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Noviello D, Chaparro M, Viganò C, Blesl A, Barberio B, Yanai H, Orlando A, Ferreiro-Iglesias R, Bezzio C, Zilli A, Molnár T, Gheorghe C, Conforti F, Innocenti T, Saibeni S, Bossuyt P, Oliveira R, Carvalhas Gabrielli AM, Losco A, Vieujean S, Tettoni E, Pirola L, Calderone S, Kornowski Cohen M, Dragoni G, Rath T, Barreiro-de Acosta M, Savarino EV, Gisbert JP, Vecchi M, Atreya R, Caprioli F. Fidaxomicin for Clostridioides difficile infection in patients with inflammatory bowel disease: a multicenter retrospective cohort study. J Crohns Colitis 2025; 19:jjaf056. [PMID: 40168072 PMCID: PMC12060865 DOI: 10.1093/ecco-jcc/jjaf056] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/27/2025] [Indexed: 04/02/2025]
Abstract
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 remain 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 centers 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, and sustained response 82% at week 12. Compared with patients with previous CDI episode, patients at first episode tended to have a lower recurrence (4.3% vs 16%; P = .06) and higher sustained response (91% vs 75%; P = .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 = .42). Five UC patients underwent colectomy. One death unrelated to CDI or IBD occurred. One moderate and 5 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.
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Affiliation(s)
- Daniele Noviello
- Department of Pathophysiology and Transplantation, University of Milan, Milano, Italy
| | - María Chaparro
- 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
| | - Chiara Viganò
- Division of Gastroenterology, Center for Autoimmune Liver Diseases, Department of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy
- European Reference Network on Hepatological Diseases ERN RARE-LIVER, Fondazione IRCCS San Gerardo dei Tintori, Monza, Italy
| | - Andreas Blesl
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Medical University of Graz, 8036 Graz, Austria
| | - Brigida Barberio
- Division of Gastroenterology, Department of Surgery Oncology and Gastroenterology DiSCOG, University of Padova, Padova, Italy
| | - Henit Yanai
- Division of Gastroenterology, Rabin Medical Center, Petah Tikva, Israel
- Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Ambrogio Orlando
- Inflammatory bowel disease Unit, “Villa Sofia-Cervello” Hospital, Palermo, Italy
| | - Rocío Ferreiro-Iglesias
- Gastroenterology Department, Complejo Hospitalario Universitario de Santiago, Santiago de Compostela, A Coruña, Spain
| | - Cristina Bezzio
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele (MI), Italy
- IBD Center, Department of Gastroenterology, IRCCS Humanitas Research Hospital, Rozzano (MI), Italy
| | - Alessandra Zilli
- Department of Gastroenterology & Endoscopy, IRCCS San Raffaele Hospital, Milan, Italy
| | - Tamás Molnár
- Department of Internal Medicine, University of Szeged, Szeged, Hungary
| | - Cristian Gheorghe
- Center of Gastroenterology and Hepatology, Fundeni Clinical Institute, 022328 Bucharest, Romania
- Faculty of Medicine, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania
| | - Francesco Conforti
- Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Tommaso Innocenti
- 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
| | - Simone Saibeni
- IBD Centre, Gastroenterology Unit, Rho Hospital, ASST Rhodense, 20017 Rho, Italy
| | - Peter Bossuyt
- Imelda GI Clinical Research Center, Imelda General Hospital, Bonheiden, Belgium
| | - Raquel Oliveira
- Gastroenterology Department, Unidade Local de Saúde do Algarve, Portimão, Portugal
- School of Medicine, Life and Health Sciences Research Institute (ICVS), University of Minho, Braga, Portugal
| | | | - Alessandra Losco
- Gastroenterology and Digestive Endoscopy Unit, ASST Santi Paolo e Carlo, Ospedale San Carlo, Milan, Italy
| | - Sophie Vieujean
- Hepato-Gastroenterology and Digestive Oncology, University Hospital CHU of Liège, Liège, Belgium
| | - Enrico Tettoni
- Gastroenterology and Digestive Endoscopy Unit, Fondazione Poliambulanza Istituto Ospedaliero, Brescia, Italy
- Università Cattolica del Sacro Cuore, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
| | - Lorena Pirola
- Division of Gastroenterology, Center for Autoimmune Liver Diseases, Department of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy
- European Reference Network on Hepatological Diseases ERN RARE-LIVER, Fondazione IRCCS San Gerardo dei Tintori, Monza, Italy
| | - Silvia Calderone
- Inflammatory bowel disease Unit, “Villa Sofia-Cervello” Hospital, Palermo, Italy
| | - Maya Kornowski Cohen
- Division of Gastroenterology, Rabin Medical Center, Petah Tikva, Israel
- Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Gabriele Dragoni
- 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
| | - Timo Rath
- Department of Medicine 1, Universitätsklinikum Erlangen and Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany
| | - Manuel Barreiro-de Acosta
- Gastroenterology Department, Complejo Hospitalario Universitario de Santiago, Santiago de Compostela, A Coruña, Spain
| | - Edoardo Vincenzo Savarino
- Division of Gastroenterology, Department of Surgery Oncology and Gastroenterology DiSCOG, University of Padova, Padova, Italy
| | - Javier Pérez Gisbert
- 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
| | - Maurizio Vecchi
- Department of Pathophysiology and Transplantation, University of Milan, Milano, Italy
- Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Raja Atreya
- Department of Medicine 1, Universitätsklinikum Erlangen and Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany
| | - Flavio Caprioli
- Department of Pathophysiology and Transplantation, University of Milan, Milano, Italy
- Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy
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Le PH, Chen CL, Kuo CJ, Yeh PJ, Chen CC, Chen YC, Chiu CT, Cheng HT, Tsou YK, Pan YB, Chiu CH. Impact of Clostridioides difficile Infection on Clinical Outcomes in Hospitalized IBD Patients and the Role of Fecal Microbiota Transplantation: A Retrospective Cohort Study. Kaohsiung J Med Sci 2025; 41:e70002. [PMID: 40091757 DOI: 10.1002/kjm2.70002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2024] [Revised: 01/21/2025] [Accepted: 02/05/2025] [Indexed: 03/19/2025] Open
Abstract
Clostridioides difficile infection (CDI) worsens the prognosis of patients with inflammatory bowel disease (IBD). This retrospective cohort study aimed to evaluate the risk factors, clinical manifestations, and outcomes of CDI in hospitalized patients with IBD, including those with toxin A/B results between April 2007 and April 2021. Patients were classified into the CDI and control groups. Patients with IBD and recurrent or refractory CDI underwent fecal microbiota transplantation (FMT). A total of 144 inpatients with IBD-45 in the CDI group and 99 in the control group-were analyzed. The incidence of CDI in inpatients with IBD was 31%. The Risk factors for CDI included longer IBD duration, biological therapy failure, and biological use. More patients in the CDI group presented with abdominal pain (77.8% vs. 55.6%, p = 0.011). In the antibiotic treatment-only group, the symptom improvement rate was 60.7% (17/28), the microbiological cure rate was 89.3% (25/28), and the overall success rate was 71.4% (20/28). After antibiotic treatment and FMT, 71.4% (10/14) of the patients tested negative for CDI, and 64.3% (9/14) had improved clinical symptoms. CDI led to more hospitalizations (median two times [range 0-12] vs. median one time [range 0-19], p = 0.008), a lower steroid-free remission rate (46.7% vs. 67.7%, p = 0.017), and higher Mayo scores (median 5 points [range 2-12] vs. median 3 points [range 0-12]). Patients who received FMT had fewer hospitalizations and fewer IBD-related complications during follow-up than those who received antibiotics alone. FMT should be considered in patients with IBD with refractory or recurrent CDI to improve clinical outcomes.
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Affiliation(s)
- Puo-Hsien Le
- Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Taoyuan, Linkou, Taiwan
- Chang Gung Inflammatory Bowel Disease Center, Chang Gung Memorial Hospital, Taoyuan, Linkou, Taiwan
- Chang Gung Microbiota Therapy Center, Chang Gung Memorial Hospital, Taoyuan, Linkou, Taiwan
- Taiwan Association for the Study of Intestinal Diseases (TASID), Taoyuan, Taiwan
| | - Chyi-Liang Chen
- Molecular Infectious Disease Research Center, Chang Gung Memorial Hospital, Taoyuan, Linkou, Taiwan
| | - Chia-Jung Kuo
- Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Taoyuan, Linkou, Taiwan
- Chang Gung Inflammatory Bowel Disease Center, Chang Gung Memorial Hospital, Taoyuan, Linkou, Taiwan
- Chang Gung Microbiota Therapy Center, Chang Gung Memorial Hospital, Taoyuan, Linkou, Taiwan
- Taiwan Association for the Study of Intestinal Diseases (TASID), Taoyuan, Taiwan
| | - Pai-Jui Yeh
- Chang Gung Inflammatory Bowel Disease Center, Chang Gung Memorial Hospital, Taoyuan, Linkou, Taiwan
- Chang Gung Microbiota Therapy Center, Chang Gung Memorial Hospital, Taoyuan, Linkou, Taiwan
- Department of Pediatric Gastroenterology, Chang Gung Memorial Hospital, Taoyuan, Linkou, Taiwan
| | - Chien-Chang Chen
- Chang Gung Inflammatory Bowel Disease Center, Chang Gung Memorial Hospital, Taoyuan, Linkou, Taiwan
- Chang Gung Microbiota Therapy Center, Chang Gung Memorial Hospital, Taoyuan, Linkou, Taiwan
- Department of Pediatric Gastroenterology, Chang Gung Memorial Hospital, Taoyuan, Linkou, Taiwan
| | - Yi-Ching Chen
- Chang Gung Microbiota Therapy Center, Chang Gung Memorial Hospital, Taoyuan, Linkou, Taiwan
- Division of Pediatric Infectious Diseases, Department of Pediatrics, Chang Gung Memorial Hospital, Taoyuan, Linkou, Taiwan
| | - Cheng-Tang Chiu
- Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Taoyuan, Linkou, Taiwan
- Chang Gung Inflammatory Bowel Disease Center, Chang Gung Memorial Hospital, Taoyuan, Linkou, Taiwan
- Chang Gung Microbiota Therapy Center, Chang Gung Memorial Hospital, Taoyuan, Linkou, Taiwan
- Taiwan Association for the Study of Intestinal Diseases (TASID), Taoyuan, Taiwan
| | - Hao-Tsai Cheng
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, New Taipei Municipal Tucheng Hospital, New Taipei City, Tucheng, Taiwan
| | - Yung-Kuan Tsou
- Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Taoyuan, Linkou, Taiwan
| | - Yu-Bin Pan
- Biostatistical Section, Clinical Trial Center, Chang Gung Memorial Hospital, Taoyuan, Linkou, Taiwan
| | - Cheng-Hsun Chiu
- Chang Gung Microbiota Therapy Center, Chang Gung Memorial Hospital, Taoyuan, Linkou, Taiwan
- Division of Pediatric Infectious Diseases, Department of Pediatrics, Chang Gung Memorial Hospital, Taoyuan, Linkou, Taiwan
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Qi HX, Wang Q, Zhou GQ. Association of Clostridium difficile infection with clinical outcomes of patients with inflammatory bowel disease: A meta-analysis. World J Gastrointest Surg 2025; 17:100555. [PMID: 40291861 PMCID: PMC12019072 DOI: 10.4240/wjgs.v17.i4.100555] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/19/2024] [Revised: 01/07/2025] [Accepted: 02/05/2025] [Indexed: 03/29/2025] Open
Abstract
BACKGROUND Clostridium difficile infection (CDI) is common in patients with inflammatory bowel disease (IBD). AIM To assess the association of CDI with clinical outcomes of IBD. METHODS PubMed, EMBASE, Web of Science, and the Cochrane Library databases were searched from inception to March 2024. Eligible articles included observational studies that reported on outcomes such as mortality, colectomy, hospitalization, intensive care unit (ICU) admission, complication rates, and length of hospital stay in IBD patients with and without CDI. Data were extracted, and a random-effects model was used to calculate pooled odds ratios (ORs) and mean differences (MDs). RESULTS As shown in the data from 21 studies with 1249158 participants, CDI significantly increased the risk of mortality in IBD patients [pooled OR = 4.569, 95% confidence intervals (95%CI): 2.584 to 8.079]. Although the pooled OR for colectomy was 1.409 (95%CI: 0.922 to 2.155), it was not statistically significant. Similarly, CDI did not impact hospitalization (pooled OR = 1.056, 95%CI: 0.512 to 2.179) and ICU admission outcomes (pooled OR = 1.970, 95%CI: 0.420 to 9.246) of patients with IBD. The rate of complications was comparable in the two groups (pooled OR = 0.658, 95%CI: 0.378 to 1.147). However, CDI was associated with a significantly more extended hospital stay (pooled MD = 0.349 days, 95%CI: 0.002 to 0.696). CONCLUSION CDI is linked to increased mortality and prolonged hospitalization in IBD patients. These results emphasize the need for early detection and appropriate management. Implementing routine CDI screening during IBD flare-ups and stringent infection control measures could mitigate severe complications and reduce the healthcare burden.
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Affiliation(s)
- Hai-Xin Qi
- Department of Anorectal Surgery, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou 310003, Zhejiang Province, China
| | - Qi Wang
- The First School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou 310000, Zhejiang Province, China
| | - Gui-Qun Zhou
- Department of Gastroenterology, The Third Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310005, Zhejiang Province, China
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Park J, Kim S, Im JP, Lee HJ, Kim JS, Park H, Han YM, Koh SJ. Clinical Outcome of Inflammatory Bowel Disease with Clostridioides difficile Polymerase Chain Reaction Toxin-Positive/Enzyme Immunoassay Toxin-Negative: A Retrospective Cohort Study. Dig Dis Sci 2025:10.1007/s10620-025-09045-4. [PMID: 40259149 DOI: 10.1007/s10620-025-09045-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/28/2024] [Accepted: 04/04/2025] [Indexed: 04/23/2025]
Abstract
BACKGROUND Clostridioides difficile infection (CDI) frequently occurs concurrently in patients with inflammatory bowel disease (IBD), and differential diagnosis from IBD flares is critical. However, clinical management of C. difficile in IBD patients with polymerase chain reaction toxin-positive (tPCR+)/enzyme immunoassay toxin-negative (tEIA-) results has not yet been investigated. AIMS We aimed to assess the clinical significance of C. difficile tPCR+/tEIA- in patients with IBD and the impact of antibiotic treatment on IBD outcomes. METHODS This single-center, retrospective cohort study included patients with IBD with CDI test results between January 01, 2018, and August 01, 2022. First, the clinical outcomes of IBD, such as medication escalation, hospitalization, and surgery, were compared between patients with IBD with tPCR-/tEIA- and those with tPCR+/tEIA- using Cox regression and propensity score matching. Next, the clinical outcomes of IBD were assessed based on whether antibiotic treatment for CDI was administered to both groups. RESULTS Among 412 patients with IBD with PCR test, 71 (17.2%) showed tPCR+/tEIA- results. The tPCR+/tEIA- group showed no statistically significant difference in IBD outcomes compared to the tPCR-/tEIA- group. The antibiotic-treated tPCR+/tEIA- group showed a higher risk of drug escalation and admission than the tPCR-/tEIA- group, while the antibiotic-untreated tPCR+/tEIA- group did not. After drug escalation during the follow-up, the treated tPCR+/tEIA- group showed IBD outcomes similar to those of the tPCR-/tEIA- group. CONCLUSIONS In patients with IBD with indeterminate CDI, the need for antibiotics should be thoroughly assessed and proper management of underlying IBD such as drug escalation may lead to favorable outcomes.
