|
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
|
Cushing-Damm KC, Chen Y, Du X, Kuppa A, Raut C, Oliveri A, Chen VL, Vanderwerff B, Zawistowski M, Rao K, Higgins P, Speliotes EK. Genetic insight into the relationship between inflammatory bowel disease and Clostridioides difficile infection. mSphere 2024; 9:e0056724. [PMID: 39436105 PMCID: PMC11580397 DOI: 10.1128/msphere.00567-24] [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: 07/05/2024] [Accepted: 09/24/2024] [Indexed: 10/23/2024] Open
Abstract
Patients with inflammatory bowel disease (IBD) are at increased risk of Clostridioides difficile infection (CDI). Herein, we aimed to determine if genetic risk contributes to this observed association. We carried out a genome-wide association study (GWAS) analysis in the Michigan Genomics Initiative and the United Kingdom Biobank for CDI based on ICD codes and meta-analyzed these results with similar publicly accessible GWAS summary statistics from Finngen. Conditional and joint multi-SNP analyses were used to identify independent associations. Imputation of the human leukocyte antigen (HLA) region with fine mapping was used to try to identify causal HLA allele groups. Two-sample bidirectional Mendelian randomization (MR) was implemented to determine causal relationships between IBD and CDI. A total of 3,500 cases of CDI and 674,323 controls were meta-analyzed, revealing one genome-wide significant variant for CDI, HLA-C;LINC02571-rs3134745-C (P = 4.27E-08), which annotated to the major histocompatibility complex on chromosome 6. While fine mapping did not identify a statistically significant HLA allele group, there was a suggestive signal for HLA-B*35:01 (P = 4.74e-04). Using two-sample MR, genetically predicted IBD was associated with increased risk of CDI (MR Egger [odds ratio {OR} 1.16, 95% confidence interval {CI} 1.02-1.31]). Subset analysis revealed that risk was primarily driven by genetically predicted ulcerative colitis (MR Egger [OR 1.22, 95% CI 1.05-1.41]). These results highlight the importance of the host immune response in CDI pathogenesis, help explain the observed relationship between IBD and CDI, and open new avenues for targeted treatment of CDI in IBD.IMPORTANCEData from this paper (i) provide reproducible evidence that susceptibility CDI is genetically mediated, (ii) highlight genetic risk as a mechanism for the increased risk of CDI in patients with inflammatory bowel disease, and (iii) point toward anti-interleukin-23 therapy as a common therapeutic strategy.
Collapse
Affiliation(s)
- Kelly C. Cushing-Damm
- Department of Internal Medicine, Division of Gastroenterology, University of Michigan, Ann Arbor, Michigan, USA
| | - Yanhua Chen
- Department of Internal Medicine, Division of Gastroenterology, University of Michigan, Ann Arbor, Michigan, USA
| | - Xiaomeng Du
- Department of Internal Medicine, Division of Gastroenterology, University of Michigan, Ann Arbor, Michigan, USA
| | - Annapurna Kuppa
- Department of Internal Medicine, Division of Cardiology, University of Michigan, Ann Arbor, Michigan, USA
| | - Chinmay Raut
- Department of Internal Medicine, Division of Gastroenterology, University of Michigan, Ann Arbor, Michigan, USA
| | - Antonino Oliveri
- Department of Internal Medicine, Division of Gastroenterology, University of Michigan, Ann Arbor, Michigan, USA
| | - Vincent L. Chen
- Department of Internal Medicine, Division of Gastroenterology, University of Michigan, Ann Arbor, Michigan, USA
| | - Brett Vanderwerff
- Department of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, Michigan, USA
| | - Matt Zawistowski
- Department of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, Michigan, USA
| | - Krishna Rao
- Department of Internal Medicine, Division of Infectious Diseases, University of Michigan, Ann Arbor, Michigan, USA
| | - Peter Higgins
- Department of Internal Medicine, Division of Gastroenterology, University of Michigan, Ann Arbor, Michigan, USA
| | - Elizabeth K. Speliotes
- Department of Internal Medicine, Division of Gastroenterology, University of Michigan, Ann Arbor, Michigan, USA
- Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, Michigan, USA
| |
Collapse
|
|
3
|
Jacob R, Chu V, Ng W, Williams AJ, Connor S. Treatment outcomes of mild to moderate Clostridioides difficile infection in inflammatory bowel disease: an Australian experience. Intern Med J 2024. [PMID: 39422325 DOI: 10.1111/imj.16545] [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: 04/28/2024] [Accepted: 09/25/2024] [Indexed: 10/19/2024]
Abstract
BACKGROUND The incidence of Clostridioides difficile infection (CDI) in inflammatory bowel disease (IBD) is rising and associated with adverse outcomes. Optimal treatment for CDI in IBD remains unknown, with various organisations suggesting vancomycin as first-line therapy. AIM To compare treatment outcomes for metronidazole versus vancomycin in mild to moderate CDI in IBD. METHODS A retrospective analysis of IBD patients with CDI between January 2015 and December 2019 was conducted. Laboratory data and clinical outcomes were examined. RESULTS Forty-seven discrete episodes of CDI in 34 patients occurred during the study period. Fifty-three per cent (18) had Crohn's disease, 44% (15) ulcerative colitis and 3% (1) IBD unclassified. Six per cent (3/47) of CDI cases were severe and excluded. In 68% (30/44) of mild to moderate CDI, metronidazole was prescribed, with treatment failure in 20% (6/30), CDI recurrence in 13% (4/30) and 20% (6/30) experiencing a further CDI episode. Comparatively, vancomycin was prescribed in 23% (10/44) without any treatment failures; however, 10% (1/10) had CDI recurrence and 40% (4/10) experienced another CDI episode. No statistically significant difference was noted between metronidazole and vancomycin therapy for treatment failure (P = 0.31), CDI recurrence (P = 1.0) or further CDI episodes (P = 0.23). Proton-pump inhibitor therapy was the only risk factor associated with a higher rate of the composite outcome and remained significant on multivariate logistic regression (odds ratio 12.99 (95% confidence interval = 1.21-139.97), P = 0.03). CONCLUSION Metronidazole compared to vancomycin for treatment of mild to moderate CDI in IBD is effective however may be associated with higher rates of treatment failure.
Collapse
Affiliation(s)
- Rachael Jacob
- Department of Gastroenterology & Hepatology, Liverpool Hospital, Sydney, New South Wales, Australia
| | | | - Watson Ng
- Department of Gastroenterology & Hepatology, Liverpool Hospital, Sydney, New South Wales, Australia
| | - Astrid-Jane Williams
- Department of Gastroenterology & Hepatology, Liverpool Hospital, Sydney, New South Wales, Australia
- South Western Sydney Clinical School, University of New South Wales, Sydney, New South Wales, Australia
| | - Susan Connor
- Department of Gastroenterology & Hepatology, Liverpool Hospital, Sydney, New South Wales, Australia
- South Western Sydney Clinical School, University of New South Wales, Sydney, New South Wales, Australia
- The Ingham Institute for Applied Medical Research, Sydney, New South Wales, Australia
| |
Collapse
|
|
4
|
Muñiz Pedrogo DA, Sears CL, Melia JMP. Colorectal Cancer in Inflammatory Bowel Disease: A Review of the Role of Gut Microbiota and Bacterial Biofilms in Disease Pathogenesis. J Crohns Colitis 2024; 18:1713-1725. [PMID: 38703073 DOI: 10.1093/ecco-jcc/jjae061] [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: 11/17/2023] [Revised: 01/31/2024] [Accepted: 05/03/2024] [Indexed: 05/06/2024]
Abstract
The risk of colorectal cancer [CRC] is increased in patients with inflammatory bowel disease [IBD], particularly in extensive ulcerative colitis [UC] and Crohn's colitis. Gut microbiota have been implicated in the pathogenesis of CRC via multiple mechanisms, including the release of reactive oxygen species and genotoxins, and induction of inflammation, as well as activation of the immune response. Gut microbiota can enhance their carcinogenic and proinflammatory properties by organising into biofilms, potentially making them more resistant to the host's immune system and to antibiotics. Colonic biofilms have the capacity to invade colonic tissue and accelerate tumorigenesis in tumour-prone models of mice. In the context of IBD, the prevalence of biofilms has been estimated to be up to 95%. Although the relationship between chronic inflammation and molecular mediators that contribute to IBD-associated CRC is well established, the role of gut microbiota and biofilms in this sequence is not fully understood. Because CRC can still arise in the absence of histological inflammation, there is a growing interest in identifying chemopreventive agents against IBD-associated CRC. Commonly used in the treatment of UC, 5-aminosalicylates have antimicrobial and anticarcinogenic properties that might have a role in the chemoprevention of CRC via the inhibition or modulation of carcinogenic gut microbiota and potentially of biofilm formation. Whether biologics and other IBD-targeted therapies can decrease the progression towards dysplasia and CRC, via mechanisms independent of inflammation, is still unknown. Further research is warranted to identify potential new microbial targets in therapy for chemoprevention of dysplasia and CRC in IBD.
