Cited by 743Inflammatory Bowel DiseaseDiverticular Disease and ComplicationsOcular Diseases and Behçet’s Syndrome

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Controlled trial of metronidazole treatment for prevention of crohn's recurrence after ileal resection

Rutgeerts, Paul, Hiele, Martin, Geboes, Karel, Peeters, Marc, Penninckx, Freddy, Aerts, Raymond, Kerremans, Raymond·1995·Gastroenterology

DOI 10.1016/0016-5085(95)90121-3

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Abstract

Background/aims New lesions recur within weeks to months after ileal resection and ileocolonic anastomosis for Crohn's ileitis. A double-blind controlled trial was performed using metronidazole to prevent recurrence after ileal resection.Methods Sixty patients who underwent curative ileal resection and primary anastomosis were included within 1 week after surgery. Thirty patients received metronidazole (20 mg/kg body wt) daily for 3 months, and 30 patients received placebo. Treatment was then discontinued. Nine patients dropped out during treatment, 7 in the metronidazole group and 2 in the placebo arm.Results At 12 weeks, 21 of 28 patients (75%) in the placebo group had recurrent lesions in the neoterminal ileum as compared with 12 of 23 patients (52%) in the metronidazole group (P = 0.09). The incidence of severe endoscopic recurrence was significantly reduced by metronidazole (3 of 23; 13%) as compared with placebo (12 of 28; 43%; P = 0.02). Patients in the metronidazole arm had more frequent side effects. Metronidazole therapy statistically reduced the clinical recurrence rates at 1 year (4% vs. 25%). Reductions at 2 years (26% vs. 43%) and 3 years (30% vs. 50%) were not significant.Conclusions Metronidazole therapy for 3 months decreases the severity of early recurrence of Crohn's disease in the neoterminal ileum after resection and seems to delay symptomatic recurrence.

