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1
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Meza-Torres J, Tinevez JY, Crouzols A, Mary H, Kim M, Hunault L, Chamorro-Rodriguez S, Lejal E, Altamirano-Silva P, Groussard D, Gobaa S, Peltier J, Chassaing B, Dupuy B. Clostridioides difficile binary toxin CDT induces biofilm-like persisting microcolonies. Gut Microbes 2025; 17:2444411. [PMID: 39719371 DOI: 10.1080/19490976.2024.2444411] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/19/2024] [Revised: 11/07/2024] [Accepted: 12/09/2024] [Indexed: 12/26/2024] Open
Abstract
Clinical symptoms of Clostridioides difficile infection (CDI) range from diarrhea to pseudomembranous colitis. A major challenge in managing CDI is the high rate of relapse. Several studies correlate the production of CDT binary toxin by clinical strains of C. difficile with higher relapse rates. Although the mechanism of action of CDT on host cells is known, its exact contribution to CDI is still unclear. To understand the physiological role of CDT during CDI, we established two hypoxic relevant intestinal models, Transwell and Microfluidic Intestine-on-Chip systems. Both were challenged with the epidemic strain UK1 CDT+ and its isogenic CDT- mutant. We report that CDT induces mucin-associated microcolonies that increase C. difficile colonization and display biofilm-like properties by enhancing C. difficile resistance to vancomycin. Importantly, biofilm-like microcolonies were also observed in the cecum and colon of infected mice. Hence, our study shows that CDT induces biofilm-like microcolonies, increasing C. difficile persistence and risk of relapse.
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Affiliation(s)
- Jazmin Meza-Torres
- Pathogenesis of Bacterial Anaerobes, Department of Microbiology, Institut Pasteur, Université Paris-Cité, UMR-CNRS 6047, Paris, France
| | - Jean-Yves Tinevez
- Image Analysis Hub, Department of Cell Biology and Infection, Institut Pasteur, Université Paris Cité, Paris, France
| | - Aline Crouzols
- Pathogenesis of Bacterial Anaerobes, Department of Microbiology, Institut Pasteur, Université Paris-Cité, UMR-CNRS 6047, Paris, France
| | - Héloïse Mary
- Biomaterials and Microfluidics Core Facility, Department of Developmental and Stem Cell Biology, Institut Pasteur, Université Paris Cité, Paris, France
| | - Minhee Kim
- Biomaterials and Microfluidics Core Facility, Department of Developmental and Stem Cell Biology, Institut Pasteur, Université Paris Cité, Paris, France
| | - Lise Hunault
- Antibodies in Therapy and Pathology, Department of Immunology, Institut Pasteur, Paris, France
| | - Susan Chamorro-Rodriguez
- Pathogenesis of Bacterial Anaerobes, Department of Microbiology, Institut Pasteur, Université Paris-Cité, UMR-CNRS 6047, Paris, France
| | - Emilie Lejal
- Institute for Integrative Biology of the Cell (I2BC), Université Paris-Saclay, CEA, CNRS, Gif-sur-Yvette, France
| | - Pamela Altamirano-Silva
- Centro de Investigación en Enfermedades Tropicales, Universidad de Costa Rica, San José, Costa Rica
| | | | - Samy Gobaa
- Biomaterials and Microfluidics Core Facility, Department of Developmental and Stem Cell Biology, Institut Pasteur, Université Paris Cité, Paris, France
| | - Johann Peltier
- Institute for Integrative Biology of the Cell (I2BC), Université Paris-Saclay, CEA, CNRS, Gif-sur-Yvette, France
| | - Benoit Chassaing
- Microbiome-Host Interactions, Department of Microbiology, Institut Pasteur, Université Paris Cité, INSERM U1306, Paris, France
- Mucosal Microbiota in Chronic Inflammatory Diseases, INSERM U1016, CNRS UMR 8104, Université Paris Cité, Paris, France
| | - Bruno Dupuy
- Pathogenesis of Bacterial Anaerobes, Department of Microbiology, Institut Pasteur, Université Paris-Cité, UMR-CNRS 6047, Paris, France
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2
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Tucker EC, Angelica B, Mathias RM, Edwards L, Bryant RV, Costello SP. Outcomes of Fecal Microbiota Transplantation for Clostridioides difficile Infection in South Australia. Open Forum Infect Dis 2025; 12:ofaf149. [PMID: 40160347 PMCID: PMC11950531 DOI: 10.1093/ofid/ofaf149] [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] [Received: 09/27/2024] [Accepted: 03/11/2025] [Indexed: 04/02/2025] Open
Abstract
Background Fecal microbiota transplantation (FMT) sourced from a bank of prescreened anaerobically processed frozen donor stool has been available in South Australia since 2013. This study aimed to evaluate the real-world clinical and safety outcomes of FMT for recurrent, refractory, and/or severe or fulminant Clostridioides difficile infection (CDI) facilitated via this centralized facility. Methods Donor screening test data were prospectively collected on all donors who passed prescreening evaluations between April 2013 and August 2023. The South Australian FMT for CDI database prospectively recorded outcomes for consecutive patients who underwent FMT for CDI from August 2013 to May 2023 in South Australia. Results An overall 98 potential donors passed prescreening assessments and underwent laboratory screening tests: 32 (33%) had tests that failed, 5 (5%) had incomplete screening, and 61 (62%) passed. Detection of an extended-spectrum β-lactamase-producing organism (9/65, 14%) was the common reason for ineligibility following completion of screening tests. In total 220 cases of CDI were recorded, and follow-up data were available in 216. Primary cure occurred in 84% of cases (182/216): 88% (132/150) for recurrent CDI, 76% (50/66) for refractory CDI, 85% (51/60) for severe disease, and 65% (17/26) for fulminant disease. Repeat FMT was delivered in 23 of 34 cases (68%), with secondary cure in 74% (17/23 cases). Serious adverse events were observed in 6 patients overall (3%). No deaths were directly attributable to FMT. Conclusions FMT was safe and efficacious for management of recurrent and refractory CDI over a 10-year period in a real-world prospective Australian cohort. Further studies to optimize the use of FMT for severe and fulminant CDI are warranted.
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Affiliation(s)
- Emily C Tucker
- Infectious Diseases Unit, Central Adelaide Local Health Network, Adelaide, Australia
- School of Medicine, Faculty of Health and Medical Sciences, The University of Adelaide, Adelaide, Australia
- BiomeBank, Adelaide, Australia
| | - Bianca Angelica
- School of Medicine, Faculty of Health and Medical Sciences, The University of Adelaide, Adelaide, Australia
- Inflammatory Bowel Disease Service, Department of Gastroenterology, The Queen Elizabeth Hospital, Woodville, Australia
| | - Ryan M Mathias
- School of Medicine, Faculty of Health and Medical Sciences, The University of Adelaide, Adelaide, Australia
- Inflammatory Bowel Disease Service, Department of Gastroenterology, The Queen Elizabeth Hospital, Woodville, Australia
| | - Louisa Edwards
- Inflammatory Bowel Disease Service, Department of Gastroenterology, The Queen Elizabeth Hospital, Woodville, Australia
| | - Robert V Bryant
- School of Medicine, Faculty of Health and Medical Sciences, The University of Adelaide, Adelaide, Australia
- BiomeBank, Adelaide, Australia
- Inflammatory Bowel Disease Service, Department of Gastroenterology, The Queen Elizabeth Hospital, Woodville, Australia
| | - Samuel P Costello
- School of Medicine, Faculty of Health and Medical Sciences, The University of Adelaide, Adelaide, Australia
- BiomeBank, Adelaide, Australia
- Inflammatory Bowel Disease Service, Department of Gastroenterology, The Queen Elizabeth Hospital, Woodville, Australia
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3
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Longhitano A, Roder C, Blackmore T, Campbell A, May M, Athan E. Australasian Society of Infectious Diseases updated guidelines for the management of Clostridioides difficile infection in adults and children in Australia and New Zealand. Intern Med J 2025; 55:503-513. [PMID: 40035163 DOI: 10.1111/imj.16638] [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: 02/03/2024] [Accepted: 12/22/2024] [Indexed: 03/05/2025]
Abstract
Clostridioides difficile infection (CDI) is associated with significant morbidity and mortality within the Australian population. Treatment recommendations for CDI pose challenges at both community and hospital-based levels due to the recurrent, refractory and potentially severe nature of the disease. Since the last published Australasian guidelines in 2016, new therapeutic options are available, prompting a necessary update to management recommendations. On behalf of the Australasian Society of Infectious Diseases, we present the updated guidelines for the management of CDI in adults and children exploring the changes to treatment recommendations - including the replacement of oral metronidazole with vancomycin for initial CDI and the emerging role for fidaxomicin and faecal-microbiota transplant.