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Affiliation(s)
- Junseok Park
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea
| | - Seulji Kim
- Department of Internal Medicine, Korea Institute of Radiological and Medical Sciences, Korea Cancer Center Hospital, Seoul, Korea
| | - Jong Pil Im
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Hyun Jung Lee
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Joo Sung Kim
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Hyunsun Park
- Department of Dermatology, Seoul National University College of Medicine, Seoul, Korea
| | - Yoo Min Han
- Department of Internal Medicine and Healthcare Research Institute, Seoul National University Hospital Healthcare System Gangnam Center, Seoul, Korea
| | - Seong-Joon Koh
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea.
- Department of Internal Medicine and Liver Research Institute, Laboratory of Intestinal Mucosa and SkinImmunology, Seoul National University College of Medicine, 101 Daehak-Ro, Jongno-Gu, Seoul, 03080, Korea.
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Alsabbagh Alchirazi K, Hamid O, Qapaja T, Aldiabat M, Azzouz N, Alkhayyat M, Regueiro M. Racial Disparities in Utilization of Medications and Disease Outcomes in Inflammatory Bowel Disease Patients. CROHN'S & COLITIS 360 2025; 7:otaf021. [PMID: 40260307 PMCID: PMC12010087 DOI: 10.1093/crocol/otaf021] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/16/2024] [Indexed: 04/23/2025] Open
Abstract
Background Although traditionally associated with White European ancestry, inflammatory bowel disease (IBD) has increased among different races and ethnicities. Large studies conducted in the United States and Canada have identified more complex disease phenotypes among Black patients. Our study aimed to investigate disparities in IBD treatments and outcomes between Black and White patients in the United States. Methods Using the TriNetX database, adult IBD patients were divided into 2 groups based on race: Black and White patients with IBD, Crohn's disease (CD), or ulcerative colitis (UC). Medical therapy and disease outcomes were evaluated in both groups with 1:1 propensity-score matching. Methodologic limitations include the potential for missing data, lack of information on socioeconomic strata, and patient-level medication coverage plans. Results In comparison to White patients, Black patients with CD were less likely to receive advanced therapies; Adalimumab (adjusted odds ratio- aOR 0.89), Certolizumab (0.81), Vedolizumab (0.66), Ustekinumab (0.82), or Tofacitinib (0.58). Black patients with UC were less likely to receive advanced therapies; Adalimumab (0.83), Golimumab (0.62), Vedolizumab (0.69), Ustekinumab (0.73), or Tofacitinib (0.55). Black patients with IBD were at higher odds of utilizing corticosteroids (CD 1.18 and UC 1.20) and opioids (CD 1.26 and UC 1.09). Black patients with CD had higher rates of hospitalization (1.35) and perianal abscess (1.56), perianal fistula (1.28), and intestinal fistula (1.38). Black patients with UC had higher rates of hospitalization (1.29), Clostridioides difficile infection (1.11), and toxic megacolon (1.34). Conclusions There were racial disparities in IBD medical therapy and disease outcomes. Black IBD patients had lower treatment with advanced therapies, higher opioid and corticosteroid use, and higher IBD-related complications.
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Affiliation(s)
| | - Osama Hamid
- Department of Gastroenterology and Hepatology, University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Thabet Qapaja
- Department of Hospital Medicine, Washington University in St. Louis, St. Louis, MO, USA
| | - Mohammad Aldiabat
- Department of Hospital Medicine, Washington University in St. Louis, St. Louis, MO, USA
| | - Nour Azzouz
- Department of Gastroenterology and Hepatology, Cleveland Clinic, Cleveland, OH, USA
| | - Motasem Alkhayyat
- Department of Gastroenterology and Hepatology, Indiana University, Indianapolis, IN, USA
| | - Miguel Regueiro
- Department of Gastroenterology and Hepatology, Cleveland Clinic, Cleveland, OH, USA
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Bejcek A, Ancha A, Lewis M, Beaver R, Tecson K, Bomar J, Johnson C. Antibiotic use and risk of Clostridioides difficile infection in patients with inflammatory bowel disease. J Gastroenterol Hepatol 2024; 39:2417-2423. [PMID: 39148287 DOI: 10.1111/jgh.16720] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/05/2023] [Revised: 06/23/2024] [Accepted: 07/30/2024] [Indexed: 08/17/2024]
Abstract
BACKGROUND AND AIM Patients with inflammatory bowel disease (IBD) have an increased risk of Clostridioides difficile infection (CDI) compared with those without IBD, which is worsened with antibiotic usage. While prior studies have shown a correlation between CDI development and certain classes of antibiotics, the IBD population has not been well represented. This study evaluates the rates of CDI with outpatient antibiotic use in patients with IBD. METHODS We conducted a retrospective cohort study composed of patients with IBD and compared the incidence of CDI in patients who received an outpatient prescription for antibiotics (6694 patients) against those without prescriptions (6025 patients) from 2014 to 2020 at our institution. We compared CDI rates based on nine antibiotic classes: penicillins, cephalosporins, sulfonamides, tetracyclines, macrolides, quinolones, clindamycin, metronidazole, and nitrofurantoin. RESULTS The risk of CDI was low (0.7%) but significantly higher for those with antibiotic exposure (0.9% vs 0.5%, P = 0.005) and had a positive correlation with a smoking history. The increased risk of CDI in the IBD population was attributable to the clindamycin and metronidazole classes (odds ratio = 4.7, 95% confidence interval: 1.9-11.9, P = 0.001; odds ratio = 3.6, 95% confidence interval: 2.1-6.2, P < 0.0001, respectively). CONCLUSIONS The use of clindamycin or metronidazole prescribed in an outpatient setting was associated with a statistically significant increased risk of CDI in patients with IBD. Although the association between clindamycin and CDI is a well-established and common finding, the association between metronidazole and CDI is unique in this study.
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Affiliation(s)
- Alexis Bejcek
- Division of Gastroenterology, Department of Medicine, Baylor Scott & White Medical Center, Temple, Texas, USA
| | - Anupama Ancha
- Division of Internal Medicine, Department of Medicine, Baylor Scott & White Medical Center, Temple, Texas, USA
| | - Megan Lewis
- Division of Gastroenterology, Department of Medicine, Baylor Scott & White Medical Center, Temple, Texas, USA
| | - Ryan Beaver
- Division of Infectious Diseases, Department of Medicine, Baylor Scott & White Medical Center, Temple, Texas, USA
| | - Kristen Tecson
- Baylor Scott & White Research Institute, Baylor Scott & White Health, Dallas, Texas, USA
| | - Jaccallene Bomar
- Baylor Scott & White Research Institute, Baylor Scott & White Health, Dallas, Texas, USA
| | - Christopher Johnson
- Division of Gastroenterology, Department of Medicine, Baylor Scott & White Medical Center, Temple, Texas, USA
- Department of Medicine, Baylor College of Medicine, Temple, Texas, USA
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Lauricella S, Brucchi F, Cavalcoli F, Rausa E, Cassini D, Miccini M, Vitellaro M, Cirocchi R, Costa G. Current Management of Acute Severe Ulcerative Colitis: New Insights on the Surgical Approaches. J Pers Med 2024; 14:580. [PMID: 38929801 PMCID: PMC11204779 DOI: 10.3390/jpm14060580] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2024] [Revised: 05/16/2024] [Accepted: 05/27/2024] [Indexed: 06/28/2024] Open
Abstract
Acute severe ulcerative colitis (ASUC) is a life-threatening medical emergency with considerable morbidity. Despite recent advances in medical IBD therapy, colectomy rates for ASUC remain high. A scoping review of published articles on ASUC was performed. We collected data, such as general information of the disease, diagnosis and initial assessment, and available medical and surgical treatments focusing on technical aspects of surgical approaches. The most relevant articles were considered in this scoping review. The management of ASUC is challenging; currently, personalized treatment for it is unavailable. Sequential medical therapy should be administrated, preferably in high-volume IBD centers with close patient monitoring and indication for surgery in those cases with persistent symptoms despite medical treatment, complications, and clinical worsening. A total colectomy with end ileostomy is typically performed in the acute setting. Managing rectal stump is challenging, and all individual and technical aspects should be considered. Conversely, when performing elective colectomy for ASUC, a staged surgical procedure is usually preferred, thus optimizing the patients' status preoperatively and minimizing postoperative complications. The minimally invasive approach should be selected whenever technically feasible. Robotic versus laparoscopic ileal pouch-anal anastomosis (IPAA) has shown similar outcomes in terms of safety and postoperative morbidity. The transanal approach to ileal pouch-anal anastomosis (Ta-IPAA) is a recent technique for creating an ileal pouch-anal anastomosis via a transanal route. Early experiences suggest comparable short- and medium-term functional results of the transanal technique to those of traditional approaches. However, there is a need for additional comparative outcomes data and a better understanding of the ideal training and implementation pathways for this procedure. This manuscript predominantly explores the surgical treatment of ASUC. Additionally, it provides an overview of currently available medical treatment options that the surgeon should reasonably consider in a multidisciplinary setting.
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Affiliation(s)
- Sara Lauricella
- Colorectal Surgery Division, Department of Surgery, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 Milan, Italy
| | | | - Federica Cavalcoli
- Gastroenterology and Endoscopy Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 Milan, Italy
| | - Emanuele Rausa
- Colorectal Surgery Division, Department of Surgery, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 Milan, Italy
| | - Diletta Cassini
- General and Emergency Surgery, Sesto San Giovanni Hospital, 20099 Milan, Italy
| | | | - Marco Vitellaro
- Colorectal Surgery Division, Department of Surgery, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 Milan, Italy
| | - Roberto Cirocchi
- Digestive and Emergency Surgery Unit, S. Maria Hospital Trust, 05100 Terni, Italy
| | - Gianluca Costa
- Department of Life Science, Health, and Health Professions, Link Campus University, 00165 Rome, Italy
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8
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Kucharzik T, Dignass A, Atreya R, Bokemeyer B, Esters P, Herrlinger K, Kannengiesser K, Kienle P, Langhorst J, Lügering A, Schreiber S, Stallmach A, Stein J, Sturm A, Teich N, Siegmund B. Aktualisierte S3-Leitlinie Colitis ulcerosa (Version 6.2). ZEITSCHRIFT FUR GASTROENTEROLOGIE 2024; 62:769-858. [PMID: 38718808 DOI: 10.1055/a-2271-0994] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 07/02/2024]
Affiliation(s)
- T Kucharzik
- Klinik für Allgemeine Innere Medizin und Gastroenterologie, Städtisches Klinikum Lüneburg, Lüneburg, Deutschland
| | - A Dignass
- Medizinische Klinik I, Agaplesion Markus Krankenhaus, Frankfurt, Deutschland
| | - R Atreya
- Medizinische Klinik 1 Gastroent., Pneumologie, Endokrin., Universitätsklinikum Erlangen, Erlangen, Deutschland
| | - B Bokemeyer
- Interdisziplinäres Crohn Colitis Centrum Minden - ICCCM, Minden, Deutschland
| | - P Esters
- Medizinische Klinik I, Agaplesion Markus Krankenhaus, Frankfurt, Deutschland
| | - K Herrlinger
- Innere Medizin I, Asklepios Klinik Nord, Hamburg, Deutschland
| | - K Kannengiesser
- Klinik für Allgemeine Innere Medizin und Gastroenterologie, Städtisches Klinikum Lüneburg, Lüneburg, Deutschland
| | - P Kienle
- Abteilung für Allgemein- und Viszeralchirurgie, Theresienkrankenhaus, Mannheim, Deutschland
| | - J Langhorst
- Klinik für Integrative Medizin und Naturheilkunde, Sozialstiftung Bamberg Klinikum am Bruderwald, Bamberg, Deutschland
| | - A Lügering
- Medizinisches Versorgungszentrum Portal 10, Münster, Deutschland
| | - S Schreiber
- Klinik für Innere Medizin I, Universitätsklinikum Schleswig Holstein, Kiel, Deutschland
| | - A Stallmach
- Klinik für Innere Medizin IV Gastroenterologie, Hepatologie, Infektiologie, Universitätsklinikum Jena, Jena, Deutschland
| | - J Stein
- Abteilung Innere Medizin mit Schwerpunkt Gastroenterologie, Krankenhaus Sachsenhausen, Frankfurt, Deutschland
| | - A Sturm
- Klinik für Innere Medizin mit Schwerpunkt Gastroenterologie, DRK Kliniken Berlin Westend, Berlin, Deutschland
| | - N Teich
- Internistische Gemeinschaftspraxis, Leipzig, Deutschland
| | - B Siegmund
- Medizinische Klinik für Gastroenterologie, Infektiologie und Rheumatologie, Charité Campus Benjamin Franklin - Universitätsmedizin Berlin, Berlin, Deutschland
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9
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Santiago P, Coelho-Prabhu N, Lennon R, Rui S, Rajauria P, Friton J, Raffals LE, Deepali F, Daoud N, Farraye FA, Tuck J, Malik T, Leleiko NS, Shapiro J, Shah SA, Sands BE, Ungaro RC. Baseline Clinical Factors Are Associated With Risk of Complications in Crohn's Disease: Appraisal of the American Gastroenterological Association Clinical Care Pathway. Am J Gastroenterol 2024; 119:147-154. [PMID: 37713528 DOI: 10.14309/ajg.0000000000002498] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/24/2023] [Accepted: 08/18/2023] [Indexed: 09/17/2023]
Abstract
INTRODUCTION The American Gastroenterological Association (AGA) has compiled risk factors that may be predictive of disease complications in Crohn's disease (CD) and ulcerative colitis (UC). The aim of this study was to evaluate the performance of the AGA risk factors for risk stratification in UC and CD. METHODS We included participants of 2 cohorts: the Ocean State Crohn's and Colitis Area Registry cohort and the Mayo Clinic cohort. Baseline clinical risk factors were extracted according to the AGA pathway. Our primary end point was defined as follows: (i) any inflammatory bowel disease related-hospitalization, (ii) any inflammatory bowel disease-related bowel surgery, or (iii) any progression of disease. We analyzed the association of the number of AGA risk factors with our end point. Statistical multivariable modeling was performed with Cox proportional hazards model. RESULTS A total of 412 patients with CD were included. Comparing ≥3 risk factors with 0-1 risk factor, we found a significantly increased risk of complications in both the Ocean State Crohn's and Colitis Area Registry cohort (hazard ratio [HR] 2.75, 95% confidence interval 1.71-4.41) and Mayo Clinic cohort (HR 2.07, 95% confidence interval 1.11-3.84). Diagnosis at younger age (HR 2.07), perianal disease (HR 1.99), and B2/B3 behavior (HR 1.92) were significantly associated with disease complications. We did not observe a consistent association between number of risk factors nor any specific individual risk factors and risk of disease complications in the 265 patients with UC included. DISCUSSION We found a significant association between the number of AGA risk factors and the risk of disease complication in CD; this association was not significant in UC. The presence of ≥ 3 risk factors in CD leads to the highest risk of complications. The AGA care pathway is a useful tool to stratify patients who are at higher risk of disease complications in patients with CD.
