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Shin JH, Jackson-Akers JY, Hoang SC, Behm BW, Warren CA. Fulminant Clostridioides difficile Infection: A Journey into the Unknown! Med Clin North Am 2025; 109:721-734. [PMID: 40185558 DOI: 10.1016/j.mcna.2025.01.001] [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] [Indexed: 04/07/2025]
Abstract
Clostridioides difficile is 1 of the 5 urgent antibiotic resistance threats in the United States as reported by the Centers for Disease Control and Prevention. Fulminant C difficile infection (CDI), characterized by hallmarks of critical illness such as hypotension, shock, or megacolon, has been difficult to define and treat. In this article, we describe the diagnostic criteria for fulminant CDI, clinical factors and inflammatory markers. We review the currently recommended treatment modalities including antibiotics and surgical interventions, colectomy, and diverting loop ileostomy. We also included treatment approaches that are still investigational such as intestinal microbiota transplant, tigecycline, and intravenous immunoglobulin.
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Affiliation(s)
- Jae H Shin
- Infectious Disease, Hoag Memorial Hospital Presbyterian, 1 Hoag Drive, Newport Beach, CA 92663, USA
| | | | - Sook C Hoang
- Colorectal Surgery, University of Virginia, 1215 Lee Street, Charlottesville, VA 22903, USA
| | - Brian W Behm
- Division of Gastroenterology, University of Virginia, 1300 Jefferson Park Avenue, Charlottesville, VA 22903, USA
| | - Cirle A Warren
- Division of Infectious Diseases and International Health, University of Virginia, 345 Crispell Drive, Charlottesville, VA 22903, USA.
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2
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L'Huillier JC, Guo WA. The always evolving diagnosis and management of Clostridioides difficile colitis: What you need to know. J Trauma Acute Care Surg 2025; 98:357-367. [PMID: 39509684 DOI: 10.1097/ta.0000000000004474] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2024]
Abstract
ABSTRACT The diagnosis, pharmacologic management, and surgical options for Clostridioides difficile infection (CDI) are rapidly evolving, which presents a challenge for the busy surgeon to remain up to date on the latest clinical guidelines. This review provides an evidence-based practical guide for CDI management tailored to the needs of surgeons and surgical intensivists. Historically, the diagnosis of CDI relied on slow cell culture cytotoxicity neutralization assays, but now, the rapidly resulting nucleic acid amplification tests and enzyme immunoassays have become mainstream. In terms of antibiotic therapy, metronidazole and oral vancomycin were the main "workhorse" antibiotics in the early 2000s, but large randomized controlled trials have now demonstrated that fidaxomicin produces superior results. Regarding surgical intervention, total abdominal colectomy was once the only procedure of choice; however, diverting loop ileostomy with colonic lavage is emerging as a viable alternative. Finally, novel adjuncts such as fecal microbiota transplantation and targeted therapy against toxin B (bezlotoxumab) are playing an increasingly important role in the management of CDI.
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Affiliation(s)
- Joseph C L'Huillier
- From the Department of Surgery (J.C.L., W.A.G.), Jacobs School of Medicine and Biomedical Sciences, and Division of Health Services Policy and Practice, Department of Epidemiology and Environmental Health (J.C.L.), School of Public Health and Health Professions, University at Buffalo; and Division of Trauma, Critical Care, and Acute Care Surgery, Department of Surgery (J.C.L., W.A.G.), Erie County Medical Center, Buffalo, New York
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3
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Khanna S. Microbiota restoration for recurrent Clostridioides difficile infection. Panminerva Med 2024; 66:417-426. [PMID: 39382853 DOI: 10.23736/s0031-0808.24.05111-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/10/2024]
Abstract
Since the publication of the recent North American and European guidelines on management of Clostridioides difficile infection (CDI), new evidence describing the epidemiology, testing and treatment of CDI has emerged. Despite all advances in infection control and antibiotic stewardship, the incidence and burden of CDI in the hospitals and the community remains at a stable high. Coupled with the incidence of primary CDI, there is a stable high incidence of recurrent CDI. Testing for primary and recurrent CDI remains a clinical challenge owing to high sensitivity of the PCR (leading to false positives) and somewhat limited sensitivity of EIA for toxin. The pathophysiology of recurrent CDI involves an ongoing disruption of the microbiota owing to the infection and the treatment of CDI employed. Broad spectrum antibiotics such as vancomycin leads to further disruption of microbiota compared to fidaxomicin which has a lower disruption of the microbiota and leads to fewer recurrences. Owing to these data fidaxomicin is considered as the first line antibiotic for recurrent CDI. Intravenous bezlotoxumab is a monoclonal antibody that reduces the risk of recurrence in high-risk patients but does not restore the microbiota. Experimental fecal microbiota transplantation (FMT) has been available for more than a decade. Owing to the success of FMT, two new non-invasive donor dependent Food and Drug Administration (FDA) approved therapies have been available since late 2022. This review summarizes all these conundrums regarding CDI and provides clinical pearls to use in day-to-day practice.
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Affiliation(s)
- Sahil Khanna
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA -
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4
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Abstract
Severe colitis is a well-defined condition encompassing several etiologies but is most often caused by severe ulcerative colitis or Clostridioides difficile infection. Severe colitis can evolve into toxic colitis, or toxic megacolon when associated with bowel dilation and systemic manifestations, resulting in a life-threatening scenario where multidisciplinary management is often required. Medical management continues to play an important role in the initial treatment of toxic megacolon. However, timely surgical intervention can be lifesaving.
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Affiliation(s)
- Marjorie R. Liggett
- Department of Surgery, Feinberg School of Medicine, Northwestern University, Chicago, Illinois
| | - Hasan B. Alam
- Department of Surgery, Feinberg School of Medicine, Northwestern University, Chicago, Illinois
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Ina EA, Ziton S, Dourvetakis K, Corallo JP. Loop Ileostomy With Colonic Lavage: Case Report of an Alternative to Total Colectomy in the Setting of Fulminant Clostridium difficile Colitis. Cureus 2024; 16:e73141. [PMID: 39650985 PMCID: PMC11624037 DOI: 10.7759/cureus.73141] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2024] [Accepted: 11/06/2024] [Indexed: 12/11/2024] Open
Abstract
Fulminant Clostridium difficile colitis is a severe and potentially life-threatening form of Clostridium difficile-associated bacterial disease leading to inflammation and damage to the colon. Complications such as toxic megacolon, sepsis, and multi-organ failure commonly occur in individuals with compromised immune systems and recent antibiotic use. Management of Clostridium difficile colitis involves optimization of fluid and electrolyte balance, and elimination of bacteria commonly by administering vancomycin or fidaxomicin. In cases where pharmacological management has been ineffective, fecal microbiota transplantation and surgical intervention demonstrated success. Historically, surgical intervention has involved a total abdominal colectomy with end ileostomy; however, other surgical options have shown increasing benefits with preservation of the colon. This case report aims to provide an example of an alternative management strategy for fulminant Clostridium difficile infections, via the use of a loop ileostomy and colonic lavage. The combination of loop ileostomy and colonic lavage promotes bowel rest, removes toxins, and promotes healing while decreasing inflammation. As with all management modalities, it is essential to recognize the associated complications. The potential benefits should be carefully weighed against the risks on a case-by-case basis with the help of a multidisciplinary team as illustrated through this case report. Overall, early recognition and treatment of fulminant Clostridium difficile colitis using loop ileostomy and colonic lavage prevents further disease progression and improves patient outcomes.
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Affiliation(s)
- Emily A Ina
- Osteopathic Medical School, Nova Southeastern University Dr. Kiran C. Patel College of Osteopathic Medicine, Fort Lauderdale, USA
| | - Shirley Ziton
- General Surgery, Broward Health Medical Center, Fort Lauderdale, USA
| | - Kirk Dourvetakis
- General Surgery, Nova Southeastern University Dr. Kiran C. Patel College of Osteopathic Medicine, Fort Lauderdale, USA
| | - Joseph P Corallo
- General Surgery, Broward Health and South Florida Surgical Specialists, Fort Lauderdale, USA
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Ke F, Dong ZH, Bu F, Li CN, He QT, Liu ZC, Lu J, Yu K, Wang DG, Xu HN, Ye CT. Clostridium difficile infection following colon subtotal resection in a patient with gallstones: A case report and review of literature. World J Gastrointest Surg 2024; 16:3048-3056. [PMID: 39351567 PMCID: PMC11438826 DOI: 10.4240/wjgs.v16.i9.3048] [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: 03/28/2024] [Revised: 07/02/2024] [Accepted: 07/10/2024] [Indexed: 09/18/2024] Open
Abstract
BACKGROUND Clostridium difficile (C. difficile) infection (CDI) is a rare clinical disease caused by changes in the intestinal microenvironment, which has a variety of causes and a poor prognosis, and for which there is no standardized clinical treatment. CASE SUMMARY A patient experienced recurrent difficulty in bowel movements over the past decade. Recently, symptoms worsened within the last ten days, leading to a clinic visit due to constipation. The patient was subsequently referred to our department. Preoperatively, the patient was diagnosed with obstructed colon accompanied by gallstones. Empirical antibiotics were administered both before and after surgery to prevent infection. On the fourth day post-surgery, symptoms of CDI emerged. Stool cultures confirmed the presence of C. difficile DNA. Treatment involved a combination of vancomycin and linezolid, resulting in the patient's successful recovery upon discharge. However, the patient failed to adhere to the prescribed medication after discharge and was discovered deceased during a follow-up two months later. CONCLUSION CDI is the leading cause of nosocomial post-operative care, with limited clinical cases and poor patient prognosis, and comprehensive clinical treatment guidelines are still lacking. This infection can be triggered by a variety of factors, including intestinal hypoxia, inappropriate antibiotic use, and bile acid circulation disorders. In patients with chronic bowel disease and related etiologies, prompt preoperative attention to possible CDI and preoperative bowel preparation is critical. Adequate and prolonged medication should be maintained in the treatment of CDI to prevent recurrence of the disease.
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Affiliation(s)
- Feng Ke
- Department of General Surgery, Affiliated Hospital of Changchun University of Chinese Medicine, Changchun 130000, Jilin Province, China
| | - Zhen-Hua Dong
- Department of Gastrointestinal Surgery, The First Hospital of Jilin University, Changchun 130061, Jilin Province, China
| | - Fan Bu
- Department of Plastic and Aesthetic Surgery, The First Hospital of Jilin University, Changchun 130061, Jilin Province, China
| | - Cheng-Nan Li
- Department of Encephalopathy Rehabilitation, Chaoyi Hospital, Yanbian Korean Autonomous Prefecture, Yanji 133000, Jilin Province, China
| | - Qi-Tong He
- Department of Gastrointestinal Surgery, The First Hospital of Jilin University, Changchun 130061, Jilin Province, China
| | - Zhi-Cheng Liu
- Department of Gastrointestinal Surgery, The First Hospital of Jilin University, Changchun 130061, Jilin Province, China
| | - Ji Lu
- Department of Urology, The First Hospital of Jilin University, Changchun 130061, Jilin Province, China
| | - Kai Yu
- Department of Urology, The First Hospital of Jilin University, Changchun 130061, Jilin Province, China
| | - Da-Guang Wang
- Department of Gastrointestinal Surgery, The First Hospital of Jilin University, Changchun 130061, Jilin Province, China
| | - He-Nan Xu
- Department of Gastrointestinal Surgery, The First Hospital of Jilin University, Changchun 130061, Jilin Province, China
| | - Chang-Tao Ye
- Department of Urology, The First Hospital of Jilin University, Changchun 130061, Jilin Province, China
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7
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Aljaafreh A, Hojeij M, Ataya K, Patel N, Ayoubi ARA, Khatib DE, Ahmed Y, Nassar H, Bourji HE. Total abdominal colectomy versus diverting loop ileostomy with colonic lavage for fulminant clostridium difficile colitis: an updated systematic review and meta-analysis of outcomes. Langenbecks Arch Surg 2024; 409:272. [PMID: 39240331 DOI: 10.1007/s00423-024-03458-x] [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: 07/14/2024] [Accepted: 08/23/2024] [Indexed: 09/07/2024]
Abstract
PURPOSE Diverting Loop Ileostomy (DLI) with intraoperative colonic lavage has emerged as a potential alternative to Total Abdominal Colectomy (TAC) for treating Fulminant Clostridium Difficile Colitis (FCDC). This study aims to provide an updated review comparing DLI with TAC in managing FCDC. METHODS A systematic literature search was conducted using PubMed, Scopus, and Embase to identify retrospective and prospective studies comparing DLI with TAC for fulminant CDC treatment. A meta-analysis was performed to evaluate postoperative mortality rates and complications using R Studio version 4.4.1, calculating odds ratios (ORs) with 95% confidence intervals via the Mantel-Haenszel method. Heterogeneity was assessed using the Cochrane Q test and I2 statistics. RESULTS Our search yielded 228 relevant citations, of which 7 studies with a total of 7,048 patients were included. Of these, 1,728 underwent DLI. The mean age was 63.33 years in the DLI group and 65.74 years in the TAC group. Compared to TAC, DLI had significantly lower postoperative mortality (OR 0.75; 95% CI 0.62-0.90; P = 0.002; I2 = 34%). Trial sequential analysis for postoperative mortality rates showed the benefit of DLI with a sufficiently powered sample. The DLI group also had a significantly higher rate of ostomy reversal (OR 5.68; 95% CI 2.35-13.72; P < 0.001; I2 = 36%). Postoperative complications, such as thromboembolic events, surgical site infections, urinary tract infections, renal failure, and pneumonia, were not significantly different. CONCLUSION DLI shows a lower postoperative mortality rate and higher ostomy reversal rate than TAC, suggesting it as a potential organ-preserving, minimally invasive alternative. Further high-quality studies and trials are needed to confirm these findings.
