|
1
|
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. [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.
Collapse
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
| |
Collapse
|
|
2
|
Vitikainen K, Kase M, Meriranta L, Molander P, af Björkesten CG, Anttila VJ, Arkkila P. Higher disease activity of inflammatory bowel disease predisposes to Clostridioides difficile infection. Therap Adv Gastroenterol 2025; 18:17562848251318292. [PMID: 39963249 PMCID: PMC11831662 DOI: 10.1177/17562848251318292] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/11/2024] [Accepted: 01/06/2025] [Indexed: 02/20/2025] Open
Abstract
Background Clostridioides difficile infection (CDI) is a clinical challenge associated with poor outcomes in patients with inflammatory bowel disease (IBD). Objectives To identify clinical risk factors for CDI and its recurrence among patients with IBD. Design Case-control cohort study of IBD patients with and without episodes of CDI. Methods A case-control study of 279 IBD patients with CDI. Medical history and IBD-related symptoms 3 months preceding a toxin-positive CDI were recorded and compared with age- and sex-matched IBD patients without CDI. Outcomes of CDI in IBD patients were recorded 2-6 months after CDI. Results Based on clinical symptoms and fecal calprotectin levels, IBD is active before CDI. Recently diagnosed IBD seemed to increase the risk for CDI. Corticosteroid usage frequently preceded CDI episodes. Advanced therapies were not associated with CDI. Antibiotic intake was not registered before CDI in 30% of the episodes. Recurrent CDI (rCDI) occurred in 30% (84/279) of IBD-CDI patients and 67% (90/135) of those episodes were registered within 90 days from the preceding episode. Most (79%) rCDI patients had ulcerative colitis (UC). CDI could complicate underlying IBD by increasing the need for escalation in IBD-related medical therapy and leading to hospitalization but it did not seem to increase the risk of colectomy. Conclusion The major risk factors associated with CDI in IBD patients were IBD activity before infection, UC and colonic Crohn's disease, short duration of IBD, corticosteroid usage, and hospitalization. Patients with active IBD and a shorter disease duration may benefit from more frequent follow-ups in the early stages, as they appear to be at higher risk of developing CDI.
Collapse
Affiliation(s)
- Krista Vitikainen
- HUS Helsinki University Hospital, Haartmaninkatu 4, P.O. Box 340, Helsinki 00029, Finland
| | - Merit Kase
- HUS Helsinki University Hospital, Helsinki, Finland
| | | | - Pauliina Molander
- Abdominal Center, Gastroenterology, HUS Helsinki University Hospital and Helsinki University, Helsinki, Finland
| | - Clas-Göran af Björkesten
- Abdominal Center, Gastroenterology, HUS Helsinki University Hospital and Helsinki University, Helsinki, Finland
| | - Veli-Jukka Anttila
- Department of Infectious Diseases, Helsinki University Hospital and Helsinki University, Helsinki, Finland
| | - Perttu Arkkila
- Abdominal Center, Gastroenterology, HUS Helsinki University Hospital and Helsinki University, Helsinki, Finland
| |
Collapse
|
|
3
|
Allegretti JR, Feuerstadt P, Knapple WL, Orenstein R, Pinton P, Sheh A, Khanna S. Safety and Efficacy of Fecal Microbiota, Live-jslm (REBYOTA®), for the Prevention of Recurrent Clostridioides difficile Infection in Participants With Inflammatory Bowel Disease in PUNCH CD3-OLS. Inflamm Bowel Dis 2025:izae291. [PMID: 39862395 DOI: 10.1093/ibd/izae291] [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: 08/09/2024] [Indexed: 01/27/2025]
Abstract
BACKGROUND Fecal microbiota, live-jslm (RBL; REBYOTA®), is the first single-dose, broad consortia, microbiota-based live biotherapeutic approved by the US Food and Drug Administration to prevent recurrent Clostridioides difficile infection (rCDI) in adults following standard-of-care antimicrobials. Inflammatory bowel disease (IBD) is a common risk factor for rCDI, yet patients with IBD are often excluded from prospective trials. This subgroup analysis of PUNCH CD3-OLS (NCT03931941) evaluated the safety and efficacy of RBL in participants with rCDI and IBD. METHODS Participants with IBD (ulcerative colitis [UC], Crohn's disease [CD], or unspecified) who had rCDI were included. Treatment-emergent adverse event (TEAE) data were collected for up to 6 months following RBL administration. Efficacy outcomes included treatment success at 8 weeks and sustained clinical response at 6 months. RESULTS Overall, 793 participants were enrolled, and 697 received RBL; 74 had IBD (UC: n = 45; CD: n = 25; unspecified IBD: n = 4). TEAEs within 8 weeks of administration were reported by 45.9% and 47.5% of participants with and without IBD, respectively; most were mild or moderate gastrointestinal symptoms. Serious TEAEs within 8 weeks of administration were reported by 1.4% and 4.2% of participants with and without IBD, respectively. The treatment success rate at 8 weeks was 78.9%, and the sustained clinical response rate at 6 months was 91.1% in participants with IBD, similar to rates in participants without IBD (73.2% and 91.0%, respectively). CONCLUSIONS The results of this subgroup analysis of PUNCH CD3-OLS suggest RBL is safe and efficacious in patients with IBD.
Collapse
Affiliation(s)
- Jessica R Allegretti
- Division of Gastroenterology, Hepatology and Endoscopy, Department of Medicine, Brigham & Women's Hospital, Boston, MA, USA
| | - Paul Feuerstadt
- Division of Digestive Disease, Yale University School of Medicine, New Haven, CT, USA
- PACT-Gastroenterology Center, Hamden, CT, USA
| | | | - Robert Orenstein
- Division of Infectious Diseases, Department of Internal Medicine, Mayo Clinic, Phoenix, AZ, USA
| | - Philippe Pinton
- Global Research and Medical, Ferring Pharmaceuticals A/S, Kastrup, Denmark
| | | | - Sahil Khanna
- Department of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA
| |
Collapse
|
|
4
|
Abstract
Severe colitis is a well-defined condition encompassing several etiologies but is most often caused by severe ulcerative colitis or Clostridioides difficile infection. Severe colitis can evolve into toxic colitis, or toxic megacolon when associated with bowel dilation and systemic manifestations, resulting in a life-threatening scenario where multidisciplinary management is often required. Medical management continues to play an important role in the initial treatment of toxic megacolon. However, timely surgical intervention can be lifesaving.
Collapse
Affiliation(s)
- Marjorie R. Liggett
- Department of Surgery, Feinberg School of Medicine, Northwestern University, Chicago, Illinois
| | - Hasan B. Alam
- Department of Surgery, Feinberg School of Medicine, Northwestern University, Chicago, Illinois
| |
Collapse
|
|
5
|
Gravina AG, Pellegrino R, Iascone V, Palladino G, Federico A, Zagari RM. Impact of Helicobacter pylori Eradication on Inflammatory Bowel Disease Onset and Disease Activity: To Eradicate or Not to Eradicate? Diseases 2024; 12:179. [PMID: 39195178 DOI: 10.3390/diseases12080179] [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: 07/01/2024] [Revised: 07/23/2024] [Accepted: 08/07/2024] [Indexed: 08/29/2024] Open
Abstract
Helicobacter pylori infection has significant epidemiological relevance due to the carcinogenic nature of this bacterium, which is potentially associated with cancer. When detected, it should ideally be eradicated using a treatment that currently involves a combination of gastric acid suppressors and multiple antibiotics. However, this treatment raises questions regarding efficacy and safety profiles in patients with specific comorbidities, including inflammatory bowel diseases (IBD). Eradication therapy for H. pylori includes components associated with adverse gastrointestinal events, such as Clostridioides difficile colitis. This necessitates quantifying this risk through dedicated studies to determine whether this antimicrobial treatment could be significantly associated with IBD relapse or exacerbation of pre-existing IBD, as well as whether it could potentially lead to the de novo onset of IBD. Although the available evidence is reassuring about the safety of eradication therapy in patients with IBD, it is limited, and there are no specific recommendations for this particular situation in the leading international IBD and H. pylori guidelines. Therefore, studies need to evaluate the efficacy and safety profiles of the available antimicrobial regimens for H. pylori eradication in patients with IBD, both in clinical trial settings and in real-life studies.