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Affiliation(s)
- Priscila Santiago
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA
| | | | - Ryan Lennon
- Department of Quantitative Health Sciences, Mayo Clinic, Rochester, Minnesota, USA
| | - Shumin Rui
- The Henry D Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Palak Rajauria
- The Henry D Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Jessica Friton
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA
| | - Laura E Raffals
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA
| | - Fnu Deepali
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA
| | - Nader Daoud
- Division of Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, Florida, USA
| | - Francis A Farraye
- Division of Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, Florida, USA
| | - Jaclyn Tuck
- Division of Gastroenterology and Hepatology, Mayo Clinic, Scottsdale, Arizona, USA
| | - Talha Malik
- Division of Gastroenterology and Hepatology, Mayo Clinic, Scottsdale, Arizona, USA
| | - Neal S Leleiko
- Division of Pediatric Gastroenterology, Department of Pediatrics, Columbia University Medical Center, New York, New York, USA
| | - Jason Shapiro
- Department of Pediatric Gastroenterology, Warren Alpert Medical School of Brown University, Providence
| | - Samir A Shah
- Division of Gastroenterology, Warren Alpert Medical School of Brown University, Providence
| | - Bruce E Sands
- The Henry D Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Ryan C Ungaro
- The Henry D Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, New York, USA
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10
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Calméjane L, Laharie D, Kirchgesner J, Uzzan M. Review article: Updated management of acute severe ulcerative colitis: From steroids to novel medical strategies. United European Gastroenterol J 2023; 11:722-732. [PMID: 37475143 PMCID: PMC10576604 DOI: 10.1002/ueg2.12442] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/30/2023] [Accepted: 06/15/2023] [Indexed: 07/22/2023] Open
Abstract
Acute severe ulcerative colitis (ASUC) occurs in up to 25% of patients with ulcerative colitis (UC). Therapeutic approaches have evolved during the past years with the increasing bio exposure of admitted patients and the extension of the number of approved drugs for UC. In this review, we aimed to summarize the latest evidence in short-term and long-term medical strategies for ASUC. In addition to general principles such as venous thromboembolism prophylaxis, screening for triggering and worsening factors and close monitoring, first-line therapy for ASUC remains intravenous corticosteroids. In naive patients, the optimum maintenance strategy for steroid-responding patients does not necessarily include biologics. Second-line therapy includes infliximab or calcineurin inhibitors (CNIs) with similar short- and long-term colectomy rates. Despite its pathophysiological relevance, there is insufficient evidence to promote intensified induction with infliximab. Prior treatment exposure is a cornerstone for guiding therapeutic choice of short- and long-term therapies in the context of ASUC: in anti-TNF exposed patients, CNIs may be favored as a bridge therapy to vedolizumab or ustekinumab. Third-line salvage therapy could be a therapeutic option in selected patients referred to expert centers. Additionally, evidence is accumulating regarding the use of tofacitinib in ASUC.
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Affiliation(s)
| | - David Laharie
- CHU de BordeauxHôpital Haut‐LévêqueService d’Hépato‐gastroentérologie et Oncologie Digestive – Université de BordeauxBordeauxFrance
| | - Julien Kirchgesner
- Gastroenterology DepartmentSorbonne UniversitéSaint‐Antoine HospitalParisFrance
| | - Mathieu Uzzan
- Gastroenterology DepartmentParis Est Créteil University UPECHenri Mondor HospitalFédération Hospitalo‐Universitaire TRUE InnovaTive theRapy for ImmUne DisordErsCréteilFrance
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11
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Kucharzik T, Dignass A, Atreya R, Bokemeyer B, Esters P, Herrlinger K, Kannengiesser K, Kienle P, Langhorst J, Lügering A, Schreiber S, Stallmach A, Stein J, Sturm A, Teich N, Siegmund B. [Not Available]. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2023; 61:1046-1134. [PMID: 37579791 DOI: 10.1055/a-2060-0935] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 08/16/2023]
Affiliation(s)
- T Kucharzik
- Klinik für Allgemeine Innere Medizin und Gastroenterologie, Städtisches Klinikum Lüneburg, Lüneburg, Deutschland
| | - A Dignass
- Medizinische Klinik I, Agaplesion Markus Krankenhaus, Frankfurt, Deutschland
| | - R Atreya
- Medizinische Klinik 1 Gastroent., Pneumologie, Endokrin., Universitätsklinikum Erlangen, Erlangen, Deutschland
| | - B Bokemeyer
- Interdisziplinäres Crohn Colitis Centrum Minden - ICCCM, Minden, Deutschland
| | - P Esters
- Medizinische Klinik I, Agaplesion Markus Krankenhaus, Frankfurt, Deutschland
| | - K Herrlinger
- Innere Medizin I, Asklepios Klinik Nord, Hamburg, Deutschland
| | - K Kannengiesser
- Klinik für Allgemeine Innere Medizin und Gastroenterologie, Städtisches Klinikum Lüneburg, Lüneburg, Deutschland
| | - P Kienle
- Abteilung für Allgemein- und Viszeralchirurgie, Theresienkrankenhaus, Mannheim, Deutschland
| | - J Langhorst
- Klinik für Integrative Medizin und Naturheilkunde, Sozialstiftung Bamberg Klinikum am Bruderwald, Bamberg, Deutschland
| | - A Lügering
- Medizinisches Versorgungszentrum Portal 10, Münster, Deutschland
| | - S Schreiber
- Klinik für Innere Medizin I, Universitätsklinikum Schleswig Holstein, Kiel, Deutschland
| | - A Stallmach
- Klinik für Innere Medizin IV Gastroenterologie, Hepatologie, Infektiologie, Universitätsklinikum Jena, Jena, Deutschland
| | - J Stein
- Abteilung Innere Medizin mit Schwerpunkt Gastroenterologie, Krankenhaus Sachsenhausen, Frankfurt, Deutschland
| | - A Sturm
- Klinik für Innere Medizin mit Schwerpunkt Gastroenterologie, DRK Kliniken Berlin Westend, Berlin, Deutschland
| | - N Teich
- Internistische Gemeinschaftspraxis, Leipzig, Deutschland
| | - B Siegmund
- Medizinische Klinik für Gastroenterologie, Infektiologie und Rheumatologie, Charité Campus Benjamin Franklin - Universitätsmedizin Berlin, Berlin, Deutschland
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12
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AlKhormi A, Altheyabi AM, AlGhamdi SA, Alshahrani O, Alotay AA, Deeb A. The prevalence and clinical characteristics of Clostridium difficile infection in Saudi patients admitted with inflammatory bowel disease: A case-control study. Saudi J Gastroenterol 2023; 29:251-255. [PMID: 37282448 PMCID: PMC10445497 DOI: 10.4103/sjg.sjg_476_22] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/07/2022] [Revised: 12/22/2022] [Accepted: 05/04/2023] [Indexed: 06/08/2023] Open
Abstract
Background Inflammatory bowel disease (IBD) patients are at increased risk of Clostridium difficile infection (CDI), causing significant morbidity and mortality. This study examined CDI's prevalence, predisposing factors, and clinical outcomes in Saudi hospitalized IBD patients. Methods : A retrospective case-control study was conducted at a tertiary medical city in Riyadh, Saudi Arabia. All Saudi adult patients with IBD, admitted over the preceding four years were identified from the hospital's database. Eligible patients were divided into those with CDI and those without CDI. Binary logistic regression was used to determine the predisposing factors for CDI among admitted IBD patients. Results During the study period, 95 patients were admitted with IBD. Crohn's disease (CD) was the predominant type (71.6%), whereas 28.4% of the patients were with ulcerative colitis (UC). Only 16 (16.8%) patients had positive CDI. CDI-positive patients tend to have hypertension and previous use of steroids. Patients with UC tend to have a higher risk of CDI than those with CD. Most patients recovered from the CDI (81.3%) with a median time to CDI clearance of 14 days. Three patients (18.8%) had recurrent CDI; among them, one died. Conclusion The prevalence of CDI in Saudi IBD patients is similar to that reported elsewhere. UC, steroid treatment, and hypertension are risk factors for CDI in IBD patients. Recurrence of CDI in IBD patients is common and associated with a poor prognosis.
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Affiliation(s)
- Abdulrahman AlKhormi
- Department of Internal Medicine, Gastroenterology Division, King Abdulaziz Medical City, National Guard Health Affairs, Riyadh, Saudi Arabia
- Division of Gastroenterology, Department of Internal Medicine, King Abdulaziz Medical City, Riyadh, Saudi Arabia
| | - Abdullah M. Altheyabi
- Department of Internal Medicine, Gastroenterology Division, King Abdulaziz Medical City, National Guard Health Affairs, Riyadh, Saudi Arabia
- Division of Gastroenterology, Department of Internal Medicine, King Abdulaziz Medical City, Riyadh, Saudi Arabia
| | - Saud A. AlGhamdi
- Department of Internal Medicine, Gastroenterology Division, King Abdulaziz Medical City, National Guard Health Affairs, Riyadh, Saudi Arabia
| | - Osama Alshahrani
- Department of Internal Medicine, Gastroenterology Division, King Abdulaziz Medical City, National Guard Health Affairs, Riyadh, Saudi Arabia
| | - Abdulwahed A. Alotay
- Department of Medicine, College of Medicine, Imam Mohammad Bin Saud Islamic University, Riyadh, Saudi Arabia
| | - Ahmad Deeb
- Division of Gastroenterology, Department of Internal Medicine, King Abdulaziz Medical City, Riyadh, Saudi Arabia
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13
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Tariq R, Syed T, Yadav D, Prokop LJ, Singh S, Loftus EV, Pardi DS, Khanna S. Outcomes of Fecal Microbiota Transplantation for C. difficile Infection in Inflammatory Bowel Disease : A Systematic Review and Meta-analysis. J Clin Gastroenterol 2023; 57:285-293. [PMID: 34864789 DOI: 10.1097/mcg.0000000000001633] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/27/2021] [Accepted: 10/10/2021] [Indexed: 12/10/2022]
Abstract
BACKGROUND Fecal microbiota transplantation (FMT) is a safe and effective therapy for recurrent Clostridioides difficile infection (CDI). Data on FMT for CDI in patients with underlying inflammatory bowel disease (IBD) are emerging but conflicting. We performed a systematic review and meta-analysis to describe the efficacy and safety of FMT for CDI in IBD and its impact on IBD outcomes. METHODS A systematic search of multiple databases including Embase, Scopus, and Web of Science was performed. Our primary analysis focused on pooled rate of CDI resolution after single and multiple FMTs in IBD patients. Additional analyses included rates of IBD-associated outcomes (flare, surgery, symptom improvement) after FMT. The random-effects model was used to calculate pooled rates. RESULTS Among 457 adult patients, 363 had CDI resolution after first FMT with a pooled cure rate of 78% [95% confidence interval (CI): 73%-83%; I2 =39%]. Overall pooled rate cure rate with single and multiple FMTs was 88% (95% CI: 81%-94%; I2 =73%). The pooled rate of an IBD flare after FMT was 26.8% (95% CI: 22.5%-31.6%; I2 =9%) and of colectomy was 7.3% (95% CI: 4.7%-10.5%; I2 =56%). Among 141 pediatric patients, 106 had CDI resolution after first FMT with pooled cure rate of 78% (95% CI: 58%-93%; I2 =59%). Overall pooled cure rate with single and multiple FMTs was 77% (95% CI: 50%-96%; I2 =63%). The pooled rate of an IBD flare after FMT was 10.8% (95% CI: 5.7%-18.5% I2 =43%), and of colectomy was 10.3% (95% CI: 2.1%-30.2% I2 =23%). CONCLUSIONS FMT appears to be a highly effective therapy for preventing recurrent CDI in patients with IBD. Patients who fail a single FMT may benefit from multiple FMTs.
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Affiliation(s)
- Raseen Tariq
- Division of Gastroenterology and Hepatology
- Department of Internal Medicine, Rochester General Hospital
| | - Tausif Syed
- Department of Internal Medicine, Unity Hospital, Rochester, NY
| | | | | | - Siddharth Singh
- Division of Gastroenterology and Hepatology, University of California San Diego, La Jolla, CA
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14
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Outcomes of clostridioides difficile infection on inflammatory bowel disease patients undergoing colonic resection: A propensity score weighted NSQIP analysis. Am J Surg 2023; 225:553-557. [PMID: 36376114 DOI: 10.1016/j.amjsurg.2022.10.061] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2022] [Revised: 10/16/2022] [Accepted: 10/28/2022] [Indexed: 11/05/2022]
Abstract
BACKGROUND Inflammatory bowel disease (IBD) patients are at risk for Clostridioides difficile infection (CDI). The majority of published outcomes data feature medically treated patients. We aimed to analyze outcomes in a large cohort of surgical IBD patients diagnosed with CDI. METHODS All patients with IBD in the ACS NSQIP Colectomy and Proctectomy (2015-2019) modules were identified. The IBD-CDI and IBD cohorts were propensity score weighted on demographic and surgical factors and compared. RESULTS In the entire unmatched cohort (n = 12,782), 119/0.93% patients were diagnosed with CDI (74.2% Crohn's/25.7% UC/Indeterminate colitis) within 30-days of surgery. After propensity score weighting, IBD-CDI was associated with increased risk of readmission (OR 4.55 [3.09-6.71], p < 0.001), reoperation (3.17 [1.81-5.52], p < 0.001) and any complication (2.16 [1.47-3.17], p < 0.001). Any SSI (2.58 [1.67-3.98]), organ space SSI (2.49 [1.51-4.11], both p < 0.001), prolonged ventilation (4.03 [1.39-11.69],p = 0.01), acute renal failure (15.06 [4.26-53.26],p < 0.001), stroke (12.36 [1.26-121.06],p = 0.03), sepsis (2.4 [1.39-4.15],p = 0.002) and septic shock (3.29 [1.36-7.96],p = 0.008) were also higher in the IBD-CDI cohort. Mean length of stay was increased by 39% in CDI patients. CONCLUSION Post colonic resection, IBD-CDI patients have worse outcomes than IBD patients without CDI. These patients represent a particularly vulnerable cohort who require close monitoring for the development of postoperative complications.
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15
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Ostrowski S, Croft A. Viral Enteric Infections in Acute Severe Ulcerative Colitis. J Crohns Colitis 2022; 16:1335-1339. [PMID: 35165696 DOI: 10.1093/ecco-jcc/jjac028] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/21/2021] [Revised: 01/29/2022] [Accepted: 02/13/2022] [Indexed: 02/08/2023]
Abstract
BACKGROUND AND AIMS Excluding superimposed enteric infection is critical in the management of acute severe ulcerative colitis [ASUC]. Whilst infection with Clostridium difficile and cytomegalovirus have been shown to increase colectomy and mortality rates, no data exist regarding the impact of common viral enteropathogens in ASUC. Our aim was to determine if viral enteric infection in ASUC alters the severity or outcomes of these episodes. METHODS This was a retrospective review of cases presenting to a large tertiary centre. Data were obtained from an in-house, prospectively maintained inflammatory bowel disease database. We identified all ASUC cases treated between October 2015 and January 2021 and compared those testing positive for adenovirus 40/41, human rotavirus or norovirus GI by faecal multiplex polymerase chain reaction [PCR] to those testing negative. RESULTS We identified 147 patients with ASUC and faecal multiplex PCR testing for viral pathogens. In total, 22/147 patients [14.9%] tested positive, two of whom tested positive for two viruses. The infected and non-infected cohorts did not differ significantly with regard to admission C-reactive protein [81.7 vs 76.6, p = 0.77], Mayo endoscopic subscore [2.4 vs 2.3, p = 0.43], length of hospital admission [7.9 vs 7.9 p = 0.99], requirement for rescue therapy [59% vs 56%, p = 0.75] or colectomy rate [4.5% vs 4.1%, p = 0.69]. CONCLUSIONS Infection with viral enteropathogens was common in our ASUC cohort, but did not appear to affect disease severity at presentation, the need for rescue therapy or the success rate of rescue therapy.