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Affiliation(s)
- Almoutuz Aljaafreh
- Department of Surgery, St George's University Hospital NHS Foundation Trust, Beirut, Lebanon
| | - Moussa Hojeij
- Faculty of Medical Sciences, Lebanese University, Beirut, Lebanon.
| | - Karim Ataya
- Department of Surgery, Homerton University Hospital London, London, UK
| | - Neha Patel
- Department of General Surgery, Government Medical College Surat, Surat, 39001, India
| | | | - Dalida El Khatib
- Faculty of Medical Sciences, Lebanese University, Beirut, Lebanon
| | - Yusuf Ahmed
- Department of General Surgery, Dammam Medical Complex, Dammam, Saudi Arabia
| | - Hussein Nassar
- Department of Surgery, Royal London Hospital, London, UK
| | - Hussein El Bourji
- Department of Surgery, University of Pittsburgh, Pittsburgh, PA, USA
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Manthey CF, Epple HJ, Keller KM, Lübbert C, Posovszky C, Ramharter M, Reuken P, Suerbaum S, Vehreschild M, Weinke T, Addo MM, Stallmach A, Lohse AW. S2k-Leitlinie Gastrointestinale Infektionen der Deutschen Gesellschaft für Gastroenterologie, Verdauungs- und Stoffwechselkrankheiten (DGVS). ZEITSCHRIFT FUR GASTROENTEROLOGIE 2024; 62:1090-1149. [PMID: 38976986 DOI: 10.1055/a-2240-1428] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 07/10/2024]
Affiliation(s)
- Carolin F Manthey
- I. Medizinische Klinik und Poliklinik - Schwerpunkt Gastroenterologie; Sektionen Infektions- und Tropenmedizin, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Deutschland
- Gemeinschaftspraxis Innere Medizin Witten, Witten, Deutschland
| | - Hans-Jörg Epple
- Antibiotic Stewardship, Vorstand Krankenversorgung, Universitätsmedizin Berlin, Berlin, Deutschland
| | - Klaus-Michael Keller
- Klinik für Kinder- und Jugendmedizin, Helios Dr. Horst Schmidt Kliniken, Klinik für Kinder- und Jugendmedizin, Wiesbaden, Deutschland
| | - Christoph Lübbert
- Bereich Infektiologie und Tropenmedizin, Medizinische Klinik I (Hämatologie, Zelltherapie, Infektiologie und Hämostaseologie), Universitätsklinikum Leipzig, Leipzig, Deutschland
| | | | - Michael Ramharter
- I. Medizinische Klinik und Poliklinik - Schwerpunkt Gastroenterologie; Sektionen Infektions- und Tropenmedizin, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Deutschland
| | - Philipp Reuken
- Klinik für Innere Medizin IV (Gastroenterologie, Hepatologie, Infektiologie, Zentrale Endoskopie), Universitätsklinikum Jena, Jena, Deutschland
| | - Sebastian Suerbaum
- Universität München, Max von Pettenkofer-Institut für Hygiene und Medizinische Mikrobiologie, München, Deutschland
| | - Maria Vehreschild
- Medizinische Klinik II, Universitätsklinikum Frankfurt, Frankfurt, Deutschland
| | - Thomas Weinke
- Klinik für Gastroenterologie und Infektiologie, Klinikum Ernst von Bergmann, Potsdam, Deutschland
| | - Marylyn M Addo
- I. Medizinische Klinik und Poliklinik - Schwerpunkt Gastroenterologie; Sektionen Infektions- und Tropenmedizin, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Deutschland
- Institut für Infektionsforschung und Impfstoffentwicklung Sektion Infektiologie, I. Med. Klinik, Zentrum für Innere Medizin, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Deutschland
| | - Andreas Stallmach
- Klinik für Innere Medizin IV (Gastroenterologie, Hepatologie, Infektiologie, Zentrale Endoskopie), Universitätsklinikum Jena, Jena, Deutschland
| | - Ansgar W Lohse
- I. Medizinische Klinik und Poliklinik - Schwerpunkt Gastroenterologie; Sektionen Infektions- und Tropenmedizin, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Deutschland
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9
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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.
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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
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Clarke LM, Allegretti JR. Review article: The epidemiology and management of Clostridioides difficile infection-A clinical update. Aliment Pharmacol Ther 2024; 59:1335-1349. [PMID: 38534216 DOI: 10.1111/apt.17975] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/12/2023] [Revised: 01/01/2024] [Accepted: 03/16/2024] [Indexed: 03/28/2024]
Abstract
BACKGROUND Clostridioides difficile is the most common cause of healthcare-associated infection, and severe cases can result in significant complications. While anti-microbial therapy is central to infection management, adjunctive therapies may be utilised as preventative strategies. AIM This article aims to review updates in the epidemiology, diagnosis, and management, including treatment and prevention, of C. difficile infections. METHODS A narrative review was performed to evaluate the current literature between 1986 and 2023. RESULTS The incidence of C. difficile infection remains significantly high in both hospital and community settings, though with an overall decline in recent years and similar surveillance estimates globally. Vancomycin and fidaxomicin remain the first line antibiotics for treatment of non-severe C. difficile infection, though due to lower recurrence rates, infectious disease society guidelines now favour use of fidaxomicin. Faecal microbiota transplantation should still be considered to prevent recurrent C. difficile infection. However, in the past year the field has had a significant advancement with the approval of the first two live biotherapeutic products-faecal microbiota spores-live brpk, an oral capsule preparation, and faecal microbiota live-jslm-both indicated for the prevention of recurrent C. difficile infection, with additional therapies on the horizon. CONCLUSION Although the prevalence of C. difficile infection remains high, there have been significant advances in the development of novel therapeutics and preventative measures following changes in recent practice guidelines, and will continue to evolve in the future.
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Affiliation(s)
- Lindsay M Clarke
- Division of Gastroenterology, Hepatology and Endoscopy, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - Jessica R Allegretti
- Division of Gastroenterology, Hepatology and Endoscopy, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA
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11
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Pumiglia L, Wilson L, Rashidi L. Clostridioides difficile Colitis. Surg Clin North Am 2024; 104:545-556. [PMID: 38677819 DOI: 10.1016/j.suc.2023.11.005] [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: 04/29/2024]
Abstract
Clostridioides difficile colitis is an important source of hospital-acquired diarrhea associated with antibiotic use. Symptoms are profuse watery diarrhea, typically following a course of antibiotics; however, some cases of fulminant disease may manifest with shock, ileus, or megacolon. Nonfulminant colitis is treated with oral fidaxomicin. C difficile colitis has a high potential for recurrence, and recurrent episodes are also treated with fidaxomicin. Bezlotoxumab is another medication that may be used in populations at high risk for further recurrence. Fulminant disease is treated with maximal medical therapy and early surgical consultation. Antibiotic stewardship is critical to preventing C difficile colitis.
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Affiliation(s)
- Luke Pumiglia
- Department of General Surgery, Madigan Army Medical Center, 9040 Jackson Avenue, Joint Base Lewis-McChord, WA 98431, USA
| | - Lexi Wilson
- Department of Colorectal Surgery, Swedish Medical Center, 747 Broadway, Seattle, WA 98122, USA
| | - Laila Rashidi
- Department of Surgery, MultiCare Health Care System, Washington State University, 3124 19th Street Suite 220, Tacoma, WA 98405, USA.
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12
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Shirley DA, Tornel W, Warren CA, Moonah S. Clostridioides difficile Infection in Children: Recent Updates on Epidemiology, Diagnosis, Therapy. Pediatrics 2023; 152:e2023062307. [PMID: 37560802 PMCID: PMC10471512 DOI: 10.1542/peds.2023-062307] [Citation(s) in RCA: 15] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 05/31/2023] [Indexed: 08/11/2023] Open
Abstract
Clostridioides (formerly Clostridium) difficile is the most important infectious cause of antibiotic-associated diarrhea worldwide and a leading cause of healthcare-associated infection in the United States. The incidence of C. difficile infection (CDI) in children has increased, with 20 000 cases now reported annually, also posing indirect educational and economic consequences. In contrast to infection in adults, CDI in children is more commonly community-associated, accounting for three-quarters of all cases. A wide spectrum of disease severity ranging from asymptomatic carriage to severe diarrhea can occur, varying by age. Fulminant disease, although rare in children, is associated with high morbidity and even fatality. Diagnosis of CDI can be challenging as currently available tests detect either the presence of organism or disease-causing toxin but cannot distinguish colonization from infection. Since colonization can be high in specific pediatric groups, such as infants and young children, biomarkers to aid in accurate diagnosis are urgently needed. Similar to disease in adults, recurrence of CDI in children is common, affecting 20% to 30% of incident cases. Metronidazole has long been considered the mainstay therapy for CDI in children. However, new evidence supports the safety and efficacy of oral vancomycin and fidaxomicin as additional treatment options, whereas fecal microbiota transplantation is gaining popularity for recurrent infection. Recent advancements in our understanding of emerging epidemiologic trends and management of CDI unique to children are highlighted in this review. Despite encouraging therapeutic advancements, there remains a pressing need to optimize CDI therapy in children, particularly as it pertains to severe and recurrent disease.
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Affiliation(s)
| | | | - Cirle A. Warren
- Infectious Diseases and International Health, Department of Medicine
- Complicated C. difficile Clinic, UVA Health, University of Virginia, Charlottesville, Virginia
| | - Shannon Moonah
- Infectious Diseases and International Health, Department of Medicine
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13
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Ivashkin VT, Lyashenko OS, Drapkina OM, Alexeeva OP, Alekseenko SA, Andreev DN, Baranovsky AY, Goloshchapov OV, Zheleznova NV, Zolnikova OY, Kliaritskaia IL, Korochanskaya NV, Lapina TL, Maev IV, Maslennikov RV, Myazin RG, Pavlov PV, Perekalina MV, Pisarenko NA, Povtoreyko AV, Poluektova EA, Sekretareva LA, Tkachev AV, Troshkina YM, Trukhmanov AS, Ulyanin AI, Filatova SG, Tsukanov VV, Shifrin OS. Clinical Practice Guidelines of the Scientific Society for the Clinical Study of Human Microbiome, of the Russian Gastroenterological Association and the Russian Society for the Prevention of Noncommunicable Diseases on the Diagnosis and Treatment of <i>Clostridioides difficile</i> (<i>C. difficile</i>)-associated Disease in Adults. RUSSIAN JOURNAL OF GASTROENTEROLOGY, HEPATOLOGY, COLOPROCTOLOGY 2023; 33:85-119. [DOI: 10.22416/1382-4376-2023-33-3-85-119] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 07/26/2024]
Abstract
Аim: the clinical practice guidelines intended for gastroenterologists, internal medicine specialists, infectious disease specialists, general practitioners (family doctors), coloproctologists, surgeons and endoscopists present modern methods of diagnosis, prevention and treatment of C. difficile-associated disease.Key points. C. difficile-associated disease is a disease that develops when the diversity of the intestinal microbiota decreases and C. difficile excessively colonizes the colon, the toxins of which damage the intestinal muco-epithelial barrier, followed by the development of inflammation in the colon wall, with diarrhea being a characteristic clinical manifestation. The clinical presentation of the disease can vary from asymptomatic carriage, mild to moderate diarrhea that resolves on its own, to profuse watery diarrhea and pseudomembranous colitis with development of life-threatening complications. The diagnosis of C. difficile-associated disease is based on an assessment of the clinical presentation, medical history, an objective examination of the patient and laboratory stool tests. The disease severity is determined by clinical symptoms and laboratory findings. Additional diagnostic methods that are used according to indications and contribute to the assessment of severity include endoscopy of the colon and abdominal cavity imaging methods. Treatment should be initiated in cases of characteristic clinical presentation of C. difficile-associated disease and positive laboratory stool testing. The choice of drug and treatment regimen depends on the severity of the episode, the presence of complications, and whether the episode is initial, recurrent, or reinfection.Conclusion. Determination of target groups of patients for the diagnosis of clostridial infection is important in preventing overdiagnosis and subsequent unnecessary treatment. Timely diagnosis and treatment of C. difficile-associated disease help avoiding the development of life-threatening complications and improve the prognosis and quality of life of patients.