Collapse
Affiliation(s)
- Antonietta Gerarda Gravina
- Hepatogastroenterology Division, Department of Precision Medicine, University of Campania Luigi Vanvitelli, 80138 Naples, Italy
| | - Raffaele Pellegrino
- Hepatogastroenterology Division, Department of Precision Medicine, University of Campania Luigi Vanvitelli, 80138 Naples, Italy
| | - Veronica Iascone
- Department of Medical and Surgical Sciences, University of Bologna, 40138 Bologna, Italy
- Esophagus and Stomach Organic Diseases Unit, IRCSS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy
| | - Giovanna Palladino
- Hepatogastroenterology Division, Department of Precision Medicine, University of Campania Luigi Vanvitelli, 80138 Naples, Italy
| | - Alessandro Federico
- Hepatogastroenterology Division, Department of Precision Medicine, University of Campania Luigi Vanvitelli, 80138 Naples, Italy
| | - Rocco Maurizio Zagari
- Department of Medical and Surgical Sciences, University of Bologna, 40138 Bologna, Italy
- Esophagus and Stomach Organic Diseases Unit, IRCSS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy
| |
Collapse
|
|
6
|
Zhang Y, Chu X, Wang L, Yang H. Global patterns in the epidemiology, cancer risk, and surgical implications of inflammatory bowel disease. Gastroenterol Rep (Oxf) 2024; 12:goae053. [PMID: 38984068 PMCID: PMC11233070 DOI: 10.1093/gastro/goae053] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/21/2024] [Revised: 04/10/2024] [Accepted: 04/22/2024] [Indexed: 07/11/2024] Open
Abstract
Inflammatory bowel disease (IBD), mainly including ulcerative colitis and Crohn's disease, imposes a huge medical and economic burden worldwide. Recently, the diagnosis, treatment, and surveillance of IBD have advanced rapidly, which has changed the epidemiology, cancer risk, and surgery risk of IBD. Here, we reviewed the recent literature on the epidemiology, IBD-related cancer, and IBD-related surgery. We created a choropleth map to show the worldwide incidence trend for Crohn's disease and ulcerative colitis. We also found that the cancer risk and surgery risk of IBD are declining and discussed some risk factors associated with them. Based on the recent trend, we proposed several suggestions and hoped to reduce the global burden of IBD as far as possible.
Collapse
Affiliation(s)
- Yiming Zhang
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, P. R. China
| | - Xiaotian Chu
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, P. R. China
| | - Li Wang
- Department of Epidemiology and Biostatistics, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences; School of Basic Medicine Peking Union Medical College, Beijing, P. R. China
| | - Hong Yang
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, P. R. China
| |
Collapse
|
|
7
|
Pantel H, Reddy VB. Management of Colonic Emergencies. Surg Clin North Am 2023; 103:1133-1152. [PMID: 37838460 DOI: 10.1016/j.suc.2023.06.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/16/2023]
Abstract
The etiology of colonic emergencies includes a wide-ranging and diverse set of pathologic conditions. Fortunately, for the surgeon treating a patient with one of these emergencies, the surgical management of these various causes is limited to choosing among proximal diversion, segmental colectomy with or without proximal diversion, or a total abdominal colectomy with end ileostomy (or rarely, an ileorectal anastomosis). The nuanced complexity in these situations usually revolves around the nonsurgical and/or endoscopic options and deciding when to proceed to the operating room.
Collapse
Affiliation(s)
- Haddon Pantel
- Colon and Rectal Surgery, Yale University School of Medicine, 450 George Street, New Haven, CT 06510, USA
| | - Vikram B Reddy
- Colon and Rectal Surgery, Yale University School of Medicine, 450 George Street, New Haven, CT 06510, USA.
| |
Collapse
|
|
8
|
Bai M, Guo H, Zheng XY. Inflammatory bowel disease and Clostridium difficile infection: clinical presentation, diagnosis, and management. Therap Adv Gastroenterol 2023; 16:17562848231207280. [PMID: 38034098 PMCID: PMC10685799 DOI: 10.1177/17562848231207280] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/10/2023] [Accepted: 09/24/2023] [Indexed: 12/02/2023] Open
Abstract
As a frequent complication of inflammatory bowel disease (IBD), Clostridium difficile infection (CDI) was confirmed to not only aggravate the symptoms of IBD but also result in unexpected outcomes, including death. With the increasing prevalence rate of IBD and the updating of CDI diagnosis, the incidence of CDI in IBD patients is also seen rising. Although a detection method consisting of glutamate dehydrogenase immunoassay or nucleic acid amplification test and then toxin A/B enzyme immunoassay was recommended and widely adopted, the diagnosis of CDI in IBD is still a challenge because of the overlap between the symptoms of CDI in IBD and CDI itself. Vancomycin and fidaxomicin are the first-line therapy for CDI in IBD; however, the treatment has different effects due to the complexity of IBD patients' conditions and the choice of different treatment schemes. Although the use of fecal microbial transplantation is now in the ascendant for IBD management, the prospects are still uncertain and the prevention and treatment of the recurrence of CDI in IBD remain a clinical challenge. In this paper, the epidemiology, pathophysiology, clinical manifestation, prevention, and therapy of CDI in IBD were summarized and presented.
Collapse
Affiliation(s)
- Mei Bai
- Department of Gastroenterology, Chongqing General Hospital, Chongqing, China
| | - Hong Guo
- Department of Gastroenterology, Chongqing General Hospital, 28 Jinshan Avenue, Yubei District, Chongqing 401147, China
| | - Xiao-Yao Zheng
- Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai, China
| |
Collapse
|
|
9
|
Dalal RS, Mitri J, Goodrick H, Allegretti JR. Risk of Gastrointestinal Infections After Initiating Vedolizumab and Anti-TNFα Agents for Ulcerative Colitis. J Clin Gastroenterol 2023; 57:714-720. [PMID: 36156528 PMCID: PMC9898464 DOI: 10.1097/mcg.0000000000001733] [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: 01/31/2022] [Accepted: 05/20/2022] [Indexed: 02/06/2023]
Abstract
GOALS Characterize and compare the risk of Clostridioides difficile infection (CDI) and cytomegalovirus colitis (CMVC) after initiation of vedolizumab or anti-tumor necrosis factor (TNF)α agents for ulcerative colitis (UC). BACKGROUND Immunosuppression is a risk factor for gastrointestinal infections including CDI and CMVC among patients with UC; however, the risk according to the biological class is poorly understood. STUDY A retrospective cohort study of adults with UC involving the initiation of vedolizumab or anti-TNFα agents during June 1, 2014 to December 31, 2020 was conducted at a large academic health system. The primary outcomes for both CDI and CMVC analyses were first CDI or CMVC after biological initiation. The secondary outcome for the CDI analysis was severe CDI (>10,000 white blood cells or serum creatinine >1.5 mg/dL). Independent variables included demographics and UC history/severity factors. Inverse probability of treatment weighted Cox regression was performed to assess the hazard of CDI by biological group. Due to few outcomes, CMVC was reported descriptively. RESULTS A total of 805 UC patients initiated vedolizumab (n=195) or anti-TNFα agents (n=610). There were 43 CDIs and 11 severe CDIs over 1436 patient-years. The inverse probability of treatment weighted Cox regression demonstrated no association between CDI and vedolizumab versus anti-TNFα (hazard ratio 0.33, 95% confidence interval 0.05-2.03), but identified a significantly lower hazard of severe CDI for vedolizumab versus anti-TNFα (hazard ratio 0.10, 95% confidence interval 0.01-0.76). There were 5 cases of CMVC, all in the anti-TNFα group. CONCLUSIONS There was a lower adjusted risk of severe CDI but not total CDI associated with vedolizumab. CMVC was not observed after initiating vedolizumab. These findings may provide reassurance regarding the use of vedolizumab when also considering the risk of gastrointestinal infections.