Collapse
Affiliation(s)
- David A Muñiz Pedrogo
- Division of Gastroenterology and Hepatology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Cynthia L Sears
- Division of Infectious Diseases, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA
- Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Joanna M P Melia
- Division of Gastroenterology and Hepatology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| |
Collapse
|
|
5
|
Di Bella S, Sanson G, Monticelli J, Zerbato V, Principe L, Giuffrè M, Pipitone G, Luzzati R. Clostridioides difficile infection: history, epidemiology, risk factors, prevention, clinical manifestations, treatment, and future options. Clin Microbiol Rev 2024; 37:e0013523. [PMID: 38421181 PMCID: PMC11324037 DOI: 10.1128/cmr.00135-23] [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: 03/02/2024] Open
Abstract
SUMMARYClostridioides difficile infection (CDI) is one of the major issues in nosocomial infections. This bacterium is constantly evolving and poses complex challenges for clinicians, often encountered in real-life scenarios. In the face of CDI, we are increasingly equipped with new therapeutic strategies, such as monoclonal antibodies and live biotherapeutic products, which need to be thoroughly understood to fully harness their benefits. Moreover, interesting options are currently under study for the future, including bacteriophages, vaccines, and antibiotic inhibitors. Surveillance and prevention strategies continue to play a pivotal role in limiting the spread of the infection. In this review, we aim to provide the reader with a comprehensive overview of epidemiological aspects, predisposing factors, clinical manifestations, diagnostic tools, and current and future prophylactic and therapeutic options for C. difficile infection.
Collapse
Affiliation(s)
- Stefano Di Bella
- Clinical Department of
Medical, Surgical and Health Sciences, Trieste
University, Trieste,
Italy
| | - Gianfranco Sanson
- Clinical Department of
Medical, Surgical and Health Sciences, Trieste
University, Trieste,
Italy
| | - Jacopo Monticelli
- Infectious Diseases
Unit, Trieste University Hospital
(ASUGI), Trieste,
Italy
| | - Verena Zerbato
- Infectious Diseases
Unit, Trieste University Hospital
(ASUGI), Trieste,
Italy
| | - Luigi Principe
- Microbiology and
Virology Unit, Great Metropolitan Hospital
“Bianchi-Melacrino-Morelli”,
Reggio Calabria, Italy
| | - Mauro Giuffrè
- Clinical Department of
Medical, Surgical and Health Sciences, Trieste
University, Trieste,
Italy
- Department of Internal
Medicine (Digestive Diseases), Yale School of Medicine, Yale
University, New Haven,
Connecticut, USA
| | - Giuseppe Pipitone
- Infectious Diseases
Unit, ARNAS Civico-Di Cristina
Hospital, Palermo,
Italy
| | - Roberto Luzzati
- Clinical Department of
Medical, Surgical and Health Sciences, Trieste
University, Trieste,
Italy
| |
Collapse
|
|
6
|
Kelly CR, Allegretti JR. Review Article: Gastroenterology and Clostridium difficile Infection: Past, Present, and Future. Clin Infect Dis 2023; 77:S463-S470. [PMID: 38051967 DOI: 10.1093/cid/ciad644] [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: 12/07/2023] Open
Abstract
Research and innovation around Clostridium difficile infection (CDI) has been a multidisciplinary endeavor since discovery of the organism in 1978. The field of gastroenterology has contributed to our understanding of CDI as a disease caused by disruptions in the gut microbiome and led to advances in therapeutic manipulation of gut microbiota, including fecal microbiota transplantation. The high incidence of CDI in patients with inflammatory bowel disease and treatment of the infection in this population have been of particular interest to gastroenterologists. The emergence of standardized, approved live biotherapeutic products for treatment of recurrent CDI is an inflection point in our management of this difficult clinical problem, and real-world performance of these therapies will inform optimal treatment algorithms.
Collapse
Affiliation(s)
- Colleen R Kelly
- Harvard Medical School, Boston, Massachusetts, USA
- Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA
| | - Jessica R Allegretti
- Harvard Medical School, Boston, Massachusetts, USA
- Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA
| |
Collapse
|
|
7
|
Wu R, Xiong R, Li Y, Chen J, Yan R. Gut microbiome, metabolome, host immunity associated with inflammatory bowel disease and intervention of fecal microbiota transplantation. J Autoimmun 2023; 141:103062. [PMID: 37246133 DOI: 10.1016/j.jaut.2023.103062] [Citation(s) in RCA: 19] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2023] [Revised: 05/05/2023] [Accepted: 05/08/2023] [Indexed: 05/30/2023]
Abstract
Gut dysbiosis has been associated with inflammatory bowel disease (IBD), one of the most common gastrointestinal diseases. The microbial communities play essential roles in host physiology, with profound effects on immune homeostasis, directly or via their metabolites and/or components. There are increasing clinical trials applying fecal microbiota transplantation (FMT) with Crohn's disease (CD) and ulcerative colitis (UC). The restoration of dysbiotic gut microbiome is considered as one of the mechanisms of FMT therapy. In this work, latest advances in the alterations in gut microbiome and metabolome features in IBD patients and experimental mechanistic understanding on their contribution to the immune dysfunction were reviewed. Then, the therapeutic outcomes of FMT on IBD were summarized based on clinical remission, endoscopic remission and histological remission of 27 clinical trials retrieved from PubMed which have been registered on ClinicalTrials.gov with the results been published in the past 10 years. Although FMT is established as an effective therapy for both subtypes of IBD, the promising outcomes are not always achieved. Among the 27 studies, only 11 studies performed gut microbiome profiling, 5 reported immune response alterations and 3 carried out metabolome analysis. Generally, FMT partially restored typical changes in IBD, resulted in increased α-diversity and species richness in responders and similar but less pronounced shifts of patient microbial and metabolomics profiles toward donor profiles. Measurements of immune responses to FMT mainly focused on T cells and revealed divergent effects on pro-/anti-inflammatory functions. The very limited information and the extremely confounding factors in the designs of the FMT trials significantly hindered a reasonable conclusion on the mechanistic involvement of gut microbiota and metabolites in clinical outcomes and an analysis of the inconsistencies.
Collapse
Affiliation(s)
- Rongrong Wu
- State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macao, China.
| | - Rui Xiong
- State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macao, China.
| | - Yan Li
- State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macao, China.
| | - Junru Chen
- State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macao, China.
| | - Ru Yan
- State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macao, China.
| |
Collapse
|
|
8
|
Porcari S, Baunwall SMD, Occhionero AS, Ingrosso MR, Ford AC, Hvas CL, Gasbarrini A, Cammarota G, Ianiro G. Fecal microbiota transplantation for recurrent C. difficile infection in patients with inflammatory bowel disease: A systematic review and meta-analysis. J Autoimmun 2023; 141:103036. [PMID: 37098448 DOI: 10.1016/j.jaut.2023.103036] [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] [Received: 01/17/2023] [Revised: 03/26/2023] [Accepted: 04/04/2023] [Indexed: 04/27/2023]
Abstract
Fecal microbiota transplantation (FMT) is known to be highly effective in patients with recurrent Clostridioides difficile infection (rCDI), but its role in patients who also suffer from inflammatory bowel disease (IBD) is unclear. Therefore, we performed a systematic review and meta-analysis to evaluate the efficacy and safety of FMT for the treatment of rCDI in patients with IBD. We searched the available literature until November 22, 2022 to identify studies that included patients with IBD treated with FMT for rCDI, reporting efficacy outcomes after at least 8 weeks of follow-up. The proportional effect of FMT was summarized with a generalized linear mixed-effect model fitting a logistic regression accounting for different intercepts among studies. We identified 15 eligible studies, containing 777 patients. Overall, FMT achieved high cure rates of rCDI, 81% for single FMT, based on all included studies and patients, and 92% for overall FMT, based on nine studies with 354 patients, respectively. We found a significant advantage of overall FMT over single FMT in improving cure rates of rCDI (from 80% to 92%, p = 0.0015). Serious adverse events were observed in 91 patients (12% of the overall population), with the most common being hospitalisation, IBD-related surgery, or IBD flare. In conclusion, in our meta-analysis FMT achieved high cure rates of rCDI in patients with IBD, with a significant advantage of overall FMT over single FMT, similar to data observed in patients without IBD. Our findings support the use of FMT as a treatment for rCDI in patients with IBD.