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Affiliation(s)
- Anthony Longhitano
- Department of Infectious Diseases, Barwon Health, Geelong, Victoria, Australia
| | - Christine Roder
- Barwon Health, Barwon Southwest Public Health Unit, Geelong, Victoria, Australia
| | - Tim Blackmore
- Department of Microbiology, Wellington Southern Community Laboratories, Wellington, New Zealand
| | - Anita Campbell
- Department of Infectious Diseases, Perth Children's Hospital, Perth, Western Australia, Australia
| | - Meryta May
- Department of Microbiology, Sullivan Nicolaides Pathology, Brisbane, Queensland, Australia
| | - Eugene Athan
- Department of Infectious Diseases, Barwon Health, Geelong, Victoria, Australia
- Barwon Health, Barwon Southwest Public Health Unit, Geelong, Victoria, Australia
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Stolz BJ, Abouelkhair AA, Seleem MN. Screening novel antiviral compounds to treat Clostridioides difficile infections. PLoS One 2024; 19:e0309624. [PMID: 39671442 PMCID: PMC11642915 DOI: 10.1371/journal.pone.0309624] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2024] [Accepted: 11/27/2024] [Indexed: 12/15/2024] Open
Abstract
Clostridioides difficile is a major cause of nosocomial infections, often associated with individuals who have gut dysbiosis from previous antibiotic therapies. C. difficile infections (CDI) have a high recurrence rate and impose significant financial and mortality burdens on the healthcare system. Therefore, novel anti-C. difficile drugs are urgently needed to treat and reduce the severity and recurrence of infection. In this study, we screened a library of 618 antiviral drugs to identify a potential candidate for repurposing as novel anti-C. difficile therapeutics. Following our preliminary screening, we identified 9 novel compounds that inhibited C. difficile at a concentration of 16 μM or lower. Among these, 4 antiviral compounds demonstrated the most potent anti-C. difficile activity against a panel of 15 C. difficile isolates, with minimum inhibitory concentrations (MICs) comparable to the drug of choice, vancomycin. These include rottlerin (MIC50 = 0.25 μg/mL), α-mangostin (MIC50 = 1 μg/mL), dryocrassin ABBA (MIC50 = 1 μg/mL), and obefazimod (MIC50 = 4 μg/mL). All exhibited minimal to no activity against representative members of the human gut microbiota. Interestingly, α-mangostin, a natural xanthone derived from the mangosteen fruit, exhibited strong bactericidal action, clearing a high inoculum of C. difficile in less than an hour. All other drugs exhibited bacteriostatic activity. Given their characteristics, these compounds show great promise as novel treatments for CDI.
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Affiliation(s)
- Brice J. Stolz
- Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, Virginia, United States of America
- Center for One Health Research, Virginia Polytechnic Institute and State University, Blacksburg, Virginia, United States of America
| | - Ahmed A. Abouelkhair
- Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, Virginia, United States of America
- Center for One Health Research, Virginia Polytechnic Institute and State University, Blacksburg, Virginia, United States of America
| | - Mohamed N. Seleem
- Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, Virginia, United States of America
- Center for One Health Research, Virginia Polytechnic Institute and State University, Blacksburg, Virginia, United States of America
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5
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Herbin SR, Crum H, Gens K. Breaking the Cycle of Recurrent Clostridioides difficile Infections: A Narrative Review Exploring Current and Novel Therapeutic Strategies. J Pharm Pract 2024; 37:1361-1373. [PMID: 38739837 DOI: 10.1177/08971900241248883] [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: 05/16/2024]
Abstract
Clostridioides difficile is a toxin-producing bacteria that is a main cause of antibiotic-associated diarrhea. Clostridioides difficile infections (CDI) are associated with disruptions within the gastrointestinal (GI) microbiota which can be further exacerbated by CDI-targeted antibiotic treatment thereby causing recurrent CDI (rCDI) and compounding the burden placed on patients and the healthcare system. Treatment of rCDI consists of antibiotics which can be paired with preventative therapeutics, such as bezlotoxumab or fecal microbiota transplants (FMTs), if sustained clinical response is not obtained. Newer preventative strategies have been recently approved to assist in restoring balance within the GI system with the goal of preventing recurrent infections.
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Affiliation(s)
- Shelbye R Herbin
- Antimicrobial Stewardship and Medication Safety, John D. Dingell VA Medical Center, Detroit, MI, USA
| | - Hannah Crum
- Mercy Hospital Southeast, Cape Girardeau, MO, USA
| | - Krista Gens
- Allina Health, Minneapolis, MN, USA
- Abbott Northwestern Hospital, Minneapolis, MN, USA
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6
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Moore SE, Song M, Swingler EA, Furmanek S, Chandler T, Smith D, Brenneman MT, Wilde AM. Comparing rates of recurrent infection for first occurrence of Clostridioides difficile between tapered oral vancomycin and standard vancomycin: a retrospective, propensity matched cohort study. Infect Control Hosp Epidemiol 2024:1-7. [PMID: 39400010 DOI: 10.1017/ice.2024.117] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/15/2024]
Abstract
OBJECTIVE To compare rates of Clostridioides difficile infection (CDI) recurrence following initial occurrence treated with tapered enteral vancomycin compared to standard vancomycin. DESIGN Retrospective cohort study. SETTING Community health system. PATIENTS Adults ≥18 years of age hospitalized with positive C. difficile polymerase chain reaction or toxin enzyme immunoassay who were prescribed either standard 10-14 days of enteral vancomycin four times daily or a 12-week tapered vancomycin regimen. METHODS Retrospective propensity score pair matched cohort study. Groups were matched based on age < or ≥ 65 years and receipt of non-C. difficile antibiotics during hospitalization or within 6 months post-discharge. Recurrence rates were analyzed via logistic regression conditioned on matched pairs and reported as conditional odds ratios. The primary outcome was recurrence rates compared between standard vancomycin versus tapered vancomycin for treatment of initial CDI. RESULTS The CDI recurrence rate at 6 months was 5.3% (4/75) in the taper cohort versus 28% (21/75) in the standard vancomycin cohort. The median time to CDI recurrence was 115 days versus 20 days in the taper and standard vancomycin cohorts, respectively. When adjusted for matching, patients in the taper arm were less likely to experience CDI recurrence at 6 months when compared to standard vancomycin (cOR = 0.19, 95% CI 0.07-0.56, p < 0.002). CONCLUSIONS Larger prospective trials are needed to elucidate the clinical utility of tapered oral vancomycin as a treatment option to achieve sustained clinical cure in first occurrences of CDI.
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Affiliation(s)
- Sarah E Moore
- Norton Healthcare, Norton Infectious Diseases Institute, Louisville, KY, USA
| | - Matthew Song
- Norton Healthcare, Norton Infectious Diseases Institute, Louisville, KY, USA
| | - Elena A Swingler
- Norton Healthcare, Norton Infectious Diseases Institute, Louisville, KY, USA
| | - Stephen Furmanek
- Norton Healthcare, Norton Infectious Diseases Institute, Louisville, KY, USA
| | - Thomas Chandler
- Norton Healthcare, Norton Infectious Diseases Institute, Louisville, KY, USA
| | - Dakota Smith
- Norton Healthcare, Department of Pharmacy, Louisville, KY, USA
| | | | - Ashley M Wilde
- Norton Healthcare, Norton Infectious Diseases Institute, Louisville, KY, USA
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7
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Feuerstadt P, Crawford CV, Tan X, Pokhilko V, Bancke L, Ng S, Guthmueller B, Bidell MR, Tillotson G, Johnson S, Skinner AM. Fecal Microbiota, Live-jslm for the Prevention of Recurrent Clostridioides difficile Infection : Subgroup Analysis of PUNCH CD2 and PUNCH CD3. J Clin Gastroenterol 2024; 58:818-824. [PMID: 38019088 PMCID: PMC11305620 DOI: 10.1097/mcg.0000000000001947] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/18/2023] [Accepted: 10/19/2023] [Indexed: 11/30/2023]
Abstract
GOALS To assess fecal microbiota, live-jslm (REBYOTA, abbreviated as RBL, formerly RBX2660) efficacy and safety in participants grouped by recurrent Clostridioides difficile infection (rCDI) risk factors and treatment-related variables. BACKGROUND RBL is the first microbiota-based live biotherapeutic approved by the US Food and Drug Administration for the prevention of rCDI in adults after antibiotic treatment for rCDI. STUDY Treatment success rates across subgroups for PUNCH CD3 (NCT03244644) were estimated using a Bayesian hierarchical model, borrowing data from PUNCH CD2 (NCT02299570). Treatment-emergent adverse events were summarized for the double-blind treatment period within 8 weeks. RESULTS Treatment differences between RBL and placebo at 8 weeks were similar to the total population for most subgroups. Treatment effect sizes were similar between CDI tests, higher for oral vancomycin courses >14 days versus ≤14 days and higher for antibiotic washout periods of 3 days versus ≤2 days. The largest reductions in the rate of rCDI with RBL versus placebo were observed for participants with a 3-day CDI antibiotic washout period and participants with ≥4 previous CDI episodes. Most RBL-treated participants experienced TEAEs that were mild or moderate in severity and related to preexisting conditions. CONCLUSION This analysis provides further evidence of RBL efficacy and safety across subgroups, including those at high risk for rCDI.