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Affiliation(s)
- V. T. Ivashkin
- I.M. Sechenov First Moscow State University (Sechenov University)
| | - O. S. Lyashenko
- I.M. Sechenov First Moscow State University (Sechenov University)
| | - O. M. Drapkina
- National Medical Research Center for Therapy and Preventive Medicine
| | | | | | - D. N. Andreev
- A.I. Yevdokimov Moscow State University of Medicine and Dentistry
| | | | | | | | - O. Yu. Zolnikova
- I.M. Sechenov First Moscow State University (Sechenov University)
| | | | | | - T. L. Lapina
- I.M. Sechenov First Moscow State University (Sechenov University)
| | - I. V. Maev
- A.I. Yevdokimov Moscow State University of Medicine and Dentistry
| | | | | | - P. V. Pavlov
- I.M. Sechenov First Moscow State University (Sechenov University)
| | | | | | | | - E. A. Poluektova
- I.M. Sechenov First Moscow State University (Sechenov University)
| | | | | | | | - A. S. Trukhmanov
- I.M. Sechenov First Moscow State University (Sechenov University)
| | - A. I. Ulyanin
- I.M. Sechenov First Moscow State University (Sechenov University)
| | | | - V. V. Tsukanov
- Federal Research Center “Krasnoyarsk Science Center of the Siberian Branch of the Russian Academy of Sciences”
| | - O. S. Shifrin
- I.M. Sechenov First Moscow State University (Sechenov University)
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14
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Kanjee Z, Allegretti JR, Alonso CD, Burns RB. How Would You Manage This Patient With Clostridioides difficile Infection? : Grand Rounds Discussion From Beth Israel Deaconess Medical Center. Ann Intern Med 2023; 176:1101-1108. [PMID: 37549387 DOI: 10.7326/m23-0754] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 08/09/2023] Open
Abstract
The Infectious Diseases Society of America/Society for Healthcare Epidemiology of America and the American College of Gastroenterology recently released updated guidelines on management of patients with Clostridioides difficile infection. Although these 2 guidelines generally agree, there are a few important differences in their advice to clinicians. In these rounds, 2 experts, an infectious diseases specialist and a gastroenterologist, discuss antibiotic treatment options for nonsevere disease, the role of fecal microbiota transplantation for fulminant disease, and the use of bezlotoxumab to prevent recurrence in the context of Ms. C, a 48-year-old woman with fulminant C difficile infection.
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Affiliation(s)
- Zahir Kanjee
- Division of General Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts (Z.K., R.B.B.)
| | - Jessica R Allegretti
- Division of Gastroenterology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts (J.R.A.)
| | - Carolyn D Alonso
- Division of Infectious Diseases, Beth Israel Deaconess Medical Center; Harvard Medical School, Boston, Massachusetts (C.D.A.)
| | - Risa B Burns
- Division of General Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts (Z.K., R.B.B.)
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15
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Tah S, Khan S, Kashyap S. Uncommon Presentation of Clostridioides difficile in the Small Bowel: A Case Report and Review of Literature. Cureus 2023; 15:e43460. [PMID: 37711949 PMCID: PMC10498804 DOI: 10.7759/cureus.43460] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/14/2023] [Indexed: 09/16/2023] Open
Abstract
Clostridioides difficile infection (CDI) is a prevalent source of hospital-acquired diarrhea. The most common presentation of CDI is colitis. In cases of fulminant colitis/toxic megacolon, a colectomy and end ileostomy are part of the treatment plan. There is evidence to suggest that it may be beneficial to surgically treat severe complex CDI by constructing a loop ileostomy for fecal stream diversion followed by colonic lavage, also referred to as the Pittsburgh protocol, which has demonstrated decreased death rates in this patient population. In our case study, we present a rare case of a 60-year-old female patient diagnosed with fulminant small bowel CDI requiring resection of the necrotic small bowel. This was followed by creating an ileostomy and the Pittsburgh protocol, leading to a complete recovery. With an increasing incidence of CDI, it is important to be aware of the small bowel C. difficile infection and its treatment.
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Affiliation(s)
- Sunanda Tah
- Surgery, Saint James School of Medicine, Arnos Vale, VCT
- Surgery, Beckley Appalachian Regional Healthcare (ARH) Hospital, Beckley, USA
| | - Saqib Khan
- Surgery, Avalon University School of Medicine, Willemstad, CUW
- Surgery, Beckley Appalachian Regional Healthcare (ARH) Hospital, Beckley, USA
| | - Sarang Kashyap
- Surgery, Beckley Appalachian Regional Healthcare (ARH) Hospital, Beckley, USA
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16
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Reveles KR, Yang M, Garcia-Horton V, Edwards ML, Guo A, Lodise T, Bochan M, Tillotson G, Dubberke ER. Economic Impact of Recurrent Clostridioides difficile Infection in the USA: A Systematic Literature Review and Cost Synthesis. Adv Ther 2023; 40:3104-3134. [PMID: 37210680 PMCID: PMC10272265 DOI: 10.1007/s12325-023-02498-x] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2023] [Accepted: 03/15/2023] [Indexed: 05/22/2023]
Abstract
INTRODUCTION Up to 35% of patients with a first episode of Clostridioides difficile infection (CDI) develop recurrent CDI (rCDI), and of those, up to 65% experience multiple recurrences. A systematic literature review (SLR) was conducted to review and summarize the economic impact of rCDI in the United States of America. METHODS English-language publications reporting real-world healthcare resource utilization (HRU) and/or direct medical costs associated with rCDI in the USA were searched in MEDLINE, MEDLINE In-Process, Embase, and the Cochrane Library databases over the past 10 years (2012-2022), as well as in selected scientific conferences that publish research on rCDI and its economic burden over the past 3 years (2019-2022). HRU and costs identified through the SLR were synthesized to estimate annual rCDI-attributable direct medical costs to inform the economic impact of rCDI from a US third-party payer's perspective. RESULTS A total of 661 publications were retrieved, and 31 of them met all selection criteria. Substantial variability was found across these publications in terms of data source, patient population, sample size, definition of rCDI, follow-up period, outcomes reported, analytic approach, and methods to adjudicate rCDI-attributable costs. Only one study reported rCDI-attributable costs over 12 months. Synthesizing across the relevant publications using a component-based cost approach, the per-patient per-year rCDI-attributable direct medical cost was estimated to range from $67,837 to $82,268. CONCLUSIONS While real-world studies on economic impact of rCDI in the USA suggested a high-cost burden, inconsistency in methodologies and results reporting warranted a component-based cost synthesis approach to estimate the annual medical cost burden of rCDI. Utilizing available literature, we estimated the average annual rCDI-attributable medical costs to allow for consistent economic assessments of rCDI and identify the budget impact on US payers.
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Affiliation(s)
- Kelly R Reveles
- College of Pharmacy, The University of Texas at Austin, Austin, TX, USA
| | - Min Yang
- Analysis Group, 111 Huntington Avenue, 14th Floor, Boston, MA, 02199, USA.
| | | | | | - Amy Guo
- Medical Affairs, Ferring Pharmaceuticals, Parsippany, NJ, USA
| | - Thomas Lodise
- Albany College of Pharmacy and Health Sciences, Albany, NY, USA
| | | | | | - Erik R Dubberke
- Division of Infectious Diseases, Washington University School of Medicine in St. Louis, St. Louis, MO, USA
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17
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Lodise T, Guo A, Yang M, Cook EE, Song W, Yang D, Wang Q, Zhao A, Bochan M. Cost-Effectiveness Analysis of REBYOTA™ (Fecal Microbiota, Live-jslm [FMBL]) Versus Standard of Care for the Prevention of Recurrent Clostridioides difficile Infection in the USA. Adv Ther 2023; 40:2784-2800. [PMID: 37093359 PMCID: PMC10220097 DOI: 10.1007/s12325-023-02505-1] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2023] [Accepted: 03/24/2023] [Indexed: 04/25/2023]
Abstract
INTRODUCTION Recurrent Clostridioides difficile infection (rCDI) is common and associated with considerable clinical and economic consequences. REBYOTA™ (fecal microbiota, live-jslm [FMBL]) is a microbiota-based live biotherapeutic approved for the prevention of rCDI following antibiotic treatment for rCDI. We sought to evaluate cost-effectiveness of FMBL compared to standard of care (SOC) from a US third-party payer perspective among patients with one or more (≥ 1) recurrences. METHODS A Markov model with a lifetime time horizon was developed. The model population included adult patients who had ≥ 1 recurrence after a primary CDI episode and had completed ≥ 1 round of antibiotics, or had ≥ 2 severe CDI episodes resulting in hospitalization within the last year. The model consisted of six health states with an 8-week model cycle: rCDI, absence of CDI after recurrence, colectomy, ileostomy, ileostomy reversal, and death. Drug costs and rCDI-related medical costs were estimated in 2022 US dollars and discounted at 3% annually. Deterministic sensitivity analyses were performed. RESULTS Compared to SOC, FMBL at $9000/course resulted in an incremental cost-effectiveness ratio (ICER) of $18,727 per quality-adjusted life year (QALY) gained. The incremental cost was $5336 (FMBL $79,236, SOC $73,900) and the incremental effectiveness was 0.285 QALYs (FMBL 10.346, SOC 10.061). The cumulative drug acquisition and administration costs for the FMBL and SOC arms were $24,245 and $16,876, while rCDI-related medical costs for FMBL and SOC were $54,991 and $57,024, respectively. The ICER in the subgroup of patients at first recurrence was $13,727 per QALY gained. FMBL remained cost-effective across all sensitivity analyses. CONCLUSIONS FMBL was found to be cost-effective compared to SOC for the prevention of rCDI with more benefits among patients at first recurrence, with an ICER far below the payer ICER threshold of $100,000. Patients treated with FMBL experienced higher total QALYs and reduced healthcare resource utilization, including reduced hospitalizations.
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Affiliation(s)
- Thomas Lodise
- Albany College of Pharmacy and Health Sciences, Albany, NY, USA
| | - Amy Guo
- HEOR & RWE, Medical Affairs, Ferring Pharmaceuticals, Inc., 100 Interpace Parkway, Parsippany, NJ, 07054, USA.
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18
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Lodise T, Guo A, Yang M, Cook EE, Song W, Yang D, Wang Q, Zhao A, Bochan M. Budget Impact Analysis of REBYOTA™ (Fecal Microbiota, Live-jslm [FMBL]) for Preventing Recurrent Clostridioides difficile Infection in the US. Adv Ther 2023; 40:2801-2819. [PMID: 37093360 PMCID: PMC10219864 DOI: 10.1007/s12325-023-02506-0] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/24/2023] [Indexed: 04/25/2023]
Abstract
INTRODUCTION Patients with Clostridioides difficile infection (CDI) often experience recurrences (rCDI), which are associated with high morbidity, mortality, and healthcare expenditures. REBYOTA™ (fecal microbiota, live-jslm [FMBL]) is a microbiota-based live biotherapeutic approved for the prevention of rCDI following antibiotic treatment for rCDI. We quantified the budget impact of FMBL during the first 3 years following introduction from a third-party US payer perspective. METHODS A decision-tree model was used to estimate the budget impact of one-course FMBL by comparing costs under the scenario with FMBL to the scenario without FMBL (standard of care) in patients with one or more (≥ 1) recurrences after a primary episode of CDI and had completed ≥ 1 round of antibiotic treatments. Drug costs, rCDI-related medical costs, and budget impact over 1-3 years were estimated in 2022 US dollars. One-way sensitivity analyses were performed. RESULTS For an insurance plan with a population size of 1,000,000, 468 patients per year were estimated to have ≥ 1 rCDI. The budget impact of one-course FMBL at $9000/course was cost-saving at an» average of -$0.0039 on a per-member-per-month (PMPM) basis, an average of -$8.30 on a per-treated-member-per-month (PTMPM) basis, and a total of -$139,865 on a plan level assuming 5%, 15%, and 20% of patients receive FMBL over 1-3 years, respectively. The scenario with FMBL entry was associated with higher drug costs (difference at $0.0474 PMPM; $101.26 PTMPM; $1,706,445 total plan) and lower rCDI-related medical costs (difference at -$0.0513 PMPM; -$109.56 PTMPM; -$1,846,309 total plan). The budget impact of FMBL in patients at first rCDI was cost-saving at -$0.0139 PMPM, -$84.78 PTMPM, corresponding to an annual savings of $500,022. CONCLUSIONS FMBL has a cost-saving budget impact for a US payer, with higher initial drug costs being offset by savings in rCDI-related medical costs. Greater cost saving was found in patients at first recurrence.
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Affiliation(s)
- Thomas Lodise
- Albany College of Pharmacy and Health Sciences, Albany, NY, USA
| | - Amy Guo
- Medical Affairs, Ferring Pharmaceuticals, Inc, 100 Interpace Parkway, Parsippany, NJ, 07054, USA.
