[en] [en] BACKGROUND AND AIMS: Inflammatory bowel disease (IBD) patients with Clostridioides difficile infection (CDI) are at increased risk of adverse outcomes. Data on fidaxomicin use in IBD remains scarce. We assessed the effectiveness and safety of fidaxomicin for CDI and its impact on IBD outcomes in a large international cohort.
METHODS: Adult patients with ulcerative colitis (UC) or Crohn's disease (CD) treated with fidaxomicin for documented CDI were retrospectively included. The primary outcome was CDI recurrence rate within 8 weeks (C. difficile toxin detection and CDI-targeted therapy). Secondary outcomes included sustained response (no CDI-targeted therapy within 12 weeks), IBD therapy escalation, colectomy rate, and all-cause mortality within 30, 90, and 180 days.
RESULTS: Ninety-six patients (57 UC and 39 CD) from 20 IBD centres were included. Most were on advanced IBD therapy. Half had a previous CDI episode, 15% a severe episode. CDI recurrence rate was 10% at week 8, sustained response 82% at week 12. Compared to patients with previous CDI episode, patients at first episode tended to have a lower recurrence (4.3 vs 16%; p=0.06) and higher sustained response (91 vs 75%; p=0.04) rate. IBD therapy escalation was required in 48% with a numerically lower need for patients achieving vs not-achieving sustained response within 30 days (12 vs 20%; p=0.42). Five UC patients underwent colectomy. One death unrelated to CDI or IBD occurred. One moderate and five mild adverse events were reported.
CONCLUSIONS: Fidaxomicin was effective and safe in IBD patients with CDI, with greater effectiveness in CDI-naïve patients, potentially influencing short-term IBD outcomes.
Disciplines :
Gastroenterology & hepatology
Author, co-author :
Noviello, Daniele ; University of Milan, Department of Pathophysiology and Transplantation, Milano, Italy
Chaparro, María; Gastrointestinal Unit of Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-Princesa), Universidad Autónoma de Madrid (UAM), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain
Viganò, Chiara ; Division of Gastroenterology- Center for Autoimmune Liver Diseases- Department of Medicine and Surgery- University of Milano-Bicocca ; European Reference Network on Hepatological Diseases ERN RARE-LIVER- Fondazione IRCCS San Gerardo dei Tintori, Monza, Italy
Blesl, Andreas ; Division of Gastroenterology and Hepatology, Department of Internal Medicine, Medical University of Graz, 8036 Graz, Austria
Barberio, Brigida; Division of Gastroenterology, Department of Surgery Oncology and Gastroenterology DiSCOG, University of Padova, Padova, Italy
Yanai, Henit ; Division of Gastroenterology, Rabin Medical Center, Petah Tikva, Israel, Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
Ferreiro-Iglesias, Rocío; Gastroenterology Department, Complejo Hospitalario Universitario de Santiago, Santiago de Compostela, A Coruña, Spain
Bezzio, Cristina ; Department of Biomedical Sciences, Humanitas University, Pieve Emanuele (MI), Italy ; IBD Center, Department of Gastroenterology, IRCCS Humanitas Research Hospital, Rozzano (MI), Italy
Zilli, Alessandra ; Department of Gastroenterology & Endoscopy, IRCCS San Raffaele Hospital, Milan, Italy
Molnár, Tamás ; Department of Internal Medicine, University of Szeged, Szeged, Hungary
Gheorghe, Cristian; Center of Gastroenterology and Hepatology, Fundeni Clinical Institute, 022328 Bucharest, Romania, Faculty of Medicine, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania
Conforti, Francesco; Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
Innocenti, Tommaso ; Gastroenterology Research Unit, Department of Experimental and Clinical Biochemical Sciences "Mario Serio", University of Florence, Florence, Italy ; IBD Referral Center, Clinical Gastroenterology Unit, Careggi University Hospital, Florence, Italy
Saibeni, Simone ; IBD Centre, Gastroenterology Unit, Rho Hospital, ASST Rhodense, 20017 Rho, Italy
Bossuyt, Peter ; Imelda GI Clinical Research Center, Imelda General Hospital, Bonheiden, Belgium
Oliveira, Raquel ; Gastroenterology Department, Unidade Local de Saúde do Algarve, Portimão Unit, Portugal ; School of Medicine, Life and Health Sciences Research Institute (ICVS), University of Minho, Braga, Portugal
Carvalhas Gabrielli, Anna Maria; Gastroenterology Unit, ASST Fatebenefratelli-Sacco, L. Sacco Hospital, Milano, Italy
Losco, Alessandra; Gastroenterology and Digestive Endoscopy Unit, ASST Santi Paolo e Carlo, Ospedale San Carlo, Milan, Italy
Vieujean, Sophie ; Université de Liège - ULiège > Département des sciences cliniques > Hépato-gastroentérologie
Tettoni, Enrico; Gastroenterology and Digestive Endoscopy Unit, Fondazione Poliambulanza Istituto Ospedaliero, Brescia, Italy ; Università Cattolica del Sacro Cuore, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