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Affiliation(s)
- Paul Feuerstadt
- Yale School of Medicine, Division of Digestive Diseases, New Haven, CT
- PACT Gastroenterology Center, Hamden, CT
| | | | - Xing Tan
- Ferring Pharmaceuticals, Parsippany, NJ
| | | | | | - Samson Ng
- Ferring Pharmaceuticals, Parsippany, NJ
| | | | | | | | - Stuart Johnson
- Edward Hines Jr. Veterans Affairs Hospital, Department of Research and Medicine, Hines, IL
- Loyola University Medical Center, Department of Medicine, Fahey Center, Maywood, IL
| | - Andrew M. Skinner
- Edward Hines Jr. Veterans Affairs Hospital, Department of Research and Medicine, Hines, IL
- Loyola University Medical Center, Department of Medicine, Fahey Center, Maywood, IL
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8
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Khilnani GC, Tiwari P, Mittal S, Kulkarni AP, Chaudhry D, Zirpe KG, Todi SK, Mohan A, Hegde A, Jagiasi BG, Krishna B, Rodrigues C, Govil D, Pal D, Divatia JV, Sengar M, Gupta M, Desai M, Rungta N, Prayag PS, Bhattacharya PK, Samavedam S, Dixit SB, Sharma S, Bandopadhyay S, Kola VR, Deswal V, Mehta Y, Singh YP, Myatra SN. Guidelines for Antibiotics Prescription in Critically Ill Patients. Indian J Crit Care Med 2024; 28:S104-S216. [PMID: 39234229 PMCID: PMC11369928 DOI: 10.5005/jp-journals-10071-24677] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2024] [Accepted: 03/20/2024] [Indexed: 09/06/2024] Open
Abstract
How to cite this article: Khilnani GC, Tiwari P, Mittal S, Kulkarni AP, Chaudhry D, Zirpe KG, et al. Guidelines for Antibiotics Prescription in Critically Ill Patients. Indian J Crit Care Med 2024;28(S2):S104-S216.
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Affiliation(s)
- Gopi C Khilnani
- Department of Pulmonary, Critical Care and Sleep Medicine, PSRI Hospital, New Delhi, India
| | - Pawan Tiwari
- Department of Pulmonary, Critical Care and Sleep Medicine, AIIMS, New Delhi, India
| | - Saurabh Mittal
- Department of Pulmonary, Critical Care and Sleep Medicine, AIIMS, New Delhi, India
| | - Atul P Kulkarni
- Division of Critical Care Medicine, Department of Anaesthesia, Critical Care and Pain, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, Maharashtra, India
| | - Dhruva Chaudhry
- Department of Pulmonary and Critical Care Medicine, University of Health Sciences, Rohtak, Haryana, India
| | - Kapil G Zirpe
- Department of Neuro Trauma Unit, Grant Medical Foundation, Pune, Maharashtra, India
| | - Subhash K Todi
- Department of Critical Care, AMRI Hospital, Kolkata, West Bengal, India
| | - Anant Mohan
- Department of Pulmonary, Critical Care and Sleep Medicine, AIIMS, New Delhi, India
| | - Ashit Hegde
- Department of Medicine & Critical Care, P D Hinduja National Hospital, Mumbai, India
| | - Bharat G Jagiasi
- Department of Critical Care, Kokilaben Dhirubhai Ambani Hospital, Navi Mumbai, Maharashtra, India
| | - Bhuvana Krishna
- Department of Critical Care Medicine, St John's Medical College and Hospital, Bengaluru, India
| | - Camila Rodrigues
- Department of Microbiology, P D Hinduja National Hospital, Mumbai, India
| | - Deepak Govil
- Department of Critical Care and Anesthesia, Medanta – The Medicity, GuruGram, Haryana, India
| | - Divya Pal
- Department of Critical Care and Anesthesia, Medanta – The Medicity, GuruGram, Haryana, India
| | - Jigeeshu V Divatia
- Department of Anaesthesiology, Critical Care and Pain, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, Maharashtra, India
| | - Manju Sengar
- Department of Medical Oncology, Tata Memorial Center, Homi Bhabha National Institute, Mumbai, Maharashtra, India
| | - Mansi Gupta
- Department of Pulmonary Medicine, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
| | - Mukesh Desai
- Department of Immunology, Pediatric Hematology and Oncology Bai Jerbai Wadia Hospital for Children, Mumbai, Maharashtra, India
| | - Narendra Rungta
- Department of Critical Care & Anaesthesiology, Rajasthan Hospital, Jaipur, India
| | - Parikshit S Prayag
- Department of Transplant Infectious Diseases, Deenanath Mangeshkar Hospital, Pune, Maharashtra, India
| | - Pradip K Bhattacharya
- Department of Critical Care Medicine, Rajendra Institute of Medical Sciences, Ranchi, Jharkhand, India
| | - Srinivas Samavedam
- Department of Critical Care, Ramdev Rao Hospital, Hyderabad, Telangana, India
| | - Subhal B Dixit
- Department of Critical Care, Sanjeevan and MJM Hospital, Pune, Maharashtra, India
| | - Sudivya Sharma
- Department of Anaesthesiology, Critical Care and Pain, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, Maharashtra, India
| | - Susruta Bandopadhyay
- Department of Critical Care, AMRI Hospitals Salt Lake, Kolkata, West Bengal, India
| | - Venkat R Kola
- Department of Critical Care Medicine, Yashoda Hospitals, Hyderabad, Telangana, India
| | - Vikas Deswal
- Consultant, Infectious Diseases, Medanta - The Medicity, Gurugram, Haryana, India
| | - Yatin Mehta
- Department of Critical Care and Anesthesia, Medanta – The Medicity, GuruGram, Haryana, India
| | - Yogendra P Singh
- Department of Critical Care, Max Super Speciality Hospital, Patparganj, New Delhi, India
| | - Sheila N Myatra
- Department of Anaesthesiology, Critical Care and Pain, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, Maharashtra, India
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9
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Eubank TA, Dureja C, Garey KW, Hurdle JG, Gonzales-Luna AJ. Reduced Vancomycin Susceptibility in Clostridioides difficile Is Associated With Lower Rates of Initial Cure and Sustained Clinical Response. Clin Infect Dis 2024; 79:15-21. [PMID: 38382090 PMCID: PMC11259216 DOI: 10.1093/cid/ciae087] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2023] [Revised: 02/08/2024] [Accepted: 02/14/2024] [Indexed: 02/23/2024] Open
Abstract
BACKGROUND Epidemiologic studies have shown decreasing vancomycin susceptibility among clinical Clostridioides difficile isolates, but the impact on patient outcomes is unknown. We hypothesized that reduced vancomycin susceptibility would be associated with decreased rates of sustained clinical response (SCR). METHODS This multicenter cohort study included adults with C. difficile infection (CDI) treated with oral vancomycin between 2016 and 2021. Clostridioides difficile isolates underwent agar dilution vancomycin susceptibility testing, ribotyping, and Sanger sequencing of the vancomycin resistance vanR gene. Reduced susceptibility was defined as vancomycin minimum inhibitory concentration (MIC) >2 μg/mL. The primary outcome was 30-day SCR; secondary outcomes were 14-day initial cure, 30-day recurrence, and 30-day mortality. Exploratory analysis assessed the association between the VanR Thr115Ala polymorphism, susceptibility, and outcomes. RESULTS A high proportion (34% [102/300]) of C. difficile isolates exhibited reduced vancomycin susceptibility (range, 0.5-16 μg/mL; MIC50/90 = 2/4 μg/mL). Ribotype 027 accounted for the highest proportion (77.4% [41/53]) of isolates with reduced vancomycin susceptibility. Overall, 83% (249) of patients achieved 30-day SCR. Reduced vancomycin susceptibility was associated with lower rates of 30-day SCR (76% [78/102]) than vancomycin-susceptible strains (86% [171/198]; P = .031). A significantly lower rate of 14-day initial cure was also observed among individuals infected with strains with reduced vancomycin susceptibility (89% vs 96%; P = .04). Reduced susceptibility remained an independent predictor of 30-day SCR in multivariable modeling (odds ratio, 0.52 [95% confidence interval, .28-.97]; P = .04). CONCLUSIONS Reduced vancomycin susceptibility in C. difficile was associated with decreased odds of 30-day SCR and lower 14-day initial cure rates in the studied patient cohort.