Collapse
Affiliation(s)
- Rahul S Dalal
- Division of Gastroenterology Department of Medicine, Hepatology and Endoscopy, Brigham and Women's Hospital, Harvard Medical School, Boston, MA
| | | | | | | |
Collapse
|
|
10
|
Sangurima L, Malik MM, Ganatra N, Siby R, Kumar S, Khan S, Cheriachan D, Mohammed L. Clostridioides difficile Infection in Inflammatory Bowel Disease Patients: A Systematic Review of Risk Factors and Approach in Management. Cureus 2023; 15:e43134. [PMID: 37692651 PMCID: PMC10484035 DOI: 10.7759/cureus.43134] [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: 06/30/2023] [Accepted: 08/08/2023] [Indexed: 09/12/2023] Open
Abstract
Clostridioides difficile infection (CDI) is one of the most common diseases associated with medical care, having a more significant impact on patients with inflammatory bowel disease (IBD). The latest studies have proposed a change in management for CDI in IBD patients. This study aims to perform a systematic review that explores the risk factors associated with the infection and the most optimal approach in management. Multiple databases were used for this research, including PubMed, Google Scholar, Science Direct, and Cochrane Library. Studies published in the last five years in the English language were selected based on pre-established criteria. The quality assessment used was the Assessment of Multiple Systematic Review, the Newcastle-Ottawa Scale, and the Scale for the Assessment of Narrative Review Articles. Twelve studies met the inclusion criteria in this systematic review, including literature reviews, a case and control study, and systematic reviews and meta-analyses. Based on the findings in this research, we conclude that the treatment for an initial episode of CDI in IBD patients is the use of antibiotics, vancomycin, or fidaxomicin. For episodes of recurrent CDI (rCDI), fetal microbiota transplantation should be considered. The most common risk factors associated are gut microbiota disturbances, the use of antibiotics, and hospitalization. Due to a wide range of risk factors mentioned in some studies but disregarded in others, further research is needed to determine the most prevalent risk factors.
Collapse
Affiliation(s)
- Leslie Sangurima
- Internal Medicine, California Institute of Behavioral Neurosciences and Psychology, Fairfield, USA
| | | | - Nency Ganatra
- Internal Medicine, California Institute of Behavioral Neurosciences and Psychology, Fairfield, USA
| | - Rosemary Siby
- Internal Medicine, California Institute of Behavioral Neurosciences and Psychology, Fairfield, USA
| | - Sanjay Kumar
- Internal Medicine, Bahria University Medical and Dental College, Pakistan Navy Ship (PNS) Shifa Hospital, Karachi, PAK
| | - Sara Khan
- Internal Medicine, California Institute of Behavioral Neurosciences and Psychology, Fairfield, USA
| | - Doju Cheriachan
- Emergency Medicine, California Institute of Behavioral Neurosciences and Psychology, Fairfield, USA
| | - Lubna Mohammed
- Internal Medicine, California Institute of Behavioral Neurosciences and Psychology, Fairfield, USA
| |
Collapse
|
|
11
|
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.
Collapse
|
|
12
|
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.
Collapse
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
| |
Collapse
|
|
13
|
Li Y, Sheng L, Jena PK, Gilbert MC, Wan YJY, Mao H. Retinoic Acid Signaling Is Compromised in DSS-Induced Dysbiosis. Nutrients 2022; 14:2788. [PMID: 35889745 PMCID: PMC9315703 DOI: 10.3390/nu14142788] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2022] [Revised: 06/29/2022] [Accepted: 06/30/2022] [Indexed: 02/04/2023] Open
Abstract
Obesity and malnutrition both cause dysbiosis and dampen retinoic acid (RA) signaling pathways, which play pivotal roles in biological processes. The current study evaluates a hypothesis that colitis-associated dysbiosis also has systemic negative impacts on RA signaling. Thus, we studied the effects of inflammation, under a vitamin A-sufficient condition, on RA signaling using mouse colitis models induced by dextran sulfate sodium. That data showed that intestinal inflammation resulted in reduced RA signaling in the liver, brain, gut, and adipose tissues measured by analyzing the expression of genes encoding for the synthesis, oxidation, transport, and receptor of RA. The expression of RA-regulated gut homing molecules including α4β7 integrin, and CCR9, along with MADCAM1 were all reduced in colitis mice revealing compromised immunity due to reduced RA signaling. The data also showed that the development of colitis was accompanied by dysbiosis featured with reduced Lactobacillaceae and Verrucomicrobiaceae but an expansion of Erysipelotrichaceae and others. Colitis resulted in reduced butyrate-producing bacteria and increased methane-generating bacteria. Additionally, dysbiosis was associated with induced Il-1β, Ifn-γ, and Tnf-α mRNA but reduced Il-22, Il-17f, and Rorγt transcripts in the colon. Together, intestinal inflammation inhibits RA signaling in multiple organs. RA is essential in regulating various biological processes, it is critical to detect RA signaling reduction in tissues even when vitamin A deficiency is absent. Moreover, probiotics can potentially prevent dysbiosis and reverse compromised RA signaling, having systemic health benefits.
Collapse
Affiliation(s)
- Yongchun Li
- Department of Gastroenterology, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, China;
- Department of Infectious Diseases, The Six Affiliated Hospital, South China University of Technology, Foshan 528200, China
- Department of Pathology and Laboratory Medicine, University of California Davis, Sacramento, CA 95817, USA; (L.S.); (P.K.J.); (M.C.G.)
| | - Lili Sheng
- Department of Pathology and Laboratory Medicine, University of California Davis, Sacramento, CA 95817, USA; (L.S.); (P.K.J.); (M.C.G.)
| | - Prasant Kumar Jena
- Department of Pathology and Laboratory Medicine, University of California Davis, Sacramento, CA 95817, USA; (L.S.); (P.K.J.); (M.C.G.)
| | - Miranda Claire Gilbert
- Department of Pathology and Laboratory Medicine, University of California Davis, Sacramento, CA 95817, USA; (L.S.); (P.K.J.); (M.C.G.)
| | - Yu-Jui Yvonne Wan
- Department of Pathology and Laboratory Medicine, University of California Davis, Sacramento, CA 95817, USA; (L.S.); (P.K.J.); (M.C.G.)
| | - Hua Mao
- Department of Gastroenterology, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, China;
| |
Collapse
|
|
14
|
Sweeney JR, Crawford CV, Yantiss RK. Histological features of Clostridioides difficile colitis in patients with inflammatory bowel disease. Histopathology 2022; 81:312-318. [PMID: 35758181 DOI: 10.1111/his.14702] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2022] [Revised: 05/14/2022] [Accepted: 06/09/2022] [Indexed: 01/18/2023]
Abstract
AIMS Patients with inflammatory bowel disease (IBD) are at increased risk for Clostridioides difficile infection, although clinically important infections can be difficult to recognise. C. difficile infection does not produce pseudomembranes when it occurs in IBD patients. These individuals may also be colonised by the organism, in which case diarrhoeal symptoms are not necessarily attributed to C. difficile. We performed this study to determine whether any features distinguished C. difficile-associated colitis from an IBD flare. METHODS AND RESULTS We reviewed the clinical, endoscopic and biopsy findings from 50 patients with established IBD and worsening diarrhoea, including 22 with concurrent positive C. difficile stool toxin polymerase chain reaction (PCR) assays and 28 with negative C. difficile assay results. We found that C. difficile-infected patients had symptoms and endoscopic findings that were indistinguishable from active IBD. Although most biopsy samples from patients with C. difficile infection showed chronic active colitis indistinguishable from IBD, some displayed neutrophilic infiltrates unaccompanied by plasma cell-rich inflammation involving superficial (41%) and crypt (18%) epithelium as well as neutrophilic infiltrates within lamina propria distant from foci of cryptitis (32%). All three of these features were significantly more common among infected than uninfected patients (4, 0 and 4%; P = 0.002, P = 0.03 and P = 0.02, respectively). CONCLUSIONS Although colonic biopsies from IBD patients with C. difficile infection usually lack features that aid distinction from colitic flares, some cases show an acute colitis pattern not seen in IBD alone. When identified in biopsies from symptomatic IBD patients, these changes should alert pathologists to the possibility of this clinically important infection.
Collapse
Affiliation(s)
- Jacob R Sweeney
- Department of Pathology and Laboratory Medicine, Cleveland Clinic, Cleveland, OH, USA
| | - Carl V Crawford
- Division of Gastroenterology and Hepatology, Weill Cornell Medicine, New York, NY, USA
| | - Rhonda K Yantiss
- Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, USA
| |
Collapse
|
|
15
|
Fang SB, Song YQ, Zhang CY, Wang LB. Risk factors for Clostridioides difficile infection in children and adolescents with inflammatory bowel disease: a systematic review and meta-analysis. World J Pediatr 2022; 18:27-36. [PMID: 34800281 DOI: 10.1007/s12519-021-00486-1] [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: 08/31/2021] [Accepted: 11/07/2021] [Indexed: 11/26/2022]
Abstract
BACKGROUND Risk factors and consequences associated with Clostridioides difficile infection (CDI) in children and adolescents with inflammatory bowel disease (IBD) are still uncertain. We conduct a systematic review and meta-analysis to assess risk factors and outcomes associated with CDI in children and adolescents with IBD. METHODS PubMed, EMBASE and Cochrane Library databases were searched from inception to 24th February, 2021. Studies investigating risk factors, bowel surgery rate in pediatric IBD patients with and without CDI were included. Random-effects model was used for calculating summary estimates. Newcastle-Ottawa scale (NOS) was used for quality assessment. RESULTS Fourteen studies, comprising 17,114 patients, were included. There was a significant association between 5-aminosalicylic acid (5-ASA) use and CDI [odds ratio (OR) = 1.95, 95% confidence interval (CI) 1.26-3.03], with minimal heterogeneity (I2 = 0.00%). Increased risk of active disease (OR = 4.66, 95% CI 2.16-10.07) were associated with CDI in those studies performed in high quality score (NOS > 6) and significantly higher CDI rates in studies conducted outside USA (OR = 2.94, 95% CI 1.57-5.58). The bowel surgery rate in IBD with CDI was 3.8-57.1%, compared to that in IBD without CDI (0-21.3%). All studies were of moderate to high quality. CONCLUSIONS 5-ASA use and active disease might be risk factors associated with CDI in children and adolescents with IBD. Bowel surgery rates associated with CDI in IBD patients varied greatly. Large-scale clinical studies on CDI in children and adolescents with IBD are still needed to verify risk factors and outcomes.