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19
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McKechnie T, Khamar J, Lee Y, Tessier L, Passos E, Doumouras A, Hong D, Eskicioglu C. Total Abdominal Colectomy Versus Diverting Loop Ileostomy and Antegrade Colonic Lavage for Fulminant Clostridioides Colitis: Analysis of the National Inpatient Sample 2016-2019. J Gastrointest Surg 2023:10.1007/s11605-023-05682-0. [PMID: 37081220 DOI: 10.1007/s11605-023-05682-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/23/2023] [Accepted: 04/10/2023] [Indexed: 04/22/2023]
Abstract
BACKGROUND When surgery is indicated for fulminant Clostridioides difficile infection (CDI), total abdominal colectomy (TAC) is the most common approach. Diverting loop ileostomy (DLI) with antegrade colonic lavage has been introduced as a colon-sparing surgical approach. Prior analyses of National Inpatient Sample (NIS) data suggested equivalent postoperative outcomes between groups but did not evaluate healthcare resource utilization. As such, we aimed to analyze a more recent NIS cohort to compare these two approaches in terms of both postoperative outcomes and healthcare resource utilization. METHODS A retrospective analysis of the NIS from 2016 to 2019 was conducted. The primary outcome was postoperative in-hospital morbidity. Secondary outcomes included postoperative in-hospital mortality, system-specific postoperative complications, total admission cost, and length of stay (LOS). Univariable and multivariable regressions were utilized to compare the two operative approaches. RESULTS In total, 886 patients underwent TAC and 409 patients underwent DLI with antegrade colonic lavage. Adjusted analyses demonstrated no difference between groups in postoperative in-hospital morbidity (aOR 0.96, 95%CI 0.64-1.44, p = 0.851) or in-hospital mortality (aOR 1.15, 95%CI 0.81-1.64, p = 0.436). Patients undergoing TAC experienced significantly decreased total admission cost (MD $79,715.34, 95%CI 133,841-25,588, p = 0.004) and shorter postoperative LOS (MD 4.06 days, 95%CI 6.96-1.15, p = 0.006). CONCLUSIONS There are minimal differences between TAC and DLI with antegrade colonic lavage for fulminant CDI in terms of postoperative morbidity and mortality. Healthcare resource utilization, however, is significantly improved when patients undergo TAC as evidenced by clinically important decreases in total admission cost and postoperative LOS.
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Affiliation(s)
- Tyler McKechnie
- Division of General Surgery, Department of Surgery, McMaster University, Hamilton, ON, L8N 4A6, Canada
| | - Jigish Khamar
- Michael G. DeGroote School of Medicine, McMaster University, Hamilton, Ontario, Canada
| | - Yung Lee
- Division of General Surgery, Department of Surgery, McMaster University, Hamilton, ON, L8N 4A6, Canada
- Harvard T.H. Chan School of Public Health, Harvard University, Boston, MA, USA
| | - Léa Tessier
- Michael G. DeGroote School of Medicine, McMaster University, Hamilton, Ontario, Canada
| | - Edward Passos
- Division of General Surgery, Department of Surgery, McMaster University, Hamilton, ON, L8N 4A6, Canada
- Michael G. DeGroote School of Medicine, McMaster University, Hamilton, Ontario, Canada
| | - Aristithes Doumouras
- Division of General Surgery, Department of Surgery, McMaster University, Hamilton, ON, L8N 4A6, Canada
- Michael G. DeGroote School of Medicine, McMaster University, Hamilton, Ontario, Canada
- Division of General Surgery, Department of Surgery, St. Joseph's Healthcare, Hamilton, Ontario, Canada
| | - Dennis Hong
- Division of General Surgery, Department of Surgery, McMaster University, Hamilton, ON, L8N 4A6, Canada
- Michael G. DeGroote School of Medicine, McMaster University, Hamilton, Ontario, Canada
- Division of General Surgery, Department of Surgery, St. Joseph's Healthcare, Hamilton, Ontario, Canada
| | - Cagla Eskicioglu
- Division of General Surgery, Department of Surgery, McMaster University, Hamilton, ON, L8N 4A6, Canada.
- Michael G. DeGroote School of Medicine, McMaster University, Hamilton, Ontario, Canada.
- Division of General Surgery, Department of Surgery, St. Joseph's Healthcare, Hamilton, Ontario, Canada.
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20
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Leonard JM, Pascual JL, Kaplan LJ. Dysbiome and Its Role in Surgically Relevant Medical Disease. Surg Infect (Larchmt) 2023; 24:226-231. [PMID: 37010968 PMCID: PMC10398742 DOI: 10.1089/sur.2023.019] [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] [Indexed: 04/04/2023] Open
Abstract
Several surgically relevant conditions are directly or indirectly influenced by the human microbiome. Different microbiomes may be found within, or along, specific organs and intra-organ variation is common. Such variations include those found along the course of the gastrointestinal tract as well as those on different regions of the skin. A variety of physiologic stressors and care interventions may derange the native microbiome. A deranged microbiome is termed a dysbiome and is characterized by decreased diversity and an increase in the proportion of potentially pathogenic organisms; the elaboration of virulence factors coupled with clinical consequences defines a pathobiome. Specific conditions such as Clostridium difficile colitis, inflammatory bowel disease, obesity, and diabetes mellitus are tightly linked to a dysbiome or pathobiome. Additionally, massive transfusion after injury appears to derange the gastrointestinal microbiome as well. This review explores what is known about these surgically relevant clinical conditions to chart how non-surgical interventions may support surgical undertakings or potentially reduce the need for operation.
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Affiliation(s)
- Jennifer M. Leonard
- Department of Surgery, Division of Acute Care Surgery, Washington University in St. Lous, St. Louis, Missouri, USA
| | - Jose L. Pascual
- Department of Surgery, Division of Trauma, Surgical Critical Care, and Emergency Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
- Surgical Services, Section of Surgical Critical Care, Corporal Michael J. Crescenz VA Medical Center, Philadelphia, Pennsylvania, USA
| | - Lewis J. Kaplan
- Department of Surgery, Division of Trauma, Surgical Critical Care, and Emergency Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
- Surgical Services, Section of Surgical Critical Care, Corporal Michael J. Crescenz VA Medical Center, Philadelphia, Pennsylvania, USA
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21
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Ong AW, Mathew S. Surgeons in Captivity: Thai-Burma Railway, 1942-1943. World J Surg 2023; 47:600-605. [PMID: 36443584 DOI: 10.1007/s00268-022-06845-x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/04/2022] [Indexed: 11/29/2022]
Affiliation(s)
- Adrian W Ong
- Department of Surgery, Reading Hospital, 420 S. 5th Avenue, PA, 19611, Reading, USA.
| | - Sarah Mathew
- Department of Surgery, Reading Hospital, 420 S. 5th Avenue, PA, 19611, Reading, USA
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22
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Abstract
Fecal microbiota transplantation (FMT) is the process of transplanting stool from a healthy donor into the gut of a patient for therapeutic purposes. Current guidelines recommend FMT for the prevention of multiply recurrent Clostridioides difficile infection (CDI) after two recurrences, with cure rates approaching 90%. Emerging evidence also supports the use of FMT in the management of severe and fulminant CDI, resulting in decreased mortality and colectomy rates compared with standard of care approach. FMT shows promise as salvage therapy for critically-ill, refractory CDI patients who are poor surgical candidates. FMT should be considered early in the clinical course of severe CDI, preferably within 48 hours of failing to respond to antibiotic therapy and volume resuscitation. Besides CDI, ulcerative colitis was more recently identified as a potential treatment target for FMT. Several live biotherapeutics for microbiome restoration are on the horizon.
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Affiliation(s)
- Yao-Wen Cheng
- Department of Gastroenterology, Kaiser Permanente Santa Clara Medical Center, Santa Clara, California
| | - Monika Fischer
- Division of Gastroenterology and Hepatology, Indiana University School of Medicine, Indianapolis, Indiana
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23
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Rimawi RH, Busby S, Greene WR. Severe Clostridioides difficile Infection in the Intensive Care Unit—Medical and Surgical Management. Infect Dis Clin North Am 2022; 36:889-895. [DOI: 10.1016/j.idc.2022.07.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
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Kunishima H, Ohge H, Suzuki H, Nakamura A, Matsumoto K, Mikamo H, Mori N, Morinaga Y, Yanagihara K, Yamagishi Y, Yoshizawa S. Japanese Clinical Practice Guidelines for Management of Clostridioides (Clostridium) difficile infection. J Infect Chemother 2022; 28:1045-1083. [PMID: 35618618 DOI: 10.1016/j.jiac.2021.12.011] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2021] [Revised: 11/16/2021] [Accepted: 12/13/2021] [Indexed: 12/19/2022]
Affiliation(s)
- Hiroyuki Kunishima
- Department of Infectious Diseases, St. Marianna University School of Medicine, Japan.
| | - Hiroki Ohge
- Department of Infectious Diseases, Hiroshima University Hospital, Japan
| | - Hiromichi Suzuki
- Division of Infectious Diseases, Department of Medicine, Tsukuba Medical Center Hospital, Japan
| | - Atsushi Nakamura
- Division of Infection Control and Prevention, Nagoya City University Hospital, Japan
| | - Kazuaki Matsumoto
- Division of Pharmacodynamics, Faculty of Pharmacy, Keio University, Japan
| | - Hiroshige Mikamo
- Clinical Infectious Diseases, Graduate School of Medicine, Aichi Medical University, Japan
| | - Nobuaki Mori
- Division of General Internal Medicine and Infectious Diseases, National Hospital Organization Tokyo Medical Center, Japan
| | - Yoshitomo Morinaga
- Department of Microbiology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Japan
| | - Katsunori Yanagihara
- Department of Laboratory Medicine, Nagasaki University Graduate School of Biomedical Sciences, Japan
| | - Yuka Yamagishi
- Clinical Infectious Diseases, Graduate School of Medicine, Aichi Medical University, Japan
| | - Sadako Yoshizawa
- Department of Clinical Laboratory/Department of Microbiology and Infectious Diseases, Toho University School of Medicine, Japan
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Successful Fecal Microbiota Transplant Delivered by Foley Catheter Through a Loop Ileostomy in a Patient With Severe Complicated Clostridioides difficile Infection. ACG Case Rep J 2022; 9:e00801. [PMID: 35919409 PMCID: PMC9278911 DOI: 10.14309/crj.0000000000000801] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/28/2021] [Accepted: 03/20/2022] [Indexed: 11/17/2022] Open
Abstract
Clostridioides difficile infection (CDI) is a potentially life-threatening cause of diarrhea that can result in multiple complications. Fulminant CDI that is nonresponsive to antibiotics may require surgical ileostomy or fecal microbiota transplant (FMT). We present a case of a patient with fulminant CDI requiring surgical loop ileostomy who underwent a successful FMT delivered by Foley catheter through the ileostomy with symptom resolution. Delivery of FMT using a foley catheter in a patient with an ileostomy may be safe and effective for patients who are at a higher risk of complications associated with the instillation of FMT through colonoscopy with anesthesia.
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Validation of Clinical Risk Models for Clostridioides difficile -Attributable Outcomes. Antimicrob Agents Chemother 2022; 66:e0067622. [PMID: 35727061 PMCID: PMC9295569 DOI: 10.1128/aac.00676-22] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/05/2022] Open
Abstract
Clostridioides difficile is the leading health care-associated pathogen, leading to substantial morbidity and mortality; however, there is no widely accepted model to predict C. difficile infection severity. Most currently available models perform poorly or were calibrated to predict outcomes that are not clinically relevant. We sought to validate six of the leading risk models (Age Treatment Leukocyte Albumin Serum Creatinine (ATLAS), C. difficile Disease (CDD), Zar, Hensgens, Shivashankar, and C. difficile Severity Score (CDSS)), guideline severity criteria, and PCR cycle threshold for predicting C. difficile-attributable severe outcomes (inpatient mortality, colectomy/ileostomy, or intensive care due to sepsis). Models were calculated using electronic data available within ±48 h of diagnosis (unavailable laboratory measurements assigned zero points), calibrated using a large retrospective cohort of 3,327 inpatient infections spanning 10 years, and compared using receiver operating characteristic (ROC) and precision-recall curves. ATLAS achieved the highest area under the ROC curve (AuROC) of 0.781, significantly better than the next best performing model (Zar 0.745; 95% confidence interval of AuROC difference 0.0094–0.6222; P = 0.008), and highest area under the precision-recall curve of 0.232. Current IDSA/SHEA severity criteria demonstrated moderate performance (AuROC 0.738) and PCR cycle threshold performed the worst (0.531). The overall predictive value for all models was low, with a maximum positive predictive value of 37.9% (ATLAS cutoff ≥9). No clinical model performed well on external validation, but ATLAS did outperform other models for predicting clinically relevant C. difficile-attributable outcomes at diagnosis. Novel markers should be pursued to augment or replace underperforming clinical-only models.
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Moghadamyeghaneh Z, Rahimi M, Kopatsis K, Kopatsis AP, Kopatsis A. Minimally Invasive Surgical Approach to Toxic Colitis. Am Surg 2022; 88:1411-1419. [PMID: 35331011 DOI: 10.1177/00031348221080420] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
BACKGROUND We aimed to compare outcomes of surgical treatments of toxic colitis (infectious/inflammatory/ischemic) by the extent of colectomy (partial vs total colectomy) and different surgical approaches (minimally invasive surgery (MIS) vs open). METHODS Multivariate analysis using logistic regression was used to investigate outcomes of patients with toxic colitis who underwent emergent colectomy during 2012-2019 by surgical approach and the extent of resection using NSQIP database. RESULTS Overall, 2,104 adult patients underwent emergent colectomy for toxic colitis within NSQIP database during 2012-2019. Overall, 1,578 (75.4%) underwent total colectomy with colostomy, 486 (23.2%) underwent partial colectomy with colostomy, and 28 (1.3%) underwent partial colectomy with anastomosis. Overall, 198 (9.4%) of procedures were minimally invasive (MIS) with a 40.1% conversion rate to open. Thirty days mortality and morbidity of the patients were 31 and 86%, respectively. There was no significant difference in mortality of partial colectomy without anastomosis compared to total colectomy (P = .86) and partial colectomy with anastomosis (P = .64). Anastomosis was associated with 32.3% anastomosis leakage and 17.9% reoperation. MIS approach was associated with significant decrease in mortality (8.6 vs 33.3%, AOR: .35, P < .01) and morbidity (62.9 vs 87.8%, AOR: .49, P < .01) of patients. CONCLUSION Patients with toxic colitis undergoing surgical treatment have high mortality and morbidity. An MIS approach when possible is significantly associated with decreased morbidity and mortality of patients. There was no significant difference in outcomes seen when extending the resection in multivariate analysis. Anastomosis is associated with a high anastomosis leakage and need for reoperation risk.