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Affiliation(s)
- Szymon Ostrowski
- Royal Brisbane and Women's Hospital, Department of Gastroenterology and Hepatology, Butterfield St., Herston, QLD 4029, Australia.,Mater Hospital Brisbane, Department of Gastroenterology and Hepatology, Raymond Terrace, South Brisbane, QLD 4101, Australia
| | - Anthony Croft
- Royal Brisbane and Women's Hospital, Department of Gastroenterology and Hepatology, Butterfield St., Herston, QLD 4029, Australia.,University of Queensland, St Lucia, QLD 4072, Australia
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16
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Lee MR, Kim ES. [ Clostridioides Infection in Patients with Inflammatory Bowel Disease]. THE KOREAN JOURNAL OF GASTROENTEROLOGY = TAEHAN SOHWAGI HAKHOE CHI 2022; 80:66-71. [PMID: 36004633 DOI: 10.4166/kjg.2022.097] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/15/2022] [Revised: 07/20/2022] [Accepted: 07/22/2022] [Indexed: 06/15/2023]
Abstract
Inflammatory bowel disease (IBD), comprising Crohn's disease and ulcerative colitis, is a chronic inflammatory condition of the gastrointestinal tract, which is often accompanied by altered gut microbial composition. Gut dysbiosis in IBD is considered to be the reason for the high risk of Clostridioides difficile infection (CDI) in patients with IBD. Therefore, CDI should be evaluated in IBD patients with a symptom flare. Medical treatment of non-severe CDI in IBD is similar to that in non-IBD patients and includes oral vancomycin or fidaxomicin. The risk of recurrent CDI in IBD is higher than in non-IBD patients and this could be mitigated by fecal microbiota transplantation. As CDI may worsen the clinical outcomes of IBD, patients should be carefully monitored and an escalation of IBD therapy needs to be considered when there is no improvement seen with the antimicrobial treatment of CDI. This review discusses the risk, pathophysiology, diagnosis, and management of CDI in IBD.
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Affiliation(s)
- Mi Rae Lee
- Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, Korea
| | - Eun Soo Kim
- Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, Korea
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17
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Boeriu A, Roman A, Fofiu C, Dobru D. The Current Knowledge on Clostridioides difficile Infection in Patients with Inflammatory Bowel Diseases. Pathogens 2022; 11:819. [PMID: 35890064 PMCID: PMC9323231 DOI: 10.3390/pathogens11070819] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2022] [Revised: 07/17/2022] [Accepted: 07/18/2022] [Indexed: 11/17/2022] Open
Abstract
Clostridioides difficile (C. difficile) represents a major health burden with substantial economic and clinical impact. Patients with inflammatory bowel diseases (IBD) were identified as a risk category for Clostridioides difficile infection (CDI). In addition to traditional risk factors for C. difficile acquisition, IBD-specific risk factors such as immunosuppression, severity and extension of the inflammatory disease were identified. C. difficile virulence factors, represented by both toxins A and B, induce the damage of the intestinal mucosa and vascular changes, and promote the inflammatory host response. Given the potential life-threatening complications, early diagnostic and therapeutic interventions are required. The screening for CDI is recommended in IBD exacerbations, and the diagnostic algorithm consists of clinical evaluation, enzyme immunoassays (EIAs) or nucleic acid amplification tests (NAATs). An increased length of hospitalization, increased colectomy rate and mortality are the consequences of concurrent CDI in IBD patients. Selection of CD strains of higher virulence, antibiotic resistance, and the increasing rate of recurrent infections make the management of CDI in IBD more challenging. An individualized therapeutic approach is recommended to control CDI as well as IBD flare. Novel therapeutic strategies have been developed in recent years in order to manage severe, refractory or recurrent CDI. In this article, we aim to review the current evidence in the field of CDI in patients with underlying IBD, pointing to pathogenic mechanisms, risk factors for infection, diagnostic steps, clinical impact and outcomes, and specific management.
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Affiliation(s)
- Alina Boeriu
- Gastroenterology Department, University of Medicine Pharmacy, Sciences, and Technology “George Emil Palade” Targu Mures, 540142 Targu Mures, Romania; (A.B.); (C.F.); (D.D.)
- Gastroenterology Department, Mures County Clinical Hospital, 540103 Targu Mures, Romania
| | - Adina Roman
- Gastroenterology Department, University of Medicine Pharmacy, Sciences, and Technology “George Emil Palade” Targu Mures, 540142 Targu Mures, Romania; (A.B.); (C.F.); (D.D.)
- Gastroenterology Department, Mures County Clinical Hospital, 540103 Targu Mures, Romania
| | - Crina Fofiu
- Gastroenterology Department, University of Medicine Pharmacy, Sciences, and Technology “George Emil Palade” Targu Mures, 540142 Targu Mures, Romania; (A.B.); (C.F.); (D.D.)
| | - Daniela Dobru
- Gastroenterology Department, University of Medicine Pharmacy, Sciences, and Technology “George Emil Palade” Targu Mures, 540142 Targu Mures, Romania; (A.B.); (C.F.); (D.D.)
- Gastroenterology Department, Mures County Clinical Hospital, 540103 Targu Mures, Romania
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Risk Factors, Diagnosis, and Management of Clostridioides difficile Infection in Patients with Inflammatory Bowel Disease. Microorganisms 2022; 10:microorganisms10071315. [PMID: 35889034 PMCID: PMC9319314 DOI: 10.3390/microorganisms10071315] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2022] [Revised: 06/24/2022] [Accepted: 06/27/2022] [Indexed: 12/10/2022] Open
Abstract
Clostridioides difficile infection (CDI) and inflammatory bowel disease (IBD) are two pathologies that share a bidirectional causal nexus, as CDI is known to have an aggravating effect on IBD and IBD is a known risk factor for CDI. The colonic involvement in IBD not only renders the host more prone to an initial CDI development but also to further recurrences. Furthermore, IBD flares, which are predominantly set off by a CDI, not only create a need for therapy escalation but also prolong hospital stay. For these reasons, adequate and comprehensive management of CDI is of paramount importance in patients with IBD. Microbiological diagnosis, correct evaluation of clinical status, and consideration of different treatment options (from antibiotics and fecal microbiota transplantation to monoclonal antibodies) carry pivotal importance. Thus, the aim of this article is to review the risk factors, diagnosis, and management of CDI in patients with IBD.
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Lukin D, Faleck D, Xu R, Zhang Y, Weiss A, Aniwan S, Kadire S, Tran G, Rahal M, Winters A, Chablaney S, Koliani-Pace JL, Meserve J, Campbell JP, Kochhar G, Bohm M, Varma S, Fischer M, Boland B, Singh S, Hirten R, Ungaro R, Lasch K, Shmidt E, Jairath V, Hudesman D, Chang S, Swaminath A, Shen B, Kane S, Loftus EV, Sands BE, Colombel JF, Siegel CA, Sandborn WJ, Dulai PS. Comparative Safety and Effectiveness of Vedolizumab to Tumor Necrosis Factor Antagonist Therapy for Ulcerative Colitis. Clin Gastroenterol Hepatol 2022; 20:126-135. [PMID: 33039584 PMCID: PMC8026779 DOI: 10.1016/j.cgh.2020.10.003] [Citation(s) in RCA: 28] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/03/2020] [Revised: 09/04/2020] [Accepted: 10/03/2020] [Indexed: 12/12/2022]
Abstract
BACKGROUND & AIMS We aimed to compare safety and effectiveness of vedolizumab to tumor necrosis factor (TNF)-antagonist therapy in ulcerative colitis in routine practice. METHODS A multicenter, retrospective, observational cohort study (May 2014 to December 2017) of ulcerative colitis patients treated with vedolizumab or TNF-antagonist therapy. Propensity score weighted comparisons for development of serious adverse events and achievement of clinical remission, steroid-free clinical remission, and steroid-free deep remission. A priori determined subgroup comparisons in TNF-antagonist-naïve and -exposed patients, and for vedolizumab against infliximab and subcutaneous TNF-antagonists separately. RESULTS A total of 722 (454 vedolizumab, 268 TNF antagonist) patients were included. Vedolizumab-treated patients were more likely to achieve clinical remission (hazard ratio [HR], 1.651; 95% confidence interval [CI], 1.229-2.217), steroid-free clinical remission (HR, 1.828; 95% CI, 1.135-2.944), and steroid-free deep remission (HR, 2.819; 95% CI, 1.496-5.310) than those treated with TNF antagonists. Results were consistent across subgroup analyses in TNF-antagonist-naïve and -exposed patients, and for vedolizumab vs infliximab and vs subcutaneous TNF-antagonist agents separately. Overall, there were no statistically significant differences in the risk of serious adverse events (HR, 0.899; 95% CI, 0.502-1.612) or serious infections (HR, 1.235; 95% CI, 0.608-2.511) between vedolizumab-treated and TNF-antagonist-treated patients. However, in TNF-antagonist-naïve patients, vedolizumab was less likely to be associated with serious adverse events than TNF antagonists (HR, 0.192; 95% CI, 0.049-0.754). CONCLUSIONS Treatment of ulcerative colitis with vedolizumab is associated with higher rates of remission than treatment with TNF-antagonist therapy in routine practice, and lower rates of serious adverse events in TNF-antagonist-naïve patients.
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Affiliation(s)
- Dana Lukin
- Montefiore Medical Center, New York, New York
| | - David Faleck
- Icahn School of Medicine at Mount Sinai, New York, New York
| | - Ronghui Xu
- University of California, San Diego, La Jolla, California
| | - Yiran Zhang
- University of California, San Diego, La Jolla, California
| | - Aaron Weiss
- Montefiore Medical Center, New York, New York
| | | | | | | | | | - Adam Winters
- Icahn School of Medicine at Mount Sinai, New York, New York
| | | | | | - Joseph Meserve
- University of California, San Diego, La Jolla, California
| | | | | | | | | | | | - Brigid Boland
- University of California, San Diego, La Jolla, California
| | | | - Robert Hirten
- Icahn School of Medicine at Mount Sinai, New York, New York
| | - Ryan Ungaro
- Icahn School of Medicine at Mount Sinai, New York, New York
| | - Karen Lasch
- Takeda Pharmaceuticals, Lexington, Massachusetts
| | | | - Vipul Jairath
- University of Western Ontario, London, Ontario, Canada
| | | | | | | | - Bo Shen
- Cleveland Clinic Foundation, Cleveland, Ohio
| | | | | | - Bruce E. Sands
- Icahn School of Medicine at Mount Sinai, New York, New York
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20
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Dalal RS, Allegretti JR. Diagnosis and management of Clostridioides difficile infection in patients with inflammatory bowel disease. Curr Opin Gastroenterol 2021; 37:336-343. [PMID: 33654015 PMCID: PMC8169557 DOI: 10.1097/mog.0000000000000739] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
PURPOSE OF REVIEW Clostridioides difficile infection (CDI) may complicate the course of ulcerative colitis and Crohn's disease. The clinical presentation of CDI in this population is often atypical, and patients may experience exacerbations of their underlying inflammatory bowel disease (IBD) secondary to C. difficile. In this review, we aim to review the risk factors, diagnosis, and management of CDI in the context of IBD. RECENT FINDINGS Patients with colonic involvement of their IBD are at higher risk for CDI and colonization may be more common than in the general population. Therefore, CDI is confirmed using a two-step approach to stool testing. Oral vancomycin or fidaxomicin are the preferred agents for nonfulminant disease, and oral metronidazole is no longer recommended as first-line therapy. For all patients with CDI recurrence, fecal microbiota transplant (FMT) should be considered, as this has been shown to be safe and effective. Among those who have worsening of their underlying IBD, retrospective research suggest that outcomes are improved for those who undergo escalation of immunosuppression with appropriate antimicrobial treatment of C. difficile, however prospective data are needed. SUMMARY CDI may complicate the course of IBD, however the presentation may not be typical. Therefore, all patients with worsening gastrointestinal symptoms should be evaluated for both CDI and IBD exacerbation. Providers should consider FMT for all patients with recurrent CDI as well as escalation of immunosuppression for patients who fail to improve with appropriate antimicrobial therapy.
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Affiliation(s)
- Rahul S. Dalal
- Division of Gastroenterology, Hepatology and Endoscopy, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA
| | - Jessica R. Allegretti
- Division of Gastroenterology, Hepatology and Endoscopy, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA
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21
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Sehgal K, Yadav D, Khanna S. The interplay of Clostridioides difficile infection and inflammatory bowel disease. Therap Adv Gastroenterol 2021; 14:17562848211020285. [PMID: 34104215 PMCID: PMC8170344 DOI: 10.1177/17562848211020285] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/10/2021] [Accepted: 05/06/2021] [Indexed: 02/04/2023] Open
Abstract
Inflammatory bowel disease (IBD) is a chronic disease of the intestinal tract that commonly presents with diarrhea. Clostridioides difficile infection (CDI) is one of the most common complications associated with IBD that lead to flare-ups of underlying IBD. The pathophysiology of CDI includes perturbations of the gut microbiota, which makes IBD a risk factor due to the gut microbial alterations that occur in IBD, predisposing patients CDI even in the absence of antibiotics. Superimposed CDI not only worsens IBD symptoms but also leads to adverse outcomes, including treatment failure and an increased risk of hospitalization, surgery, and mortality. Due to the overlapping symptoms and concerns with false-positive molecular tests for CDI, diagnosing CDI in patients with IBD remains a clinical challenge. It is crucial to have a high index of suspicion for CDI in patients who seem to be experiencing an exacerbation of IBD symptoms. Vancomycin and fidaxomicin are the first-line treatments for the management of CDI in IBD. Microbiota restoration therapies effectively prevent recurrent CDI in IBD patients. Immunosuppression for IBD in IBD patients with CDI should be managed individually, based on a thorough clinical assessment and after weighing the pros and cons of escalation of therapy. This review summarizes the epidemiology, pathophysiology, the diagnosis of CDI in IBD, and outlines the principles of management of both CDI and IBD in IBD patients with CDI.
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Affiliation(s)
- Kanika Sehgal
- Division of Gastroenterology and
Hepatology, Mayo Clinic, Rochester, MN, USA
| | - Devvrat Yadav
- Division of Gastroenterology and
Hepatology, Mayo Clinic, Rochester, MN, USA
| | - Sahil Khanna
- Division of Gastroenterology and
Hepatology, Mayo Clinic, 200 First St SW, Rochester, MN 55905,
USA
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22
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Axelrad JE, Cadwell KH, Colombel JF, Shah SC. The role of gastrointestinal pathogens in inflammatory bowel disease: a systematic review. Therap Adv Gastroenterol 2021; 14:17562848211004493. [PMID: 33868457 PMCID: PMC8020742 DOI: 10.1177/17562848211004493] [Citation(s) in RCA: 36] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/16/2021] [Accepted: 03/04/2021] [Indexed: 02/04/2023] Open
Abstract
The inflammatory bowel diseases (IBD), comprising Crohn's disease (CD) and ulcerative colitis (UC), are chronic, progressive, inflammatory conditions of the gastrointestinal tract. Imbalance in the gut microbial community, or dysbiosis, and the subsequent immune response, represent the critical relationship between genetic susceptibility, microbes, and environment factors, that result in IBD. Gastrointestinal pathogens - a common cause of dysbiosis - have been implicated as an environmental trigger in new onset IBD, as well as flare of existing IBD. In this article, we systematically review clinical data regarding the association between specific gastrointestinal pathogens and IBD. Numerous bacteria, viruses, fungi, and parasites have been implicated in the pathogenesis of IBD, and exacerbations of existing disease. In this article, we will also specifically discuss the less recognized microbes that have an inverse association with IBD, including certain bacterial pathogens, such as Helicobacter pylori, and parasites, such as Trichuris species. Future prospective and experimental studies are required to establish causality and clarify potential mechanisms of enteric pathogens in modifying the risk and course of IBD.