Collapse
Affiliation(s)
- Serena Porcari
- Department of Medical and Surgical Sciences, Gastroenterology Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy; Department of Translational Medicine and Surgery, Università Cattolica del Sacro Cuore, Rome, Italy
| | | | - Annamaria Sara Occhionero
- Department of Medical and Surgical Sciences, Gastroenterology Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy; Department of Translational Medicine and Surgery, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Maria Rosa Ingrosso
- Department of Medical and Surgical Sciences, Gastroenterology Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy; Department of Translational Medicine and Surgery, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Alexander Charles Ford
- Leeds Institute of Medical Research at St. James's, University of Leeds, Leeds, UK; Leeds Gastroenterology Institute, Leeds Teaching Hospitals NHS Trust, Leeds, UK
| | - Christian Lodberg Hvas
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark
| | - Antonio Gasbarrini
- Department of Medical and Surgical Sciences, Gastroenterology Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy; Department of Translational Medicine and Surgery, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Giovanni Cammarota
- Department of Medical and Surgical Sciences, Gastroenterology Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy; Department of Translational Medicine and Surgery, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Gianluca Ianiro
- Department of Medical and Surgical Sciences, Gastroenterology Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy; Department of Translational Medicine and Surgery, Università Cattolica del Sacro Cuore, Rome, Italy.
| |
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
|
Mundhra S, Thomas D, Jain S, Sahu P, Vuyyuru S, Kumar P, Kante B, Panwar R, Sahni P, Chaudhry R, Das P, Makharia G, Kedia S, Ahuja V. Low prevalence of Clostridioides difficile infection in acute severe ulcerative colitis: A retrospective cohort study from northern India. Indian J Gastroenterol 2023; 42:411-417. [PMID: 37171781 DOI: 10.1007/s12664-022-01336-2] [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: 08/09/2022] [Accepted: 12/25/2022] [Indexed: 05/13/2023]
Abstract
BACKGROUND The incidence of Clostridioides difficile infection (CDI) is high in ulcerative colitis and is associated with disease flares and adverse outcomes. However, the data on the dynamics of CDI in patients with acute severe ulcerative colitis (ASUC) is rather scarce. We evaluated the prevalence of CDI in patients with ASUC. METHODS This retrospective analysis of a prospectively maintained cohort admitted to the All India Institute of Medical Sciences, India, from May 2016 to December 2021, included patients with ASUC (as per Truelove and Witts criteria) who were tested for CDI. CDI testing was performed using enzyme-linked immunoassay for toxins A and B. Risk factors for developing CDI were analyzed along with short-term outcomes of ASUC. Steroid failure was defined as the need for medical rescue therapy or colectomy. RESULTS Total 153 patients with ASUC were included (mean age 34.92 ± 12.24 years; males 56.2%; disease duration 36 (IQR: 16-55.5) months, pancolitis 67.3%). Ninety-eight (63.4%), 72 (47%) and 10 (6.5%) patients, respectively, had received steroids, azathioprine and biologics in the past. Forty patients (26.14%) had a prior history of ASUC. Among risk factors for CDI, 14% of the patients had prior admission within 30 days, 22.2% had a recent history of antibiotics and 3.9% had long-term non-steroidal anti-inflammatory drug intake. Only one sample was positive for Clostridioides difficile toxin assay. Tissue Cytomegalovirus DNA-PCR positivity was noted in 57 patients (37.3%). Fifty-seven patients (37.3%) had steroid failure, 35 required medical rescue therapy and 30 (19.6%) required colectomy (eight after medical rescue therapy failure). CONCLUSION Despite antecedent risk factors for CDI, the overall prevalence of CDI in ASUC was low and the outcomes were determined by underlying disease severity.
Collapse
Affiliation(s)
- Sandeep Mundhra
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, 110 029, India
| | - David Thomas
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, 110 029, India
| | - Saransh Jain
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, 110 029, India
| | - Pabitra Sahu
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, 110 029, India
| | - Sudheer Vuyyuru
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, 110 029, India
| | - Peeyush Kumar
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, 110 029, India
| | - Bhaskar Kante
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, 110 029, India
| | - Rajesh Panwar
- Department of GI Surgery, All India Institute of Medical Sciences, New Delhi, 110 029, India
| | - Peush Sahni
- Department of GI Surgery, All India Institute of Medical Sciences, New Delhi, 110 029, India
| | - Rama Chaudhry
- Department of Microbiology, All India Institute of Medical Sciences, New Delhi, 110 029, India
| | - Prasenjit Das
- Department of Pathology, All India Institute of Medical Sciences, New Delhi, 110 029, India
| | - Govind Makharia
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, 110 029, India
| | - Saurabh Kedia
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, 110 029, India
| | - Vineet Ahuja
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, 110 029, India.
| |
Collapse
|
|
11
|
Drozdinsky G, Atamna A, Banai H, Ben-Zvi H, Bishara J, Eliakim-Raz N. Clinical outcomes for Clostridioides difficile associated diarrhea in inflammatory bowel disease patients versus non-IBD population: A retrospective cohort study. Medicine (Baltimore) 2023; 102:e32812. [PMID: 36820599 PMCID: PMC9907955 DOI: 10.1097/md.0000000000032812] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/28/2022] [Revised: 01/06/2023] [Accepted: 01/10/2023] [Indexed: 02/12/2023] Open
Abstract
Patients with inflammatory bowel disease (IBD) have a higher incidence of Clostridioides difficile infection (CDI). Previous studies have demonstrated negative clinical outcomes in IBD patients with CDI compared to patients without CDI. The clinical presentation of CDI is indistinguishable from IBD exacerbation, thus posing a frequent clinical dilemma on the role of Clostridioides infection in the testing, diagnosis, and treatment of these patients. To compare clinical outcomes of CDI in patients with IBD to those without IBD. Retrospective cohort of adult patients admitted to Rabin Medical Center Israel between the years 2014 and 2020 with a concurrent diagnosis of IBD and CDI. Matching 1:2 was performed between the IBD patients and the non-IBD population with respect to age and sex. Sixty-seven patients with IBD and 134 patients without IBD were included in the study. The groups' median age was 40.6 (interquartile range [IQR] of 29.8-68.9), with 45.8% male and 54.2% female. The non-IBD group had a higher Charlson score with 2 (IQR 0; 5) versus 0 (IQR 0; 4) in the IBD group (P value <.01). Patients with IBD had more exposure to systemic antibiotics, 71.1% versus 26.3% (P value <.01). In a multivariable analysis we found no difference in 90-day mortality and rate of relapse between the 2 study groups with an odds ratio of 1.709 (95% confidence interval 0.321-9.905) and odds ratio of 0.209 (95% confidence interval 0.055-1.513) respectively. In our cohort patients with IBD who present with diarrhea and concomitant CDI have similar rates of relapse and mortality compared with patients without IBD.
Collapse
Affiliation(s)
- Genady Drozdinsky
- Internal Medicine E, Rabin Medical Center Beilinson Campus, Petah-Tikva, Israel
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Alaa Atamna
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
- Infectious Diseases Unit, Rabin Medical Center, Beilinson Hospital, Petah-Tikva, Israel
| | - Hagar Banai
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
- Gastroenterology Unit, Rabin Medical Center, Beilinson Hospital, Petah-Tikva, Israel
| | - Haim Ben-Zvi
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
- Department of Clinical Microbiology, Rabin Medical Center, Beilinson Hospital, Petah-Tikva, Israel
| | - Jihad Bishara
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
- Infectious Diseases Unit, Rabin Medical Center, Beilinson Hospital, Petah-Tikva, Israel
| | - Noa Eliakim-Raz
- Internal Medicine E, Rabin Medical Center Beilinson Campus, Petah-Tikva, Israel
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
- Infectious Diseases Unit, Rabin Medical Center, Beilinson Hospital, Petah-Tikva, Israel
| |
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
|
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.
Collapse
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
| |
Collapse
|
|
14
|
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.
Collapse
|
|
15
|
Zhang L, Liu F, Xue J, Lee SA, Liu L, Riordan SM. Bacterial Species Associated With Human Inflammatory Bowel Disease and Their Pathogenic Mechanisms. Front Microbiol 2022; 13:801892. [PMID: 35283816 PMCID: PMC8908260 DOI: 10.3389/fmicb.2022.801892] [Citation(s) in RCA: 23] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2021] [Accepted: 01/25/2022] [Indexed: 12/17/2022] Open
Abstract
Inflammatory bowel disease (IBD) is a chronic inflammatory condition of the gastrointestinal tract with unknown etiology. The pathogenesis of IBD results from immune responses to microbes in the gastrointestinal tract. Various bacterial species that are associated with human IBD have been identified. However, the microbes that trigger the development of human IBD are still not clear. Here we review bacterial species that are associated with human IBD and their pathogenic mechanisms to provide an updated broad understanding of this research field. IBD is an inflammatory syndrome rather than a single disease. We propose a three-stage pathogenesis model to illustrate the roles of different IBD-associated bacterial species and gut commensal bacteria in the development of human IBD. Finally, we recommend microbe-targeted therapeutic strategies based on the three-stage pathogenesis model.