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Affiliation(s)
- Zhobin Moghadamyeghaneh
- Department of Surgery, 2012NYC Health and Hospitals-Elmhurst, Queens, NY, USA.,Department of Surgery, 5925Icahn School of Medicine at Mount Sinai/Elmhurst, Queens, NY, USA
| | - Murwarid Rahimi
- Department of Surgery, 2012NYC Health and Hospitals-Elmhurst, Queens, NY, USA
| | - Katherine Kopatsis
- Department of Surgery, 2012NYC Health and Hospitals-Elmhurst, Queens, NY, USA
| | | | - Anthony Kopatsis
- Department of Surgery, 2012NYC Health and Hospitals-Elmhurst, Queens, NY, USA.,Department of Surgery, 5925Icahn School of Medicine at Mount Sinai/Elmhurst, Queens, NY, USA
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Forrester JD, Colling KP, Diaz JJ, Faliks B, Kim PK, Tessier JM, Tung J, Huston JM. Surgical Infection Society Guidelines for Total Abdominal Colectomy versus Diverting Loop Ileostomy with Antegrade Intra-Colonic Lavage for the Surgical Management of Severe or Fulminant, Non-Perforated Clostridioides difficile Colitis. Surg Infect (Larchmt) 2022; 23:97-104. [PMID: 34619068 DOI: 10.1089/sur.2021.126] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
Background: Clostridioides difficile infection (CDI) can result in life-threatening illness requiring surgery. Surgical options for managing severe or fulminant, non-perforated C. difficile colitis include total abdominal colectomy with end ileostomy or creation of a diverting loop ileostomy with antegrade vancomycin lavage. Methods: The Surgical Infection Society's Therapeutics and Guidelines Committee convened to develop guidelines for summarizing the current SIS recommendations for total abdominal colectomy versus diverting loop ileostomy with antegrade lavage for severe or fulminant, non-perforated C. difficile colitis. PubMed, Embase, and the Cochrane database were searched for pertinent studies. Severe infection was defined as laboratory diagnosis of C. difficile infection with leukocytosis (white blood cell count of ≥15,000 cells/mL) or elevated creatinine (serum creatinine level >1.5 mg/dL). Fulminant infection was defined as laboratory diagnosis of C. difficile infection with hypotension or shock, ileus, or megacolon. Perforation was defined as complete disruption of the colon wall. Total abdominal colectomy was defined as resection of the ascending, transverse, descending, and sigmoid colon with end ileostomy. For the purpose of the guideline, the terms subtotal colectomy, total abdominal colectomy, and rectal-sparing total colectomy were used interchangeably. Diverting loop ileostomy with antegrade enema was defined as creation of both a diverting loop ileostomy with intra-operative colonic lavage and post-operative antegrade vancomycin unless otherwise specified. Evaluation of the published evidence was performed using the Grades of Recommendation Assessment, Development and Evaluation (GRADE) system. Using a process of iterative consensus, all committee members voted to accept or reject each recommendation. Results: We recommend that total abdominal colectomy be the procedure of choice for definitive therapy of severe or fulminant, non-perforated C. difficile colitis. In select patients, colon preservation using diverting loop ileostomy with intra-colonic vancomycin may be associated with higher rates of ostomy reversal and restoration of gastrointestinal continuity but may lead to development of recurrent C. difficile colitis. Conclusions: This guideline summarizes the current Surgical Infection Society recommendations regarding use of total abdominal colectomy versus diverting loop ileostomy with antegrade lavage for adults with severe or fulminant, non-perforated C. difficile infection.
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Affiliation(s)
- Joseph D Forrester
- Division of General Surgery, Department of Surgery, Stanford University, Stanford, California, USA
| | - Kristin P Colling
- Department of Trauma and Critical Care Surgery, St. Mary's Medical Center, Essentia Health, Duluth, Minnesota, USA
| | - Jose J Diaz
- Program in Trauma, Department of Surgery, University of Maryland School of Medicine/R Adams Cowley Shock Trauma Center. Baltimore, Maryland, USA
| | - Bradley Faliks
- Department of Surgery, Zucker School of Medicine at Hofstra/Northwell, Northwell Health, Hempstead, New York, USA
| | - Peter K Kim
- Department of Surgery, Jacobi Medical Center, Albert Einstein College of Medicine, Bronx, New York, USA
| | - Jeffrey M Tessier
- Division of Infectious Diseases and Geographic Medicine, University of Texas Southwestern, Dallas, Texas, USA
| | - Jamie Tung
- Division of General Surgery, Department of Surgery, Stanford University, Stanford, California, USA
| | - Jared M Huston
- Department of Surgery, Zucker School of Medicine at Hofstra/Northwell, Northwell Health, Hempstead, New York, USA
- Department of Science Education, Zucker School of Medicine at Hofstra/Northwell, Northwell Health, Hempstead, New York, USA
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Tixier EN, Verheyen E, Luo Y, Grinspan LT, Du CH, Ungaro RC, Walsh S, Grinspan AM. Systematic Review with Meta-Analysis: Fecal Microbiota Transplantation for Severe or Fulminant Clostridioides difficile. Dig Dis Sci 2022; 67:978-988. [PMID: 33748913 DOI: 10.1007/s10620-021-06908-4] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/04/2020] [Accepted: 02/19/2021] [Indexed: 12/15/2022]
Abstract
BACKGROUND Severe and fulminant Clostridioides difficile infection (CDI) is associated with significant morbidity and mortality. While fecal microbiota transplantation (FMT) has proved to be a highly effective treatment for recurrent CDI, its efficacy in severe or fulminant CDI remains uncertain. AIMS To perform a systematic review with meta-analysis evaluating clinical outcomes and safety of FMT in severe and fulminant CDI. METHODS A systemic review with meta-analysis was performed through comprehensive search of Embase, Medline (Ovid), trial registers, and conference abstracts through January 2020. Studies on FMT in severe and fulminant CDI were included. Meta-analysis was done with random effects models given heterogeneity to estimate rates of cure, mortality, and colectomy. Publication bias was assessed using Egger's test. RESULTS Sixteen studies comprised of one randomized controlled trial, four cohort studies, and eleven case series were analyzed. In total, 676 patients underwent FMT for severe or fulminant CDI. The overall rate of clinical cure after single FMT was 61.3% (95% CI 43.2-78.0%) with 10.9% (95% CI 0.2-30.2%) of patients experiencing major adverse events. The overall pooled colectomy rate after FMT was 8.2% (95% CI 0.1-23.7%) with a pooled all-cause mortality rate after FMT of 15.6% (95% CI 7.8-25.0%). CONCLUSION Low-quality data support the use of fecal microbiota transplantation in patients with severe and fulminant Clostridioides difficile infection.
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Affiliation(s)
- Emily N Tixier
- Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | | | - Yuying Luo
- Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | | | - Charles H Du
- Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Ryan C Ungaro
- Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Samantha Walsh
- Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Ari M Grinspan
- Icahn School of Medicine at Mount Sinai, New York, NY, USA.
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Clostridioides difficile from brazilian hospitals: characterization of virulence genes by whole genome sequencing. Microbes Infect 2022; 24:104953. [PMID: 35217192 DOI: 10.1016/j.micinf.2022.104953] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2021] [Revised: 01/24/2022] [Accepted: 02/15/2022] [Indexed: 12/15/2022]
Abstract
Clostridioides difficile (CD) is the most frequent cause of healthcare related diarrhea and its severity has increased in the last decade by the spread of hypervirulent strains. Most important CD virulence factor is toxin production; however, not only toxins are responsible for Clostridioides virulence. We sequenced 38 strains and analyzed the presence and integrity of 24 virulence (including toxin) genes. We identified 28 toxigenic strains, six also presented the cdt genes. Only six strains didn't present all others genes searched. All absent genes were adhesion related. Understand others CD virulence factors can lead to a best understanding on this matter.
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Carlson TJ, Gonzales-Luna AJ, Garey KW. Fulminant Clostridioides difficile Infection: A Review of Treatment Options for a Life-Threatening Infection. Semin Respir Crit Care Med 2022; 43:28-38. [PMID: 35172356 DOI: 10.1055/s-0041-1740973] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
Abstract
Fulminant Clostridioides difficile infection (FCDI) encompasses 3 to 5% of all CDI cases with associated mortality rates between 30 and 40%. Major treatment modalities include surgery and medical management with antibiotic and nonantibiotic therapies. However, identification of patients with CDI that will progress to FCDI is difficult and makes it challenging to direct medical management and identify those who may benefit from surgery. Furthermore, since it is difficult to study such a critically ill population, data investigating treatment options are limited. Surgical management with diverting loop ileostomy (LI) instead of a total abdominal colectomy (TAC) with end ileostomy has several appealing advantages, and studies have not consistently demonstrated a clinical benefit with this less-invasive strategy, so both LI and TAC remain acceptable surgical options. Successful medical management of FCDI is complicated by pharmacokinetic changes that occur in critically ill patients, and there is an absence of high-quality studies that included patients with FCDI. Recommendations accordingly include a combination of antibiotics administered via multiple routes to ensure adequate drug concentrations in the colon: intravenous metronidazole, high-dose oral vancomycin, and rectal vancomycin. Although fidaxomicin is now recommended as first-line therapy for non-FCDI, there are limited clinical data to support its use in FCDI. Several nonantibiotic therapies, including fecal microbiota transplantation and intravenous immunoglobulin, have shown success as adjunctive therapies, but they are unlikely to be effective alone. In this review, we aim to summarize diagnosis and treatment options for FCDI.
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Affiliation(s)
- Travis J Carlson
- Department of Clinical Sciences, High Point University Fred Wilson School of Pharmacy, High Point, North Carolina
| | - Anne J Gonzales-Luna
- Department of Pharmacy Practice and Translational Research, University of Houston College of Pharmacy, Houston, Texas
| | - Kevin W Garey
- Department of Pharmacy Practice and Translational Research, University of Houston College of Pharmacy, Houston, Texas
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Ahmed N, Kuo YH. Outcomes of total versus partial colectomy in fulminant Clostridium difficile colitis: a propensity matched analysis. World J Emerg Surg 2022; 17:11. [PMID: 35152901 PMCID: PMC8842562 DOI: 10.1186/s13017-022-00414-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2021] [Accepted: 01/25/2022] [Indexed: 11/10/2022] Open
Abstract
Background The Total Abdominal Colectomy (TAC) is the recommended procedure for Fulminant Clostridium Difficile Colitis (FCDC), however, occasionally, FCDC is also treated with partial colectomies. The purpose of the study was to identify the outcomes of partial colectomy in FCDC cases.
Method The National Surgical Quality Improvement Program database was accessed and eligible patients from 2012 through 2016 were reviewed. Patients 18 years and older who were diagnosed with FCDC and who underwent colectomies were included in the study. Patients’ demography, clinical characteristics, comorbidities, mortality, morbidities, length of hospital stay and discharge disposition were compared between the group who underwent partial colectomy and the group who underwent TAC. Univariate analysis followed by propensity matching was performed. A P value of < 0.05 is considered as statistically significant.
Results Out of 491 patients who qualified for the study, 93 (18.9%) patients underwent partial colectomy. The pair matched analysis showed no significant difference in patients’ characteristics and comorbidities in the two groups. There was no significant difference found in mortality between the two groups (30.1% vs. 30.1%, P > 0.99). There were no differences found in the median [95% CI] hospital length of stay (LOS) (23 days [19–31] vs. 21 [17–25], P = 0.30), post-operative complications (all P > 0.05), and discharged disposition to home ( 33.8% vs. 43.1%) or transfer to rehab (21.55 vs. 12.3%, P = 0.357) between the TAC and partial colectomy groups. Conclusion The overall 30 days mortality remains very high in FCDC. Partial colectomy did not increase risk of mortality or morbidities and LOS. Level of evidence Level IV. Study type Observational cohort.