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Affiliation(s)
| | - Ken H. Cadwell
- Division of Gastroenterology, Department of Medicine, NYU Grossman School of Medicine, New York, NY, USA,Kimmel Center for Biology and Medicine at the Skirball Institute, NYU Grossman School of Medicine, New York, NY, USA,Department of Microbiology, NYU Grossman School of Medicine, New York, NY, USA
| | - Jean-Frederic Colombel
- Division of Gastroenterology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Shailja C. Shah
- Section of Gastroenterology, Veterans Affairs Tennessee Valley Healthcare System, Nashville, TN,San Diego Health System, La Jolla, CA, USA,Division of Gastroenterology, University of California, San Diego, La Jolla, CA, USA
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23
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Clostridioides difficile exploits toxin-mediated inflammation to alter the host nutritional landscape and exclude competitors from the gut microbiota. Nat Commun 2021; 12:462. [PMID: 33469019 PMCID: PMC7815924 DOI: 10.1038/s41467-020-20746-4] [Citation(s) in RCA: 108] [Impact Index Per Article: 27.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2020] [Accepted: 12/17/2020] [Indexed: 01/04/2023] Open
Abstract
Clostridioides difficile is a bacterial pathogen that causes a range of clinical disease from mild to moderate diarrhea, pseudomembranous colitis, and toxic megacolon. Typically, C. difficile infections (CDIs) occur after antibiotic treatment, which alters the gut microbiota, decreasing colonization resistance against C. difficile. Disease is mediated by two large toxins and the expression of their genes is induced upon nutrient depletion via the alternative sigma factor TcdR. Here, we use tcdR mutants in two strains of C. difficile and omics to investigate how toxin-induced inflammation alters C. difficile metabolism, tissue gene expression and the gut microbiota, and to determine how inflammation by the host may be beneficial to C. difficile. We show that C. difficile metabolism is significantly different in the face of inflammation, with changes in many carbohydrate and amino acid uptake and utilization pathways. Host gene expression signatures suggest that degradation of collagen and other components of the extracellular matrix by matrix metalloproteinases is a major source of peptides and amino acids that supports C. difficile growth in vivo. Lastly, the inflammation induced by C. difficile toxin activity alters the gut microbiota, excluding members from the genus Bacteroides that are able to utilize the same essential nutrients released from collagen degradation. The effects of antibiotics on the gut microbiota can lead to enhanced colonization of Clostridioides difficile (C. difficile) and toxin-mediated pathogenesis. Here, using defined toxin-mutant strains and a murine model, the authors provide insights into how toxin-induced inflammation alters C. difficile metabolism, host tissue gene expression and gut microbiota, together influencing a beneficial niche for infection.
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24
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Kucharzik T, Dignass AU, Atreya R, Bokemeyer B, Esters P, Herrlinger K, Kannengießer K, Kienle P, Langhorst J, Lügering A, Schreiber S, Stallmach A, Stein J, Sturm A, Teich N, Siegmund B. [Not Available]. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2020; 58:e241-e326. [PMID: 33260237 DOI: 10.1055/a-1296-3444] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Affiliation(s)
- Torsten Kucharzik
- Klinik für Allgemeine Innere Medizin und Gastroenterologie, Klinikum Lüneburg, Lüneburg, Deutschland
| | - Axel U Dignass
- Medizinische Klinik I, Agaplesion Markus Krankenhaus, Frankfurt am Main, Deutschland
| | - Raja Atreya
- Medizinische Klinik 1, Universitätsklinikum Erlangen, Deutschland
| | - Bernd Bokemeyer
- Gastroenterologische Gemeinschaftspraxis Minden, Deutschland
| | - Philip Esters
- Medizinische Klinik I, Agaplesion Markus Krankenhaus, Frankfurt am Main, Deutschland
| | | | - Klaus Kannengießer
- Klinik für Allgemeine Innere Medizin und Gastroenterologie, Klinikum Lüneburg, Lüneburg, Deutschland
| | - Peter Kienle
- Allgemein- und Viszeralchirurgie, Theresienkrankenhaus und Sankt Hedwig-Klinik GmbH, Mannheim, Deutschland
| | - Jost Langhorst
- Klinik für Integrative Medizin und Naturheilkunde, Klinikum am Bruderwald, Bamberg, Deutschland
| | - Andreas Lügering
- Medizinisches Versorgungszentrum Portal 10, Münster, Deutschland
| | | | - Andreas Stallmach
- Gastroenterologie, Hepatologie und Infektiologie, Friedrich Schiller Universität, Jena, Deutschland
| | - Jürgen Stein
- Innere Medizin mit Schwerpunkt Gastroenterologie, Krankenhaus Sachsenhausen, Frankfurt/Main, Deutschland
| | - Andreas Sturm
- Klinik für Innere Medizin mit Schwerpunkt Gastroenterologie, DRK Kliniken Berlin Westend, Berlin, Deutschland
| | - Niels Teich
- Internistische Gemeinschaftspraxis für Verdauungs- und Stoffwechselkrankheiten, Leipzig, Deutschland
| | - Britta Siegmund
- Medizinische Klinik I, Charité Universitätsmedizin Berlin, Campus Benjamin Franklin, Berlin, Deutschland
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25
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Lam AY, Gutin LS, Nguyen Y, Velayos FS. Management of Recurrent Clostridioides Infection: A Difficile Problem in Inflammatory Bowel Disease Patients. Dig Dis Sci 2020; 65:3111-3115. [PMID: 32749638 PMCID: PMC7398857 DOI: 10.1007/s10620-020-06521-x] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Affiliation(s)
- Angela Y. Lam
- grid.280062.e0000 0000 9957 7758Department of Gastroenterology and Hepatology, Kaiser Permanente, 2350 Geary Boulevard, 2nd Floor, San Francisco, CA 94010 USA
| | - Liat S. Gutin
- grid.280062.e0000 0000 9957 7758Department of Gastroenterology and Hepatology, Kaiser Permanente, 2350 Geary Boulevard, 2nd Floor, San Francisco, CA 94010 USA
| | - Yume Nguyen
- grid.280062.e0000 0000 9957 7758Department of Gastroenterology and Hepatology, Kaiser Permanente, South San Francisco, CA USA
| | - Fernando S. Velayos
- grid.280062.e0000 0000 9957 7758Department of Gastroenterology and Hepatology, Kaiser Permanente, 2350 Geary Boulevard, 2nd Floor, San Francisco, CA 94010 USA
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26
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Lamb CA, Kennedy NA, Raine T, Hendy PA, Smith PJ, Limdi JK, Hayee B, Lomer MCE, Parkes GC, Selinger C, Barrett KJ, Davies RJ, Bennett C, Gittens S, Dunlop MG, Faiz O, Fraser A, Garrick V, Johnston PD, Parkes M, Sanderson J, Terry H, Gaya DR, Iqbal TH, Taylor SA, Smith M, Brookes M, Hansen R, Hawthorne AB. British Society of Gastroenterology consensus guidelines on the management of inflammatory bowel disease in adults. Gut 2019; 68:s1-s106. [PMID: 31562236 PMCID: PMC6872448 DOI: 10.1136/gutjnl-2019-318484] [Citation(s) in RCA: 1498] [Impact Index Per Article: 249.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/10/2019] [Revised: 06/10/2019] [Accepted: 06/10/2019] [Indexed: 02/06/2023]
Abstract
Ulcerative colitis and Crohn's disease are the principal forms of inflammatory bowel disease. Both represent chronic inflammation of the gastrointestinal tract, which displays heterogeneity in inflammatory and symptomatic burden between patients and within individuals over time. Optimal management relies on understanding and tailoring evidence-based interventions by clinicians in partnership with patients. This guideline for management of inflammatory bowel disease in adults over 16 years of age was developed by Stakeholders representing UK physicians (British Society of Gastroenterology), surgeons (Association of Coloproctology of Great Britain and Ireland), specialist nurses (Royal College of Nursing), paediatricians (British Society of Paediatric Gastroenterology, Hepatology and Nutrition), dietitians (British Dietetic Association), radiologists (British Society of Gastrointestinal and Abdominal Radiology), general practitioners (Primary Care Society for Gastroenterology) and patients (Crohn's and Colitis UK). A systematic review of 88 247 publications and a Delphi consensus process involving 81 multidisciplinary clinicians and patients was undertaken to develop 168 evidence- and expert opinion-based recommendations for pharmacological, non-pharmacological and surgical interventions, as well as optimal service delivery in the management of both ulcerative colitis and Crohn's disease. Comprehensive up-to-date guidance is provided regarding indications for, initiation and monitoring of immunosuppressive therapies, nutrition interventions, pre-, peri- and postoperative management, as well as structure and function of the multidisciplinary team and integration between primary and secondary care. Twenty research priorities to inform future clinical management are presented, alongside objective measurement of priority importance, determined by 2379 electronic survey responses from individuals living with ulcerative colitis and Crohn's disease, including patients, their families and friends.
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Affiliation(s)
- Christopher Andrew Lamb
- Newcastle University, Newcastle upon Tyne, UK
- Newcastle Upon Tyne Hospitals NHS Foundation Trust, Newcastle Upon Tyne, UK
| | - Nicholas A Kennedy
- Royal Devon and Exeter NHS Foundation Trust, Exeter, UK
- University of Exeter, Exeter, UK
| | - Tim Raine
- Cambridge University Hospitals NHS FoundationTrust, Cambridge, UK
| | - Philip Anthony Hendy
- Chelsea and Westminster Hospital NHS Foundation Trust, London, UK
- Imperial College London, London, UK
| | - Philip J Smith
- Royal Liverpool and Broadgreen University Hospitals NHS Trust, Liverpool, UK
| | - Jimmy K Limdi
- The Pennine Acute Hospitals NHS Trust, Manchester, UK
- University of Manchester, Manchester, UK
| | - Bu'Hussain Hayee
- King's College Hospital NHS Foundation Trust, London, UK
- King's College London, London, UK
| | - Miranda C E Lomer
- King's College London, London, UK
- Guy's and St Thomas' NHS Foundation Trust, London, UK
| | - Gareth C Parkes
- Barts Health NHS Trust, London, UK
- Barts and the London School of Medicine and Dentistry, London, UK
| | - Christian Selinger
- Leeds Teaching Hospitals NHS Trust, Leeds, UK
- University of Leeds, Leeds, UK
| | | | - R Justin Davies
- Cambridge University Hospitals NHS FoundationTrust, Cambridge, UK
- University of Cambridge, Cambridge, UK
| | - Cathy Bennett
- Systematic Research Ltd, Quorn, UK
- Royal College of Surgeons in Ireland (RCSI), Dublin, Ireland
| | | | - Malcolm G Dunlop
- University of Edinburgh, Edinburgh, UK
- Western General Hospital, Edinburgh, UK
| | - Omar Faiz
- Imperial College London, London, UK
- St Mark's Hospital, Harrow, UK
| | - Aileen Fraser
- University Hospitals Bristol NHS Foundation Trust, Bristol, UK
| | | | | | - Miles Parkes
- Cambridge University Hospitals NHS FoundationTrust, Cambridge, UK
| | - Jeremy Sanderson
- King's College London, London, UK
- Guy's and St Thomas' NHS Foundation Trust, London, UK
| | | | - Daniel R Gaya
- Glasgow Royal Infirmary, Glasgow, UK
- University of Glasgow, Glasgow, UK
| | - Tariq H Iqbal
- Queen Elizabeth Hospital Birmingham NHSFoundation Trust, Birmingham, UK
- University of Birmingham, Birmingham, UK
| | - Stuart A Taylor
- University College London, London, UK
- University College London Hospitals NHS Foundation Trust, London, UK
| | - Melissa Smith
- Brighton and Sussex University Hospitals NHS Trust, Brighton, UK
- Brighton and Sussex Medical School, Brighton, UK
| | - Matthew Brookes
- Royal Wolverhampton NHS Trust, Wolverhampton, UK
- University of Wolverhampton, Wolverhampton, UK
| | - Richard Hansen
- Royal Hospital for Children Glasgow, Glasgow, UK
- University of Glasgow, Glasgow, UK
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27
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Abstract
Ulcerative colitis and Crohn's disease are the principal forms of inflammatory bowel disease. Both represent chronic inflammation of the gastrointestinal tract, which displays heterogeneity in inflammatory and symptomatic burden between patients and within individuals over time. Optimal management relies on understanding and tailoring evidence-based interventions by clinicians in partnership with patients. This guideline for management of inflammatory bowel disease in adults over 16 years of age was developed by Stakeholders representing UK physicians (British Society of Gastroenterology), surgeons (Association of Coloproctology of Great Britain and Ireland), specialist nurses (Royal College of Nursing), paediatricians (British Society of Paediatric Gastroenterology, Hepatology and Nutrition), dietitians (British Dietetic Association), radiologists (British Society of Gastrointestinal and Abdominal Radiology), general practitioners (Primary Care Society for Gastroenterology) and patients (Crohn's and Colitis UK). A systematic review of 88 247 publications and a Delphi consensus process involving 81 multidisciplinary clinicians and patients was undertaken to develop 168 evidence- and expert opinion-based recommendations for pharmacological, non-pharmacological and surgical interventions, as well as optimal service delivery in the management of both ulcerative colitis and Crohn's disease. Comprehensive up-to-date guidance is provided regarding indications for, initiation and monitoring of immunosuppressive therapies, nutrition interventions, pre-, peri- and postoperative management, as well as structure and function of the multidisciplinary team and integration between primary and secondary care. Twenty research priorities to inform future clinical management are presented, alongside objective measurement of priority importance, determined by 2379 electronic survey responses from individuals living with ulcerative colitis and Crohn's disease, including patients, their families and friends.
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28
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Koliani-Pace JL, Siegel CA. Prognosticating the Course of Inflammatory Bowel Disease. Gastrointest Endosc Clin N Am 2019; 29:395-404. [PMID: 31078243 DOI: 10.1016/j.giec.2019.02.003] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Both Crohn's disease and ulcerative colitis are inflammatory bowel diseases (IBD) that can lead to progressive irreversible bowel damage. Selecting the most appropriate therapy for patients is a challenge because not all patients diagnosed with IBD have complications, and the amount of time to develop a complication is different for individuals. Models using patient characteristics, genetics, and immune responses help identify those patients who require early aggressive therapy with a goal to modify their disease course. Future research will help identify the role that the microbiome, metagenomics, metaproteomics, and microRNAs play in a patient prognosis.
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Affiliation(s)
- Jenna L Koliani-Pace
- Inflammatory Bowel Disease Center, Section of Gastroenterology and Hepatology, Dartmouth-Hitchcock Medical Center, Dartmouth-Hitchcock, 1 Medical Center Drive, Lebanon, NH 03766, USA
| | - Corey A Siegel
- Inflammatory Bowel Disease Center, Section of Gastroenterology and Hepatology, Dartmouth-Hitchcock Medical Center, Lebanon, NH 03756, USA.