Collapse
Affiliation(s)
- Sheng-Bo Fang
- Department of Pharmacy, First Hospital of Jilin University, Changchun, China
| | - Yan-Qing Song
- Department of Pharmacy, First Hospital of Jilin University, Changchun, China
| | - Chun-Yan Zhang
- Department of Pediatric Gastroenterology Unit, First Hospital of Jilin University, 71 Xinmin Street, Changchun, 130021, China
| | - Li-Bo Wang
- Department of Pediatric Gastroenterology Unit, First Hospital of Jilin University, 71 Xinmin Street, Changchun, 130021, China.
| |
Collapse
|
|
16
|
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.
Collapse
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
| |
Collapse
|
|
17
|
The American Society of Colon and Rectal Surgeons Clinical Practice Guidelines for the Management of Clostridioides difficile Infection. Dis Colon Rectum 2021; 64:650-668. [PMID: 33769319 DOI: 10.1097/dcr.0000000000002047] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
|
|
18
|
Żebrowska P, Łaczmańska I, Łaczmański Ł. Future Directions in Reducing Gastrointestinal Disorders in Children With ASD Using Fecal Microbiota Transplantation. Front Cell Infect Microbiol 2021; 11:630052. [PMID: 33718277 PMCID: PMC7952982 DOI: 10.3389/fcimb.2021.630052] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2020] [Accepted: 01/22/2021] [Indexed: 12/16/2022] Open
Abstract
Research on the use of fecal microbiota transplantation (FMT) in the treatment of disorders related to digestive system ailments in children with autism spectrum disorders (ASDs) is a new attempt in a therapeutic approach. There are very little scientific evidences available on this emerging alternative method. However, it appears to be interesting not only because of its primary outcome, relieving the gastrointestinal (GI) symptoms, but also secondary therapeutic effect of alleviating autistic behavioral symptoms. FMT seems to be also promising method in the treatment of another group of pediatric patients, children with inflammatory bowel disease (IBD). The aim of this study is to discuss the potential use of FMT and modified protocols (MTT, microbiota transfer therapy) in the treatment of GI disorders in ASD children supported by reports on another disease, IBD concerning pediatric patients. Due to the few reports of the use of FMT in the treatment of children, these two patients groups were selected, although suffering from distant health conditions: neurodevelopmental disorder and gastrointestinal tract diseases, because of the the fact that they seem related in aspects of the presence of GI symptoms, disturbed intestinal microbiota, unexplained etiology of the condition and age range of patients. Although the outcomes for all are promising, this type of therapy is still an under-researched topic, studies in the group of pediatric patients are sparse, also there is a high risk of transmission of infectious and noninfectious elements during the procedure and no long-term effects on global health are known. For those reasons all obtained results should be taken with a great caution. However, in the context of future therapeutic directions for GI observed in neurodevelopmental disorders and neurodegenerative diseases, the topic seems worthy of attention.
Collapse
Affiliation(s)
- Paulina Żebrowska
- Laboratory of Genomics and Bioinformatics, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wrocław, Poland
| | | | - Łukasz Łaczmański
- Laboratory of Genomics and Bioinformatics, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wrocław, Poland
| |
Collapse
|
|
19
|
Positivity of Stool Pathogen Sampling in Pediatric Inflammatory Bowel Disease Flares and Its Association With Disease Course. J Pediatr Gastroenterol Nutr 2021; 72:61-66. [PMID: 32796430 DOI: 10.1097/mpg.0000000000002895] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/10/2022]
Abstract
OBJECTIVES Acute exacerbations of inflammatory bowel disease (IBD) may involve enteric pathogen. We aimed to assess the frequency and outcomes of Clostridium difficille toxin (CDT) and non-CDT enteric infections in symptomatic pediatric patients with IBD. METHODS Patients' records were retrospectively searched for disease flares in which stool samples were collected for enteric pathogens. Each patient with a positive sample was matched with a patient with IBD flare and negative samples for analyzing 1-year outcomes following sampling. RESULTS A total of 618 pediatric patients with IBD [Crohn's disease, n = 439 (71%), mean age at diagnosis 13.0 ± 3.4 years, girls, n = 264 (42.7%)] had 1048 stool samples during the study period (2001-2018). Of 914 bacterial cultures, 40 (4.3%) were positive, 30 (75%) of which, positive for Campylobacter jejuni. Of 393 samples for CDT, 28 (7.1%) were positive while parasitic infection rate was 21/529 (3.9%).Overall, 19 positive C jejuni cases and 19 positive CDT cases with matching controls were examined. During 12 months of follow-up, the mean number of disease flares and emergency room visits was higher among patients with positive CDT (1.5 ± 1.4 vs 0.5 ± 0.9, P = 0.019, 1.3 ± 1.5 vs 0.4 ± 0.8, P = 0.05, respectively) with a numeric increase of surgical interventions (3 vs 0, P = 0.08). There were no significant differences in disease outcomes between patients with C jejuni infections and matched controls. CONCLUSIONS C difficile and C jejuni are the most common enteric infections among pediatric patients with IBD but only clostridial infection was associated with a more severe disease course within 12 months.
Collapse
|
|
20
|
Li Y, Chen F, Xie Y, Yang Q, Luo H, Jia P, Shi Z, Wang S, Zheng X. Feiyangchangweiyan capsule protects against ulcerative colitis in mice by modulating the OSM/OSMR pathway and improving gut microbiota. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2021; 80:153372. [PMID: 33113505 DOI: 10.1016/j.phymed.2020.153372] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/02/2019] [Revised: 09/15/2020] [Accepted: 10/01/2020] [Indexed: 06/11/2023]
Abstract
BACKGROUND Feiyangchangweiyan capsule (FYC) is a traditional Chinese medicine formulation used in the clinical treatment of acute and chronic gastroenteritis and bacterial dysentery. However, the effect of FYC on ulcerative colitis (UC) and the mechanism thereof remains unknown. PURPOSE To investigate the protective effect of FYC on UC mice induced by dextran sulfate sodium and illustrate the potential mechanism of this effect. METHODS Here, we established a model of UC mice by dextran sulfate sodium and administered with FYC. The disease activity index (DAI), colon length, myeloperoxidase (MPO) content in serum, pathological structure and ultrastructural changes, and inflammatory cell infiltration of colon tissue were evaluated. Transcriptome and 16S rDNA sequencing were employed to illuminate the mechanism of FYC in the protection of UC mice. RESULTS FYC significantly alleviates the pathological damage and the infiltration of inflammatory cells in colon tissue of dextran sulfate sodium induced UC mice, rescues shortened colon length, reduces DAI score, MPO content in serum, and pro-inflammatory factors including IL-1β, IL-6, CCL11, MCP-1 and MIP-2, and increases anti-inflammatory factors such as IL-10. Transcriptomics revealed that Oncostatin M (OSM) and its receptor (OSMR) are the critical pathway for UC treatment by FYC. OSM and OSMR increased in UC mice compared to control mice, and decreased with FYC, which was verified via measurement of OSM and OSMR mRNA and protein levels. Furthermore, we observed that FYC modulates intestinal microbiome composition (e.g., the proportion of Barnesiella/Proteobacteria) by affecting the inflammatory factors. CONCLUSION FYC exerts an effect on UC by inhibiting the OSM/OSMR pathway and regulating inflammatory factors to improve the intestinal flora.