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Affiliation(s)
- Taryn A Eubank
- Department of Pharmacy Practice and Translational Research, University of Houston College of Pharmacy
| | - Chetna Dureja
- Center of Infectious and Inflammatory Diseases, Institute of Biosciences and Technology, Texas A&M Health Science Center, Houston, Texas
| | - Kevin W Garey
- Department of Pharmacy Practice and Translational Research, University of Houston College of Pharmacy
| | - Julian G Hurdle
- Center of Infectious and Inflammatory Diseases, Institute of Biosciences and Technology, Texas A&M Health Science Center, Houston, Texas
| | - Anne J Gonzales-Luna
- Department of Pharmacy Practice and Translational Research, University of Houston College of Pharmacy
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10
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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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11
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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: 30] [Impact Index Per Article: 30.0] [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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12
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Antunes A, Tricotel A, Wilk A, Dombrowski S, Rinta-Kokko H, Andersson FL, Ghosh S. Estimating excess mortality and economic burden of Clostridioides difficile infections and recurrences during 2015-2019: the RECUR Germany study. BMC Infect Dis 2024; 24:548. [PMID: 38822244 PMCID: PMC11143700 DOI: 10.1186/s12879-024-09422-w] [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: 12/13/2023] [Accepted: 05/21/2024] [Indexed: 06/02/2024] Open
Abstract
BACKGROUND Clostridioides difficile infections (CDIs) and recurrences (rCDIs) remain a major public health challenge due to substantial mortality and associated costs. This study aims to generate real-world evidence on the mortality and economic burden of CDI in Germany using claims data between 2015 and 2019. METHODS A longitudinal and matched cohort study using retrospective data from Statutory Health Insurance (SHI) was conducted in Germany with the BKK database. Adults diagnosed with CDI in hospital and community settings between 2015 and 2018 were included in the study. Patients had a minimum follow-up of 12-months. All-cause mortality was described at 6-, 12-, and 24-months. Healthcare resource usage (HCRU) and associated costs were assessed at 12-months of follow-up. A cohort of non-CDI patients matched by demographic and clinical characteristics was used to assess excess mortality and incremental costs of HCRU. Up to three non-CDI patients were matched to each CDI patient. RESULTS A total of 9,977 CDI patients were included in the longitudinal cohort. All-cause mortality was 32%, 39% and 48% at 6-, 12-, and 24-months, respectively, with minor variations by number of rCDIs. When comparing matched CDI (n = 5,618) and non-CDI patients (n = 16,845), CDI patients had an excess mortality of 2.17, 1.35, and 0.94 deaths per 100 patient-months, respectively. HCRU and associated costs were consistently higher in CDI patients compared to non-CDI patients and increased with recurrences. Total mean and median HCRU cost per patient during follow-up was €12,893.56 and €6,050 in CDI patients, respectively, with hospitalisations representing the highest proportion of costs. A total mean incremental cost per patient of €4,101 was estimated in CDI patients compared to non-CDI patients, increasing to €13,291 in patients with ≥ 3 rCDIs. CONCLUSIONS In this real-world study conducted in Germany, CDI was associated with increased risk of death and substantial costs to health systems due to higher HCRU, especially hospitalisations. HCRU and associated costs were exacerbated by rCDIs.
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Affiliation(s)
- Ana Antunes
- IQVIA, Global Database Studies, Real World Solutions, Edifício 3, Lagoas Park, Oeiras, Lisboa, 2740 - 266, Portugal.
| | | | - Adrian Wilk
- Team Gesundheit, Gesellschaft für Gesundheitsmanagement mbH, Essen, Germany
| | | | - Hanna Rinta-Kokko
- IQVIA, Global Database Studies, Real World Solutions, Espoo, Finland
| | | | - Subrata Ghosh
- College of Medicine and Health, University College Cork, Cork, Ireland
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13
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Kucharzik T, Dignass A, Atreya R, Bokemeyer B, Esters P, Herrlinger K, Kannengiesser K, Kienle P, Langhorst J, Lügering A, Schreiber S, Stallmach A, Stein J, Sturm A, Teich N, Siegmund B. Aktualisierte S3-Leitlinie Colitis ulcerosa (Version 6.2). ZEITSCHRIFT FUR GASTROENTEROLOGIE 2024; 62:769-858. [PMID: 38718808 DOI: 10.1055/a-2271-0994] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 07/02/2024]
Affiliation(s)
- T Kucharzik
- Klinik für Allgemeine Innere Medizin und Gastroenterologie, Städtisches Klinikum Lüneburg, Lüneburg, Deutschland
| | - A Dignass
- Medizinische Klinik I, Agaplesion Markus Krankenhaus, Frankfurt, Deutschland
| | - R Atreya
- Medizinische Klinik 1 Gastroent., Pneumologie, Endokrin., Universitätsklinikum Erlangen, Erlangen, Deutschland
| | - B Bokemeyer
- Interdisziplinäres Crohn Colitis Centrum Minden - ICCCM, Minden, Deutschland
| | - P Esters
- Medizinische Klinik I, Agaplesion Markus Krankenhaus, Frankfurt, Deutschland
| | - K Herrlinger
- Innere Medizin I, Asklepios Klinik Nord, Hamburg, Deutschland
| | - K Kannengiesser
- Klinik für Allgemeine Innere Medizin und Gastroenterologie, Städtisches Klinikum Lüneburg, Lüneburg, Deutschland
| | - P Kienle
- Abteilung für Allgemein- und Viszeralchirurgie, Theresienkrankenhaus, Mannheim, Deutschland
| | - J Langhorst
- Klinik für Integrative Medizin und Naturheilkunde, Sozialstiftung Bamberg Klinikum am Bruderwald, Bamberg, Deutschland
| | - A Lügering
- Medizinisches Versorgungszentrum Portal 10, Münster, Deutschland
| | - S Schreiber
- Klinik für Innere Medizin I, Universitätsklinikum Schleswig Holstein, Kiel, Deutschland
| | - A Stallmach
- Klinik für Innere Medizin IV Gastroenterologie, Hepatologie, Infektiologie, Universitätsklinikum Jena, Jena, Deutschland
| | - J Stein
- Abteilung Innere Medizin mit Schwerpunkt Gastroenterologie, Krankenhaus Sachsenhausen, Frankfurt, Deutschland
| | - A Sturm
- Klinik für Innere Medizin mit Schwerpunkt Gastroenterologie, DRK Kliniken Berlin Westend, Berlin, Deutschland
| | - N Teich
- Internistische Gemeinschaftspraxis, Leipzig, Deutschland
| | - B Siegmund
- Medizinische Klinik für Gastroenterologie, Infektiologie und Rheumatologie, Charité Campus Benjamin Franklin - Universitätsmedizin Berlin, Berlin, Deutschland
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14
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Stallhofer J, Steube A, Katzer K, Stallmach A. Microbiota-Based Therapeutics as New Standard-of-Care Treatment for Recurrent Clostridioides difficile Infection. Visc Med 2024; 40:82-91. [PMID: 38584858 PMCID: PMC10995962 DOI: 10.1159/000535851] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2023] [Accepted: 12/14/2023] [Indexed: 04/09/2024] Open
Abstract
Background Clostridioides difficile (C. difficile) is a spore-forming bacterial species that ubiquitously exists in the environment. Colonization by C. difficile is highly prevalent in infants, while fewer than 5% of adults are asymptomatic carriers. Disruption of the microbiome, such as through antibiotic treatment, triggers the germination of bacterial spores into numerous vegetative cells. These cells then produce enterotoxins that result in watery diarrhea and colonic inflammation. If left untreated, C. difficile infection (CDI) can lead to pseudomembranous colitis with the potentially life-threatening complication of toxic megacolon. Summary Over the past few decades, the incidence, morbidity, and mortality associated with CDIs have increased. They have emerged as the primary cause of nosocomial gastrointestinal infections in industrialized countries, posing a significant burden on healthcare systems. Despite antibiotics often being the cause of CDIs, they remain the standard treatment. However, a considerable number of patients treated with antibiotics will experience recurrent CDI (rCDI). Microbiota-based therapies targeting the core issue of CDI - antibiotic-induced dysbiosis - hold promise for rCDI treatment. While data for probiotics are insufficient, numerous studies have highlighted the effectiveness of fecal microbiota transplantation (FMT) as a safe and viable therapeutic option for rCDI. This approach is now endorsed by multiple guidelines. Nonetheless, regulatory prerequisites, such as comprehensive stool donor screening, restrict the widespread adoption of FMT beyond specialized centers. Recently, the US Food and Drug Administration has approved two commercial microbiota-based therapeutics to prevent CDI recurrence. These therapeutics are available by prescription in the USA. RBX2660 (REBYOTA™) comprises a diverse consortium of live microbes derived from human stool and is administered via enema. On the other hand, SER-109 (VOWST™) is an orally administered spore-based medication. In this review, we discuss the potential of microbiota-based treatments for rCDI against the background of medico-legal challenges associated with classical FMT. Key Messages FMT has emerged as a highly effective cure for rCDI. Nonetheless, regulatory prerequisites and laborious preparation procedures impede its widespread use. The establishment of ready-to-use microbiota-based therapeutics in clinical practice is necessary. In the USA, the recent approval of the first two commercial medications, including a spore-based oral preparation, marks a significant step forward.