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29
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High Immunogenicity of the Pneumococcal Conjugated Vaccine in Immunocompromised Adults With Inflammatory Bowel Disease. Am J Gastroenterol 2019; 114:1130-1141. [PMID: 31205131 DOI: 10.14309/ajg.0000000000000289] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
INTRODUCTION Patients with inflammatory bowel disease (IBD) are predisposed to pneumococcal infections due to their underlying disease and iatrogenic immunosuppression. Vaccination with the 13-valent pneumococcal conjugated vaccine (PCV13) is recommended, but with poor take-up and few data available. We performed an open-label, phase IV, multicenter study to evaluate the safety and immunogenicity of PCV13 in adults with IBD and to analyze the influence of immunomodulating treatments on anti-pneumococcal seroresponses. METHODS We enrolled 306 patients with IBD from March 2014 through February 2016, with the following exclusion criteria: current IBD flare, pregnancy, pneumococcal immunization in the previous 5 years, and influenza immunization in the previous 4 weeks. PCV13 was administered intramuscularly. Serotype-specific vaccine responses were evaluated using an opsonophagocytic assay. Adverse events were monitored by diary cards and standardized phone interviews. RESULTS The median seroprotection rate increased significantly from 43.9% (95% confidence interval [CI], 42.3-45.5) at inclusion to 90.4% (95% CI, 89.5-91.3%; P < 0.001) after vaccination. Patients receiving anti-tumor necrosis factor agents achieved a slightly lower seroprotection rate (from 44.5% [95% CI, 42.3%-46.8%] to 86.6% [95% CI, 84.9%-88.1%]) than patients treated with other types of immunosuppressive regimens (thiopurine, methotrexate, oral corticosteroids; from 44.7% [95% CI, 41.7%-47.7%] to 93.8% [95% CI, 92.1%-95.2%]) or nonimmunosuppressive treatment (5-aminosalicylate, topical corticosteroids, vedolizumab; from 41.3% [95% CI, 37.9%-44.8%] to 95.2% [95% CI, 93.4%-96.6%]). There were no safety issues. DISCUSSION Overall, the administration of PCV13 was highly immunogenic and well tolerated, irrespective of the baseline treatment, and should be encouraged in all adults with IBD.
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30
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Fecal Microbiota Transplant for Recurrent Clostridium difficile Infection in Pediatric Inflammatory Bowel Disease. J Pediatr Gastroenterol Nutr 2019; 68:343-347. [PMID: 30320666 DOI: 10.1097/mpg.0000000000002172] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
OBJECTIVES Recurrent Clostridium difficile infection (RCDI) increases morbidity and mortality in patients with inflammatory bowel disease (IBD). Fecal microbiota transplant (FMT) is known to be very effective for RCDI in non-IBD patients with cure rates up to 91%. The same success rates of FMT have not been reported in patients with IBD with RCDI, and the data in pediatrics are limited. We aimed to determine the effectiveness of FMT for RCDI in established pediatric patients with IBD. METHODS We performed a retrospective chart review of pediatric patients with IBD and RCDI (≥3 episodes) who underwent FMT via colonoscopy at a tertiary care IBD center. The primary outcome was the rate of RCDI within 60 days post-FMT. The secondary outcomes were recurrence rate by 6 months, rate of colectomy, and time to recurrence. RESULTS Of the 8 eligible patients, 6 had ulcerative colitis, 1 had IBD-unspecified, and 1 had Crohn disease. Median (interquartile range) age was 13 (11-14) years. All patients were on vancomycin at FMT. Two patients (25%) had RCDI by 60 days post-FMT and another 3 patients had RCDI between 60 days and 6 months. The median time to recurrence was 101 (40-139) days. Two patients (25%) who developed recurrence went to colectomy after FMT. CONCLUSIONS With a cure rate of 75% at 60 days, FMT administered for the treatment of RCDI may be an effective treatment option in pediatric IBD. However, there appears to be a significant rate of late recurrence of C difficile infection after 60 days in these patients.
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Abstract
Ulcerative colitis (UC) is an idiopathic inflammatory disorder. These guidelines indicate the preferred approach to the management of adults with UC and represent the official practice recommendations of the American College of Gastroenterology. The scientific evidence for these guidelines was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) process. In instances where the evidence was not appropriate for GRADE, but there was consensus of significant clinical merit, "key concept" statements were developed using expert consensus. These guidelines are meant to be broadly applicable and should be viewed as the preferred, but not only, approach to clinical scenarios.
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Affiliation(s)
- David T Rubin
- Inflammatory Bowel Disease Center, University of Chicago Medicine, Chicago, IL, USA
| | - Ashwin N Ananthakrishnan
- Division of Gastroenterology, Crohn's and Colitis Center, Massachusetts General Hospital, Boston, MA, USA
| | - Corey A Siegel
- Section of Gastroenterology and Hepatology, Dartmouth-Hitchcock Medical Center, Lebanon, NH, USA
| | - Bryan G Sauer
- Department of Medicine, University of Virginia, Charlottesville, VA, USA
| | - Millie D Long
- Division of Gastroenterology and Hepatology, Department of Medicine, University of North Carolina, Chapel Hill, NC, USA
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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. [PMID: 29206751 DOI: 10.1097/mcg.0000000000000968] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/07/2023]
Abstract
BACKGROUND AND AIMS Clostridium difficile infection (CDI) has been associated with an increased mortality risk among patients with inflammatory bowel disease (IBD) in multiple observational studies. We performed a systematic review and meta-analysis to help clearly define the magnitude of risk in IBD patients with and without CDI, and to assess the risk in individual IBD subtypes. METHODS A systematic search of multiple electronic databases was conducted for observational studies reporting the risk of mortality in IBD, stratified by the presence of CDI. Weighted summary estimates were calculated using generalized inverse variance with random-effects model. Study quality was assessed using the Newcastle-Ottawa scale. RESULTS Ten observational studies were identified (8 from North America and 2 from Europe) and included 40,700 IBD patients with CDI and 1,320,764 IBD controls without CDI. Overall, IBD patients with CDI had a higher risk of mortality compared with IBD patients without CDI [odds ratios (OR), 4.39; 95% confidence interval (CI), 3.56-5.42; I=93%]. The results were stable in high-quality studies and in hospitalized patients. When patients were stratified by IBD type, CDI was associated with increased mortality in patients with ulcerative colitis (7 studies) (OR, 4.39; 95% CI, 3.44-5.61; I), but not in patients with Crohn's disease (4 studies) (OR, 2.21; 95% CI, 0.84-5.77; I). Individual studies were limited by an inability to control for IBD disease activity and therapeutic interventions. CONCLUSIONS On the basis of 10 observational studies with at least moderate quality, CDI seems to increase mortality risk in IBD, particularly in ulcerative colitis. These findings are a cause for concern and suggest that CDI should be managed aggressively in patients with IBD.
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Affiliation(s)
- Raseen Tariq
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN
- Department of Internal Medicine, Rochester General Hospital, Rochester, NY
| | - Cindy C Y Law
- Department of Medicine, The Ottawa Hospital IBD Centre, University of Ottawa, Ottawa, ON
| | - Sahil Khanna
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN
| | - Sanjay Murthy
- Department of Medicine, The Ottawa Hospital IBD Centre, University of Ottawa, Ottawa, ON
| | - Jeffrey D McCurdy
- Department of Medicine, The Ottawa Hospital IBD Centre, University of Ottawa, Ottawa, ON
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Balram B, Battat R, Al-Khoury A, D'Aoust J, Afif W, Bitton A, Lakatos PL, Bessissow T. Risk Factors Associated with Clostridium difficile Infection in Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis. J Crohns Colitis 2019; 13:27-38. [PMID: 30247650 DOI: 10.1093/ecco-jcc/jjy143] [Citation(s) in RCA: 42] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND AND AIM Clostridium difficile infection [CDI] is a significant concern in inflammatory bowel disease [IBD]. Risk factors and consequences associated with CDI in inflammatory bowel disease [IBD] patients are important to characterize. The aim of this research was to perform a systematic review and meta-analysis on risk factors and outcomes associated with CDI in IBD patients. METHODS Multiple databases were searched for studies investigating risk factors, colectomy and mortality risk in IBD patients with and without CDI. This was stratified by short [<3 months] and long-term [>1 year] outcomes. Summary estimates were calculated using a random-effects model. Quality assessment used the Newcastle-Ottawa scale. RESULTS Twenty-two studies met inclusion criteria. Antibiotics use within 30 days of diagnosis was associated with CDIs (odds ratio [OR]: 1.85, 95% confidence interval [CI]:1.36, 2.52). Colonic involvement in Crohn's disease patients was associated with significantly higher CDI rates [OR: 2.76, 95% CI: 1.75, 4.35]. There was a significant association between biologic medication use and CDI [OR: 1.65, 95% CI: 1.18, 2.30], with minimal heterogeneity [I2 = 4.0%]. The long-term colectomy risk was significantly higher for IBD patients with CDI compared with that for IBD patients without CDI [OR: 2.22, 95% CI: 1.17, 4.18]. Significantly higher mortality was found for CDI in IBD patients both short-term [OR: 3.84, 95% CI: 2.62, 5.61] and long-term [OR: 3.65, 95% CI: 1.58, 8.44]. Substantial heterogeneity existed. Most studies were of moderate quality. CONCLUSION Colonic involvement, and biologic and antibiotic use appear to be risk factors associated with CDI among IBD patients. CDI is associated with increased short- and long-term mortality.
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Affiliation(s)
- Bhairavi Balram
- Department of Internal Medicine, McGill University Health Center, Montreal, QC, Canada
| | - Robert Battat
- Division of Gastroenterology, Montreal General Hospital, McGill University Health Center, Montreal, QC, Canada
- Division of Gastroenterology, Jewish General Hospital, Ch. de la Côte-Sainte-Catherine, Montreal, QC, Canada
| | - Alex Al-Khoury
- Department of Internal Medicine, McGill University Health Center, Montreal, QC, Canada
| | - Julie D'Aoust
- Department of Internal Medicine, McGill University Health Center, Montreal, QC, Canada
| | - Waqqas Afif
- Division of Gastroenterology, Montreal General Hospital, McGill University Health Center, Montreal, QC, Canada
| | - Alain Bitton
- Division of Gastroenterology, Montreal General Hospital, McGill University Health Center, Montreal, QC, Canada
| | - Peter L Lakatos
- Division of Gastroenterology, Montreal General Hospital, McGill University Health Center, Montreal, QC, Canada
- First Department of Medicine, Semmelweis University, Budapest, Hungary
| | - Talat Bessissow
- Division of Gastroenterology, Montreal General Hospital, McGill University Health Center, Montreal, QC, Canada
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Barlam TF, Soria-Saucedo R, Ameli O, Cabral HJ, Kaplan WA, Kazis LE. Retrospective analysis of long-term gastrointestinal symptoms after Clostridium difficile infection in a nonelderly cohort. PLoS One 2018; 13:e0209152. [PMID: 30557401 PMCID: PMC6296708 DOI: 10.1371/journal.pone.0209152] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2018] [Accepted: 12/02/2018] [Indexed: 12/27/2022] Open
Abstract
Elderly patients and those with comorbid conditions are at high risk for poor outcomes after Clostridium difficile infection (CDI) but outcomes in a healthier, nonelderly population are not well described. We sought to investigate gastrointestinal diagnoses and CDI during hospitalizations in the 24 to 36 months after an initial episode of CDI in nonelderly patients in a cohort with an overall low prevalence of comorbid conditions. We performed a retrospective analysis of hospital admissions from 2010–2013 using the Truven MarketScan database of employment-based private insurance claims. Subjects <65 years of age and their adult dependents (> = 18 years old); a CDI diagnosis in 2011 (index date); at least 12 months of pre-index continuous enrollment; and 24–36 months of continuous post-index enrollment were included. The 12 months of each subject’s enrollment prior to the index date for a CDI served as the reference period for the analyses of that subject’s post-CDI time periods. Hospital claims during the follow-up period were evaluated for gastrointestinal diagnoses and/or CDI ICD-9 codes. The risk of gastrointestinal diagnoses was assessed using Cox proportional hazards models adjusted for a pre-specified set of baseline demographic and clinical factors. During 2011, 5,632 subjects with CDI met the inclusion criteria for our study. The risk of gastrointestinal diagnoses in patients with a CDI diagnostic code for the same admission was almost 8-fold higher 3 months post-CDI (hazard ratio (HR) = 7.56; 95% confidence interval (CI): 2.97–19.19) than for subjects without CDI and remained statistically significant until month 24 (HR = 1.47; 95% CI = 1.04–2.08). After CDI, patients remained at risk for gastrointestinal symptoms with CDI for up to two years. There is an important, long-term healthcare burden after CDI in this population.
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Affiliation(s)
- Tamar F. Barlam
- Section of Infectious Diseases, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts, United States of America
- * E-mail:
| | - Rene Soria-Saucedo
- Department of Pharmaceutical Outcomes and Policy, College of Pharmacy at the University of Florida, Gainesville, Florida, United States of America
| | - Omid Ameli
- Department of Health Law, Policy and Management, Boston University School of Public Health, Boston, Massachusetts, United States of America
| | - Howard J. Cabral
- Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts, United States of America
| | - Warren A. Kaplan
- Center for Global Health and Development, Boston University School of Public Health, Boston, Massachusetts, United States of America
| | - Lewis E. Kazis
- Health Outcomes Unit, Department of Health Law, Policy and Management, Boston University School of Public Health, Boston, Massachusetts, United States of America
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Turner D, Ruemmele FM, Orlanski-Meyer E, Griffiths AM, de Carpi JM, Bronsky J, Veres G, Aloi M, Strisciuglio C, Braegger CP, Assa A, Romano C, Hussey S, Stanton M, Pakarinen M, de Ridder L, Katsanos KH, Croft N, Navas-López VM, Wilson DC, Lawrence S, Russell RK. Management of Paediatric Ulcerative Colitis, Part 2: Acute Severe Colitis-An Evidence-based Consensus Guideline From the European Crohn's and Colitis Organization and the European Society of Paediatric Gastroenterology, Hepatology and Nutrition. J Pediatr Gastroenterol Nutr 2018; 67:292-310. [PMID: 30044358 DOI: 10.1097/mpg.0000000000002036] [Citation(s) in RCA: 151] [Impact Index Per Article: 21.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
BACKGROUND AND AIM Acute severe colitis (ASC) is one of the few emergencies in pediatric gastroenterology. Tight monitoring and timely medical and surgical interventions may improve outcomes and minimize morbidity and mortality. We aimed to standardize daily treatment of ASC in children through detailed recommendations and practice points which are based on a systematic review of the literature and consensus of experts. METHODS These guidelines are a joint effort of the European Crohn's and Colitis Organization (ECCO) and the European Society of Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN). Fifteen predefined questions were addressed by working subgroups. An iterative consensus process, including 2 face-to-face meetings, was followed by voting of the national representatives of ECCO and all members of the Paediatric Inflammatory Bowel Disease (IBD) Porto group of ESPGHAN (43 voting experts). RESULTS A total of 24 recommendations and 43 practice points were endorsed with a consensus rate of at least 91% regarding diagnosis, monitoring, and management of ASC in children. A summary flowchart is presented based on daily scoring of the Paediatric Ulcerative Colitis Activity Index. Several topics have been altered since the previous 2011 guidelines and from those published in adults. DISCUSSION These guidelines standardize the management of ASC in children in an attempt to optimize outcomes of this intensive clinical scenario.