Collapse
Affiliation(s)
- Yao Li
- Northwest University, Faculty of Life Science & Medicine, Key Laboratory Resource Biology & Biotechnology in Western China, Ministry of Education, Xi'an 710069, Shaanxi, China
| | - Fei Chen
- Department of Emergency Surgery, Wuhan No.1 Hospital, No.215 Zhongshan Road, Wuhan 430022, China
| | - Yanhua Xie
- Northwest University, Faculty of Life Science & Medicine, Key Laboratory Resource Biology & Biotechnology in Western China, Ministry of Education, Xi'an 710069, Shaanxi, China
| | - Qian Yang
- Department of Chinese Materia Medica and Natural Medicines, Air Force Medical University, Changle West Road No.169, Xi'an 710032 Shaanxi, P.R. China
| | - Huanhuan Luo
- Northwest University, Faculty of Life Science & Medicine, Key Laboratory Resource Biology & Biotechnology in Western China, Ministry of Education, Xi'an 710069, Shaanxi, China
| | - Pu Jia
- Northwest University, Faculty of Life Science & Medicine, Key Laboratory Resource Biology & Biotechnology in Western China, Ministry of Education, Xi'an 710069, Shaanxi, China
| | - Zhihui Shi
- Shaanxi Junbisha Pharmaceutical Limited Company, Xianyang 712015, Shaanxi, China
| | - Siwang Wang
- Northwest University, Faculty of Life Science & Medicine, Key Laboratory Resource Biology & Biotechnology in Western China, Ministry of Education, Xi'an 710069, Shaanxi, China; Department of Chinese Materia Medica and Natural Medicines, Air Force Medical University, Changle West Road No.169, Xi'an 710032 Shaanxi, P.R. China.
| | - Xiaohui Zheng
- Northwest University, Faculty of Life Science & Medicine, Key Laboratory Resource Biology & Biotechnology in Western China, Ministry of Education, Xi'an 710069, Shaanxi, China.
| |
Collapse
|
|
21
|
Goyal A. Clostridium Difficile and Increased Risk of Surgery in Crohn's Disease. Can Early Microbial Signatures Forecast Risk of Disease Progression? Inflamm Bowel Dis 2020; 26:1222-1224. [PMID: 31725870 DOI: 10.1093/ibd/izz278] [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: 10/15/2019] [Indexed: 12/09/2022]
Abstract
Clostridium difficile infection (CDI) is associated with dysbiosis and a higher risk of complications in patients with ulcerative colitis. This study reveals a possible association between CDI, dysbiosis, suppression of methionine synthesis, and increased risk of surgery in Crohn’s disease.
Collapse
Affiliation(s)
- Alka Goyal
- Professor of Pediatrics Division of Gastroenterology, Hepatology and Nutrition, Children's Mercy Kansas City and University of Missouri-Kansas City, Kansas City, MO, USA
| |
Collapse
|
|
22
|
Moens A, Verstockt B, Machiels K, Bossuyt P, Verdonck A, Lagrou K, van Assche G, Vermeire S, Ferrante M. Clostridium difficile infection in inflammatory bowel disease: epidemiology over two decades. Eur J Gastroenterol Hepatol 2019; 31:668-673. [PMID: 30839436 DOI: 10.1097/meg.0000000000001394] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
BACKGROUND The incidence of Clostridium difficile infection (CDI) has been rising in the overall population as well as in patients with inflammatory bowel disease (IBD). However, the incidence of CDI in IBD may be changing owing to alterations in medical therapies. OBJECTIVE The aim of this study was to establish the incidence of CDI in IBD over the past two decades and compare risk factors, disease characteristics and outcomes between IBD and non-IBD patients. PATIENTS AND METHODS In this retrospective case-control study, the incidence of CDI in IBD was followed for 18 years. The electronic database of our centre was reviewed for all stool samples received from patients admitted to gastroenterology wards or visiting the outpatient clinic. Diagnosis of CDI was based on diagnostic criteria that evolved throughout the years. RESULTS IBD patients (n=44) with CDI were found to be younger (P=0.0001), have less cardiovascular comorbidity (P=0.023), fewer prior hospitalizations (P=0.009) and fewer prior antibiotic use (P=0.005). More IBD patients were on biologic therapy (P=0.0001) or steroids (P=0.001) but less likely taking proton pump inhibitors (P=0.001). The number of stool testing per year increased as well as the median number of positive stool samples for CDI (2% in 2000-2008 to 3% in 2009-2017, P=0.032). Pseudomembranes were only seen in non-IBD patients (28%, P=0.048). There was no difference in the choice of antibiotics between IBD and non-IBD patients [metronidazole (36 vs. 51%) and vancomycin (36 vs. 26%), P=0.090 and 0.190]. The 1-year mortality rate was lower in IBD patients compared with non-IBD patients (0 vs. 32%, P=0.0001). CONCLUSION In the past two decades, the incidence of CDI in IBD and non-IBD patients has increased. However, the overall outcome of CDI in IBD patients was favourable compared with non-IBD patients.
Collapse
Affiliation(s)
- Annick Moens
- Departments of Gastroenterology and Hepatology
- Department of Chronic Diseases, Metabolism and Ageing, KU Leuven, Leuven
| | - Bram Verstockt
- Departments of Gastroenterology and Hepatology
- Department of Chronic Diseases, Metabolism and Ageing, KU Leuven, Leuven
| | - Kathleen Machiels
- Department of Chronic Diseases, Metabolism and Ageing, KU Leuven, Leuven
| | - Peter Bossuyt
- Department of Gastroenterology and Hepatology, Imelda Hospital, Bonheiden, Belgium
| | - Ann Verdonck
- Laboratory Medicine, University Hospitals Leuven
| | | | - Gert van Assche
- Departments of Gastroenterology and Hepatology
- Department of Chronic Diseases, Metabolism and Ageing, KU Leuven, Leuven
| | - Séverine Vermeire
- Departments of Gastroenterology and Hepatology
- Department of Chronic Diseases, Metabolism and Ageing, KU Leuven, Leuven
| | - Marc Ferrante
- Departments of Gastroenterology and Hepatology
- Department of Chronic Diseases, Metabolism and Ageing, KU Leuven, Leuven
| |
Collapse
|
|
23
|
Liu R, Moriggl R, Zhang D, Li H, Karns R, Ruan HB, Niu H, Mayhew C, Watson C, Bangar H, Cha SW, Haslam D, Zhang T, Gilbert S, Li N, Helmrath M, Wells J, Denson L, Han X. Constitutive STAT5 activation regulates Paneth and Paneth-like cells to control Clostridium difficile colitis. Life Sci Alliance 2019; 2:e201900296. [PMID: 30948494 PMCID: PMC6451325 DOI: 10.26508/lsa.201900296] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2019] [Revised: 03/27/2019] [Accepted: 03/27/2019] [Indexed: 12/17/2022] Open
Abstract
Clostridium difficile impairs Paneth cells, driving intestinal inflammation that exaggerates colitis. Besides secreting bactericidal products to restrain C. difficile, Paneth cells act as guardians that constitute a niche for intestinal epithelial stem cell (IESC) regeneration. However, how IESCs are sustained to specify Paneth-like cells as their niche remains unclear. Cytokine-JAK-STATs are required for IESC regeneration. We investigated how constitutive STAT5 activation (Ca-pYSTAT5) restricts IESC differentiation towards niche cells to restrain C. difficile infection. We generated inducible transgenic mice and organoids to determine the effects of Ca-pYSTAT5-induced IESC lineages on C. difficile colitis. We found that STAT5 absence reduced Paneth cells and predisposed mice to C. difficile ileocolitis. In contrast, Ca-pYSTAT5 enhanced Paneth cell lineage tracing and restricted Lgr5 IESC differentiation towards pYSTAT5+Lgr5-CD24+Lyso+ or cKit+ niche cells, which imprinted Lgr5hiKi67+ IESCs. Mechanistically, pYSTAT5 activated Wnt/β-catenin signaling to determine Paneth cell fate. In conclusion, Ca-pYSTAT5 gradients control niche differentiation. Lack of pYSTAT5 reduces the niche cells to sustain IESC regeneration and induces C. difficile ileocolitis. STAT5 may be a transcription factor that regulates Paneth cells to maintain niche regeneration.