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“Following ileocecal resection, treatment with metronidazole or ornidazole reduces the risk of endoscopic recurrence at 12 months”
Method
Strategies in the prevention of post-operative recurrence in Crohn's disease
Rutgeerts, P. (2003) · Best Practice & Research Clinical Gastroenterology · doi:10.1053/bega.2002.0358 · Cited by 87
Self-citation
Meta-Analysis of the Placebo Rates of Clinical Relapse and Severe Endoscopic Recurrence in Postoperative Crohn's Disease
Renna, S., Cammà, C., Modesto, I., Cabibbo, G., Scimeca, D., Civitavecchia, G., Mocciaro, F., Orlando, A., Enea, M., & Cottone, M. (2008) · Gastroenterology · doi:10.1053/j.gastro.2008.07.066 · Cited by 86
Inflammatory bowel disease and the eye
Ghanchi, F. D., & Rembacken, B. J. (2003) · Survey of Ophthalmology · doi:10.1016/j.survophthal.2003.08.004 · Cited by 86
Meta‐analysis: targeting the intestinal microbiota in prophylaxis for post‐operative Crohn’s disease
Doherty, G. A., Bennett, G., Cheifetz, A. S., & Moss, A. C. (2010) · Alimentary Pharmacology & Therapeutics · doi:10.1111/j.1365-2036.2010.04231.x · Cited by 84
Adalimumab in prevention of postoperative recurrence of Crohn's disease in high-risk patients
Aguas, M. (2012) · World Journal of Gastroenterology · doi:10.3748/wjg.v18.i32.4391 · Cited by 83
Evidence for the involvement of infectious agents in the pathogenesis of Crohn’s disease
Hertogh, G. D. (2008) · World Journal of Gastroenterology · doi:10.3748/wjg.14.845 · Cited by 82
State of the Art: Ibd Therapy and Clinical Trials in Ibd
Isaacs, K. L., Lewis, J. D., Sandborn, W. J., Sands, B. E., & Targan, S. R. (2005) · Inflammatory Bowel Diseases · doi:10.1097/01.mib.0000184852.84558.b2 · Cited by 82
Effects of Feeding a Probiotic Preparation (SIM) Containing Inulin on the Severity of Colitis and on the Composition of the Intestinal Microflora in HLA-B27 Transgenic Rats
Schultz, M., Munro, K., Tannock, G. W., Melchner, I., Göttl, C., Schwietz, H., Schölmerich, J., & Rath, H. C. (2004) · Clinical and Vaccine Immunology · doi:10.1128/cdli.11.3.581-587.2004 · Cited by 83
“The preventive effect of metronidazole has been confirmed in a human trial (29).”
Background
Adalimumab vs Azathioprine in the Prevention of Postoperative Crohn’s Disease Recurrence. A GETECCU Randomised Trial
López–Sanromán, A., Vera‐Mendoza, I., Domènech, E., Taxonera, C., Ruiz, V. V., Marín‐Jiménez, I., Guardiola, J., de Castro, L., Esteve, M., Iglesias, E. L., et al. (2017) · Journal of Crohn s and Colitis · doi:10.1093/ecco-jcc/jjx051 · Cited by 81
Antibiotics in IBD: Still a Role in the Biological Era?
Ledder, O., & Turner, D. (2018) · Inflammatory Bowel Diseases · doi:10.1093/ibd/izy067 · Cited by 81
Prevalence of infectious pathogens in Crohn's disease
Knösel, T., Schewe, C., Petersen, N., Dietel, M., & Petersen, I. (2009) · Pathology - Research and Practice · doi:10.1016/j.prp.2008.04.018 · Cited by 80
Operative Management of Small Bowel Crohn's Disease
Gardiner, K. R., & Dasari, B. V. M. (2007) · Surgical Clinics of North America · doi:10.1016/j.suc.2007.03.011 · Cited by 80
Faecal microbiota transplantation: applications and limitations in treating gastrointestinal disorders
Sbahi, H., & Di Palma, J. A. (2016) · BMJ Open Gastroenterology · doi:10.1136/bmjgast-2016-000087 · Cited by 75
A Systematic Review of Measurement of Endoscopic Disease Activity and Mucosal Healing in Crohnʼs Disease
Khanna, R., Bouguen, G., Feagan, B. G., D’Haens, G., Sandborn, W. J., Dubcenco, E., Baker, K. A., & Levesque, B. G. (2014) · Inflammatory Bowel Diseases · doi:10.1097/mib.0000000000000131 · Cited by 79
Molecular Cloning of aBacteroides caccaeTonB-Linked Outer Membrane Protein Identified by an Inflammatory Bowel Disease Marker Antibody
Wei, B., Dalwadi, H. N., Gordon, L. K., Landers, C. J., Bruckner, D. A., Targan, S. R., & Braun, J. G. (2001) · Infection and Immunity · doi:10.1128/iai.69.10.6044-6054.2001 · Cited by 77
“Similarly, in human IBD several lines of evidence implicate enteric bacteria as a pathogenic factor in clinical disease, particularly in Crohn’s disease (CD) (3, 33, 48).”
Background
Role of bacteria in the etiopathogenesis of inflammatory bowel disease
Barnich, N. (2007) · World Journal of Gastroenterology · doi:10.3748/wjg.v13.i42.5571 · Cited by 77
“. The role of luminal bacteria in the pathogenesis of CD is strongly supported by observations showing that clinical symptoms of CD improve when luminal bacterial levels decrease following intestinal washes and antibacterial drug administration [ 14-16 ]”
Result
Mechanism-Based Treatment Strategies for IBD: Cytokines, Cell Adhesion Molecules, JAK Inhibitors, Gut Flora, and More
Schreiner, P., Neurath, M. F., Ng, S. C., El-Omar, E. M., Sharara, A. I., Kobayashi, T., Hisamatsu, T., Hibi∥, T., & Rogler, G. (2019) · Inflammatory Intestinal Diseases · doi:10.1159/000500721 · Cited by 79
Bacteria in the pathogenesis of inflammatory bowel disease
Subramanian, S., Campbell, B. J., & Rhodes, J. M. (2006) · Current Opinion in Infectious Diseases · doi:10.1097/01.qco.0000244054.69253.f3 · Cited by 75
Probiotics in inflammatory bowel disease: a critical review
Tamboli, C., Caucheteux, C., Cortot, A., Colombel, J., & Desreumaux, P. (2003) · Best Practice & Research Clinical Gastroenterology · doi:10.1016/s1521-6918(03)00076-3 · Cited by 75
Breakdown of tolerance to the intestinal bacterial flora in inflammatory bowel disease (IBD)
MacDonald, T. T. (1995) · Clinical & Experimental Immunology · doi:10.1111/j.1365-2249.1995.tb03835.x · Cited by 75
The Role of Enteric Microflora in Inflammatory Bowel Disease: Human and Animal Studies with Probiotics and Prebiotics
Rioux, K. P., Madsen, K. L., & Fedorak, R. N. (2005) · Gastroenterology Clinics of North America · doi:10.1016/j.gtc.2005.05.005 · Cited by 73
“Interestingly, the endoscopic remission rate at 1 year in the antibiotic/VSL#3 group was similar to that previously described with metronidazole alone [50].”
Result
Use of the Crohn’s disease activity index in clinical trials of biological agents
Freeman, H. J. (2008) · World Journal of Gastroenterology · doi:10.3748/wjg.14.4127 · Cited by 72
Association between entero‐hepatic Helicobacter species and Crohn’s disease: a prospective cross‐sectional study
Laharie, D., Asencio, C., Asselineau, J., Bulois, P., Bourreille, A., MOREAU, J., Bonjean, P., Lamarque, D., Pariente, A. E., Soule, J. C., et al. (2009) · Alimentary Pharmacology & Therapeutics · doi:10.1111/j.1365-2036.2009.04034.x · Cited by 71
Crohn's disease: step up or top down therapy
Hanauer, S. B. (2003) · Best Practice & Research Clinical Gastroenterology · doi:10.1053/bega.2003.0361 · Cited by 71
Treating Inflammatory Bowel Disease During Pregnancy
Connell, W., & Miller, A. (1999) · Drug Safety · doi:10.2165/00002018-199921040-00006 · Cited by 71
Maintenance therapy for inflammatory bowel disease
Feagan, B. G. (2003) · The American Journal of Gastroenterology · doi:10.1016/j.amjgastroenterol.2003.11.002 · Cited by 69
Management of Postoperative Crohn's Disease
Ng, S. C., & Kamm, M. A. (2008) · The American Journal of Gastroenterology · doi:10.1111/j.1572-0241.2008.01795.x · Cited by 66
“Active treatment resulted in significantly less severe recurrent endoscopic lesions than placebo at 3 months, although the overall endoscopic recurrence rates at 3 months were not significantly different between the two groups (metronidazole 52% vs placebo 75%) (33).”
Background
The Use of Vedolizumab in Preventing Postoperative Recurrence of Crohn’s Disease
Yamada, A., Komaki, Y., Patel, N. M., Komaki, F., Pekow, J. R., Dalal, S. R., Cohen, R. D., Cannon, L. M., Umanskiy, K., Smith, R. K., et al. (2018) · Inflammatory Bowel Diseases · doi:10.1093/ibd/izx054 · Cited by 66
Absence of Escherichia coli, Listeria monocytogenes, and Klebsiella pneumoniae antigens within inflammatory bowel disease tissues.
Walmsley, R. S., Anthony, A., Sim, R., Pounder, R. E., & Wakefield, A. J. (1998) · Journal of Clinical Pathology · doi:10.1136/jcp.51.9.657 · Cited by 66
ICAM-1 and VCAM-1 antisense oligonucleotides attenuate in vivo leucocyte adherence and inflammation in rat inflammatory bowel disease
Rijcken, E. J. M., Krieglstein, C. F., Anthoni, C., Laukoetter, M. G., Mennigen, R., Spiegel, H. U., Senninger, N., Bennett, C. F., & Schuermann, G. (2002) · Gut · doi:10.1136/gut.51.4.529 · Cited by 66
Systematic Review and Network Meta-Analysis of Medical Therapies to Prevent Recurrence of Post-Operative Crohn’s Disease
Burr, N. E., Hall, B. J., Hamlin, P. J., Selinger, C. P., Ford, A. C., & O’Connor, A. (2018) · Journal of Crohn s and Colitis · doi:10.1093/ecco-jcc/jjy216 · Cited by 65
Crucial Role of Microbiota in Experimental Psoriasis Revealed by a Gnotobiotic Mouse Model
Stehlíková, Z., Kostovcikova, K., Kverka, M., Rossmann, P., Dvořák, J., Novosádová, I., Kostovčík, M., Coufal, Š., Šrůtková, D., Procházková, P., et al. (2019) · Frontiers in Microbiology · doi:10.3389/fmicb.2019.00236 · Cited by 66
Advances in the treatment of Crohn’s disease
Egan, L. J., & Sandborn, W. J. (2004) · Gastroenterology · doi:10.1053/j.gastro.2004.01.062 · Cited by 65
IL-7 Deficiency Prevents Development of a Non-T Cell Non-B Cell-Mediated Colitis
von Freeden-Jeffry, U., Davidson, N. J., Wiler, R., Fort, M. M., Burdach, S. E. G., & Murray, R. (1998) · The Journal of Immunology · doi:10.4049/jimmunol.161.10.5673 · Cited by 64