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Affiliation(s)
- Dan Turner
- Shaare Zedek Medical Center, The Hebrew University of Jerusalem, Jerusalem, Israel
| | - Frank M Ruemmele
- Université Paris Descartes, Sorbonne Paris Cité, APHP, Hôpital Necker Enfants Malades, Paris, France
| | | | - Anne M Griffiths
- The Hospital for Sick Children, University of Toronto, Toronto, Canada
| | | | - Jiri Bronsky
- Department of Paediatrics, University Hospital Motol, Prague, Czech Republic
| | - Gabor Veres
- Ist Department of Pediatrics, Semmelweis University, Budapest, Hungary
| | - Marina Aloi
- Pediatric Gastroenterology and Liver Unit, Sapienza University of Rome, Rome
| | - Caterina Strisciuglio
- Department of Woman, Child and General and Specialistic Surgery, University of Campania "Luigi Vanvitelli," Napoli, Italy
| | | | - Amit Assa
- Schneider Children's Hospital, Petach Tikva (affiliated to the Sackler Faculty of Medicine), Tel Aviv University, Tel Aviv, Israel
| | - Claudio Romano
- Pediatric Department, University of Messina, Messina, Italy
| | - Séamus Hussey
- National Children's Research Centre, Royal College of Surgeons of Ireland and University College Dublin, Ireland
| | | | - Mikko Pakarinen
- Helsinki University Children's Hospital, Department of Pediatric Surgery, Helsinki, Finland
| | - Lissy de Ridder
- Erasmus MC-Sophia Children's Hospital, Rotterdam, The Netherlands
| | | | - Nick Croft
- Barts and the London School of Medicine, Queen Mary University of London, London, UK
| | | | - David C Wilson
- Child Life and Health, University of Edinburgh, Edinburgh, UK
| | - Sally Lawrence
- BC Children's Hospital, University of British Columbia, Vancouver BC, Canada
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Kim DB, Lee KM, Park SH, Kim YS, Kim ES, Lee J, Jung SA, Seo GS, Lee JM. Is Clostridium difficile infection a real threat in patients with ulcerative colitis? A prospective, multicenter study in Korea. Intest Res 2018; 16:267-272. [PMID: 29743839 PMCID: PMC5934599 DOI: 10.5217/ir.2018.16.2.267] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/26/2017] [Revised: 09/25/2017] [Accepted: 10/19/2017] [Indexed: 01/05/2023] Open
Abstract
Background/Aims Clostridium difficile infection (CDI) has been reported to be a cause of flare-ups in patients with ulcerative colitis (UC). We evaluated the prevalence and clinical outcomes of CDI in patients with UC hospitalized for flare-ups. Methods This was a prospective, multicenter study including 7 academic teaching hospitals in Korea. All consecutive patients with UC admitted for disease flare-up were enrolled. We detected the presence of CDI by using enzyme immunoassay, real-time polymerase chain reaction (RT-PCR) for toxin genes, and sigmoidoscopy. Results Eighty-one consecutive patients with UC were enrolled from January 2014 to December 2015. Among 81 patients, 8 (9.9%) were diagnosed with CDI. Most of the cases were identified by RT-PCR. Enzyme immunoassay was positive in 3 of 8 patients, and only 1 had typical endoscopic findings of pseudomembranous colitis. There were no differences in demographic data, length of hospital stay, or colectomy rate between patients with and without CDI. Conclusions CDI was not a rare cause of flare-up in patients with UC in Korea. However, CDI did not appear to affect the course of UC flare-up in Korean patients. RT-PCR was sensitive in detecting CDI and can be considered a diagnostic tool in patients with UC flare-up.
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Affiliation(s)
- Dae Bum Kim
- Department of Internal Medicine, St. Vincent's Hospital, College of Medicine, The Catholic University of Korea, Suwon, Korea
| | - Kang-Moon Lee
- Department of Internal Medicine, St. Vincent's Hospital, College of Medicine, The Catholic University of Korea, Suwon, Korea
| | - Sang Hyoung Park
- Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - You Sun Kim
- Department of Internal Medicine, Seoul Paik Hospital, Inje University College of Medicine, Seoul, Korea
| | - Eun Soo Kim
- Department of Internal Medicine, Kyungpook National University Hospital, School of Medicine, Kyungpook National University, Daegu, Korea
| | - Jun Lee
- Department of Internal Medicine, Chosun University Hospital, Chosun University College of Medicine, Gwangju, Korea
| | - Sung-Ae Jung
- Department of Internal Medicine, Ewha Womans University Medical Center, Ewha Womans University School of Medicine, Seoul, Korea
| | - Geom Seog Seo
- Department of Internal Medicine, Wonkwang University Hospital, Wonkwang University College of Medicine, Iksan, Korea
| | - Ji Min Lee
- Department of Internal Medicine, St. Vincent's Hospital, College of Medicine, The Catholic University of Korea, Suwon, Korea
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Saffouri G, Gupta A, Loftus EV, Baddour LM, Pardi DS, Khanna S. The incidence and outcomes from Clostridium difficile infection in hospitalized adults with inflammatory bowel disease. Scand J Gastroenterol 2017; 52:1240-1247. [PMID: 28782372 DOI: 10.1080/00365521.2017.1362466] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/04/2017] [Revised: 07/16/2017] [Accepted: 07/16/2017] [Indexed: 02/04/2023]
Abstract
OBJECTIVES Clostridium difficile infection (CDI) may worsen outcomes in patients with inflammatory bowel disease (IBD), but large database-driven studies have conflicting results. The study objective is to analyze clinical features and outcomes in patients with CDI and IBD using the National Hospital Discharge Survey (NHDS) database from 2005 to 2009. MATERIALS AND METHODS NHDS collects the clinical information on patients dismissed from non-Federal short-stay United States hospitals. CDI and IBD patients were identified using ICD-9 codes. Demographics, diagnoses, procedures, length of stay (LOS) and dismissal information were abstracted. RESULTS Of an estimated 162 million hospitalizations; 5.62 × 105 were for IBD (0.35%); 53.2% were female. CDI developed in 3.7% of hospitalized IBD patients as compared to 0.78% of all adults (OR, 3.9; 95% CI, 3.3-4.6; p < .0001). African-Americans with IBD had a higher likelihood of CDI compared to Caucasians with IBD (OR, 1.67; 95% CI, 1.59-1.75; p < .0001). After adjusting for age, sex and comorbidities, IBD patients with CDI had a longer LOS (mean difference 1 day, p < .0001), higher all-cause, in-hospital mortality (adjusted OR, 4.5; 95% CI, 4.2-4.9; p < .0001), and a higher risk of dismissal to a care facility (adjusted OR, 2.3; 95% CI, 2.2-2.4; p < .0001). CONCLUSIONS CDI in IBD patients prolonged hospitalization and increased in-hospital mortality and likelihood of dismissal to a care-facility as compared to IBD patients without CDI. CDI was more common among African-American IBD patients compared to IBD patients of other races.
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Affiliation(s)
- George Saffouri
- a Department of Internal Medicine, Divisions of Gastroenterology and Hepatology , Mayo Clinic , Rochester , MN , USA
| | - Arjun Gupta
- b Department of Internal Medicine , University of Texas Southwestern Medical Center , Dallas , TX , USA
| | - Edward V Loftus
- a Department of Internal Medicine, Divisions of Gastroenterology and Hepatology , Mayo Clinic , Rochester , MN , USA
| | | | - Darrell S Pardi
- a Department of Internal Medicine, Divisions of Gastroenterology and Hepatology , Mayo Clinic , Rochester , MN , USA
| | - Sahil Khanna
- a Department of Internal Medicine, Divisions of Gastroenterology and Hepatology , Mayo Clinic , Rochester , MN , USA
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D’Aoust J, Battat R, Bessissow T. Management of inflammatory bowel disease with Clostridium difficile infection. World J Gastroenterol 2017; 23:4986-5003. [PMID: 28785153 PMCID: PMC5526769 DOI: 10.3748/wjg.v23.i27.4986] [Citation(s) in RCA: 54] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/24/2017] [Revised: 05/16/2017] [Accepted: 06/19/2017] [Indexed: 02/06/2023] Open
Abstract
AIM To address the management of Clostridium difficile (C. difficile) infection (CDI) in the setting of suspected inflammatory bowel disease (IBD)-flare.
METHODS A systematic search of the Ovid MEDLINE and EMBASE databases by independent reviewers identified 70 articles including a total of 932141 IBD patients or IBD-related hospitalizations.
RESULTS In those with IBD, CDI is associated with increased morbidity, including subsequent escalation in IBD medical therapy, urgent colectomy and increased hospitalization, as well as excess mortality. Vancomycin-containing regimens are effective first-line therapies for CDI in IBD inpatients. No prospective data exists with regards to the safety or efficacy of initiating or maintaining corticosteroid, immunomodulator, or biologic therapy to treat IBD in the setting of CDI. Corticosteroid use is a risk factor for the development of CDI, while immunomodulators and biologics are not.
CONCLUSION Strong recommendations regarding when to initiate IBD specific therapy in those with CDI are precluded by a lack of evidence. However, based on expert opinion and observational data, initiation or resumption of immunosuppressive therapy after 48-72 h of targeted antibiotic treatment for CDI may be considered.
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Harbord M, Eliakim R, Bettenworth D, Karmiris K, Katsanos K, Kopylov U, Kucharzik T, Molnár T, Raine T, Sebastian S, de Sousa HT, Dignass A, Carbonnel F. Third European Evidence-based Consensus on Diagnosis and Management of Ulcerative Colitis. Part 2: Current Management. J Crohns Colitis 2017; 11:769-784. [PMID: 28513805 DOI: 10.1093/ecco-jcc/jjx009] [Citation(s) in RCA: 850] [Impact Index Per Article: 106.3] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Affiliation(s)
- Marcus Harbord
- Imperial College London, and Chelsea and Westminster Hospital, London, UK
| | - Rami Eliakim
- Department of Gastroenterology and Hepatology, Chaim Sheba Medical Center, Tel Hashomer, Israel
| | | | - Konstantinos Karmiris
- Department of Gastroenterology, Venizeleio General Hospital, Heraklion, Crete, Greece
| | - Konstantinos Katsanos
- Department of Gastroenterology and Hepatology, University and Medical School of Ioannina, Ioannina, Greece
| | - Uri Kopylov
- Department of Gastroenterology, Tel-Hashomer Sheba Medical Center, and Sackler School of Medicine, Tel Aviv University, Israel
| | - Torsten Kucharzik
- Department of Internal Medicine and Gastroenterology, Hospital Lüneburg, Lüneburg, Germany
| | - Tamás Molnár
- First Department of Medicine, University of Szeged, Szeged, Hungary
| | - Tim Raine
- Department of Medicine, University of Cambridge, Cambridge, UK
| | | | - Helena Tavares de Sousa
- Gastroenterology Department, Algarve Hospital Center; Biomedical Sciences & Medicine Department, University of Algarve, Faro, Portugal
| | - Axel Dignass
- Department of Medicine I, Agaplesion Markus Hospital, Frankfurt/Main, Germany
| | - Franck Carbonnel
- Department of Gastroenterology, CHU Bicêtre, Université Paris Sud, Paris, France
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Magro F, Gionchetti P, Eliakim R, Ardizzone S, Armuzzi A, Barreiro-de Acosta M, Burisch J, Gecse KB, Hart AL, Hindryckx P, Langner C, Limdi JK, Pellino G, Zagórowicz E, Raine T, Harbord M, Rieder F. Third European Evidence-based Consensus on Diagnosis and Management of Ulcerative Colitis. Part 1: Definitions, Diagnosis, Extra-intestinal Manifestations, Pregnancy, Cancer Surveillance, Surgery, and Ileo-anal Pouch Disorders. J Crohns Colitis 2017; 11:649-670. [PMID: 28158501 DOI: 10.1093/ecco-jcc/jjx008] [Citation(s) in RCA: 1257] [Impact Index Per Article: 157.1] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/30/2016] [Accepted: 02/01/2017] [Indexed: 02/06/2023]
Affiliation(s)
- Fernando Magro
- Department of Pharmacology and Therapeutics, University of Porto; MedInUP, Centre for Drug Discovery and Innovative Medicines; Centro Hospitalar São João, Porto, Portugal
| | | | - Rami Eliakim
- Department of Gastroenterology and Hepatology, Chaim Sheba Medical Center, Tel Hashomer, Israel
| | - Sandro Ardizzone
- Gastrointestinal Unit ASST Fatebenefratelli Sacco-University of Milan-Milan, Italy
| | - Alessandro Armuzzi
- IBD Unit Complesso Integrato Columbus, Gastroenterological and Endocrino-Metabolical Sciences Department, Fondazione Policlinico Universitario Gemelli Universita' Cattolica del Sacro Cuore, Rome, Italy
| | - Manuel Barreiro-de Acosta
- Department of Gastroenterology, IBD Unit, University Hospital Santiago De Compostela (CHUS), A Coruña, Spain
| | - Johan Burisch
- Department of Gastroenterology, North Zealand University Hospital, Frederikssund, Denmark
| | - Krisztina B Gecse
- First Department of Medicine, Semmelweis University, Budapest,Hungary
| | | | - Pieter Hindryckx
- Department of Gastroenterology, University Hospital of Ghent, Ghent, Belgium
| | - Cord Langner
- Institute of Pathology, Medical University of Graz, Graz, Austria
| | - Jimmy K Limdi
- Department of Gastroenterology, Pennine Acute Hospitals NHS Trust; Institute of Inflammation and Repair, University of Manchester, Manchester, UK
| | - Gianluca Pellino
- Unit of General Surgery, Second University of Naples,Napoli, Italy
| | - Edyta Zagórowicz
- Maria Sklodowska-Curie Memorial Cancer Centre and Institute of Oncology, Department of Oncological Gastroenterology Warsaw; Medical Centre for Postgraduate Education, Department of Gastroenterology, Hepatology and Clinical Oncology, Warsaw, Poland
| | - Tim Raine
- Department of Medicine, University of Cambridge, Cambridge,UK
| | - Marcus Harbord
- Imperial College London; Chelsea and Westminster Hospital, London,UK
| | - Florian Rieder
- Department of Pathobiology /NC22, Lerner Research Institute; Department of Gastroenterology, Hepatology and Nutrition/A3, Digestive Disease and Surgery Institute, Cleveland Clinic Foundation, Cleveland, OH, USA
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Law CCY, Tariq R, Khanna S, Murthy S, McCurdy JD. Systematic review with meta-analysis: the impact of Clostridium difficile infection on the short- and long-term risks of colectomy in inflammatory bowel disease. Aliment Pharmacol Ther 2017; 45:1011-1020. [PMID: 28206678 DOI: 10.1111/apt.13972] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/07/2016] [Revised: 10/18/2016] [Accepted: 01/16/2017] [Indexed: 12/12/2022]
Abstract
BACKGROUND Clostridium difficile infection (CDI) is associated with increased mortality in inflammatory bowel disease (IBD), but the risk of colectomy is variable and has not been adequately studied. AIM To perform a systematic review and meta-analysis to assess the impact of CDI on colectomy risk in IBD. METHODS Multiple databases were searched systematically for observational studies reporting colectomy risk in IBD, stratified by the presence of CDI, and the duration of follow-up (short term 3 months, and long term at least 1 year). Weighted summary estimates were calculated using generalised inverse variance with random-effects model. Study quality was assessed using the Newcastle-Ottawa scale. RESULTS Twelve observational studies were identified and included 35 057 IBD patients with CDI, and 929 259 without CDI. CDI did not increase the short-term colectomy risk in IBD patients overall (10 studies) (OR: 1.35; 95% CI: 0.68-2.67), or in patients with ulcerative colitis (nine studies) (OR: 1.20; 95% CI: 0.39-3.76). In contrast, CDI was associated with higher long-term colectomy risk in patients with IBD overall (five studies) (OR: 2.23; 95% CI: 1.18-4.21), and in patients with ulcerative colitis (four studies) (OR: 2.96; 95% CI: 1.19-7.34). The results were stable in subgroups stratified by recruitment period, hospitalisation status and geographical location. All studies were at least of moderate quality. The results were limited in the ability to compare IBD severity and the type of anti-microbial therapy. CONCLUSION Based on 12 observational studies with at least moderate quality, Clostridium difficile infection appears to increase colectomy risk in IBD in the long- but not short- term.