Collapse
Affiliation(s)
- Ruixue Liu
- Key Laboratory of Human Disease Comparative Medicine, the Ministry of Health, Institute of Laboratory Animal Sciences, Chinese Academy Institute of Medical Sciences and Peking Union Medical College, Beijing, P.R. China
| | - Richard Moriggl
- Ludwig Boltzmann Institute for Cancer Research, Vienna, Austria
- Institute of Animal Breeding and Genetics, University of Veterinary Medicine, Vienna, Austria
- Medical University of Vienna, Vienna, Austria
| | - Dongsheng Zhang
- Division of Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical Center (CCHMC), Cincinnati, OH, USA
| | - Haifeng Li
- Key Laboratory of Human Disease Comparative Medicine, the Ministry of Health, Institute of Laboratory Animal Sciences, Chinese Academy Institute of Medical Sciences and Peking Union Medical College, Beijing, P.R. China
| | - Rebekah Karns
- Division of Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical Center (CCHMC), Cincinnati, OH, USA
| | - Hai-Bin Ruan
- Department of Integrative Biology and Physiology, University of Minnesota Medical School, Minneapolis, MI, USA
| | - Haitao Niu
- Key Laboratory of Human Disease Comparative Medicine, the Ministry of Health, Institute of Laboratory Animal Sciences, Chinese Academy Institute of Medical Sciences and Peking Union Medical College, Beijing, P.R. China
| | | | - Carey Watson
- Division of Pediatric Surgery, CCHMC, Cincinnati, OH, USA
| | - Hansraj Bangar
- Division of Infectious Diseases, CCHMC, Cincinnati, OH, USA
| | - Sang-Wook Cha
- Division of Developmental Biology, CCHMC, Cincinnati, OH, USA
| | - David Haslam
- Division of Infectious Diseases, CCHMC, Cincinnati, OH, USA
| | - Tongli Zhang
- Department of Pharmacology & Systems Physiology, University of Cincinnati College of Medicine, OH, USA
| | - Shila Gilbert
- Division of Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical Center (CCHMC), Cincinnati, OH, USA
| | - Na Li
- Key Laboratory of Human Disease Comparative Medicine, the Ministry of Health, Institute of Laboratory Animal Sciences, Chinese Academy Institute of Medical Sciences and Peking Union Medical College, Beijing, P.R. China
| | | | - James Wells
- Division of Developmental Biology, CCHMC, Cincinnati, OH, USA
- Division of Endocrinology, CCHMC, Cincinnati, OH, USA
- Center for Stem Cell and Organoid Medicine, CCHMC, Cincinnati, OH, USA
| | - Lee Denson
- Division of Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical Center (CCHMC), Cincinnati, OH, USA
- Department of Pediatrics, University of Cincinnati College of Medicine, OH, USA
| | - Xiaonan Han
- Division of Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical Center (CCHMC), Cincinnati, OH, USA
- Key Laboratory of Human Disease Comparative Medicine, the Ministry of Health, Institute of Laboratory Animal Sciences, Chinese Academy Institute of Medical Sciences and Peking Union Medical College, Beijing, P.R. China
- Department of Pediatrics, University of Cincinnati College of Medicine, OH, USA
| |
Collapse
|
|
24
|
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.
Collapse
|
|
25
|
Sartelli M, Di Bella S, McFarland LV, Khanna S, Furuya-Kanamori L, Abuzeid N, Abu-Zidan FM, Ansaloni L, Augustin G, Bala M, Ben-Ishay O, Biffl WL, Brecher SM, Camacho-Ortiz A, Caínzos MA, Chan S, Cherry-Bukowiec JR, Clanton J, Coccolini F, Cocuz ME, Coimbra R, Cortese F, Cui Y, Czepiel J, Demetrashvili Z, Di Carlo I, Di Saverio S, Dumitru IM, Eckmann C, Eiland EH, Forrester JD, Fraga GP, Frossard JL, Fry DE, Galeiras R, Ghnnam W, Gomes CA, Griffiths EA, Guirao X, Ahmed MH, Herzog T, Kim JI, Iqbal T, Isik A, Itani KMF, Labricciosa FM, Lee YY, Juang P, Karamarkovic A, Kim PK, Kluger Y, Leppaniemi A, Lohsiriwat V, Machain GM, Marwah S, Mazuski JE, Metan G, Moore EE, Moore FA, Ordoñez CA, Pagani L, Petrosillo N, Portela F, Rasa K, Rems M, Sakakushev BE, Segovia-Lohse H, Sganga G, Shelat VG, Spigaglia P, Tattevin P, Tranà C, Urbánek L, Ulrych J, Viale P, Baiocchi GL, Catena F. 2019 update of the WSES guidelines for management of Clostridioides ( Clostridium) difficile infection in surgical patients. World J Emerg Surg 2019; 14:8. [PMID: 30858872 PMCID: PMC6394026 DOI: 10.1186/s13017-019-0228-3] [Citation(s) in RCA: 85] [Impact Index Per Article: 14.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2019] [Accepted: 02/17/2019] [Indexed: 02/08/2023] Open
Abstract
In the last three decades, Clostridium difficile infection (CDI) has increased in incidence and severity in many countries worldwide. The increase in CDI incidence has been particularly apparent among surgical patients. Therefore, prevention of CDI and optimization of management in the surgical patient are paramount. An international multidisciplinary panel of experts from the World Society of Emergency Surgery (WSES) updated its guidelines for management of CDI in surgical patients according to the most recent available literature. The update includes recent changes introduced in the management of this infection.
Collapse
Affiliation(s)
- Massimo Sartelli
- Department of Surgery, Macerata Hospital, Via Santa Lucia 2, 62100 Macerata, Italy
| | - Stefano Di Bella
- Infectious Diseases Department, Trieste University Hospital, Trieste, Italy
| | - Lynne V. McFarland
- Medicinal Chemistry, School of Pharmacy, University of Washington, Seattle, WA USA
| | - Sahil Khanna
- Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, MN USA
| | - Luis Furuya-Kanamori
- Research School of Population Health, Australian National University, Acton, ACT Australia
| | - Nadir Abuzeid
- Department of Microbiology, Faculty of Medical Laboratory Sciences, Omdurman Islamic University, Khartoum, Sudan
| | - Fikri M. Abu-Zidan
- Department of Surgery, College of Medicine and Health Sciences, UAE University, Al-Ain, United Arab Emirates
| | - Luca Ansaloni
- Department of General Surgery, Bufalini Hospital, Cesena, Italy
| | - Goran Augustin
- Department of Surgery, University Hospital Centre Zagreb and School of Medicine, University of Zagreb, Zagreb, Croatia
| | - Miklosh Bala
- Trauma and Acute Care Surgery Unit, Hadassah Hebrew University Medical Center, Jerusalem, Israel
| | - Offir Ben-Ishay
- Department of General Surgery, Rambam Health Care Campus, Haifa, Israel
| | - Walter L. Biffl
- Trauma and Acute Care Surgery, Scripps Memorial Hospital La Jolla, La Jolla, CA USA
| | - Stephen M. Brecher
- Pathology and Laboratory Medicine, VA Boston Healthcare System, West Roxbury MA and BU School of Medicine, Boston, MA USA
| | - Adrián Camacho-Ortiz
- Department of Internal Medicine, University Hospital, Dr. José E. González, Monterrey, Mexico
| | - Miguel A. Caínzos
- Department of Surgery, University of Santiago de Compostela, A Coruña, Spain
| | - Shirley Chan
- Department of General Surgery, Medway Maritime Hospital, Gillingham, Kent UK
| | - Jill R. Cherry-Bukowiec
- Department of Surgery, Division of Acute Care Surgery, University of Michigan, Ann Arbor, MI USA
| | - Jesse Clanton
- Department of Surgery, West Virginia University Charleston Division, Charleston, WV USA
| | | | - Maria E. Cocuz
- Faculty of Medicine, Transilvania University, Infectious Diseases Hospital, Brasov, Romania
| | - Raul Coimbra
- Riverside University Health System Medical Center and Loma Linda University School of Medicine, Moreno Valley, CA USA
| | | | - Yunfeng Cui
- Department of Surgery, Tianjin Nankai Hospital, Nankai Clinical School of Medicine, Tianjin Medical University, Tianjin, China
| | - Jacek Czepiel
- Department of Infectious Diseases, Jagiellonian University, Medical College, Kraków, Poland
| | - Zaza Demetrashvili
- Department of Surgery, Tbilisi State Medical University, Kipshidze Central University Hospital, Tbilisi, Georgia
| | - Isidoro Di Carlo
- Department of Surgical Sciences, Cannizzaro Hospital, University of Catania, Catania, Italy
| | - Salomone Di Saverio
- Department of Surgery, Addenbrooke’s Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
| | - Irina M. Dumitru
- Clinical Infectious Diseases Hospital, Ovidius University, Constanta, Romania
| | - Christian Eckmann
- Department of General, Visceral and Thoracic Surgery, Klinikum Peine, Hospital of Medical University Hannover, Peine, Germany