Collapse
Affiliation(s)
- Li Zhang
- School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, NSW, Australia
- *Correspondence: Li Zhang,
| | - Fang Liu
- School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, NSW, Australia
| | - Jessica Xue
- Faculty of Medicine, Monash University, Melbourne, VIC, Australia
| | - Seul A. Lee
- School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, NSW, Australia
| | - Lu Liu
- School of Medical Sciences, University of New South Wales, Sydney, NSW, Australia
| | - Stephen M. Riordan
- Gastrointestinal and Liver Unit, Prince of Wales Hospital, University of New South Wales, Sydney, NSW, Australia
| |
Collapse
|
|
16
|
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.
Collapse
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
| | | | | | | | | |
Collapse
|
|
17
|
Rabinowitz LG, Gold SL, Maser EA. Management of Hospitalized Patient with Ulcerative Colitis Refractory to Corticosteroids. MANAGEMENT OF INPATIENT INFLAMMATORY BOWEL DISEASE 2022:31-67. [DOI: 10.1007/978-1-0716-1987-2_3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
|
|
18
|
Hong S, Zaki TA, Main M, Hine AM, Chang S, Hudesman D, Axelrad JE. Comparative Evaluation of Conventional Stool Testing and Multiplex Molecular Panel in Outpatients With Relapse of Inflammatory Bowel Disease. Inflamm Bowel Dis 2021; 27:1634-1640. [PMID: 33386740 PMCID: PMC9115373 DOI: 10.1093/ibd/izaa336] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/28/2020] [Indexed: 12/15/2022]
Abstract
BACKGROUND Differentiating between enteric infection and relapse of inflammatory bowel disease (IBD) is a common clinical challenge. Few studies have evaluated the impact of multiplex gastrointestinal polymerase chain reaction (GI PCR) pathogen panels on clinical practice compared to stool culture. Our aim was to compare the impact of PCR stool testing to conventional stool testing in outpatients presenting with relapse of IBD. METHODS In a retrospective cohort study of outpatients with IBD presenting to NYU Langone Health with flare from September 2015 to April 2019, we compared patients who underwent stool testing with GI PCR to age-, sex-, and IBD-subtype-matched patients who underwent culture and ova and parasite exam (conventional testing). The primary outcome was IBD therapy escalation after testing. Secondary outcomes included rates of posttesting endoscopy, abdominal radiography, antibiotics, and IBD-related emergency department visits, hospitalizations, and abdominal surgeries. RESULTS We identified 134 patients who underwent GI PCR matched to 134 patients who underwent conventional testing. Pathogens were more frequently identified on GI PCR (26 vs 5%; P < 0.01). We found that GI PCR was associated with less escalation in IBD therapy (16 vs 29%; P < 0.01) and fewer posttest endoscopies (10% vs 18%; P = 0.04), with no differences in IBD outcomes. On multivariate analysis, testing with GI PCR was associated with an odds ratio of 0.26 (95% confidence interval, 0.08-0.84; P = 0.02) for escalation of IBD therapies. CONCLUSIONS Testing with GI PCR was associated with higher rates of pathogen detection and lower rates of IBD therapy escalation and endoscopy in the outpatient setting. These changes in management were not associated with a difference in IBD outcomes.
Collapse
Affiliation(s)
- Soonwook Hong
- Department of Medicine, NYU Langone Health, New York, New York, New York, USA
- Address correspondence to: Soonwook Hong, MD, Department of Medicine, NYU Langone Health, 555 First Ave., New York, NY 10016, USA ()
| | - Timothy A Zaki
- Department of Medicine, UT Southwestern Medical Center, Dallas, Texas, USA
| | - Michael Main
- Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA
| | - Ashley M Hine
- Department of Medicine, University of Connecticut School of Medicine, Farmington, Connecticut, USA
| | - Shannon Chang
- Department of Gastroenterology, NYU Langone Health , New York, New York, USA
| | - David Hudesman
- Department of Gastroenterology, NYU Langone Health , New York, New York, USA
| | - Jordan E Axelrad
- Department of Gastroenterology, NYU Langone Health , New York, New York, USA
| |
Collapse
|
|
19
|
Houri H, Yadegar A, Zali MR. How Infection with C. difficile Infection Aggravates Inflammatory Bowel Disease: Is It CDI or the CDAI? Dig Dis Sci 2021; 66:2849-2850. [PMID: 33094453 DOI: 10.1007/s10620-020-06667-8] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 10/06/2020] [Indexed: 12/09/2022]
Affiliation(s)
- Hamidreza Houri
- Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Abbas Yadegar
- Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
| | - Mohammad Reza Zali
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| |
Collapse
|
|
20
|
Varma S, Faye AS, Kannan A, Lawlor G, Verma A, Axelrad J, Freedberg DE. Patients with More Severe IBD Get Clostridioides difficile Rather than Clostridioides difficile Increasing the Severity of IBD. Dig Dis Sci 2021; 66:3113-3123. [PMID: 32729015 DOI: 10.1007/s10620-020-06504-y] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/19/2020] [Accepted: 07/18/2020] [Indexed: 01/04/2023]
Abstract
BACKGROUND Inflammatory bowel disease (IBD) patients who have Clostridioides difficile infection (CDI) have worse outcomes. AIMS We aimed to determine whether such outcomes are the result of CDI or whether CDI occurs in patients who have more severe IBD. METHODS This was a retrospective study of patients hospitalized for ≥ 2 IBD flares from 2010 to 2019. The primary outcome was time to IBD flare between hospitalizations. First, time to flare was compared between patients who were hospitalized for a flare complicated by CDI and subsequently for a CDI-negative flare (cohort A, denoted +/-) versus patients who were hospitalized for two CDI-negative flares (cohort B, -/-). Second, time between flares was compared within the subset of cohort A patients who had three flares (cohort C, -/+/-) before and after CDI. RESULTS Time between flares was a median of 4 months (IQR 1-9) among 51 cohort A patients versus 12 months (IQR 6-38) among 51 cohort B patients (log-rank P < 0.01). In contrast, the median time between flares was similar within cohort C before and after CDI (log-rank P = 0.54). At time of the second IBD flare, patients in cohort A (+/-) were more likely to have moderate or severe disease compared to patients in cohort B (-/-). CONCLUSIONS Patients with prior CDI had shorter time to subsequent IBD flare relative to their CDI-negative counterparts. This is not likely due to CDI itself because there was no difference in time between flares before versus after acquiring CDI. Rather, patients who acquire CDI may have more severe IBD.
Collapse
Affiliation(s)
- Sanskriti Varma
- Department of Medicine, New York Presbyterian Columbia University Medical Center, 630 West 168th Street, New York, NY, 10032, USA.
| | - Adam S Faye
- Division of Digestive and Liver Diseases, Department of Medicine, College of Physicians and Surgeons, Columbia University, 622 West 168th Street, New York, NY, 10032, USA
| | - Adithya Kannan
- Vagelos College of Physicians and Surgeons, Columbia University, 630 West 168th Street, New York, NY, 10032, USA
| | - Garrett Lawlor
- Division of Digestive and Liver Diseases, Department of Medicine, College of Physicians and Surgeons, Columbia University, 622 West 168th Street, New York, NY, 10032, USA
| | - Abhishek Verma
- Department of Medicine, NYU Langone Health, 550 First Avenue, New York, NY, 10016, USA
| | - Jordan Axelrad
- Division of Gastroenterology and Hepatology, NYU School of Medicine, 550 First Avenue, New York, NY, 10016, USA
| | - Daniel E Freedberg
- Division of Digestive and Liver Diseases, Department of Medicine, College of Physicians and Surgeons, Columbia University, 622 West 168th Street, New York, NY, 10032, USA
| |
Collapse
|
|
21
|
Shrestha MP, Taleban S. Colectomy Rates Are Increasing Among Inpatients With Concomitant Ulcerative Colitis and Clostridioides difficile. J Clin Gastroenterol 2021; 55:709-715. [PMID: 32804686 DOI: 10.1097/mcg.0000000000001412] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/28/2020] [Accepted: 07/12/2020] [Indexed: 12/13/2022]
Abstract
BACKGROUND Clostridioides difficile infection (CDI) is an important cause of inflammatory bowel disease (IBD) exacerbation and is associated with increased risk of hospitalization, colectomy, and mortality. Previous analysis have reported an increasing rate of CDI and associated mortality in IBD patients. We examined the trends in CDI-associated outcomes in hospitalized patients with Crohn's disease (CD) and ulcerative colitis (UC) over the last decade. MATERIALS AND METHODS We used data from the National Inpatient Sample to identify patients hospitalized with both CDI and IBD from 2006 to 2014. Outcomes included in-hospital mortality, partial/total colectomy, hospital length of stay, and charges. Analysis included univariate and multivariate regression analysis. RESULTS Between 2006 and 2014, CDI-related hospitalizations increased in both CD (1.6% to 3.2%; P<0.001) and UC (4.9% to 8.6%; P<0.001). CDI-associated mortality in CD and UC patients decreased from 2.4% to 1.2% (P<0.001) and 11.3% to 9.7% (P<0.001), respectively. CDI-associated colectomy rate increased from 4.3% to 8.8% (P<0.001) in UC but decreased from 4.5% to 2.8% (P<0.001) in CD. In multivariable analysis, compared with 2006, there was a nonsignificant decrease in mortality in 2014 in both CD [adjusted odds ratio (AOR) 0.56, 95% confidence interval (CI) 0.25-1.24] and UC (AOR 0.81, 95% CI 0.61-1.07), but a significant increase in colectomy in 2014 only in UC (AOR 2.12, 95% CI 1.46-3.06). CONCLUSIONS CDI rates have increased in CD and UC over the last decade. Although there has been a significant increase in colectomies in UC, CDI-associated mortality in CD and UC has not increased over this time.