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Affiliation(s)
| | - Arndt Steube
- Department of Internal Medicine IV, Jena University Hospital, Jena, Germany
| | - Katrin Katzer
- Department of Internal Medicine IV, Jena University Hospital, Jena, Germany
| | - Andreas Stallmach
- Department of Internal Medicine IV, Jena University Hospital, Jena, Germany
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15
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Pearlmutter BS, Carlisle MG, Wilson BM, Sangwan N, Donskey CJ. Pulsed dosing and extended daily dosing of oral vancomycin do not facilitate clearance of Clostridioides difficile colonization in mice. Antimicrob Agents Chemother 2024; 68:e0090323. [PMID: 38095427 PMCID: PMC10777828 DOI: 10.1128/aac.00903-23] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2023] [Accepted: 09/27/2023] [Indexed: 01/11/2024] Open
Abstract
Vancomycin taper and pulse regimens are commonly used to treat recurrent Clostridioides difficile infections, but the mechanism by which these regimens might reduce recurrences is unclear. Here, we used a mouse model to test the hypothesis that pulse dosing of vancomycin after a 10-day treatment course enhances clearance of C. difficile from the intestinal tract. Mice with C. difficile colonization received 10 days of once-daily oral vancomycin followed by 20 days of treatment with saline (controls), daily vancomycin, or pulse dosing of vancomycin every 2 or 3 days. Stool samples were collected to measure the concentration of C. difficile during and after treatment, vancomycin concentrations, and growth of vegetative C. difficile during every 3 days dosing. Pulse dosing of vancomycin was not effective in maintaining suppression of C. difficile (P > 0.05 in comparison to saline controls); growth of vegetative C. difficile occurred between pulse doses when vancomycin decreased to undetectable levels. Daily dosing of vancomycin suppressed C. difficile during treatment, but recurrent colonization occurred after treatment in more than 75% of mice, and by post-treatment day 14, there was no significant difference among the control, pulse dosing, and daily dosing groups (P > 0.05). These findings demonstrate that pulse dosing of vancomycin every 2 or 3 days does not facilitate the clearance of C. difficile spores in mice. Studies are needed to examine the impact of vancomycin taper and pulsed regimens in patients.
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Affiliation(s)
- Basya S. Pearlmutter
- Research Service, Louis Stokes Cleveland VA Medical Center, Cleveland, Ohio, USA
| | - Matthew G. Carlisle
- Geriatric Research Education and Clinical Center, Louis Stokes Cleveland VA Medical Center, Cleveland, Ohio, USA
| | - Brigid M. Wilson
- Geriatric Research Education and Clinical Center, Louis Stokes Cleveland VA Medical Center, Cleveland, Ohio, USA
- Case Western Reserve University School of Medicine, Cleveland, Ohio, USA
| | - Naseer Sangwan
- Case Western Reserve University School of Medicine, Cleveland, Ohio, USA
- Lerner Research Institute/Lerner College of Medicine of Case Western Reserve University, Cleveland, Ohio, USA
| | - Curtis J. Donskey
- Geriatric Research Education and Clinical Center, Louis Stokes Cleveland VA Medical Center, Cleveland, Ohio, USA
- Lerner Research Institute/Lerner College of Medicine of Case Western Reserve University, Cleveland, Ohio, USA
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16
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Yakout A, Bi Y, Harris DM. Clostridioides Difficile: A Concise Review of Best Practices and Updates. J Prim Care Community Health 2024; 15:21501319241249645. [PMID: 38726585 PMCID: PMC11085020 DOI: 10.1177/21501319241249645] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2024] [Revised: 04/05/2024] [Accepted: 04/09/2024] [Indexed: 05/12/2024] Open
Abstract
Clostridioides difficile infection (CDI) is one of the most common and severe nosocomial infections worldwide. It can also affect healthy individuals in the community. The incidence of CDI has been on the rise globally for the past decade, necessitating a proactive approach to combat its spread; new strategies are being developed to enhance diagnostic accuracy and optimize treatment outcomes. Implementing the 2-step testing has increased diagnostic specificity, reducing the usage of CD-specific antibiotics with no concomitant increase in surgical complication rates. In 2021, the Infectious Diseases Society of America/Society for Healthcare Epidemiology of America (IDSA/SHEA) shifted its preference for initial treatment to fidaxomicin over vancomycin and metronidazole due to its lower recurrence rate. It also prioritized fidaxomicin for the treatment of recurrent CDI. There are new developments on the frontiers of fecal microbiota therapies, with RBX2660 and SER-109 approved recently by the FDA for prevention, with other microbiome-based therapies in various development and clinical trials. This review offers providers an updated and practical guide for CDI management.
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Affiliation(s)
| | - Yan Bi
- Mayo Clinic, Jacksonville, FL, USA
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17
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Gonzales-Luna AJ, Carlson TJ, Garey KW. Review Article: Safety of Live Biotherapeutic Products Used for the Prevention of Clostridioides difficile Infection Recurrence. Clin Infect Dis 2023; 77:S487-S496. [PMID: 38051970 DOI: 10.1093/cid/ciad642] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/07/2023] Open
Abstract
Live biotherapeutic products (LBPs) represent a new class of therapeutics indicated to prevent the recurrence of Clostridioides difficile infection (CDI) in adults. However, microbiota-based therapies have been used in CDI management before the Food and Drug Administration (FDA) designated this new drug class. The regulation of these microbiome-based therapies has varied, and several safety concerns have arisen over time. Requirements established by the FDA regarding the development of LBPs minimizes many of these prior concerns, and phase III trials have proven the safety and efficacy of 2 stool donor-derived LBPs: fecal microbiota, live-jslm (Rebyota™; formerly RBX2660) and fecal microbiota spores, live-brpk (Vowst™; formerly SER-109). Mild gastrointestinal side effects are common, but no severe drug-related adverse events have been reported with their use to date. A third LBP entering phase III clinical trials, VE303, follows a novel approach by sourcing bacterial strains from clonal cell banks and has demonstrated a similarly favorable safety profile.
