4.
FDA Advisory Committee meeting and ViroPharma letter, 2009. https://www.wayback.archive-it.org/7993/20170405230228. https://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/AdvisoryCommitteeforPharmaceuticalScienceandClinicalPharmacology/UCM175010.pdf . Accessed 12 Sept 2020.
Serai SD, Obuchowski NA, Venkatesh SK, et al. Repeatability of MR elastography of liver: a meta-analysis. Radiology. 2017;217:92–100.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
Cynthia W. Buness, Kevin M. Johnson, Ahmad Hassan Ali, Leina Alrabadi, Keith D. Lindor, Tamir Miloh, and Kenneth L. Cox, M.D. all declare that they have no conflict of interest.
Human rights
All procedures followed have been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments.
Informed consent
Informed consent was obtained from the patient for being included in the study.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Buness, C.W., Johnson, K.M., Ali, A.H. et al. Successful response of primary sclerosing cholangitis and associated ulcerative colitis to oral vancomycin may depend on brand and personalized dose: report in an adolescent. Clin J Gastroenterol 14, 684–689 (2021). https://doi.org/10.1007/s12328-020-01296-0
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12328-020-01296-0