Collapse
Affiliation(s)
- Manish P Shrestha
- Division of Gastroenterology and Hepatology, University of New Mexico School of Medicine, Albuquerque, NM
| | - Sasha Taleban
- Division of Gastroenterology, University of Arizona College of Medicine
- Department of Medicine, Arizona Center of Aging, Tucson, AZ
| |
Collapse
|
|
22
|
Allegretti JR, Kelly CR, Grinspan A, Mullish BH, Hurtado J, Carrellas M, Marcus J, Marchesi JR, McDonald JAK, Gerardin Y, Silverstein M, Pechlivanis A, Barker GF, Miguens Blanco J, Alexander JL, Gallagher KI, Pettee W, Phelps E, Nemes S, Sagi SV, Bohm M, Kassam Z, Fischer M. Inflammatory Bowel Disease Outcomes Following Fecal Microbiota Transplantation for Recurrent C. difficile Infection. Inflamm Bowel Dis 2021; 27:1371-1378. [PMID: 33155639 PMCID: PMC8376126 DOI: 10.1093/ibd/izaa283] [Citation(s) in RCA: 28] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/02/2020] [Indexed: 12/11/2022]
Abstract
BACKGROUND Recurrent Clostridioides difficile infection (CDI) in patients with inflammatory bowel disease (IBD) is a clinical challenge. Fecal microbiota transplantation (FMT) has emerged as a recurrent CDI therapy. Anecdotal concerns exist regarding worsening of IBD activity; however, prospective data among IBD patients are limited. METHODS Secondary analysis from an open-label, prospective, multicenter cohort study among IBD patients with 2 or more CDI episodes was performed. Participants underwent a single FMT by colonoscopy (250 mL, healthy universal donor). Secondary IBD-related outcomes included rate of de novo IBD flares, worsening IBD, and IBD improvement-all based on Mayo or Harvey-Bradshaw index (HBI) scores. Stool samples were collected for microbiome and targeted metabolomic profiling. RESULTS Fifty patients enrolled in the study, among which 15 had Crohn's disease (mean HBI, 5.8 ± 3.4) and 35 had ulcerative colitis (mean partial Mayo score, 4.2 ± 2.1). Overall, 49 patients received treatment. Among the Crohn's disease cohort, 73.3% (11 of 15) had IBD improvement, and 4 (26.6%) had no disease activity change. Among the ulcerative colitis cohort, 62% (22 of 34) had IBD improvement, 29.4% (11 of 34) had no change, and 4% (1 of 34) experienced a de novo flare. Alpha diversity significantly increased post-FMT, and ulcerative colitis patients became more similar to the donor than Crohn's disease patients (P = 0.04). CONCLUSION This prospective trial assessing FMT in IBD-CDI patients suggests IBD outcomes are better than reported in retrospective studies.
Collapse
Affiliation(s)
- Jessica R Allegretti
- Division of Gastroenterology, Hepatology and Endoscopy, Brigham and Women’s Hospital, Boston, MA, USA
- Harvard Medical School, Boston, MA, USA
| | - Colleen R Kelly
- Division of Gastroenterology, Alpert Medical School of Brown University, Providence, RI, USA
| | - Ari Grinspan
- The Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Benjamin H Mullish
- Division of Digestive Diseases, Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, Imperial College London, London, UK
| | - Jonathan Hurtado
- Division of Gastroenterology, Hepatology and Endoscopy, Brigham and Women’s Hospital, Boston, MA, USA
| | - Madeline Carrellas
- Division of Gastroenterology, Hepatology and Endoscopy, Brigham and Women’s Hospital, Boston, MA, USA
| | - Jenna Marcus
- Division of Gastroenterology, Hepatology and Endoscopy, Brigham and Women’s Hospital, Boston, MA, USA
| | - Julian R Marchesi
- Division of Digestive Diseases, Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, Imperial College London, London, UK
- School of Biosciences, Cardiff University, Cardiff, UK
| | - Julie A K McDonald
- Division of Digestive Diseases, Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, Imperial College London, London, UK
- MRC Centre for Molecular Bacteriology and Infection, Imperial College London, London, UK
| | | | | | - Alexandros Pechlivanis
- Division of Digestive Diseases, Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, Imperial College London, London, UK
- Center for Interdisciplinary Research and Innovation, School of Chemistry, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Grace F Barker
- Division of Digestive Diseases, Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, Imperial College London, London, UK
| | - Jesus Miguens Blanco
- Division of Digestive Diseases, Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, Imperial College London, London, UK
| | - James L Alexander
- Division of Digestive Diseases, Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, Imperial College London, London, UK
| | - Kate I Gallagher
- Division of Digestive Diseases, Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, Imperial College London, London, UK
| | | | - Emmalee Phelps
- Division of Gastroenterology, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Sara Nemes
- Division of Gastroenterology, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Sashidhar V Sagi
- Division of Gastroenterology, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Matthew Bohm
- Division of Gastroenterology, Indiana University School of Medicine, Indianapolis, IN, USA
| | | | - Monika Fischer
- Division of Gastroenterology, Indiana University School of Medicine, Indianapolis, IN, USA
| |
Collapse
|
|
23
|
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
|
|
24
|
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.
Collapse
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
| | | |
Collapse
|
|
25
|
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: 32] [Impact Index Per Article: 8.0] [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.
Collapse
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
| |
Collapse
|
|
26
|
Khanna S. Management of Clostridioides difficile infection in patients with inflammatory bowel disease. Intest Res 2020; 19:265-274. [PMID: 32806873 PMCID: PMC8322030 DOI: 10.5217/ir.2020.00045] [Citation(s) in RCA: 27] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/05/2020] [Accepted: 05/25/2020] [Indexed: 12/13/2022] Open
Abstract
Inflammatory bowel disease (IBD) is a common diarrheal illness with gastrointestinal and extraintestinal manifestations and complications. The most common infectious complication associated with IBD is Clostridioides difficile infection (CDI). Active IBD predisposes to CDI due to alterations in the gut microbiome. C. difficile is a toxin producing bacterium leading to worsening of underlying IBD, increasing the risk of IBD treatment failure and an increased risk of hospitalization and surgery. Since the symptoms of CDI overlap with those of an IBD flare; it is prudent to recognize that the diagnosis of CDI is challenging and diagnostic tests (nucleic-acid and toxin-based assays) should be interpreted in context of symptoms and test performance. First line treatments for management of CDI in IBD include vancomycin or fidaxomicin. Recurrence prevention strategies should be implemented to mitigate recurrent CDI risk. One needs to monitor IBD disease progression and manage immunosuppression. The risk of recurrent CDI after a primary infection is higher in IBD compared to non-IBD patients. Microbiota restoration therapies are effective to prevent recurrent CDI in IBD patients. This review summarizes the epidemiology, pathophysiology, diagnostic testing, outcomes and management of both CDI and IBD, in CDI complicating IBD.
Collapse
Affiliation(s)
- Sahil Khanna
- C. difficile Clinic and Microbial Replacement Therapy Program, Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA
| |
Collapse
|
|
27
|
Gholam-Mostafaei FS, Yadegar A, Aghdaei HA, Azimirad M, Daryani NE, Zali MR. Anti-TNF containing regimens may be associated with increased risk of Clostridioides difficile infection in patients with underlying inflammatory bowel disease. Curr Res Transl Med 2020; 68:125-130. [DOI: 10.1016/j.retram.2020.03.002] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2019] [Revised: 03/22/2020] [Accepted: 03/26/2020] [Indexed: 01/01/2023]
|
|
28
|
Jakubczyk D, Leszczyńska K, Górska S. The Effectiveness of Probiotics in the Treatment of Inflammatory Bowel Disease (IBD)-A Critical Review. Nutrients 2020; 12:nu12071973. [PMID: 32630805 PMCID: PMC7400428 DOI: 10.3390/nu12071973] [Citation(s) in RCA: 181] [Impact Index Per Article: 36.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2020] [Revised: 06/19/2020] [Accepted: 06/30/2020] [Indexed: 12/17/2022] Open
Abstract
Inflammatory bowel disease (IBD), which affects millions of people worldwide, includes two separate diseases: Crohn's disease (CD) and ulcerative colitis (UC). Although the background (chronic inflammatory state) and some of the symptoms of CD and UC are similar, both diseases differ from each other. It is becoming clear that a combination of many factors, in particular genetic background, host immune response and microbial reduced diversity status are associated with IBD. One potential strategy to prevent/treat IBD is gut modulation by probiotics. Over the last twenty years, many publications have focused on the role of probiotics in the course of IBD. The review discusses the utility of different strains of probiotics, especially Bifidobacterium spp., in all factors potentially involved in the etiology of IBD. The probiotic modulatory properties among different study models (cell lines, animal models of colitis, clinical study) are discussed and probiotic usefulness is assessed in relation to the treatment, prevention, and remission of diseases.