| | | | | | - Gustavo P. Fraga
- Division of Trauma Surgery, Hospital de Clinicas, School of Medical Sciences, University of Campinas, Campinas, Brazil
| | - Jean L. Frossard
- Service of Gastroenterology and Hepatology, Geneva University Hospital, Genève, Switzerland
| | - Donald E. Fry
- Department of Surgery, Northwestern University Feinberg School of Medicine, Chicago, IL USA
- University of New Mexico School of Medicine, Albuquerque, NM USA
| | - Rita Galeiras
- Critical Care Unit, Instituto de Investigación Biomédica de A Coruña (INIBIC), Complexo Hospitalario Universitario de A Coruña (CHUAC), Sergas, Universidade da Coruña (UDC), A Coruña, Spain
| | - Wagih Ghnnam
- Department of Surgery Mansoura, Faculty of Medicine, Mansoura University, Mansoura, Egypt
| | - Carlos A. Gomes
- Surgery Department, Hospital Universitario (HU) Terezinha de Jesus da Faculdade de Ciencias Medicas e da Saude de Juiz de Fora (SUPREMA), Hospital Universitario (HU) Universidade Federal de Juiz de Fora (UFJF), Juiz de Fora, Brazil
| | | | - Xavier Guirao
- Unit of Endocrine, Head, and Neck Surgery and Unit of Surgical Infections Support, Department of General Surgery, Parc Taulí, Hospital Universitari, Sabadell, Spain
| | - Mohamed H. Ahmed
- Department of Medicine, Milton Keynes University Hospital NHS Foundation Trust, Milton Keynes, Buckinghamshire UK
| | - Torsten Herzog
- Department of Surgery, St. Josef Hospital, Ruhr University Bochum, Bochum, Germany
| | - Jae Il Kim
- Department of Surgery, Ilsan Paik Hospital, Inje University College of Medicine, Goyang, Republic of Korea
| | - Tariq Iqbal
- Department of Gastroenterology, Queen Elizabeth Hospital, Birmingham, UK
| | - Arda Isik
- General Surgery Department, Magee Womens Hospital, UPMC, Pittsburgh, USA
| | - Kamal M. F. Itani
- Department of Surgery, VA Boston Health Care System, Boston University and Harvard Medical School, Boston, MA USA
| | | | - Yeong Y. Lee
- School of Medical Sciences, University Sains Malaysia, Kota Bharu, Kelantan Malaysia
| | - Paul Juang
- Department of Pharmacy Practice, St Louis College of Pharmacy, St Louis, MO USA
| | - Aleksandar Karamarkovic
- Faculty of Mediine University of Belgrade Clinic for Surgery “Nikola Spasic”, University Clinical Center “Zvezdara” Belgrade, Belgrade, Serbia
| | - Peter K. Kim
- Department of Surgery, Jacobi Medical Center, Albert Einstein College of Medicine, Bronx, NY USA
| | - Yoram Kluger
- Department of General Surgery, Rambam Health Care Campus, Haifa, Israel
| | - Ari Leppaniemi
- Abdominal Center, Helsinki University Hospital Meilahti, Helsinki, Finland
| | - Varut Lohsiriwat
- Department of Surgery, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Gustavo M. Machain
- Department of Surgery, Universidad Nacional de Asuncion, Asuncion, Paraguay
| | - Sanjay Marwah
- Department of Surgery, Post-Graduate Institute of Medical Sciences, Rohtak, India
| | - John E. Mazuski
- Department of Surgery, Washington University School of Medicine, Saint Louis, USA
| | - Gokhan Metan
- Department of Infectious Diseases and Clinical Microbiology, Hacettepe University Faculty of Medicine, Ankara, Turkey
| | - Ernest E. Moore
- Department of Surgery, University of Colorado, Denver Health Medical Center, Denver, CO USA
| | | | - Carlos A. Ordoñez
- Department of Surgery, Fundación Valle del Lili, Hospital Universitario del Valle, Universidad del Valle, Cali, Colombia
| | - Leonardo Pagani
- Infectious Diseases Unit, Bolzano Central Hospital, Bolzano, Italy
| | - Nicola Petrosillo
- National Institute for Infectious Diseases - INMI - Lazzaro Spallanzani IRCCS, Rome, Italy
| | - Francisco Portela
- Gastroenterology Department, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal
| | - Kemal Rasa
- Department of Surgery, Anadolu Medical Center, Kocaali, Turkey
| | - Miran Rems
- Department of Abdominal and General Surgery, General Hospital Jesenice, Jesenice, Slovenia
| | | | | | - Gabriele Sganga
- Division of Emergency Surgery, Department of Surgery, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
| | - Vishal G. Shelat
- Department of Surgery, Tan Tock Seng Hospital, Singapore, Singapore
| | - Patrizia Spigaglia
- Department of Infectious Diseases, Istituto Superiore di Sanità, Rome, Italy
| | - Pierre Tattevin
- Infectious Diseases and Intensive Care Unit, Pontchaillou University Hospital, Rennes, France
| | - Cristian Tranà
- Department of Surgery, Macerata Hospital, Via Santa Lucia 2, 62100 Macerata, Italy
| | - Libor Urbánek
- First Department of Surgery, Faculty of Medicine, Masaryk University Brno and University Hospital of St. Ann Brno, Brno, Czech Republic
| | - Jan Ulrych
- First Department of Surgery, First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, Prague, Czech Republic
| | - Pierluigi Viale
- Clinic of Infectious Diseases, St Orsola-Malpighi University Hospital, Bologna, Italy
| | - Gian L. Baiocchi
- Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy
| | - Fausto Catena
- Emergency Surgery Department, Maggiore Parma Hospital, Parma, Italy
| |
Collapse
|
|
26
|
Xu H, Tang H, Xu T, Xiao M, Li J, Tan B, Yang H, Lv H, Li Y, Qian J. Retrospective analysis of Clostridium difficile infection in patients with ulcerative colitis in a tertiary hospital in China. BMC Gastroenterol 2019; 19:3. [PMID: 30616563 PMCID: PMC6323708 DOI: 10.1186/s12876-018-0920-x] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/22/2018] [Accepted: 12/10/2018] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Many reports have documented the increasing impact of Clostridium difficile infection (CDI) in patients with ulcerative colitis (UC). We conducted a retrospective study to determine the incidence, clinical characteristics, risk factors and prognosis of CDI in patients with UC. METHODS We studied patients with UC, hospitalized between January 2010 and December 2015 in a tertiary hospital in China. Stool samples were tested for C. difficile toxins A and B (CDAB) by enzyme immunoassays in UC patients with disease flare. CDI in UC patients was diagnosed by clinical symptoms and positive CDAB test, and each case was matched with CDAB-negative patients in a 1:2 ratio. Univariate and binary logistic regression analyses were used to measure the differences between patients with and without CDI. RESULTS Thirty-four (8.92%) of 381 patients with UC were CDAB positive. Antibiotic exposure within 3 months prior to the study (P = 0.004), hospitalization within 1 month prior to the study (P = 0.025), systemic use of steroids (P = 0.002) and active cytomegalovirus (CMV) infection (P = 0.001) were higher in CDI than non-CDI patients. Binary logistic regression analysis revealed that CMV infection was associated with CDI (odds ratio = 13.502, 95% confidence interval 1.307-139.512, P = 0.029). UC patients with C. difficile and CMV co-infection had more severe colonoscopic features. CONCLUSIONS Recent use of antibiotics, prior hospitalization and systemic use of steroids increased the risk of CDI. CMV infection was an independent risk factor of CDI in patients with UC.
Collapse
Affiliation(s)
- Hui Xu
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
| | - Hao Tang
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
| | - Tao Xu
- Department of Epidemiology and Biostatistics, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & School of Basic Medicine, Peking Union Medical College, Beijing, China
| | - Meng Xiao
- Department of Clinical Laboratory, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
| | - Ji Li
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
| | - Bei Tan
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
| | - Hong Yang
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
| | - Hong Lv
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
| | - Yue Li
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China. .,, Beijing, 100730, China.
| | - Jiaming Qian
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China. .,, Beijing, 100730, China.
| |
Collapse
|
|
27
|
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] [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.