Authors: Rutgeerts, P., Hiele, M., Geboes, K., Peeters, M., Penninckx, F., Aerts, R., & Kerremans, R.
Affiliations: Universitair Ziekenhuis Leuven (BE)
ORCID: Hiele, Martin
Peeters, Marc
Penninckx, Freddy
Aerts, Raymond
Venue: Gastroenterology
Publisher: Elsevier BV
Published: 1995-06
Volume: 108
Issue: 6
Pages: 1617-1621
ISSN: 0016-5085 (ISSN-L)
DOI: 10.1016/0016-5085(95)90121-3
OpenAlex: W1980212383
Cited by: 743
References: 24
Citations by year: 2026: 3 · 2025: 11 · 2024: 14 · 2023: 14 · 2022: 6 · 2021: 13 · 2020: 18 · 2019: 17 · 2018: 13 · 2017: 26 · 2016: 27 · 2015: 28 · 2014: 28 · 2013: 25 · 2012: 28
FWCI: 10.61
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Gastroenterology (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Gastroenterology › Inflammatory Bowel Disease
Health Sciences › Medicine › Surgery › Diverticular Disease and Complications
Health Sciences › Medicine › Ophthalmology › Ocular Diseases and Behçet’s Syndrome
Keywords: metronidazole, Crohn's disease, ileal resection, ileocolic anastomosis, postoperative recurrence, recurrence prevention, endoscopic recurrence
MeSH terms: Adult, Crohn Disease, Double-Blind Method, Follow-Up Studies, Humans, Ileum, Metronidazole, Middle Aged, Recurrence

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Controlled trial of metronidazole treatment for prevention of crohn's recurrence after ileal resection

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