Collapse
|
|
29
|
Lurienne L, Bandinelli PA, Galvain T, Coursel CA, Oneto C, Feuerstadt P. Perception of quality of life in people experiencing or having experienced a Clostridioides difficile infection: a US population survey. J Patient Rep Outcomes 2020; 4:14. [PMID: 32076853 PMCID: PMC7031450 DOI: 10.1186/s41687-020-0179-1] [Citation(s) in RCA: 30] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2019] [Accepted: 02/11/2020] [Indexed: 12/19/2022] Open
Abstract
BACKGROUND Although the incidence, severity and mortality of Clostridioides (Clostridium) difficile infection (CDI) have been increasing, patients' quality of life changes resulting from CDI have not been studied thoroughly. This study aimed at exploring the consequences of CDI on quality of life through patients' perspective. METHODS An observational, cross-sectional study involving 350 participants with a self-reported CDI diagnosis was conducted through an online self-administered survey. Participants were grouped into those who had active disease ("Current CDI") and those who had a history of CDI ("Past CDI"). RESULTS One hundred fifteen participants (33%) reported Current CDI and 235 (67%) reported Past CDI. A large majority of participants admitted that their daily activities were impacted by the infection (93.9% and 64.7% of Current and Past CDI respondents respectively, p < 0.05). Physical and psychological consequences of CDI were experienced by 63.5% and 66.1% of participants with active CDI. Despite the infection being cleared, these consequences were still frequently experienced in Past CDI cohort with similar rates (reported by 73.2% of respondents for both, physical consequences p = 0.08; psychological consequences p = 0.21). After the infection, 56.6% of respondents noted that post-CDI symptoms remained; 40.9% believed they would never get rid of them. CONCLUSIONS While the societal burden of CDI is well described in the literature, our study is one of the first aimed at understanding the major burden of CDI on quality of life. Our results highlight the long-lasting nature of CDI and further reinforce the need for enhanced therapeutics in the prevention and treatment of this devastating infection.
Collapse
Affiliation(s)
- Lise Lurienne
- Da Volterra, 172 rue de Charonne, 75011, Paris, France.
| | | | | | | | | | - Paul Feuerstadt
- Yale School of Medicine, New Haven, CT, USA
- Gastroenterology Center of Connecticut, Hamden, CT, USA
| |
Collapse
|
|
30
|
Azimirad M, Krutova M, Balaii H, Kodori M, Shahrokh S, Azizi O, Yadegar A, Aghdaei HA, Zali MR. Coexistence of Clostridioides difficile and Staphylococcus aureus in gut of Iranian outpatients with underlying inflammatory bowel disease. Anaerobe 2020; 61:102113. [DOI: 10.1016/j.anaerobe.2019.102113] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2019] [Revised: 10/31/2019] [Accepted: 11/03/2019] [Indexed: 01/09/2023]
|
|
31
|
Insights into the Role of Human Gut Microbiota in Clostridioides difficile Infection. Microorganisms 2020; 8:microorganisms8020200. [PMID: 32023967 PMCID: PMC7074861 DOI: 10.3390/microorganisms8020200] [Citation(s) in RCA: 43] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2020] [Revised: 01/29/2020] [Accepted: 01/31/2020] [Indexed: 12/18/2022] Open
Abstract
Clostridioides difficile infection (CDI) has emerged as a major health problem worldwide. A major risk factor for disease development is prior antibiotic use, which disrupts the normal gut microbiota by altering its composition and the gut’s metabolic functions, leading to the loss of colonization resistance and subsequent CDI. Data from human studies have shown that the presence of C. difficile, either as a colonizer or as a pathogen, is associated with a decreased level of gut microbiota diversity. The investigation of the gut’s microbial communities, in both healthy subjects and patients with CDI, elucidate the role of microbiota and improve the current biotherapeutics for patients with CDI. Fecal microbiota transplantation has a major role in managing CDI, aiming at re-establishing colonization resistance in the host gastrointestinal tract by replenishing the gut microbiota. New techniques, such as post-genomics, proteomics and metabolomics analyses, can possibly determine in the future the way in which C. difficile eradicates colonization resistance, paving the way for the development of new, more successful treatments and prevention. The aim of the present review is to present recent data concerning the human gut microbiota with a focus on its important role in health and disease.
Collapse
|
|
32
|
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
| |
Collapse
|
|
33
|
Long-Duration Oral Vancomycin to Treat Clostridioides difficile in Patients With Inflammatory Bowel Disease Is Associated With a Low Rate of Recurrence. Am J Gastroenterol 2019; 114:1904-1908. [PMID: 31714359 DOI: 10.14309/ajg.0000000000000460] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVES Patients with inflammatory bowel disease (IBD) are susceptible to Clostridioides difficile infections (CDIs), suffering from greater morbidity and mortality than the general population. Previous studies have proven the efficacy of oral vancomycin therapy in CDI, but there are no definitive guidelines to treat patients with IBD. We assessed the relationship between the length of vancomycin therapy and rates of CDI recurrence and reinfection in patients with IBD. METHODS We compared rates of CDI recurrence and reinfection in Crohn's disease and ulcerative colitis (UC) patients receiving long-duration (LD) and short-duration (SD) oral vancomycin therapy, defined as 21-42 days and 10-14 days, respectively. Recurrence and reinfection were defined as positive C. difficile toxin assay by polymerase chain reaction within 8 weeks of the end of antibiotic therapy and after 8 weeks of the end of antibiotic therapy, respectively. The Fisher exact test was used to test for significance, and multivariate logistic regression models were constructed to control for other covariables. RESULTS One hundred thirty-four patients with IBD (57 ulcerative colitis and 77 Crohn's disease) met inclusion criteria. LD vancomycin had a 1.8% incidence of CDI recurrence, compared with 11.7% in the SD vancomycin group (odds ratio = 0.13, P = 0.043). CDI reinfection rates and time to reinfection were not significantly different (LD 14.0% vs SD 16.9%, P = NS). Multivariate logistic regression models showed that treatment with LD vancomycin had lower odds for recurrence than SD vancomycin (odds ratio = 0.03, P = 0.021). DISCUSSION LD vancomycin is associated with lower rates of CDI recurrence compared with SD vancomycin therapy. These results will help guide clinical decisions and the development of a prospective trial.
Collapse
|
|
34
|
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: 1456] [Impact Index Per Article: 242.7] [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.
Collapse
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
| | | |
Collapse
|
|
35
|
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.
Collapse
|
|
36
|
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.
Collapse
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.
| |
Collapse
|
|
37
|
Shrestha MP, Taleban S. Obesity Is Associated with Increased Risk of Colectomy in Inflammatory Bowel Disease Patients Hospitalized with Clostridium difficile Infection. Dig Dis Sci 2019; 64:1632-1639. [PMID: 30569334 DOI: 10.1007/s10620-018-5423-7] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/20/2018] [Accepted: 12/07/2018] [Indexed: 02/07/2023]
Abstract
BACKGROUND Obesity and inflammatory bowel disease (IBD) are associated with increased risk of Clostridium difficile infection (CDI). The effect of obesity on IBD course and development of complications is poorly understood. We performed this study to examine the effect of obesity on CDI-related morbidity and mortality in hospitalized patients with IBD. METHODS We used data from the National Inpatient Sample across five study years (2010-2014) to identify patients ≥ 18 years hospitalized with both CDI and IBD. We compared the outcomes of in-hospital mortality, partial or total colectomy, hospital length of stay, and hospital charges between obese and non-obese IBD-CDI patients. Analysis included univariate and multivariate linear and logistic regression analyses. RESULTS Of 304,298 hospitalized patients with IBD, 13,517 (4.4%) patients had CDI. Of these, 996 (7.4%) patients were obese. Obese IBD-CDI patients had a higher risk of colectomy (adjusted odds ratio, AOR 1.60, 95% CI 1.30-1.96; p < 0.001), longer hospital length of stay (difference 0.8 days, 95% CI 0.02-1.58; p = 0.04), and higher hospital charges (difference $11,051, 95% CI 1939-20,163; p = 0.02) than non-obese IBD-CDI patients, but no significant difference in mortality was found between the two groups. CONCLUSIONS Obesity is associated with a 60% increase in the risk of colectomy, longer hospital stay, and higher charges in IBD patients hospitalized with CDI. Further epidemiological and clinical studies are needed to confirm these findings.