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Affiliation(s)
- C C Y Law
- Division of Gastroenterology and Hepatology, The Ottawa Hospital, Ottawa, ON, Canada
| | - R Tariq
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA
| | - S Khanna
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA
| | - S Murthy
- Division of Gastroenterology and Hepatology, The Ottawa Hospital, Ottawa, ON, Canada
| | - J D McCurdy
- Division of Gastroenterology and Hepatology, The Ottawa Hospital, Ottawa, ON, Canada
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Gu YB, Zhang MC, Sun J, Lv KZ, Zhong J. Risk factors and clinical outcome of Clostridium difficile infection in patients with IBD: A single-center retrospective study of 260 cases in China. J Dig Dis 2017; 18:207-211. [PMID: 28251812 DOI: 10.1111/1751-2980.12461] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/07/2016] [Revised: 02/21/2017] [Accepted: 02/27/2017] [Indexed: 12/11/2022]
Abstract
OBJECTIVE Clostridium difficile infection (CDI) may lead to poor outcomes in patients with inflammatory bowel disease (IBD). In this study we aimed to investigate the cumulative incidence, risk factors and outcome of CDI in patients with IBD in a single center in China. METHODS The clinical features and endoscopic profiles of consecutive IBD patients admitted to Ruijin Hospital, Shanghai Jiaotong University School of Medicine between January 2013 and December 2015 were retrospectively analyzed. CDI was diagnosed based on a positive polymerase chain reaction (PCR) stool test. RESULTS A total of 260 patients with IBD were enrolled, including 176 with Crohn's disease (CD) and 84 with ulcerative colitis (UC). Altogether 13 (5.0%) patients were diagnosed with CDI. The incidence of CDI was 4.0% (7/176) in CD and 7.1% (6/84) in UC, respectively. The endoscopic feature of pseudomembrane was found in four (33.3%) IBD-CDI patients, and pseudomembrane and deep ulcers were significantly correlated with CDI (P < 0.001 and P = 0.006, respectively). Hemoglobin (Hb) <100 g/L was found to be associated with CDI (OR 3.48, 95% CI 1.04-11.61, P = 0.043). Patients in the CDI group showed a higher risk of developing abdominal abscesses than those in the non-CDI group (OR 6.09, 95% CI 1.8-15.2, P = 0.003). CONCLUSIONS PCR-based fecal test for CDI should be performed in these IBD patients. Hb <100 g/L may be an important risk factor for CDI in IBD. For patients with CDI, antibiotics should be administered promptly to prevent abdominal abscess.
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Affiliation(s)
- Yu Bei Gu
- Department of Gastroenterology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Mao Chen Zhang
- Department of Gastroenterology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Jing Sun
- Department of Gastroenterology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Ke Zhi Lv
- Department of Colorectal Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Jie Zhong
- Department of Gastroenterology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
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Tang YM, Stone CD. Clostridium difficile infection in inflammatory bowel disease: challenges in diagnosis and treatment. Clin J Gastroenterol 2017; 10:112-123. [PMID: 28210836 DOI: 10.1007/s12328-017-0719-2] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/27/2016] [Accepted: 02/02/2017] [Indexed: 12/12/2022]
Abstract
The problem of Clostridium difficile infection (CDI) has reached epidemic proportions, particularly in industrialized nations. The pathophysiology, disease course and the potential complications are well appreciated in the general hospitalized patient. However, when CDI occurs in the setting of inflammatory bowel disease (IBD), a number of distinct differences in the diagnosis and clinical management of the infection in this population should be appreciated by gastroenterologists, hospitalists and other care providers. This review highlights the unique aspects of CDI when it occurs in IBD patients with an emphasis on the challenge of distinguishing persistent infection from exacerbation of underlying chronic colitis. An understanding of how CDI may differ in presentation and how management should be altered can prevent serious and life-threatening complications.
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Affiliation(s)
- Ying M Tang
- Section of Gastroenterology and Hepatology, Division of Gastroenterology and Hepatology, University of Nevada School of Medicine, 1701 W. Charleston Blvd, Suite 230, Las Vegas, NV, 89102, USA
| | - Christian D Stone
- Comprehensive Digestive Institute of Nevada, 8530 W. Sunset Rd, Suite 230, Las Vegas, NV, 89113, USA.
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Clostridium difficile Infection and Risk of Colectomy in Patients with Inflammatory Bowel Disease: A Bias-adjusted Meta-analysis. Inflamm Bowel Dis 2017; 23:200-207. [PMID: 28079620 DOI: 10.1097/mib.0000000000000998] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
BACKGROUND Clostridium difficile infection (CDI) is a common complication of inflammatory bowel diseases (IBDs) and is associated with worse outcome. Variable rates of colectomy have been reported among IBD complicated by CDI. We conducted a systematic review and meta-analysis of studies to assess the association between CDI and colectomy among patients with IBD. METHODS The literature was systematically searched using PubMed from inception through April 2016. Studies were limited to cohort, case-control, and cross-sectional studies reporting colectomy risk stratified by CDI in patients with IBD. We estimated summary ORs and 95% CIs using the quality-effects model. Study quality was assessed using an adaptation of the Newcastle-Ottawa scale. RESULTS Six studies were included in the meta-analysis, comprising 8 data sets. Results from meta-analysis showed that CDI was a significant risk factor for colectomy among patients with IBD, mainly patients with ulcerative colitis, almost doubling the odds (OR 1.90; 95% CI, 1.23-2.93). There was significant heterogeneity across studies (Q = 22.02, P < 0.001; I = 68%). Funnel plots were grossly asymmetrical. Results of sensitivity analysis restricting studies to those reporting ulcerative colitis only and studies using laboratory tests to confirm CDI were consistent with the result from the main analysis. CONCLUSIONS CDI is a significant risk factor for colectomy in patients with IBD. Further research is needed to investigate the attributable risks of surgery due to CDI among patients with Crohn's disease.
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Newman KM, Rank KM, Vaughn BP, Khoruts A. Treatment of recurrent Clostridium difficile infection using fecal microbiota transplantation in patients with inflammatory bowel disease. Gut Microbes 2017; 8:303-309. [PMID: 28102756 PMCID: PMC5479399 DOI: 10.1080/19490976.2017.1279377] [Citation(s) in RCA: 58] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/03/2023] Open
Abstract
We recently compared results of fecal microbiota transplantation (FMT) in patients with refractory, recurrent Clostridium difficile infection (rCDI), with and without underlying inflammatory bowel disease (IBD). Here we extend this cohort and analyze outcomes in greater detail by subtype of IBD. We find that FMT is generally effective in breaking the cycle of CDI recurrence, but its effects on overall IBD progression are much less predictable. We discuss several challenges intrinsic to this complex clinical situation and outline the next steps that can address these challenges going forward.
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Affiliation(s)
- Krista M. Newman
- Department of Medicine, University of Minnesota, Minneapolis, Minnesota, USA
| | - Kevin M. Rank
- Department of Medicine, University of Minnesota, Minneapolis, Minnesota, USA
| | - Byron P. Vaughn
- Department of Medicine, University of Minnesota, Minneapolis, Minnesota, USA
| | - Alexander Khoruts
- Department of Medicine, University of Minnesota, Minneapolis, Minnesota, USA,Center for Immunology and BioTechnology Institute, University of Minnesota, Twin Cities Campus, Minneapolis, Minnesota, USA,CONTACT Dr. Alexander Khoruts 2101 6th St. SE, Walling Biomedical Sciences Building; Room 3–184, Minneapolis, MN 55414
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McCurdy JD, Enders FT, Khanna S, Bruining DH, Jones A, Killian JM, Tariq R, Smyrk TC, Loftus EV. Increased Rates of Clostridium difficile Infection and Poor Outcomes in Patients with IBD with Cytomegalovirus. Inflamm Bowel Dis 2016; 22:2688-2693. [PMID: 27755270 DOI: 10.1097/mib.0000000000000939] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
BACKGROUND Clostridium difficile infection (CDI) and Cytomegalovirus (CMV) reactivation are associated with disease exacerbations and poor outcomes in inflammatory bowel disease (IBD). Therefore, we assessed the association between these organisms in patients with IBD and the impact on colectomy. METHODS A retrospective case-control study was conducted to assess CDI prevalence in patients with IBD with a tissue diagnosis of CMV compared with matched IBD controls without CMV from 2005 to 2011. We also assessed the impact of coinfection on colectomy risk for patients coinfected with CMV and CDI compared with IBD patients with CMV alone (CMV controls) or matched IBD patients with CDI alone (CDI controls). Colectomy-free survival was assessed using Kaplan-Meier methods, and statistical significance was determined using Log-rank analysis for unmatched comparisons and by generalized estimating equations in Cox regression for matched comparisons. RESULTS CDI was more common in IBD patients with CMV (n = 12/68; 17.6%) than in matched IBD controls (n = 12/144; 8.25%) (P = 0.046). A nonsignificant increase in high-grade disease (5 or more CMV inclusions by immunohistochemistry) was detected in coinfected patients compared with CMV controls (P = 0.15). Colectomy-free survival at 1 year was 30% (95% confidence interval, 12.0-74.7) for coinfected patients and was significantly less compared with 71.5% (95% confidence interval, 58.0-88.2) of CDI controls (P < 0.001) and was numerically less than 57.1% (95% confidence interval, 44.1-74.0) of CMV controls (P = 0.095). CONCLUSIONS CDI occurs more frequently in IBD patients with CMV reactivation and is associated with poor outcomes. Patients with IBD with CMV should be tested for CDI and managed aggressively.
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Affiliation(s)
- Jeffrey D McCurdy
- *Division of Gastroenterology and Hepatology, University of Ottawa, Ottawa, Ontario, Canada; †Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota; ‡Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, Minnesota; and §Department of Anatomical Pathology, Mayo Clinic, Rochester, Minnesota
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Ulcerative Colitis Patients With Clostridium difficile are at Increased Risk of Death, Colectomy, and Postoperative Complications: A Population-Based Inception Cohort Study. Am J Gastroenterol 2016; 111:691-704. [PMID: 27091322 DOI: 10.1038/ajg.2016.106] [Citation(s) in RCA: 49] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/03/2015] [Accepted: 01/01/2016] [Indexed: 12/11/2022]
Abstract
OBJECTIVES Clostridium difficile (C. difficile) may worsen the prognosis of ulcerative colitis (UC). The objectives of this study were to: (i) validate the International Classification of Diseases-10 (ICD-10) code for C. difficile; (ii) determine the risk of C. difficile infection after diagnosis of UC; (iii) evaluate the effect of C. difficile infection on the risk of colectomy; and (iv) assess the association between C. difficile and postoperative complications. METHODS The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated by comparing ICD-10 codes for C. difficile with stool toxin tests. A population-based surveillance cohort of newly diagnosed UC patients living in Alberta, Canada were identified from 2003 to 2009 (n=1,754). The effect of a C. difficile infection on colectomy was modeled using competing risk survival regression after adjusting for covariates. The effect of a C. difficile infection on postoperative complications was assessed using a mixed effects logistic regression model. RESULTS The sensitivity, specificity, PPV, and NPV of the ICD-10 code for C. difficile were 82.1%, 99.4%, 88.4%, and 99.1%, respectively. The risk of C. difficile infection within 5 years of diagnosis with UC was 3.4% (95% confidence interval (CI): 2.5-4.6%). The risk of colectomy was higher among UC patients diagnosed with C. difficile (sub-hazard ratio (sHR)=2.36; 95% CI: 1.47-3.80). C. difficile increased the risk of postoperative complications (odds ratio=4.84; 95% CI: 1.28-18.35). C. difficile was associated with mortality (sHR=2.56 times; 95% CI: 1.28-5.10). CONCLUSIONS C. difficile diagnosis worsens the prognosis of newly diagnosed patients with UC by increasing the risk of colectomy, postoperative complications, and death.
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Kassam Z, Fabersunne CC, Smith MB, Alm EJ, Kaplan GG, Nguyen GC, Ananthakrishnan AN. Clostridium difficile associated risk of death score (CARDS): a novel severity score to predict mortality among hospitalised patients with C. difficile infection. Aliment Pharmacol Ther 2016; 43:725-33. [PMID: 26849527 PMCID: PMC5094350 DOI: 10.1111/apt.13546] [Citation(s) in RCA: 61] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/13/2015] [Revised: 11/14/2015] [Accepted: 01/12/2016] [Indexed: 12/27/2022]
Abstract
BACKGROUND Clostridium difficile infection (CDI) is a public health threat and associated with significant mortality. However, there is a paucity of objectively derived CDI severity scoring systems to predict mortality. AIM To develop a novel CDI risk score to predict mortality entitled: Clostridium difficile associated risk of death score (CARDS). METHODS We obtained data from the United States 2011 Nationwide Inpatient Sample (NIS) database. All CDI-associated hospitalisations were identified using discharge codes (ICD-9-CM, 008.45). Multivariate logistic regression was utilised to identify independent predictors of mortality. Clostridium difficile associated risk of death score was calculated by assigning a numeric weight to each parameter based on their odds ratio in the final logistic model. Predictive properties of model discrimination were assessed using the c-statistic and validated in an independent sample using the 2010 NIS database. RESULTS We identified 77 776 hospitalisations, yielding an estimate of 374 747 cases with an associated diagnosis of CDI in the US, 8% of whom died in the hospital. The eight severity score predictors were identified on multivariate analysis: age, cardiopulmonary disease, malignancy, diabetes, inflammatory bowel disease, acute renal failure, liver disease and ICU admission, with weights ranging from -1 (for diabetes) to 5 (for ICU admission). The overall risk score in the cohort ranged from 0 to 18. Mortality increased significantly as CARDS increased. CDI-associated mortality was 1.2% with a CARDS of 0 compared to 100% with CARDS of 18. The model performed equally well in our validation cohort. CONCLUSION Clostridium difficile associated risk of death score is a promising simple severity score to predict mortality among those hospitalised with C. difficile infection.
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Affiliation(s)
- Zain Kassam
- Massachusetts Institute of Technology, Cambridge, MA, United States,OpenBiome, Medford, MA, United States
| | - Camila Cribb Fabersunne
- Harvard Medical School, Boston, MA, United States,Harvard School of Public Health, Boston, MA, United States
| | - Mark B. Smith
- Massachusetts Institute of Technology, Cambridge, MA, United States,OpenBiome, Medford, MA, United States
| | - Eric J. Alm
- Massachusetts Institute of Technology, Cambridge, MA, United States
| | | | - Geoffrey C. Nguyen
- Mount Sinai Hospital Centre for Inflammatory Bowel Disease, University of Toronto, Toronto, ON, Canada
| | - Ashwin N. Ananthakrishnan
- Harvard Medical School, Boston, MA, United States,Massachusetts General Hospital, Boston, MA, United States
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