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Manrai M, Upreti R. Editorial: Rejuvenating the Microbiome in Recurrent Clostridioides difficile Infection with Fecal Microbiota Transplant. JOURNAL OF GASTROINTESTINAL INFECTIONS 2022; 12:007-008. [DOI: 10.1055/s-0042-1757421] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/16/2024]
Affiliation(s)
- Manish Manrai
- Department of Internal Medicine, Armed Forces Medical College, Pune, Maharashtra, India
| | - Rohit Upreti
- Department of Internal Medicine, Military Hospital, Dimapur, Nagaland, India
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Sartelli M. Healthcare-associated infections in the surgical setting: How to prevent and treat them. ADVANCES IN HUMAN BIOLOGY 2022. [DOI: 10.4103/aihb.aihb_53_22] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
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van Prehn J, Reigadas E, Vogelzang EH, Bouza E, Hristea A, Guery B, Krutova M, Norén T, Allerberger F, Coia JE, Goorhuis A, van Rossen TM, Ooijevaar RE, Burns K, Scharvik Olesen BR, Tschudin-Sutter S, Wilcox MH, Vehreschild MJGT, Fitzpatrick F, Kuijper EJ. European Society of Clinical Microbiology and Infectious Diseases: 2021 update on the treatment guidance document for Clostridioides difficile infection in adults. Clin Microbiol Infect 2021; 27 Suppl 2:S1-S21. [PMID: 34678515 DOI: 10.1016/j.cmi.2021.09.038] [Citation(s) in RCA: 332] [Impact Index Per Article: 83.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2021] [Revised: 09/23/2021] [Accepted: 09/30/2021] [Indexed: 12/13/2022]
Abstract
SCOPE In 2009, the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) published the first treatment guidance document for Clostridioides difficile infection (CDI). This document was updated in 2014. The growing literature on CDI antimicrobial treatment and novel treatment approaches, such as faecal microbiota transplantation (FMT) and toxin-binding monoclonal antibodies, prompted the ESCMID study group on C. difficile (ESGCD) to update the 2014 treatment guidance document for CDI in adults. METHODS AND QUESTIONS Key questions on CDI treatment were formulated by the guideline committee and included: What is the best treatment for initial, severe, severe-complicated, refractory, recurrent and multiple recurrent CDI? What is the best treatment when no oral therapy is possible? Can prognostic factors identify patients at risk for severe and recurrent CDI and is there a place for CDI prophylaxis? Outcome measures for treatment strategy were: clinical cure, recurrence and sustained cure. For studies on surgical interventions and severe-complicated CDI the outcome was mortality. Appraisal of available literature and drafting of recommendations was performed by the guideline drafting group. The total body of evidence for the recommendations on CDI treatment consists of the literature described in the previous guidelines, supplemented with a systematic literature search on randomized clinical trials and observational studies from 2012 and onwards. The Grades of Recommendation Assessment, Development and Evaluation (GRADE) system was used to grade the strength of our recommendations and the quality of the evidence. The guideline committee was invited to comment on the recommendations. The guideline draft was sent to external experts and a patients' representative for review. Full ESCMID endorsement was obtained after a public consultation procedure. RECOMMENDATIONS Important changes compared with previous guideline include but are not limited to: metronidazole is no longer recommended for treatment of CDI when fidaxomicin or vancomycin are available, fidaxomicin is the preferred agent for treatment of initial CDI and the first recurrence of CDI when available and feasible, FMT or bezlotoxumab in addition to standard of care antibiotics (SoC) are preferred for treatment of a second or further recurrence of CDI, bezlotoxumab in addition to SoC is recommended for the first recurrence of CDI when fidaxomicin was used to manage the initial CDI episode, and bezlotoxumab is considered as an ancillary treatment to vancomycin for a CDI episode with high risk of recurrence when fidaxomicin is not available. Contrary to the previous guideline, in the current guideline emphasis is placed on risk for recurrence as a factor that determines treatment strategy for the individual patient, rather than the disease severity.
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Affiliation(s)
- Joffrey van Prehn
- Department of Medical Microbiology, Centre for Infectious Diseases, Leiden University Medical Center, Leiden, the Netherlands
| | - Elena Reigadas
- Department of Clinical Microbiology and Infectious Diseases, Hospital General Universitario Gregorio Marañón, Madrid, Spain
| | - Erik H Vogelzang
- Department of Medical Microbiology and Infection Control, Amsterdam University Medical Center, Location VUmc, Amsterdam, the Netherlands
| | - Emilio Bouza
- Department of Clinical Microbiology and Infectious Diseases, Hospital General Universitario Gregorio Marañón, Madrid, Spain
| | - Adriana Hristea
- University of Medicine and Pharmacy Carol Davila, National Institute for Infectious Diseases Prof Dr Matei Bals, Romania
| | - Benoit Guery
- Infectious Diseases Specialist, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland
| | - Marcela Krutova
- Department of Medical Microbiology, Charles University in Prague and Motol University Hospital, Czech Republic
| | - Torbjorn Norén
- Faculty of Medicine and Health, Department of Laboratory Medicine, National Reference Laboratory for Clostridioides difficile, Clinical Microbiology, Örebro University Hospital, Örebro, Sweden
| | | | - John E Coia
- Department of Clinical Microbiology, Hospital South West Jutland and Department of Regional Health Research IRS, University of Southern Denmark, Esbjerg, Denmark
| | - Abraham Goorhuis
- Department of Infectious Diseases, Amsterdam University Medical Centers, Academic Medical Center, Amsterdam, the Netherlands
| | - Tessel M van Rossen
- Department of Medical Microbiology and Infection Control, Amsterdam University Medical Center, Location VUmc, Amsterdam, the Netherlands
| | - Rogier E Ooijevaar
- Department of Gastroenterology, Amsterdam University Medical Center, Location VUmc, Amsterdam, the Netherlands
| | - Karen Burns
- Departments of Clinical Microbiology, Beaumont Hospital & Royal College of Surgeons in Ireland, Dublin, Ireland
| | | | - Sarah Tschudin-Sutter
- Department of Infectious Diseases and Infection Control, University Hospital Basel, University Basel, Universitatsspital, Basel, Switzerland
| | - Mark H Wilcox
- Department of Microbiology, Old Medical, School Leeds General Infirmary, Leeds Teaching Hospitals & University of Leeds, Leeds, United Kingdom
| | - Maria J G T Vehreschild
- German Centre for Infection Research (DZIF), Partner Site Bonn-Cologne, Cologne, Germany; Department of Internal Medicine, Infectious Diseases, University Hospital Frankfurt, Goethe University Frankfurt, Frankfurt am Main, Germany
| | - Fidelma Fitzpatrick
- Department of Clinical Microbiology, Beaumont Hospital, Dublin, Ireland; Department of Clinical Microbiology, Royal College of Surgeons in Ireland, Dublin, Ireland
| | - Ed J Kuijper
- Department of Medical Microbiology, Centre for Infectious Diseases, Leiden University Medical Center, Leiden, the Netherlands; National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands.
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Htwe P, Aung H, Kywe B, Niang PT, Oo TS, Monhandas S, Kelly L, Goldman DL. Endotoxin Acts Synergistically With Clostridioides difficile Toxin B to Increase Interleukin 1β Production: A Potential Role for the Intestinal Biome in Modifying the Severity of C. difficile Colitis. J Infect Dis 2021; 224:1556-1565. [PMID: 33780547 DOI: 10.1093/infdis/jiab165] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2020] [Accepted: 03/25/2021] [Indexed: 01/04/2023] Open
Abstract
BACKGROUND Inflammation is a crucial driver of host damage in patients with Clostridioides difficile colitis. We examined the potential for the intestinal microbiome to modify inflammation in patients with C. difficile colitis via the effects of gut-derived endotoxin on cytokine production. METHODS Endotoxin from Escherichia coli and Pseudomonas aeruginosa as well as stool-derived endotoxin were tested for their ability to enhance interleukin 1β (IL-1β) and tumor necrosis factor alpha (TNF-α) production by toxin B-stimulated peripheral blood mononuclear cells. Inflammasome and Toll-like receptor 4 (TLR4) blocking studies were done to discern the importance of these pathways, while metagenomic studies were done to characterize predominant organisms from stool samples. RESULTS Endotoxin significantly enhanced the ability of C. difficile toxin B to promote IL-1β production but not TNF-α. The magnitude of this effect varied by endotoxin type and was dependent on combined inflammasome and TLR4 activation. Stool-derived endotoxin exhibited a similar synergistic effect on IL-1β production with less synergy observed for stools that contained a high proportion of γ-proteobacteria. CONCLUSIONS The ability of endotoxin to enhance IL-1β production highlights a manner by which the microbiome can modify inflammation and severity of C. difficile disease. This information may be useful in devising new therapies for severe C. difficile colitis.
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Affiliation(s)
- Pyae Htwe
- Department of Pediatrics, Children's Hospital at Montefiore and the Albert Einstein College of Medicine, Bronx, New York, USA
| | - Htay Aung
- Department of Pediatrics, Children's Hospital at Montefiore and the Albert Einstein College of Medicine, Bronx, New York, USA
| | - Bohm Kywe
- Department of Pediatrics, Children's Hospital at Montefiore and the Albert Einstein College of Medicine, Bronx, New York, USA
| | - Phyu T Niang
- Department of Pediatrics, Children's Hospital at Montefiore and the Albert Einstein College of Medicine, Bronx, New York, USA
| | - Thar Sann Oo
- Department of Pediatrics, Children's Hospital at Montefiore and the Albert Einstein College of Medicine, Bronx, New York, USA
| | - Sindhu Monhandas
- Department of Pediatrics, Children's Hospital at Montefiore and the Albert Einstein College of Medicine, Bronx, New York, USA
| | - Libusha Kelly
- Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York, USA.,Department of Systems and Computational Biology, Albert Einstein College of Medicine, Bronx, New York, USA
| | - David L Goldman
- Department of Pediatrics, Children's Hospital at Montefiore and the Albert Einstein College of Medicine, Bronx, New York, USA.,Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York, USA
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Phanchana M, Harnvoravongchai P, Wongkuna S, Phetruen T, Phothichaisri W, Panturat S, Pipatthana M, Charoensutthivarakul S, Chankhamhaengdecha S, Janvilisri T. Frontiers in antibiotic alternatives for Clostridioides difficile infection. World J Gastroenterol 2021; 27:7210-7232. [PMID: 34876784 PMCID: PMC8611198 DOI: 10.3748/wjg.v27.i42.7210] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/21/2021] [Revised: 05/12/2021] [Accepted: 10/25/2021] [Indexed: 02/06/2023] Open
Abstract
Clostridioides difficile (C. difficile) is a gram-positive, anaerobic spore-forming bacterium and a major cause of antibiotic-associated diarrhea. Humans are naturally resistant to C. difficile infection (CDI) owing to the protection provided by healthy gut microbiota. When the gut microbiota is disturbed, C. difficile can colonize, produce toxins, and manifest clinical symptoms, ranging from asymptomatic diarrhea and colitis to death. Despite the steady-if not rising-prevalence of CDI, it will certainly become more problematic in a world of antibiotic overuse and the post-antibiotic era. C. difficile is naturally resistant to most of the currently used antibiotics as it uses multiple resistance mechanisms. Therefore, current CDI treatment regimens are extremely limited to only a few antibiotics, which include vancomycin, fidaxomicin, and metronidazole. Therefore, one of the main challenges experienced by the scientific community is the development of alternative approaches to control and treat CDI. In this Frontier article, we collectively summarize recent advances in alternative treatment approaches for CDI. Over the past few years, several studies have reported on natural product-derived compounds, drug repurposing, high-throughput library screening, phage therapy, and fecal microbiota transplantation. We also include an update on vaccine development, pre- and pro-biotics for CDI, and toxin antidote approaches. These measures tackle CDI at every stage of disease pathology via multiple mechanisms. We also discuss the gaps and concerns in these developments. The next epidemic of CDI is not a matter of if but a matter of when. Therefore, being well-equipped with a collection of alternative therapeutics is necessary and should be prioritized.
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Affiliation(s)
- Matthew Phanchana
- Department of Molecular Tropical Medicine and Genetics, Faculty of Tropical Medicine, Mahidol University, Bangkok 10400, Thailand
| | | | - Supapit Wongkuna
- Department of Biochemistry, Faculty of Science, Mahidol University, Bangkok 10400, Thailand
| | - Tanaporn Phetruen
- Department of Biochemistry, Faculty of Science, Mahidol University, Bangkok 10400, Thailand
| | - Wichuda Phothichaisri
- Department of Biochemistry, Faculty of Science, Mahidol University, Bangkok 10400, Thailand
| | - Supakan Panturat
- Department of Biochemistry, Faculty of Science, Mahidol University, Bangkok 10400, Thailand
| | - Methinee Pipatthana
- Department of Biochemistry, Faculty of Science, Mahidol University, Bangkok 10400, Thailand
| | - Sitthivut Charoensutthivarakul
- School of Bioinnovation and Bio-based Product Intelligence, Faculty of Science, Mahidol University, Bangkok 10400, Thailand
| | | | - Tavan Janvilisri
- Department of Biochemistry, Faculty of Science, Mahidol University, Bangkok 10400, Thailand
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Ressler A, Wang J, Rao K. Defining the black box: a narrative review of factors associated with adverse outcomes from severe Clostridioides difficile infection. Therap Adv Gastroenterol 2021; 14:17562848211048127. [PMID: 34646358 PMCID: PMC8504270 DOI: 10.1177/17562848211048127] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/31/2021] [Accepted: 08/31/2021] [Indexed: 02/04/2023] Open
Abstract
In the United States, Clostridioides difficile infection (CDI) is the leading cause of healthcare-associated infection, affecting nearly half a million people and resulting in more than 20,000 in-hospital deaths every year. It is therefore imperative to better characterize the intricate interplay between C. difficile microbial factors, host immunologic signatures, and clinical features that are associated with adverse outcomes of severe CDI. In this narrative review, we discuss the implications of C. difficile genetics and virulence factors in the molecular epidemiology of CDI, and the utility of early biomarkers in predicting the clinical trajectory of patients at risk of developing severe CDI. Furthermore, we identify associations between host immune factors and CDI outcomes in both animal models and human studies. Next, we highlight clinical factors including renal dysfunction, aging, blood biomarkers, level of care, and chronic illnesses that can affect severe CDI diagnosis and outcome. Finally, we present our perspectives on two specific treatments pertinent to patient outcomes: metronidazole administration and surgery. Together, this review explores the various venues of CDI research and highlights the importance of integrating microbial, host, and clinical data to help clinicians make optimal treatment decisions based on accurate prediction of disease progression.