Collapse
Affiliation(s)
- Manish P Shrestha
- Department of Medicine, University of Arizona College of Medicine, Tucson, AZ, USA
| | - Sasha Taleban
- Division of Gastroenterology, University of Arizona College of Medicine, 1501 N Campbell Ave, PO Box 24502B, Tucson, AZ, 85724, USA. .,Department of Medicine, Arizona Center of Aging, Tucson, AZ, USA.
| |
Collapse
|
|
38
|
Gong SS, Fan YH, Han QQ, Lv B, Xu Y. Nested case-control study on risk factors for opportunistic infections in patients with inflammatory bowel disease. World J Gastroenterol 2019; 25:2240-2250. [PMID: 31143074 PMCID: PMC6526151 DOI: 10.3748/wjg.v25.i18.2240] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/21/2019] [Revised: 03/11/2019] [Accepted: 03/30/2019] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND When opportunistic infections occur, patients with inflammatory bowel disease (IBD) commonly display a significantly increased rate of morbidity and mortality. With increasing use of immunosuppressive agents and biological agents, opportunistic infections are becoming a hot topic in the perspective of drug safety in IBD patients. Despite the well-established role of opportunistic infections in the prognosis of IBD patients, there are few epidemiological data investigating the incidence of opportunis-tic infections in IBD patients in China. Besides, the risk factors for opportunistic infection in Chinese IBD patients remain unclear.
AIM To predict the incidence of opportunistic infections related to IBD in China, and explore the risk factors for opportunistic infections.
METHODS A single-center, prospective study of IBD patients was conducted. The patients were followed for up to 12 mo to calculate the incidence of infections. For each infected IBD patient, two non-infected IBD patients were selected as controls. A conditional logistic regression analysis was used to assess associations between putative risk factors and opportunistic infections, which are represented as odds ratios (OR) and 95% confidence intervals (CIs).
RESULTS Seventy (28.11%) out of 249 IBD patients developed opportunistic infections. Clostridium difficile infections and respiratory syncytial virus infections were found in 24 and 16 patients, respectively. In a univariate analysis, factors such as the severity of IBD, use of an immunosuppressant or immunosuppressants, high levels of fecal calprotectin, and C-reactive protein or erythrocyte sedimentation rate were individually related to a significantly increased risk of opportunistic infection. Multivariate analysis indicated that the use of any immunosuppressant yielded an OR of 3.247 (95%CI: 1.128-9.341), whereas the use of any two immunosuppressants yielded an OR of 6.457 (95%CI: 1.726-24.152) for opportunistic infection. Interestingly, when immunosuppressants were used in combination with infliximab (IFX) or 5-aminosalicylic acid, a significantly increased risk of opportunistic infection was also observed. The relative risk of opportunistic infection was greatest in IBD patients with severe disease activity (OR = 9.090; 95%CI: 1.532-53.941, relative to the remission stage). However, the use of IFX alone did not increase the risk of opportunistic infection.
CONCLUSION Factors such as severe IBD, elevated levels of fecal calprotectin, and the use of immunosuppressive medications, especially when used in combination, are major risk factors for opportunistic infections in IBD patients. The use of IFX alone does not increase the risk of opportunistic infection.
Collapse
Affiliation(s)
- Shan-Shan Gong
- Department of Gastroenterology, First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310006, Zhejiang Province, China
| | - Yi-Hong Fan
- Department of Gastroenterology, First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310006, Zhejiang Province, China
| | - Qing-Qing Han
- Department of Gastroenterology, First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310006, Zhejiang Province, China
| | - Bin Lv
- Department of Gastroenterology, First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310006, Zhejiang Province, China
| | - Yi Xu
- Department of Gastroenterology, First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310006, Zhejiang Province, China
| |
Collapse
|
|
39
|
Macaluso FS, Cavallaro F, Felice C, Mazza M, Armuzzi A, Gionchetti P, Vecchi M, Orlando A. Risk factors and timing for colectomy in chronically active refractory ulcerative colitis: A systematic review. Dig Liver Dis 2019; 51:613-620. [PMID: 30826279 DOI: 10.1016/j.dld.2019.01.018] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/28/2018] [Revised: 01/20/2019] [Accepted: 01/21/2019] [Indexed: 12/11/2022]
Abstract
BACKGROUND In patients with chronic refractory ulcerative colitis (UC) the precise timing for indication to colectomy is unclear. AIMS We performed a systematic review of the literature on the risk factors for colectomy in patients with chronic refractory UC in the biologic era. METHODS PubMed Central/Medline and Embase were systemically searched for records published between January 2000 and December 2017. Current evidence was summarized and filtered by expert opinion. RESULTS 70 studies were included in the qualitative synthesis. Several factors were found to be associated with a higher or reduced risk for colectomy, including variables at baseline - such as progression from proctitis/left-sided to extensive colitis, extensive colitis at diagnosis, high baseline C Reactive Protein or erythrocyte sedimentation rate, male gender, and younger age at diagnosis - previous medical history, and factors arising during therapy with biologics, including the absence of clinical response after induction with infliximab or adalimumab, and the lack of mucosal healing during therapy with anti-TNFs. CONCLUSIONS Two main points may help physicians to decide when the surgical option may be considered in patients with chronic refractory UC: (1) a first risk stratification can be obtained by analyzing factors at baseline and medical history, including the previous exposure to anti-TNFs; (2) during therapy with biologics, the early assessment (after 12-16 weeks of treatment) of clinical and endoscopic response is a strong predictor of the subsequent risk of colectomy.
Collapse
Affiliation(s)
| | - Flaminia Cavallaro
- Gastroenterology & Digestive Endoscopy Unit, IRCCS Policlinico San Donato, Milano, Italy
| | - Carla Felice
- IBD Unit, "Presidio Columbus" Foundation Hospital "A. Gemelli IRCCS" - Sacro Cuore Catholic University, Rome
| | - Marta Mazza
- Department of Medical and Surgical Sciences (DIMEC), Policlinico S.Orsola-Malpighi, University of Bologna, Italy
| | - Alessandro Armuzzi
- IBD Unit, "Presidio Columbus" Foundation Hospital "A. Gemelli IRCCS" - Sacro Cuore Catholic University, Rome
| | - Paolo Gionchetti
- Department of Medical and Surgical Sciences (DIMEC), Policlinico S.Orsola-Malpighi, University of Bologna, Italy
| | - Maurizio Vecchi
- Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Department of Pathophysiology and Organ Transplantation, University of Milan, Italy
| | | |
Collapse
|
|
40
|
Shoaei P, Shojaei H, Jalali M, Khorvash F, Hosseini SM, Ataei B, Vakili B, Ebrahimi F, Tavakoli H, Esfandiari Z, Weese JS. Clostridium difficile isolated from faecal samples in patients with ulcerative colitis. BMC Infect Dis 2019; 19:361. [PMID: 31039738 PMCID: PMC6492486 DOI: 10.1186/s12879-019-3965-8] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2018] [Accepted: 04/08/2019] [Indexed: 12/18/2022] Open
Abstract
BACKGROUND Ulcerative colitis (UC) is an inflammatory bowel disease (IBD) that is widely identified worldwide. This study aimed to investigate the phenotypic characterization and molecular typing of Clostridium difficile isolates among patients with UC at an inflammatory bowel disease clinic in Iran. METHODS In this cross-sectional study, conducted from April 2015 to December 2015, 85 UC patients were assessed for C.difficile infection (CDI). C. difficile isolates were characterized based on their toxin profile and antimicrobial resistance pattern. Multi-locus sequence typing analysis (MLST) and PCR ribotyping were performed to define the genetic relationships between different lineages of toxigenic strains. RESULTS The prevalence of C. difficile isolates was 31.8% (27/85) in patients, of those 15 patients (17.6%) had CDI. Three different sequence types (STs) identified based on MLST among the toxigenic isolates, that is ST54 (33.3%), ST2 (53.3%), and ST37 (13.6%). C. difficile strains were divided into four different PCR-ribotypes (012, 014, 017 and IR1). The most common ribotype was 014 accounting for 48.3% (7/15) of all strains. The strains isolated during the first episode and recurrence of CDI usually belonged to PCR ribotype 014 (ST2). A high rate of CDI recurrence (14.1%, 12/85) experienced in UC patients. Colonization of the gastrointestinal tract with non-toxigenic C. difficile strains was frequent among patients with mild disease. All C. difficile isolates were susceptible to metronidazole, and vancomycin, 86 and 67% of isolates were resistant to clindamycin and erythromycin respectively. There was no correlation between the toxin type and antibiotic resistance (p > 0.05). CONCLUSION Overall CDI is rather prevalent in UC patients. All patients with CDI experienced moderate to severe disease and exposed to different antimicrobial and anti-inflammatory agents. Close monitoring and appropriate management including early detection and fast treatment of CDI will improve UC outcomes.