Collapse
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
| |
Collapse
|
|
28
|
Impact of superimposed Clostridium difficile infection in Crohn's or ulcerative colitis flares in the outpatient setting. Int J Colorectal Dis 2018; 33:1285-1294. [PMID: 29926235 DOI: 10.1007/s00384-018-3105-8] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 06/13/2018] [Indexed: 02/04/2023]
Abstract
PURPOSE The prospective assessment of Clostridium difficile infection (CDI) impact in inflammatory bowel disease (IBD) flare in outpatient setting has been poorly investigated. We aimed to evaluate the prevalence and the associated factors with CDI in IBD outpatients presenting colitis flares as well as the outcomes following treatment. METHODS In this prospective cohort study, conducted from October, 2014, to July, 2016, 120 IBD patients (55% presenting colitis flare) and 40 non-IBD controls were assessed for CDI. Multivariate regression analysis was performed to identify predictors of CDI. Outcome analysis was estimated for recurrent CDI, hospitalization, colectomy, and CDI-associated mortality. RESULTS The number of patients with CDI was significantly higher in IBD patients experiencing flares than in both inactive IBD and non-IBD groups (28.8 vs. 5.6 vs. 0%, respectively; p = 0.001). Females (OR = 1.39, 95% CI, 1.13-17.18), younger age (OR = 0.77, 95% CI, 0.65-0.92), steroid treatment (OR = 7.42, 95% CI, 5.17-40.20), and infliximab therapy (OR = 2.97, 95% CI, 1.99-24.63) were found to be independently associated with CDI. There was a dose-related increase in the risks of CDI on patients which had taken prednisone. Those treated with vancomycin had a satisfactory response to therapy, but 21% presented recurrent CDI and 16% were hospitalized. Neither necessity of colectomy nor mortality was noticed in any patient during the investigation. CONCLUSIONS In IBD outpatients presenting colitis flares, CDI is highly prevalent. Females, younger age, infliximab, and notably steroid therapy were independently associated with CDI. Most patients with CDI experienced mild-to-moderate disease, and prompt treatment with vancomycin was highly effective, which seems to reduce the serious complication risks.
Collapse
|
|
29
|
Barber GE, Hendler S, Okafor P, Limsui D, Limketkai BN. Rising Incidence of Intestinal Infections in Inflammatory Bowel Disease: A Nationwide Analysis. Inflamm Bowel Dis 2018; 24:1849-1856. [PMID: 29722832 DOI: 10.1093/ibd/izy086] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/10/2017] [Indexed: 12/18/2022]
Abstract
BACKGROUND Intestinal infections are common in patients with inflammatory bowel disease (IBD) and may mimic IBD flares. In this study, we estimate the changing incidence of intestinal infections among IBD hospitalizations and assess the impact of intestinal infections on key hospitalization metrics. METHODS The National Inpatient Sample (NIS) was analyzed for hospitalizations from IBD between 1998 and 2014. Intestinal infections were identified using ICD-9-CM codes, and incidence for each infection was calculated for Crohn's disease (CD) and ulcerative colitis (UC). Linear and logistic regression analyses were used to assess the effects of intestinal infections on hospitalization duration, charges, and mortality. RESULTS There were 4,030,620 hospitalizations for IBD between 1998 and 2014. The annual incidence of intestinal infections rose from 26.2 to 70.6 infections per 1000 IBD hospitalizations (Ptrend < 0.01). A main driver of this rising incidence was Clostridium difficile infections, which increased from 7.8 to 32.1 per 1000 CD hospitalizations and from 23.0 to 84.7 per 1000 UC hospitalizations (Ptrend < 0.01). The incidence of other intestinal infections increased from 10.2 to 15.3 per 1000 CD hospitalizations and 16.5 to 25.3 per 1000 UC hospitalizations. Intestinal infections and particularly C. difficile infections were associated with longer hospitalizations, greater hospital charges, and greater all-cause mortality. CONCLUSIONS The incidence of intestinal infections among hospitalized IBD patients has increased over the past 15 years, primarily driven by C. difficile infections. Intestinal infections are associated with length of stay, hospital charges, and all-cause mortality. More aggressive measures for prevention of C. difficile infections are needed. 10.1093/ibd/izy086_video1izy086.video15779257979001.
Collapse
Affiliation(s)
- Grant E Barber
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Palo Alto, California
| | - Steven Hendler
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Palo Alto, California
| | - Philip Okafor
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Palo Alto, California
| | - David Limsui
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Palo Alto, California
| | - Berkeley N Limketkai
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Palo Alto, California
| |
Collapse
|
|
30
|
Metronidazole or Rifaximin for Treatment of Clostridium difficile in Pediatric Patients with Inflammatory Bowel Disease: A Randomized Clinical Trial. Inflamm Bowel Dis 2017; 23:2209-2214. [PMID: 29084080 DOI: 10.1097/mib.0000000000001249] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Abstract
BACKGROUND Interestingly, Clostridium difficile infection (CDI) worsens the course of inflammatory bowel disease (IBD); however, there is a paucity of data regarding the treatment of CDI in this group of patients. METHODS This was a prospective, single-blind trial. Children with flare of IBD and CDI were randomly assigned to receive metronidazole or rifaximin orally for 14 days. CDI was diagnosed based on a positive well-type enzyme immunoassay (EIA) toxins A/B stool test for C. difficile toxins A and/or B. The cure rate was defined as the percentage of patients with a negative EIA stool test for C. difficile toxins A/B measured 4 weeks after the end of treatment. Recurrence was defined as a repeat CDI within 2 to 8 weeks. RESULTS In total, we included 31 patients with IBD including 12 patients with Crohn's disease and 19 with ulcerative colitis. Of them, 17 received metronidazole and 14 received rifaximin. There were no statistically significant differences between the 2 study groups including age, type of treatment, and disease activity. There was no statistically significant difference in the cure rate between patients treated with metronidazole and rifaximin (70.6% versus 78.6%, respectively, P = 0.5). We found no difference in recurrence rate between the 2 study treatment types (17% versus 0%, respectively, P = 0.3). We did not find an association between immunosuppressive therapy and CDI cure rate or CDI recurrence rate. CONCLUSIONS Metronidazole and rifaximin were similarly effective treatments for CDI in pediatric patients with IBD.
Collapse
|
|
31
|
Lasting Impact of Clostridium difficile Infection in Inflammatory Bowel Disease: A Propensity Score Matched Analysis. Inflamm Bowel Dis 2017; 23:2180-2188. [PMID: 29084081 PMCID: PMC5685936 DOI: 10.1097/mib.0000000000001251] [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] [Indexed: 02/06/2023]
Abstract
BACKGROUND Patients with inflammatory bowel disease are at an increased risk of Clostridium difficile infection (CDI), but the impact of CDI on disease severity is unclear. The aim of this study was to determine the effect of CDI on long-term disease outcome in a matched cohort of patients with inflammatory bowel disease. METHODS Patients who tested positive for infection formed the CDI-positive group. We generated a 1:2 propensity matched case to control cohort based on risk factors for CDI in the year before infection. Health care utilization data (emergency department use, hospitalizations, and telephone encounters), medications, laboratories, disease activity, and quality-of-life metrics were compared by CDI status. RESULTS A total of 198 patients (66 CDI and 132 matched controls) were included (56.6% women; 60.1% Crohn's disease, and 39.9% ulcerative colitis). In the year of infection, having CDI was significantly associated with more steroid and antibiotic exposure, elevated C-reactive protein or erythrocyte sedimentation rate, low vitamin D, increased disease activity, worse quality of life, and increased health care utilization (all P < 0.01). During the next year after infection, patients with CDI continued to have increased exposure to CDI-targeted antibiotics (P < 0.001) and other antibiotics (P = 0.02). They also continued to have more clinic visits (P = 0.02), telephone encounters (P = 0.001), and increased health care financial charges (P = 0.001). CONCLUSIONS CDI in inflammatory bowel disease is significantly associated with markers of disease severity, increased health care utilization and poor quality of life during the year of infection, and a 5-fold increase in health care charges in the year after infection (see Video Abstract, Supplemental Digital Content, http://links.lww.com/IBD/B658).
Collapse
|
|
32
|
Nelson A, Tsai HH. Editorial: Clostridium difficile and inflammatory bowel disease - is it always a bad combination? Aliment Pharmacol Ther 2017; 45:1368-1369. [PMID: 28417498 DOI: 10.1111/apt.14039] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/08/2022]
Affiliation(s)
- A Nelson
- Inflammatory Bowel Diseases Unit, Department of Gastroenterology, Castle Hill Hospital, Cottingham, UK
| | - H H Tsai
- Inflammatory Bowel Diseases Unit, Department of Gastroenterology, Castle Hill Hospital, Cottingham, UK
| |
Collapse
|