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Affiliation(s)
- Anne J Gonzales-Luna
- Department of Pharmacy and Translational Research, University of Houston College of Pharmacy, Houston, Texas, USA
| | - Travis J Carlson
- Pharmacotherapy Division, College of Pharmacy, The University of Texas at Austin, San Antonio, Texas, USA
- Pharmacotherapy Education and Research Center, Joe R. and Teresa Lozano Long School of Medicine, University of Texas Health San Antonio, San Antonio, Texas, USA
- University Hospital, University Health, San Antonio, Texas, USA
| | - Kevin W Garey
- Department of Pharmacy and Translational Research, University of Houston College of Pharmacy, Houston, Texas, USA
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18
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Porcari S, Severino A, Rondinella D, Bibbò S, Quaranta G, Masucci L, Maida M, Scaldaferri F, Sanguinetti M, Gasbarrini A, Cammarota G, Ianiro G. Fecal microbiota transplantation for recurrent Clostridioides difficile infection in patients with concurrent ulcerative colitis. J Autoimmun 2023; 141:103033. [PMID: 37085337 DOI: 10.1016/j.jaut.2023.103033] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2023] [Revised: 03/05/2023] [Accepted: 03/17/2023] [Indexed: 04/23/2023]
Abstract
AIMS Clostridioides difficile infection (CDI) is a major challenge for healthcare systems. Inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn's disease, is a risk factor for primary and recurrent CDI (rCDI). Moreover, CDI itself often worsens the clinical picture of IBD, increasing the risk of complications. Fecal microbiota transplantation (FMT) is a highly effective treatment for rCDI, but data from patients with IBD and CDI are limited and often referred to mixed cohorts. We aimed to report outcomes from a cohort of patients with UC treated with FMT for rCDI superinfection. METHODS AND RESULTS In a retrospective, single-centre cohort study we evaluated characteristics and outcomes of patients with UC who received FMT for rCDI. The primary outcome was negative C. difficile toxin 8 weeks after FMT. Thirty-five patients were included in the analysis. Sixteen patients were cured after single FMT, while 19 patients received repeat FMT. Overall, FMT cured rCDI in 32 patients (91%), and repeat FMT was significantly associated with sustained cure of CDI compared with single FMT (84% vs 50%, p = 0.018). Twenty-four patients (69%) experienced remission or an amelioration of UC activity. Serious adverse events were not observed. CONCLUSIONS In our cohort of patients with UC, FMT was highly effective in curing rCDI without severe adverse events and repeat FMT was significantly associated with CDI cure. Most patients also experienced remission or amelioration of UC activity after FMT. Our findings suggest that a sequential FMT protocol may be used routinely in patients with UC and rCDI.
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Affiliation(s)
- Serena Porcari
- Digestive Disease Center, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy; Dipartimento Universitario di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Andrea Severino
- Digestive Disease Center, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy; Dipartimento Universitario di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Debora Rondinella
- Digestive Disease Center, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy; Dipartimento Universitario di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Stefano Bibbò
- Digestive Disease Center, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy; Dipartimento Universitario di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Gianluca Quaranta
- Microbiology Unit, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Luca Masucci
- Microbiology Unit, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Marcello Maida
- Gastroenterology and Endoscopy Unit, S. Elia-Raimondi Hospital, Caltanissetta, Italy
| | - Franco Scaldaferri
- Digestive Disease Center, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy; Dipartimento Universitario di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Maurizio Sanguinetti
- Microbiology Unit, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Antonio Gasbarrini
- Digestive Disease Center, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy; Dipartimento Universitario di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Giovanni Cammarota
- Digestive Disease Center, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy; Dipartimento Universitario di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Gianluca Ianiro
- Digestive Disease Center, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy; Dipartimento Universitario di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Rome, Italy.
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19
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Chaar A, Damianos J, Rizwan R, Al-Nahhas H, Mansoor MS, Sharma P, Malik U, Feuerstadt P. First Clostridioides difficile Recurrence Is Highest Following Concomitant Antimicrobial Administration During and Within 30 Days of Treatment. Dig Dis Sci 2023; 68:4221-4229. [PMID: 37665427 DOI: 10.1007/s10620-023-08091-0] [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: 02/21/2023] [Accepted: 08/21/2023] [Indexed: 09/05/2023]
Abstract
BACKGROUND Clostridioides difficile infection (CDI) is an epidemic with the strongest risk factor being antibiotic usage. Patients who get CDI frequently require concomitant antibiotics for other indications around the time of their infection. AIMS To assess the recurrence of CDI (rCDI) in patients receiving concomitant antibiotics at the same time or shortly thereafter treatment of CDI. METHODS We retrospectively reviewed records for patients with their first inpatient CDI episode. Patients were grouped into those who didn't receive concomitant antibiotics (noABx), those receiving antibiotics at the same time as treatment of CDI (ABxDURING), those receiving antibiotics within 30-days of completion of CDI therapy (ABxAFTER) and those who received antibiotics both during and after CDI treatment (ABxDuringAfter). Our primary outcome was recurrence within 14-90 days; other outcomes included ICU stay at the time of diagnosis, 30-day ICU transfer, 30-day colectomy, and readmission. RESULTS 457 patients had CDI during admission (mean age: 66.4 years, 51.9% female). 64.1% were exposed to concomitant antibiotics. Recurrence rates were 4.3%, 6.1%, 13.8% and 19.1%, for noABx, ABxDURING, ABxAFTER and ABxDuringAfter, respectively. Patients with ABxDuringAfter had the highest rates of rCDI when compared to noABx [OR 5.67, 95% CI (2.18-14.72)]. CONCLUSIONS There is a high rate of utilization of non-CDI antibiotics during or shortly after completing CDI treatment with high rates of recurrence within 90-days. Concomitant antimicrobials alter the opportunity for the microbiota to re-grow and worsens dysbiosis leading to increases in recurrence. Concomitant antimicrobial stewardship remains important in patients being treated for CDI and shortly after treatment.
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Affiliation(s)
- Abdelkader Chaar
- Department of Internal Medicine, Yale School of Medicine, New Haven, CT, USA
- Department of Medicine, Yale-New Haven Hospital, New Haven, CT, USA
| | - John Damianos
- Department of Internal Medicine, Yale School of Medicine, New Haven, CT, USA
| | - Rabia Rizwan
- Department of Internal Medicine, Yale School of Medicine, New Haven, CT, USA
- Department of Medicine, Yale-New Haven Hospital, New Haven, CT, USA
| | | | | | - Prabin Sharma
- Department of Gastroenterology, Hartford Healthcare, St Vincent's Medical Center, Bridgeport, CT, USA
| | - Umer Malik
- Division of Gastroenterology, Albany Medical Center, Albany, NY, USA
| | - Paul Feuerstadt
- Section of Digestive Diseases, Yale School of Medicine, New Haven, CT, USA.
- PACT-Gastroenterology Center, 2200 Whitney Avenue, Hamden, CT, 06518, USA.
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20
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Lo Porto D, Mularoni A, Castagnola E, Saffioti C. Clostridioides difficile infection in the allogeneic hematopoietic cell transplant recipient. Transpl Infect Dis 2023; 25 Suppl 1:e14159. [PMID: 37787395 DOI: 10.1111/tid.14159] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2023] [Revised: 09/09/2023] [Accepted: 09/14/2023] [Indexed: 10/04/2023]
Abstract
Clostridioides difficile (CD) is one of the most important causes of diarrhea in hospitalized patients, in particular those who undergo an allogeneic hematopoietic cell transplant (allo-HCT) and who are more at risk of developing a CD infection (CDI) due to frequent hospitalizations, iatrogenic immunosuppression, and prolonged antibiotic cycles. CDI may represent a severe condition in allo-HCT patients, increasing the length of hospitalization, influencing the intestinal microbiome with a bidirectional association with graft-versus-host disease, and leading to unfavorable outcomes, including death. The diagnosis of CDI requires the exclusion of other probable causes of diarrhea in HCT patients and is based on highly sensitive and highly specific tests to distinguish colonization from infection. In adult patients, fidaxomicin is recommended as first-line, with oral vancomycin as an alternative agent. Bezlotoxumab may be used to reduce the risk of recurrence. In pediatric patients, vancomycin and metronidazole are still suggested as first-line therapy, but fidaxomicin will probably become standard in pediatrics in the near future. Because of insufficient safety data, fecal microbiota transplantation is not routinely recommended in HCT in spite of promising results for the management of recurrences in other populations.