Collapse
Affiliation(s)
- Parisa Shoaei
- Nosocomial Infection Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Hasan Shojaei
- Department of Microbiology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Mohammad Jalali
- School of Food Science and Nutrition, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Farzin Khorvash
- Nosocomial Infection Research Center, Isfahan University of Medical Sciences, Isfahan, Iran.
| | - Sayed Mohsen Hosseini
- Epidemiology and biostatics department, Isfahan University of Medical sciences, Isfahan, Iran
| | - Behrooz Ataei
- Infectious Diseases and Tropical Medicine Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Bahareh Vakili
- Department of Microbiology, Science and Research Branch, Islamic Azad University, Tehran, Iran
| | - Fatemeh Ebrahimi
- Department of Microbiology, Islamic Azad University of Falavarjan, Isfahan, Iran
| | - Hossein Tavakoli
- Department of Physiology and Pathophysiology, University of Manitoba, Winnipeg, MB, Canada
| | - Zahra Esfandiari
- Department of Research and Development, Vice Chancellory for food and drug, Isfahan, Iran
| | - J Scott Weese
- Department of Pathobiology and Centre for Public Health and Zoonoses, Ontario Veterinary College, University of Guelph, Guelph, Canada
| |
Collapse
|
|
41
|
Solanky D, Pardi DS, Loftus EV, Khanna S. Colon Surgery Risk With Corticosteroids Versus Immunomodulators or Biologics in Inflammatory Bowel Disease Patients With Clostridium difficile Infection. Inflamm Bowel Dis 2019; 25:610-619. [PMID: 30260451 PMCID: PMC6783902 DOI: 10.1093/ibd/izy291] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/10/2018] [Indexed: 12/11/2022]
Abstract
BACKGROUND Inflammatory bowel disease (IBD) is an independent risk factor for Clostridium difficile infection (CDI), and CDI often precipitates IBD exacerbation. Because CDI cannot be distinguished clinically from an IBD exacerbation, management is difficult. We aimed to assess factors associated with adverse outcomes in IBD with CDI, including the role of escalating or de-escalating IBD therapy and CDI treatment. METHODS Records for patients with IBD and CDI from 2008 to 2013 were abstracted for variables including IBD severity before CDI diagnosis, CDI management, subsequent IBD exacerbation, CDI recurrence, and colon surgery. Colon surgery was defined as resection of any colonic segment within 1 year after CDI diagnosis. RESULTS We included 137 IBD patients (median age, 46 years; 55% women): 70 with ulcerative colitis (51%), 63 with Crohn's disease (46%), and 4 with indeterminate colitis (3%). Overall, 70% of CDIs were mild-moderate, 14% were severe, and 15% were severe-complicated. Clostridium difficile infection treatment choice did not vary by infection severity (P = 0.27). Corticosteroid escalation (odds ratio [OR], 5.94; 95% confidence interval [CI], 2.03-17.44) was a positive predictor of colon surgery within 1 year after CDI; older age (OR, 0.09; 95% CI, 0.01-0.44) was a negative predictor. Modifying the corticosteroid regimen did not affect CDI recurrence or risk of future IBD exacerbation. Adverse outcomes did not differ with CDI antibiotic regimens or biologic or immunomodulator regimen modification. CONCLUSIONS Corticosteroid escalation for IBD during CDI was associated with higher risk of colon surgery. Type of CDI treatment did not influence IBD outcomes. Prospective studies are needed to further elucidate optimal management in this high-risk population.
Collapse
Affiliation(s)
- Dipesh Solanky
- Mayo Clinic School of Medicine, Mayo Clinic College of Medicine and Science, Rochester, Minnesota, USA
| | - Darrell S Pardi
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA
| | - Edward V Loftus
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA
| | - Sahil Khanna
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA,Address correspondence to: Sahil Khanna, MBBS, Division of Gastroenterology and Hepatology, Mayo Clinic, 200 First St SW, Rochester, MN 55905, USA. E-mail:
| |
Collapse
|
|
42
|
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
|
|
43
|
Rubin DT, Ananthakrishnan AN, Siegel CA, Sauer BG, Long MD. ACG Clinical Guideline: Ulcerative Colitis in Adults. Am J Gastroenterol 2019; 114:384-413. [PMID: 30840605 DOI: 10.14309/ajg.0000000000000152] [Citation(s) in RCA: 968] [Impact Index Per Article: 161.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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.
Collapse
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
| |
Collapse
|
|
44
|
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
|
|
45
|
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] [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.
Collapse
|
|
46
|
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
|
|
47
|
Enteric Infections Are Common in Patients with Flares of Inflammatory Bowel Disease. Am J Gastroenterol 2018; 113:1530-1539. [PMID: 30072777 PMCID: PMC7939066 DOI: 10.1038/s41395-018-0211-8] [Citation(s) in RCA: 64] [Impact Index Per Article: 9.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/08/2018] [Accepted: 06/29/2018] [Indexed: 02/08/2023]
Abstract
OBJECTIVES Few studies have examined the role of non-Clostridium difficile enteric infections in flares of inflammatory bowel disease (IBD). Our objective was to investigate enteric infection detected by multiplex PCR stool testing in patients with IBD. METHODS We performed a cross-sectional analysis of 9403 patients who underwent 13,231 stool tests with a gastrointestinal pathogen PCR panel during a diarrheal illness from March 2015 to May 2017. Our primary outcome was the presence of an infection. Secondary outcomes included endoscopic and histologic predictors of infection, and IBD outcomes following testing. RESULTS A total of 277 patients with Crohn's disease (CD), 300 patients with ulcerative colitis (UC), and 8826 patients without IBD underwent 454, 503, and 12,275 tests, respectively. Compared to patients without IBD, patients with IBD were less likely to test positive (CD 18.1%, UC 16.1%, no IBD 26.6%, p < 0.001). Compared to patients without IBD, CD had a higher prevalence of norovirus (p = 0.05) and Campylobacter (p = 0.043), whereas UC had a lower prevalence of norovirus (p = 0.001) and a higher prevalence of Campylobacter (p = 0.013), Plesiomonas (p = 0.049), and Escherichia coli species (p < 0.001). Of 77 patients who underwent endoscopy, there were no major endoscopic or histologic predictors of a positive test. Patients who tested negative were more likely to have IBD therapy escalated (p = 0.004). Enteric infection did not impact IBD outcomes following testing (log-rank 0.224). CONCLUSIONS Non-Clostridium difficile enteric infections were identified in 17% of symptomatic patients with IBD. Endoscopic and histologic findings may not differentiate flare from infection. Norovirus and E.coli may play an important role in flare of IBD.
Collapse
|
|
48
|
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
|
|
49
|
Micic D, Hirsch A, Setia N, Rubin DT. Enteric infections complicating ulcerative colitis. Intest Res 2018; 16:489-493. [PMID: 30090049 PMCID: PMC6077301 DOI: 10.5217/ir.2018.16.3.489] [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: 10/04/2017] [Revised: 04/30/2018] [Accepted: 05/10/2018] [Indexed: 12/18/2022] Open
Abstract
Enteric infections have previously been postulated to play a role in the pathogenesis of inflammatory bowel disease (IBD), however, little evidence exists in the etiologic role of specific enteric infections in the development of IBD. When encountered in the setting of IBD, enteric infections pose a clinical challenge in management given the competing treatment strategies for infectious conditions and autoimmune disorders. Here we present the case of a young male with enteric infections complicating a new diagnosis of IBD. Our patient's initial clinical presentation included diagnoses of Klebsiella oxytoca isolation and Clostridium difficile infection. Directed therapies to include withdrawal of antibiotics and fecal microbiota transplantation were performed without resolution of clinical symptoms. Given persistence of symptoms and active colitis, the patient was diagnosed with ulcerative colitis (UC), requiring treatments directed at severe UC to include cyclosporine therapy. The finding of multiple enteric infections in a newly presenting patient with IBD is an unexpected finding that has treatment implications.
Collapse
Affiliation(s)
- Dejan Micic
- Section of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, University of Chicago, Chicago, IL, USA
| | - Ayal Hirsch
- Section of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, University of Chicago, Chicago, IL, USA
| | - Namrata Setia
- Department of Pathology, University of Chicago, Chicago, IL, USA
| | - David T Rubin
- Section of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, University of Chicago, Chicago, IL, USA
| |
Collapse
|
|
50
|
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
|