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Affiliation(s)
- Adam Ressler
- Division of Infectious Diseases, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, USA
| | - Joyce Wang
- Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI, USA
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Hanson RM, Wagner AJ. A Novel Surgical Treatment for Pediatric Fulminant Clostridium Difficile Colitis. Pediatrics 2021; 149:e2021051365. [PMID: 34593648 PMCID: PMC9645682 DOI: 10.1542/peds.2021-051365] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 09/23/2021] [Indexed: 01/02/2023] Open
Abstract
Pediatric patients rarely present with severe, complicated Clostridium difficile colitis. The medical and surgical management of pediatric patients is primarily based on evidence from adult populations, in which standard therapy often includes subtotal colectomy and end ileostomy. New evidence in adults suggests that a diverting loop ileostomy and colonic lavage is an effective alternative for the management of refractory severe, complicated C difficile colitis. We report the case of a 15-year-old female patient who developed severe, complicated C difficile colitis. After failing medical management, she underwent a diverting loop ileostomy with antegrade colonic lavage and recovered uneventfully. There is limited literature on the medical management of C difficile –associated disease in pediatric patients and even less information on the medical or surgical management of severe, complicated C difficile colitis in pediatrics. Diverting loop ileostomy and colonic lavage should be considered as an alternative to subtotal colectomy and end ileostomy in a pediatric patient with severe, complicated C difficile colitis.
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40
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Baunwall SMD, Dahlerup JF, Engberg JH, Erikstrup C, Helms M, Juel MA, Kjeldsen J, Nielsen HL, Nilsson AC, Rode AA, Vinter-Jensen L, Hvas CL. Danish national guideline for the treatment of Clostridioides difficile infection and use of faecal microbiota transplantation (FMT). Scand J Gastroenterol 2021; 56:1056-1077. [PMID: 34261379 DOI: 10.1080/00365521.2021.1922749] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Aim: This Danish national guideline describes the treatment of adult patients with Clostridioides (formerly Clostridium) difficile (CD) infection and the use of faecal microbiota transplantation (FMT). It suggests minimum standard for implementing an FMT service.Method: Four scientific societies appointed members for a working group which conducted a systematic literature review and agreed on the text and recommendations. All clinical recommendations were evalluated for evidence level and grade of recommendation.Results: In CD infection, the use of marketed and experimental antibiotics as well as microbiota-based therapies including FMT are described. An algorithm for evaluating treatment effect is suggested. The organisation of FMT, donor recruitment and screening, laboratory preparation, clinical application and follow-up are described.Conclusion: Updated evidence for the treatment of CD infection and the use of FMT is provided.
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Affiliation(s)
| | - Jens Frederik Dahlerup
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark
| | | | - Christian Erikstrup
- Department of Clinical Immunology, Aarhus University Hospital, Aarhus, Denmark
| | - Morten Helms
- Department of Infectious Diseases, Hvidovre Hospital, Hvidovre, Denmark
| | | | - Jens Kjeldsen
- Department of Gastroenterology, Odense University Hospital, Odense, Denmark
| | - Hans Linde Nielsen
- Department of Clinical Microbiology, Aalborg University Hospital, Aalborg, Denmark
| | | | - Anne Abildtrup Rode
- Department of Internal Medicine, Zealand University Hospital, Roskilde, Denmark
| | - Lars Vinter-Jensen
- Department of Gastroenterology, Aalborg University Hospital, Aalborg, Denmark
| | - Christian Lodberg Hvas
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark
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41
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Coccolini F, Improta M, Sartelli M, Rasa K, Sawyer R, Coimbra R, Chiarugi M, Litvin A, Hardcastle T, Forfori F, Vincent JL, Hecker A, Ten Broek R, Bonavina L, Chirica M, Boggi U, Pikoulis E, Di Saverio S, Montravers P, Augustin G, Tartaglia D, Cicuttin E, Cremonini C, Viaggi B, De Simone B, Malbrain M, Shelat VG, Fugazzola P, Ansaloni L, Isik A, Rubio I, Kamal I, Corradi F, Tarasconi A, Gitto S, Podda M, Pikoulis A, Leppaniemi A, Ceresoli M, Romeo O, Moore EE, Demetrashvili Z, Biffl WL, Wani I, Tolonen M, Duane T, Dhingra S, DeAngelis N, Tan E, Abu-Zidan F, Ordonez C, Cui Y, Labricciosa F, Perrone G, Di Marzo F, Peitzman A, Sakakushev B, Sugrue M, Boermeester M, Nunez RM, Gomes CA, Bala M, Kluger Y, Catena F. Acute abdomen in the immunocompromised patient: WSES, SIS-E, WSIS, AAST, and GAIS guidelines. World J Emerg Surg 2021; 16:40. [PMID: 34372902 PMCID: PMC8352154 DOI: 10.1186/s13017-021-00380-1] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2021] [Accepted: 06/18/2021] [Indexed: 02/08/2023] Open
Abstract
Immunocompromised patients are a heterogeneous and diffuse category frequently presenting to the emergency department with acute surgical diseases. Diagnosis and treatment in immunocompromised patients are often complex and must be multidisciplinary. Misdiagnosis of an acute surgical disease may be followed by increased morbidity and mortality. Delayed diagnosis and treatment of surgical disease occur; these patients may seek medical assistance late because their symptoms are often ambiguous. Also, they develop unique surgical problems that do not affect the general population. Management of this population must be multidisciplinary.This paper presents the World Society of Emergency Surgery (WSES), Surgical Infection Society Europe (SIS-E), World Surgical Infection Society (WSIS), American Association for the Surgery of Trauma (AAST), and Global Alliance for Infection in Surgery (GAIS) joined guidelines about the management of acute abdomen in immunocompromised patients.
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Affiliation(s)
- Federico Coccolini
- grid.144189.10000 0004 1756 8209General, Emergency and Trauma Surgery Department, Pisa University Hospital, Via Paradisa, 2, 56124 Pisa, Italy
| | - Mario Improta
- grid.8982.b0000 0004 1762 5736Emergency Department, Pavia University Hospital, Pavia, Italy
| | | | - Kemal Rasa
- Department of Surgery, Anadolu Medical Center, Kocaali, Turkey
| | - Robert Sawyer
- grid.268187.20000 0001 0672 1122General Surgery Department, Western Michigan University, Kalamazoo, MI USA
| | - Raul Coimbra
- grid.488519.90000 0004 5946 0028Department of General Surgery, Riverside University Health System Medical Center, Moreno Valley, CA USA
| | - Massimo Chiarugi
- grid.144189.10000 0004 1756 8209General, Emergency and Trauma Surgery Department, Pisa University Hospital, Via Paradisa, 2, 56124 Pisa, Italy
| | - Andrey Litvin
- grid.410686.d0000 0001 1018 9204Department of Surgical Disciplines, Immanuel Kant Baltic Federal University, Kaliningrad, Russia
| | - Timothy Hardcastle
- Emergency and Trauma Surgery, Inkosi Albert Luthuli Central Hospital, Mayville, South Africa
| | - Francesco Forfori
- grid.144189.10000 0004 1756 8209Intensive Care Unit, Pisa University Hospital, Pisa, Italy
| | - Jean-Louis Vincent
- grid.4989.c0000 0001 2348 0746Departement of Intensive Care, Erasme Univ Hospital, Université Libre de Bruxelles, Bruxelles, Belgium
| | - Andreas Hecker
- grid.411067.50000 0000 8584 9230Departementof General and Thoracic Surgery, University Hospital of Giessen, Giessen, Germany
| | - Richard Ten Broek
- grid.10417.330000 0004 0444 9382General Surgery, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Luigi Bonavina
- grid.416351.40000 0004 1789 6237General Surgery, San Donato Hospital, Milano, Italy
| | - Mircea Chirica
- grid.450307.5General Surgery, CHUGA-CHU Grenoble Alpes UGA-Université Grenoble Alpes, Grenoble, France
| | - Ugo Boggi
- grid.144189.10000 0004 1756 8209General Surgery, Pisa University Hospital, Pisa, Italy
| | - Emmanuil Pikoulis
- grid.5216.00000 0001 2155 08003rd Department of Surgery, Attiko Hospital, National & Kapodistrian University of Athens, Athens, Greece
| | - Salomone Di Saverio
- grid.18887.3e0000000417581884General Surgery, Varese University Hospital, Varese, Italy
| | - Philippe Montravers
- grid.411119.d0000 0000 8588 831XDépartement d’Anesthésie-Réanimation, CHU Bichat Claude Bernard, Paris, France
| | - Goran Augustin
- grid.4808.40000 0001 0657 4636Department of Surgery, Zagreb University Hospital Centre and School of Medicine, University of Zagreb, Zagreb, Croatia
| | - Dario Tartaglia
- grid.144189.10000 0004 1756 8209General, Emergency and Trauma Surgery Department, Pisa University Hospital, Via Paradisa, 2, 56124 Pisa, Italy
| | - Enrico Cicuttin
- grid.144189.10000 0004 1756 8209General, Emergency and Trauma Surgery Department, Pisa University Hospital, Via Paradisa, 2, 56124 Pisa, Italy
| | - Camilla Cremonini
- grid.144189.10000 0004 1756 8209General, Emergency and Trauma Surgery Department, Pisa University Hospital, Via Paradisa, 2, 56124 Pisa, Italy
| | - Bruno Viaggi
- grid.24704.350000 0004 1759 9494ICU Department, Careggi University Hospital, Firenze, Italy
| | - Belinda De Simone
- grid.418056.e0000 0004 1765 2558Department of Digestive, Metabolic and Emergency Minimally Invasive Surgery, Centre Hospitalier Intercommunal de Poissy/Saint Germain en Laye, Saint Germain en Laye, France
| | - Manu Malbrain
- grid.8767.e0000 0001 2290 8069Faculty of Engineering, Department of Electronics and Informatics, Vrije Universiteit Brussel, Brussels, Belgium
| | - Vishal G. Shelat
- General and Emergency Surgery, Tan Tock Seng Hospital, Kuala Lumpur, Malaysia
| | - Paola Fugazzola
- grid.8982.b0000 0004 1762 5736General and Emergency Surgery, Pavia University Hospital, Pavia, Italy
| | - Luca Ansaloni
- grid.8982.b0000 0004 1762 5736General and Emergency Surgery, Pavia University Hospital, Pavia, Italy
| | - Arda Isik
- grid.411776.20000 0004 0454 921XGeneral Surgery, School of Medicine, Istanbul Medeniyet University, Istanbul, Turkey
| | - Ines Rubio
- grid.81821.320000 0000 8970 9163Department of General Surgery, La Paz University Hospital, Madrid, Spain
| | - Itani Kamal
- grid.38142.3c000000041936754XGeneral Surgery, VA Boston Health Care System, Boston University, Harvard Medical School, Boston, MA USA
| | - Francesco Corradi
- grid.144189.10000 0004 1756 8209Intensive Care Unit, Pisa University Hospital, Pisa, Italy
| | - Antonio Tarasconi
- grid.411482.aGeneral Surgery, Parma University Hospital, Parma, Italy
| | - Stefano Gitto
- grid.8404.80000 0004 1757 2304Gastroenterology and Transplant Unit, Firenze University Hospital, Firenze, Italy
| | - Mauro Podda
- grid.7763.50000 0004 1755 3242General and Emergency Surgery, Cagliari University Hospital, Cagliari, Italy
| | - Anastasia Pikoulis
- grid.5216.00000 0001 2155 0800Medical Department, National & Kapodistrian University of Athens, Athens, Greece
| | - Ari Leppaniemi
- grid.15485.3d0000 0000 9950 5666Abdominal Center, Helsinki University and Helsinki University Hospital, Helsinki, Finland
| | - Marco Ceresoli
- grid.18887.3e0000000417581884General Surgery, Monza University Hospital, Monza, Italy
| | - Oreste Romeo
- grid.268187.20000 0001 0672 1122Department of Surgery, Western Michigan University School of Medicine, Kalamazoo, MI USA
| | - Ernest E. Moore
- grid.239638.50000 0001 0369 638XTrauma Surgery, Denver Health, Denver, CL USA
| | - Zaza Demetrashvili
- grid.412274.60000 0004 0428 8304General Surgery, Tbilisi State Medical University, Tbilisi, Georgia
| | - Walter L. Biffl
- grid.415402.60000 0004 0449 3295Emergency and Trauma Surgery, Scripps Memorial Hospital La Jolla, La Jolla, CA USA
| | - Imitiaz Wani
- General Surgery, Government Gousia Hospital, Srinagar, Kashmir India
| | - Matti Tolonen
- grid.15485.3d0000 0000 9950 5666Abdominal Center, Helsinki University and Helsinki University Hospital, Helsinki, Finland
| | | | - Sameer Dhingra
- National Institute of Pharmaceutical Education and Research, Hajipur (NIPER-H), Vaishali, Bihar India
| | - Nicola DeAngelis
- grid.50550.350000 0001 2175 4109General Surgery Department, Henry Mondor University Hospital, Paris, France
| | - Edward Tan
- grid.10417.330000 0004 0444 9382Emergency Medicine, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Fikri Abu-Zidan
- General Surgery, UAE University Hospital, Sharjah, United Arab Emirates
| | - Carlos Ordonez
- grid.8271.c0000 0001 2295 7397Division of Trauma and Acute Care Surgery, Department of Surgery, Fundación Valle del Lili, Universidad del Valle, Cali, Colombia
| | - Yunfeng Cui
- grid.265021.20000 0000 9792 1228Department of Surgery, Tianjin Nankai Hospital, Nankai Clinical School of Medicine, Tianjin Medical University, Tianjin, China
| | | | - Gennaro Perrone
- grid.411482.aGeneral Surgery, Parma University Hospital, Parma, Italy
| | | | - Andrew Peitzman