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Affiliation(s)
- Davide Lo Porto
- Unit of Infectious Diseases, IRCCS-ISMETT Istituto Mediterraneo per i Trapianti e Terapie ad Alta Specializzazione, Palermo, Italy
| | - Alessandra Mularoni
- Unit of Infectious Diseases, IRCCS-ISMETT Istituto Mediterraneo per i Trapianti e Terapie ad Alta Specializzazione, Palermo, Italy
| | - Elio Castagnola
- Pediatric Infectious Diseases Unit, IRCCS Istituto Giannina Gaslini, Genoa, Italy
| | - Carolina Saffioti
- Pediatric Infectious Diseases Unit, IRCCS Istituto Giannina Gaslini, Genoa, Italy
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21
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Berry P, Khanna S. Recurrent Clostridioides difficile Infection: Current Clinical Management and Microbiome-Based Therapies. BioDrugs 2023; 37:757-773. [PMID: 37493938 DOI: 10.1007/s40259-023-00617-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/13/2023] [Indexed: 07/27/2023]
Abstract
Clostridioides difficile is one of the most important causes of healthcare-associated diarrhea. The high incidence and recurrence rates of C. difficile infection, as well as its associated morbidity and mortality, are great concerns. The most common complication of C. difficile infection is recurrence, with rates of 20-30% after a primary infection and 60% after three or more episodes. Medical management of recurrent C. difficile infection involves a choice of therapy that is different from the antibiotic used in the primary episode. Patients with recurrent C. difficile infection also benefit from fecal microbiota transplantation or standardized microbiome restoration therapies (approved or experimental) to restore eubiosis. In contrast to antibiotics, microbiome restoration therapies restore a normal gut flora and eliminate C. difficile colonization and infection. Fecal microbiota transplantation in recurrent C. difficile infection has demonstrated higher success rates than vancomycin, fidaxomicin, or placebo. Fecal microbiota transplantation has traditionally been considered safe, with the most common adverse reactions being abdominal discomfort, and diarrhea, and rare serious adverse events. Significant heterogeneity and a lack of standardization regarding the process of preparation, and administration of fecal microbiota transplantation remain a major pitfall. Standardized microbiome-based therapies provide a promising alternative. In the ECOSPOR III trial of SER-109, an oral formulation of bacterial spores, a significant reduction in the recurrence rate (12%) was observed compared with placebo (40%). In the phase III PUNCH CD3 trial, RBX2660 also demonstrated high efficacy rates of 70.6% versus 57.5%. Both these agents are now US Food and Drug Administration approved for recurrent C. difficile infection. Other standardized microbiome-based therapies currently in the pipeline are VE303, RBX7455, and MET-2. Antibiotic neutralization strategies, vaccines, passive monoclonal antibodies, and drug repurposing are other therapeutic strategies being explored to treat C. difficile infection.
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Affiliation(s)
- Parul Berry
- All India Institute of Medical Sciences, New Delhi, India
| | - Sahil Khanna
- Division of Gastroenterology and Hepatology, C. difficile Clinic and Microbiome Restoration Program, Mayo Clinic, 200 1st Street SW, Rochester, MN, 55905, USA.
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22
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Kucharzik T, Dignass A, Atreya R, Bokemeyer B, Esters P, Herrlinger K, Kannengiesser K, Kienle P, Langhorst J, Lügering A, Schreiber S, Stallmach A, Stein J, Sturm A, Teich N, Siegmund B. [Not Available]. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2023; 61:1046-1134. [PMID: 37579791 DOI: 10.1055/a-2060-0935] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 08/16/2023]
Affiliation(s)
- T Kucharzik
- Klinik für Allgemeine Innere Medizin und Gastroenterologie, Städtisches Klinikum Lüneburg, Lüneburg, Deutschland
| | - A Dignass
- Medizinische Klinik I, Agaplesion Markus Krankenhaus, Frankfurt, Deutschland
| | - R Atreya
- Medizinische Klinik 1 Gastroent., Pneumologie, Endokrin., Universitätsklinikum Erlangen, Erlangen, Deutschland
| | - B Bokemeyer
- Interdisziplinäres Crohn Colitis Centrum Minden - ICCCM, Minden, Deutschland
| | - P Esters
- Medizinische Klinik I, Agaplesion Markus Krankenhaus, Frankfurt, Deutschland
| | - K Herrlinger
- Innere Medizin I, Asklepios Klinik Nord, Hamburg, Deutschland
| | - K Kannengiesser
- Klinik für Allgemeine Innere Medizin und Gastroenterologie, Städtisches Klinikum Lüneburg, Lüneburg, Deutschland
| | - P Kienle
- Abteilung für Allgemein- und Viszeralchirurgie, Theresienkrankenhaus, Mannheim, Deutschland
| | - J Langhorst
- Klinik für Integrative Medizin und Naturheilkunde, Sozialstiftung Bamberg Klinikum am Bruderwald, Bamberg, Deutschland
| | - A Lügering
- Medizinisches Versorgungszentrum Portal 10, Münster, Deutschland
| | - S Schreiber
- Klinik für Innere Medizin I, Universitätsklinikum Schleswig Holstein, Kiel, Deutschland
| | - A Stallmach
- Klinik für Innere Medizin IV Gastroenterologie, Hepatologie, Infektiologie, Universitätsklinikum Jena, Jena, Deutschland
| | - J Stein
- Abteilung Innere Medizin mit Schwerpunkt Gastroenterologie, Krankenhaus Sachsenhausen, Frankfurt, Deutschland
| | - A Sturm
- Klinik für Innere Medizin mit Schwerpunkt Gastroenterologie, DRK Kliniken Berlin Westend, Berlin, Deutschland
| | - N Teich
- Internistische Gemeinschaftspraxis, Leipzig, Deutschland
| | - B Siegmund
- Medizinische Klinik für Gastroenterologie, Infektiologie und Rheumatologie, Charité Campus Benjamin Franklin - Universitätsmedizin Berlin, Berlin, Deutschland
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23
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McFarland LV, Goldstein EJC, Kullar R. Microbiome-Related and Infection Control Approaches to Primary and Secondary Prevention of Clostridioides difficile Infections. Microorganisms 2023; 11:1534. [PMID: 37375036 DOI: 10.3390/microorganisms11061534] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2023] [Revised: 05/30/2023] [Accepted: 06/02/2023] [Indexed: 06/29/2023] Open
Abstract
Clostridioides difficile infections (CDIs) have decreased in the past years, but since 2021, some hospitals have reported an increase in CDI rates. CDI remains a global concern and has been identified as an urgent threat to healthcare. Although multiple treatment options are available, prevention strategies are more limited. As CDI is an opportunistic infection that arises after the normally protective microbiome has been disrupted, preventive measures aimed at restoring the microbiome have been tested. Our aim is to update the present knowledge on these various preventive strategies published in the past five years (2018-2023) to guide clinicians and healthcare systems on how to best prevent CDI. A literature search was conducted using databases (PubMed, Google Scholar, and clinicaltrials.gov) for phase 2-3 clinical trials for the primary or secondary prevention of CDI and microbiome and probiotics. As the main factor for Clostridium difficile infections is the disruption of the normally protective intestinal microbiome, strategies aimed at restoring the microbiome seem most rational. Some strains of probiotics, the use of fecal microbial therapy, and live biotherapeutic products offer promise to fill this niche; although, more large randomized controlled trials are needed that document the shifts in the microbiome population.
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Affiliation(s)
| | | | - Ravina Kullar
- Expert Stewardship Inc., Newport Beach, CA 92663, USA
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24
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Drapkina OM, Lazebnik LB, Bakulin IG, Zhuravleva MS, Bakulina NV, Skazyvaeva EV, Sitkin SI, Skalinskaya MI, Solovyeva OI, Eremina EY, Tikhonov SV, Fil' TS, Pilat TL, Kuznetsova YG, Khanferyan RA, Livzan MA, Osipenko MF, Abdulganieva DI, Tarasova LV, Khavkin AI. <i>Clostridioides difficile</i> infection: diagnosis, treatment, and prevention Clinical guidelines of the Russian Scientific Medical Society of Internal Medicine, the Gastroenterological Scientific Society of Russia, and the North- West Society of Gastroenterologists and Hepatologists. EXPERIMENTAL AND CLINICAL GASTROENTEROLOGY 2023:4-32. [DOI: 10.31146/1682-8658-ecg-210-2-4-32] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/26/2023]
Abstract
Clostridioides difficile infection (CDI) is the most common cause of antibiotic-associated diarrhea, and an important cause of nosocomial infection. Since the publication of the National Guidelines (2016, 2017), new data have been accumulated on the genetic structure and pathogenic properties of the most common causative agent of severe forms of antibiotic- associated diarrhea, which has led to the reclassifi cation of the pathogen, formerly known as Clostridium diffi cile, to Clostridioides difficile. Laboratory algorithms have been developed to diagnose CDI and determine the toxigenicity of strains reliably. New data on the effectiveness of antibacterials have been published, monoclonal antibodies to toxin B (bezlotoxumab) have been introduced into clinical practice to prevent CDI recurrence, and fecal microbiota transplantation has been proposed. Over the past 5 years, many international guidelines on the management of adult patients with CDI have also been updated (USA, EU). In the last decade, including due to the COVID-19 pandemic, there has been an increase in CDI incidence. Considering therelevance of CDI, new data on the pathogen, and domestic features, the Russian Scientific Medical Society of Internal Medicine, the Gastroenterological Scientific Society of Russia, and the North-West Society of Gastroenterologists and Hepatologists developed these clinical guidelines.