Pirola, Lorena; Division of Gastroenterology- Center for Autoimmune Liver Diseases- Department of Medicine and Surgery- University of Milano-Bicocca ; European Reference Network on Hepatological Diseases ERN RARE-LIVER- Fondazione IRCCS San Gerardo dei Tintori, Monza, Italy
Kornowski Cohen, Maya; Division of Gastroenterology, Rabin Medical Center, Petah Tikva, Israel, Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
Dragoni, Gabriele; Gastroenterology Research Unit, Department of Experimental and Clinical Biochemical Sciences "Mario Serio", University of Florence, Florence, Italy ; IBD Referral Center, Clinical Gastroenterology Unit, Careggi University Hospital, Florence, Italy
Rath, Timo; Department of Medicine 1, Universitätsklinikum Erlangen and Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany
Barreiro-de Acosta, Manuel ; Gastroenterology Department, Complejo Hospitalario Universitario de Santiago, Santiago de Compostela, A Coruña, Spain
Savarino, Edoardo Vincenzo ; Division of Gastroenterology, Department of Surgery Oncology and Gastroenterology DiSCOG, University of Padova, Padova, Italy
Gisbert, Javier Pérez ; Gastrointestinal Unit of Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-Princesa), Universidad Autónoma de Madrid (UAM), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain
Vecchi, Maurizio ; University of Milan, Department of Pathophysiology and Transplantation, Milano, Italy ; Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
Atreya, Raja ; Department of Medicine 1, Universitätsklinikum Erlangen and Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany
Caprioli, Flavio ; University of Milan, Department of Pathophysiology and Transplantation, Milano, Italy ; Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
Singh H, Nugent Z, Yu BN, Lix LM, Targownik LE, Bernstein CN. Higher incidence of clostridium difficile infection among individuals with inflammatory bowel disease. Gastroenterology. 2017;153:430-438.e2.
Nguyen GC, Kaplan GG, Harris ML, Brant SR. A national survey of the prevalence and impact of Clostridium difficile infection among hospitalized inflammatory bowel disease patients. Am J Gastroenterol. 2008;103:1443-1450.
Balram B, Battat R, Al-Khoury A, et al. Risk factors associated with clostridium difficile infection in inflammatory bowel disease: a systematic review and meta-analysis. J Crohns Colitis. 2019;13:27-38.
Jodorkovsky D, Young Y, Abreu MT. Clinical outcomes of patients with ulcerative colitis and co-existing Clostridium difficile infection. Dig Dis Sci. 2010;55:415-420.
Murthy SK, Steinhart AH, Tinmouth J, Austin PC, Daneman N, Nguyen GC. Impact of Clostridium difficile colitis on 5-year health outcomes in patients with ulcerative colitis. Aliment Pharmacol Ther. 2012;36:1032-1039.
Jen MH, Saxena S, Bottle A, Aylin P, Pollok RCG. Increased health burden associated with Clostridium difficile diarrhoea in patients with inflammatory bowel disease. Aliment Pharmacol Ther. 2011;33:1322-1331.
Tariq R, Law CCY, Khanna S, Murthy S, McCurdy JD. The impact of clostridium difficile infection on mortality in patients with inflammatory bowel disease: a systematic review and meta-analysis. J Clin Gastroenterol. 2019;53:127-133.
Kelly CR, Fischer M, Allegretti JR, et al. ACG clinical guidelines: prevention, diagnosis, and treatment of Clostridioides difficile infections. Am J Gastroenterol. 2021;116:1124-1147.
Kucharzik T, Ellul P, Greuter T, et al. ECCO guidelines on the prevention, diagnosis, and management of infections in inflammatory bowel disease. J Crohns Colitis. 2021;15:879-913.
Horton HA, Dezfoli S, Berel D, et al. Antibiotics for treatment of Clostridioides difficile infection in hospitalized patients with inflammatory bowel disease. Antimicrob Agents Chemother. 2014;58:5054-5059.
Lei DK, Ollech JE, Andersen M, et al. Long-Duration oral vancomycin to treat Clostridioides difficile in patients with inflammatory bowel disease is associated with a low rate of recurrence. Am J Gastroenterol. 2019;114:1904-1908.
Högenauer C, Mahida Y, Stallmach A, et al. Pharmacokinetics and safety of fidaxomicin in patients with inflammatory bowel disease and Clostridium difficile infection: an open-label Phase IIIb/IV study (PROFILE). J Antimicrob Chemother. 2018;73:3430-3441.
Vehreschild MJGT, Taori S, Goldenberg SD, et al. Fidaxomicin for the treatment of Clostridium difficile infection (CDI) in at-risk patients with inflammatory bowel disease, fulminant CDI, renal impairment or hepatic impairment: a retrospective study of routine clinical use (ANEMONE). Eur J Clin Microbiol Infect Dis. 2018;37:2097-2106.
Spiceland CM, Khanna S, Pardi DS. Outcomes with fidaxomicin therapy in Clostridium difficile infection. J Clin Gastroenterol. 2018;52:151-154.