- grid.21925.3d0000 0004 1936 9000General Surgery, University of Pittsburgh School of Medicine, Pittsburgh, USA
| | - Boris Sakakushev
- First Clinic of General Surgery, University Hospital St George Plovdiv, Plovdiv, Bulgaria
| | - Michael Sugrue
- General Surgery, Letterkenny Hospital, Letterkenny, Ireland
| | - Marja Boermeester
- grid.5650.60000000404654431Department of Surgery, Academic Medical Center, Amsterdam, Netherlands
| | | | - Carlos Augusto Gomes
- Department of Surgery, Faculdade de Ciências Médicas e da Saúde de Juiz de Fora, Hospital Universitário Terezinha de Jesus, Juiz de Fora, Brazil
| | - Miklosh Bala
- grid.17788.310000 0001 2221 2926General Surgery, Hadassah Hospital, Jerusalem, Israel
| | - Yoram Kluger
- General Sugery, Ramabam Medical Centre, Tel Aviv, Israel
| | - Fausto Catena
- grid.411482.aGeneral Surgery, Parma University Hospital, Parma, Italy
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Reinke CE, Lim RB. Minimally invasive acute care surgery. Curr Probl Surg 2021; 59:101031. [PMID: 35227422 DOI: 10.1016/j.cpsurg.2021.101031] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2021] [Accepted: 05/16/2021] [Indexed: 12/07/2022]
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Reinke CE, Lim RB. Minimally Invasive Acute Care Surgery. Curr Probl Surg 2021. [DOI: 10.1016/j.cpsurg.2021.101033] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/07/2022]
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Kelly CR, Fischer M, Allegretti JR, LaPlante K, Stewart DB, Limketkai BN, Stollman NH. ACG Clinical Guidelines: Prevention, Diagnosis, and Treatment of Clostridioides difficile Infections. Am J Gastroenterol 2021; 116:1124-1147. [PMID: 34003176 DOI: 10.14309/ajg.0000000000001278] [Citation(s) in RCA: 299] [Impact Index Per Article: 74.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/30/2020] [Accepted: 03/25/2021] [Indexed: 02/06/2023]
Abstract
Clostridioides difficile infection occurs when the bacterium produces toxin that causes diarrhea and inflammation of the colon. These guidelines indicate the preferred approach to the management of adults with C. difficile infection 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 process. In instances where the evidence was not appropriate for Grading of Recommendations Assessment, Development, and Evaluation 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 the only, approach to clinical scenarios.
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Affiliation(s)
- Colleen R Kelly
- Division of Gastroenterology, Warren Alpert Medical School of Brown University, Providence, Rhode Island, USA
| | - Monika Fischer
- Division of Gastroenterology, Indiana University, Indianapolis, Indiana, USA
| | - Jessica R Allegretti
- Division of Gastroenterology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - Kerry LaPlante
- Department of Pharmacy Practice, University of Rhode Island College of Pharmacy, Kingston, Rhode Island, USA
| | - David B Stewart
- Department of Surgery, University of Arizona Health Sciences, Tucson, Arizona, USA
| | - Berkeley N Limketkai
- Division of Digestive Diseases, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California, USA
| | - Neil H Stollman
- Division of Gastroenterology, Alta Bates Summit Medical Center, East Bay Center for Digestive Health, Oakland, California, USA
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45
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Poylin V, Hawkins AT, Bhama AR, Boutros M, Lightner AL, Khanna S, Paquette IM, Feingold DL. The American Society of Colon and Rectal Surgeons Clinical Practice Guidelines for the Management of Clostridioides difficile Infection. Dis Colon Rectum 2021; 64:650-668. [PMID: 33769319 DOI: 10.1097/dcr.0000000000002047] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Affiliation(s)
- Vitaliy Poylin
- Division of Gastrointestinal Surgery, Northwestern Medicine, Chicago, Illinois
| | - Alexander T Hawkins
- Department of Surgery, Section of Colon & Rectal Surgery, Vanderbilt University Medical Center, Nashville, Tennessee
| | - Anuradha R Bhama
- Department of Surgery, Division of Colon & Rectal Surgery, Rush University Medical Center, Chicago, Illinois
| | - Marylise Boutros
- Jewish General Hospital, McGill University, Montreal, Quebec, Canada
| | - Amy L Lightner
- Department of Colorectal Surgery, Digestive Disease Surgery Institute, Cleveland Clinic, Cleveland, Ohio
| | - Sahil Khanna
- Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | - Ian M Paquette
- Department of Surgery, University of Cincinnati, Cincinnati, Ohio
| | - Daniel L Feingold
- Section of Colorectal Surgery, Rutgers University, New Brunswick, New Jersey
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Hospitalized Older Patients with Clostridioides difficile Infection Refractory to Conventional Antibiotic Therapy Benefit from Fecal Microbiota Transplant. ACTA ACUST UNITED AC 2021; 3. [PMID: 34263258 PMCID: PMC8277114 DOI: 10.20900/agmr20210012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022]
Abstract
Background: Options for Clostridioides difficile infection (CDI) refractory to conventional therapy are limited. Fecal microbiota transplant (FMT) is considered safe and effective treatment for recurrent CDI and could be a treatment option for refractory CDI. We investigated the efficacy and safety of FMT in hospitalized patients who were not responding to standard treatments for CDI. Methods: Electronic medical records of patients who received FMT inpatient for refractory CDI were reviewed as part of quality improvement efforts to evaluate safety and efficacy of FMT in inpatient setting. Results: Between July 2014 and December 2019, 9 patients (age 60–96) received FMT for CDI as inpatient for refractory or fulminant CDI. Most (7 of 9) of these patients had pseudomembranous colitis and underwent multiple FMTs (mean 2.15, range 1 to 3). Five patients had complete resolution and one patient had diarrhea that was C. difficile-negative. There was one recurrent CDI and two deaths, one of which may have been related to FMT or CDI. Compared to recurrent CDI at diagnosis, patients with refractory CDI had higher WBC and neutrophil counts, which decreased after FMT. The overall cure rate of FMT in refractory cases was 66.7%. Conclusions: This study shows moderate efficacy of FMT for treatment of refractory CDI although multiple FMT treatment may need to be administered in the presence of pseudomembranous colitis. Inpatient FMT may be an alternative strategy for managing refractory CDI in this population of patients who may not have any effective medical treatment available.
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Ferrari L, Fichera A. Clostridioides Difficile Infection. Dis Colon Rectum 2021; 64:151-155. [PMID: 33315710 DOI: 10.1097/dcr.0000000000001900] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Affiliation(s)
- Linda Ferrari
- Guy's and St. Thomas National Health Service Foundation Trust, London, United Kingdom
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48
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Kampouri E, Croxatto A, Prod’hom G, Guery B. Clostridioides difficile Infection, Still a Long Way to Go. J Clin Med 2021; 10:jcm10030389. [PMID: 33498428 PMCID: PMC7864166 DOI: 10.3390/jcm10030389] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2020] [Revised: 01/12/2021] [Accepted: 01/14/2021] [Indexed: 12/11/2022] Open
Abstract
Clostridioides difficile is an increasingly common pathogen both within and outside the hospital and is responsible for a large clinical spectrum from asymptomatic carriage to complicated infection associated with a high mortality. While diagnostic methods have considerably progressed over the years, the optimal diagnostic algorithm is still debated and there is no single diagnostic test that can be used as a standalone test. More importantly, the heterogeneity in diagnostic practices between centers along with the lack of robust surveillance systems in all countries and an important degree of underdiagnosis due to lack of clinical suspicion in the community, hinder a more accurate evaluation of the burden of disease. Our improved understanding of the physiopathology of CDI has allowed some significant progress in the treatment of CDI, including a broader use of fidaxomicine, the use of fecal microbiota transplantation for multiples recurrences and newer approaches including antibodies, vaccines and new molecules, already developed or in the pipeline. However, the management of CDI recurrences and severe infections remain challenging and the main question remains: how to best target these often expensive treatments to the right population. In this review we discuss current diagnostic approaches, treatment and potential prevention strategies, with a special focus on recent advances in the field as well as areas of uncertainty and unmet needs and how to address them.
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Affiliation(s)
- Eleftheria Kampouri
- Infectious Diseases Service, Department of Medicine, University Hospital and University of Lausanne, 1011 Lausanne, Switzerland;
| | - Antony Croxatto
- Institute of Microbiology, Department of Medical Laboratory and Pathology, University Hospital and University of Lausanne, 1011 Lausanne, Switzerland; (A.C.); (G.P.)
| | - Guy Prod’hom
- Institute of Microbiology, Department of Medical Laboratory and Pathology, University Hospital and University of Lausanne, 1011 Lausanne, Switzerland; (A.C.); (G.P.)
| | - Benoit Guery
- Infectious Diseases Service, Department of Medicine, University Hospital and University of Lausanne, 1011 Lausanne, Switzerland;
- Correspondence: ; Tel.: +41-21-314-1643
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Diagnostic and therapy of severe Clostridioides difficile infections in the ICU. Curr Opin Crit Care 2021; 26:450-458. [PMID: 32739967 DOI: 10.1097/mcc.0000000000000753] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
PURPOSE OF REVIEW The purpose of the review is to provide all the recent data focusing on the diagnostic and treatment of Clostridioides difficile infection in patients admitted in the ICU. RECENT FINDINGS In the ICU, diagnosis remains complicated with a large number of alternative diagnosis. The treatment classically relies on vancomycin but fidaxomicin and fecal microbiota transplantation are now potential solutions in selected indications. SUMMARY Data on ICU-related CDI remain limited and conflicting. To date, there is no unique and simple way to obtain a diagnosis for CDI, the combination of clinical signs and a two-step testing algorithm remains the recommended gold-standard. Two molecules can be proposed for first line treatment: vancomycin and fidaxomicin. Although metronidazole may still be discussed as a treatment option for mild CDI in low-risk patients, its use for ICU-patients does not seem reasonable. Several reports suggest that fecal microbiota transplantation could be discussed, as it is well tolerated and associated with a high rate of clinical cure. CDI is a dynamic and active area of research with new diagnostic techniques, molecules, and management concepts likely changing our approach to this old disease in the near future.
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50
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Shellito AD, Russell MM. Diverting Loop Ileostomy for Clostridium Difficile Colitis: A Systematic Review and Meta-analysis. Am Surg 2021; 86:1269-1276. [PMID: 33284670 DOI: 10.1177/0003134820964213] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
Diverting loop ileostomy (DLI) with colonic lavage has been proposed as an alternative to total abdominal colectomy (TAC) for fulminant Clostridium difficile infection (CDI). Controversy exists regarding the mortality benefit and outcomes of this surgical approach. We conducted a MEDLINE database search for articles between 1999 and 2019 pertaining to DLI for the surgical treatment of CDI. Five articles met the inclusion criteria. Four studies were retrospective and one was a prospective matched cohort study. 3683 patients were included in the 5 studies; 733 patients (20%) underwent DLI, while 2950 patients (80%) underwent TAC. The only shared outcome measure across all 5 studies was mortality. The overall mortality rate for the entire cohort undergoing both procedures was 30.3%. There was no statistically significant difference in pooled mortality between DLI and TAC (OR: .73; 95% CI, .45-1.2; P = .22). Reporting of other postoperative outcomes was variable. Fulminant CDI remains a life-threatening condition with high mortality. Loop ileostomy may be a viable surgical alternative to total colectomy with similar mortality; however, further work is needed to determine specific patient characteristics that warrant routine use of DLI.
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Affiliation(s)
| | - Marcia M Russell
- VA Greater Los Angeles Healthcare System and David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
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