Koop AH, Travers PM, Khanna S, Pardi DS, Farraye FA, Hashash JG. Fidaxomicin treatment for Clostridioides difficile infection in patients with inflammatory bowel disease. J Gastroenterol Hepatol. 2023;38:1910-1916.
Maaser C, Sturm A, Vavricka SR, et al.; European Crohn's and Colitis Organisation [ECCO] and the European Society of Gastrointestinal and Abdominal Radiology [ESGAR]. ECCO-ESGAR guideline for diagnostic assessment in IBD Part 1: initial diagnosis, monitoring of known IBD, detection of complications. J Crohns Colitis. 2019;13:144-164.
Truelove SC, Witts LJ. Cortisone in ulcerative colitis; preliminary report on a therapeutic trial. Br Med J. 1954;2:375-378.
Zar FA, Bakkanagari SR, Moorthi KM, Davis MB. A comparison of vancomycin and metronidazole for the treatment of Clostridium difficile-associated diarrhea, stratified by disease severity. Clin Infect Dis. 2007;45:302-307.
Harris PA, Taylor R, Thielke R, Payne J, Gonzalez N, Conde JG. Research electronic data capture (REDCap)-a metadata-driven methodology and workflow process for providing translational research informatics support. J Biomed Inform. 2009;42:377-381.
Polivkova S, Krutova M, Capek V, Sykorova B, Benes J. Fidaxomicin versus metronidazole, vancomycin and their combination for initial episode, first recurrence and severe Clostridioides difficile infection - An observational cohort study. Int J Infect Dis. 2021;103:226-233.
Louie TJ, Miller MA, Mullane KM, et al.; OPT-80-003 Clinical Study Group. Fidaxomicin versus vancomycin for Clostridium difficile infection. N Engl J Med. 2011;364:422-431.
Cornely OA, Crook DW, Esposito R, et al.; OPT-80-004 Clinical Study Group. Fidaxomicin versus vancomycin for infection with Clostridium difficile in Europe, Canada, and the USA: a double-blind, non-inferiority, randomised controlled trial. Lancet Infect Dis. 2012;12:281-289.
Ma GK, Brensinger CM, Wu Q, Lewis JD. Increasing incidence of multiply recurrent Clostridium difficile infection in the United States: a cohort study. Ann Intern Med. 2017;167:152-158.
Goren I, Fallek Boldes O, Boldes T, et al. Post-discharge outcomes of elderly patients hospitalized for inflammatory bowel disease flare complicated by Clostridioides difficile infection. J Crohns Colitis. 2024;21:jjae161.
Gros B, Soto P, Causse M, Marín S, Iglesias E, Benítez JM. Impact of Clostridioides difficile infection in patients admitted with ulcerative colitis. Scand J Gastroenterol. 2023;58:232-239.
Khanna S, Shin A, Kelly CP. Management of clostridium difficile infection in inflammatory bowel disease: expert review from the clinical practice updates committee of the AGA Institute. Clin Gastroenterol Hepatol. 2017;15:166-174.
Solanky D, Pardi DS, Loftus EV, Khanna S. Colon surgery risk with corticosteroids versus immunomodulators or biologics in inflammatory bowel disease patients with Clostridium difficile infection. Inflamm Bowel Dis. 2019;25:610-619.
Lukin DJ, Lawlor G, Hudesman DP, et al.; IBD-ReMEdY Study (Research, Mentoring, Education New York). Escalation of immunosuppressive therapy for inflammatory bowel disease is not associated with adverse outcomes after infection with Clostridium difficile. Inflamm Bowel Dis. 2019;25:775-781.
Ben-Horin S, Margalit M, Bossuyt P, et al.; European Crohn's and Colitis Organization (ECCO). Combination immunomodulator and antibiotic treatment in patients with inflammatory bowel disease and Clostridium difficile infection. Clin Gastroenterol Hepatol. 2009;7:981-987.
Kariv R, Navaneethan U, Venkatesh PG, Lopez R, Shen B. Impact of Clostridium difficile infection in patients with ulcerative colitis. J Crohns Colitis. 2011;5:34-40.
Ananthakrishnan AN, McGinley EL, Saeian K, Binion DG. Temporal trends in disease outcomes related to Clostridium difficile infection in patients with inflammatory bowel disease. Inflamm Bowel Dis. 2011;17:976-983.
Bernard R, Hammami MB, Arnold FW, et al. Clostridioides difficile toxin is infrequently detected in inflammatory bowel disease and does not associate with clinical outcomes. Gut Pathog. 2022;14:36.
Allegretti JR, Feuerstadt P, Knapple WL, et al. Safety and Efficacy of Fecal Microbiota, Live-jslm (REBYOTA®), for the prevention of recurrent Clostridioides difficile infection in participants with inflammatory bowel disease in PUNCH CD3-OLS. Inflamm Bowel Dis. 2025;25:izae291.
Duricek M, Halmova K, Krutova M, Sykorova B, Benes J. Is shorter also better in the treatment of Clostridioides difficile infection? J Antimicrob Chemother. 2024;79:1413-1417.