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Affiliation(s)
- O. M. Drapkina
- National Medical Research Center for Therapy and Preventive Medicine
| | - L. B. Lazebnik
- A. I. Yevdokimov Moscow State University of Medicine and Dentistry
| | - I. G. Bakulin
- North-Western state medical University named after I. I. Mechnikov
| | - M. S. Zhuravleva
- North-Western state medical University named after I. I. Mechnikov
| | - N. V. Bakulina
- North-Western state medical University named after I. I. Mechnikov
| | - E. V. Skazyvaeva
- North-Western state medical University named after I. I. Mechnikov
| | - S. I. Sitkin
- North-Western state medical University named after I. I. Mechnikov; Almazov National Medical Research Centre
| | | | - O. I. Solovyeva
- North-Western state medical University named after I. I. Mechnikov
| | | | - S. V. Tikhonov
- North-Western state medical University named after I. I. Mechnikov
| | - T. S. Fil'
- North-Western state medical University named after I. I. Mechnikov
| | - T. L. Pilat
- Izmerov Research Institute of Occupational Health
| | | | | | | | | | | | | | - A. I. Khavkin
- Veltischev Research and Clinical Institute for Pediatrics and Pediatric Surgery, Pirogov Russian National Research Medical University
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25
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Wang R. Clostridioides difficile infection: microbe-microbe interactions and live biotherapeutics. Front Microbiol 2023; 14:1182612. [PMID: 37228365 PMCID: PMC10203151 DOI: 10.3389/fmicb.2023.1182612] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2023] [Accepted: 04/03/2023] [Indexed: 05/27/2023] Open
Abstract
Clostridioides difficile is a gram-positive, spore-forming, obligate anaerobe that infects the colon. C. difficile is estimated to cause nearly half a million cases in the United States annually, with about 29,000 associated deaths. Unfortunately, the current antibiotic treatment is not ideal. While antibiotics can treat the infections, they also disrupt the gut microbiota that mediates colonization resistance against enteric pathogens, including C. difficile; disrupted gut microbiota provides a window of opportunity for recurrent infections. Therefore, therapeutics that restore the gut microbiota and suppress C. difficile are being evaluated for safety and efficacy. This review will start with mechanisms by which gut bacteria affect C. difficile pathogenesis, followed by a discussion on biotherapeutics for recurrent C. difficile infections.
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26
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Lim VW, Tomaru T, Chua B, Ma Y, Yanagihara K. Budget Impact Analysis of Adopting a One-Step Nucleic Acid Amplification Testing (NAAT) Alone Diagnostic Pathway for Clostridioides difficile in Japan Compared to a Two-Step Algorithm with Glutamate Dehydrogenase/Toxin Followed by NAAT. Diagnostics (Basel) 2023; 13:diagnostics13081463. [PMID: 37189564 DOI: 10.3390/diagnostics13081463] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2023] [Revised: 04/06/2023] [Accepted: 04/15/2023] [Indexed: 05/17/2023] Open
Abstract
Clostridioides difficile infection (CDI) is a major healthcare-associated infection that leads to a significant health economic burden in Japan. Using a decision tree model, we evaluated the budget impact of adopting a one-step nucleic acid amplification test (NAAT) alone pathway compared to a two-step diagnostic algorithm with glutamate dehydrogenase (GDH) and toxin antigen, followed by NAAT. The analysis was conducted from the government payer's perspective for 100,000 symptomatic, hospitalized adults requiring a CDI diagnostic test. One-way sensitivity analysis was conducted for all data inputs. The NAAT alone strategy costed JPY 225,886,360 (USD 2,424,714) more, but was more effective, resulting in 1749 more patients accurately diagnosed and 91 fewer deaths compared to the two-step algorithm. Additionally, the NAAT alone pathway costed JPY 26,146 (USD 281) less per true positive CDI diagnosed. The total budget impact, and cost per CDI diagnosed was most sensitive to GDH sensitivity in one-way sensitivity analysis, where a lower GDH sensitivity resulted in greater cost savings with the NAAT alone pathway. Findings from this budget impact analysis can guide the adoption of a NAAT alone pathway for CDI diagnosis in Japan.
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Affiliation(s)
- Vanessa W Lim
- Health Economics and Outcomes Research, Becton Dickinson Holdings Pte. Ltd., 2 International Business Park Road, Singapore 609930, Singapore
| | - Takeshi Tomaru
- Health Economics and Outcomes Research, Nippon Becton Dickinson Company, Ltd., Akasaka Garden City 15-1, Akasaka 4-Chome, Minato-ku, Tokyo 107-0052, Japan
| | - Brandon Chua
- Health Economics and Outcomes Research, Becton Dickinson Holdings Pte. Ltd., 2 International Business Park Road, Singapore 609930, Singapore
- Saw Swee Hock School of Public Health, National University of Singapore, 12 Science Drive 2, #10-02, Singapore 117549, Singapore
| | - Yan Ma
- Health Economics and Outcomes Research, Becton Dickinson Holdings Pte. Ltd., 2 International Business Park Road, Singapore 609930, Singapore
| | - Katsunori Yanagihara
- Department of Laboratory Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki University Hospital, Sakamoto 1-12-4, Nagasaki City 852-8523, Japan
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27
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Genomic epidemiology and transmission dynamics of recurrent Clostridioides difficile infection in Western Australia. Eur J Clin Microbiol Infect Dis 2023; 42:607-619. [PMID: 36940050 PMCID: PMC10105659 DOI: 10.1007/s10096-023-04569-x] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2022] [Accepted: 02/09/2023] [Indexed: 03/21/2023]
Abstract
Recurrent cases of Clostridioides difficile infection (rCDI) remain one of the most common and serious challenges faced in the management of CDI. The accurate distinction between a relapse (caused by infection with the same strain) and reinfection (caused by a new strain) has implications for infection control and prevention, and patient therapy. Here, we used whole-genome sequencing to investigate the epidemiology of 94 C. difficile isolates from 38 patients with rCDI in Western Australia. The C. difficile strain population comprised 13 sequence types (STs) led by ST2 (PCR ribotype (RT) 014, 36.2%), ST8 (RT002, 19.1%) and ST34 (RT056, 11.7%). Among 38 patients, core genome SNP (cgSNP) typing found 27 strains (71%) from initial and recurring cases differed by ≤ 2 cgSNPs, suggesting a likely relapse of infection with the initial strain, while eight strains differed by ≥ 3 cgSNPs, suggesting reinfection. Almost half of patients with CDI relapse confirmed by WGS suffered episodes that occurred outside the widely used 8-week cut-off for defining rCDI. Several putative strain transmission events between epidemiologically unrelated patients were identified. Isolates of STs 2 and 34 from rCDI cases and environmental sources shared a recent evolutionary history, suggesting a possible common community reservoir. For some rCDI episodes caused by STs 2 and 231, within-host strain diversity was observed, characterised by loss/gain of moxifloxacin resistance. Genomics improves discrimination of relapse from reinfection and identifies putative strain transmission events among patients with rCDI. Current definitions of relapse and reinfection based on the timing of recurrence need to be reconsidered.
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Feuerstadt P, Theriault N, Tillotson G. The burden of CDI in the United States: a multifactorial challenge. BMC Infect Dis 2023; 23:132. [PMID: 36882700 PMCID: PMC9990004 DOI: 10.1186/s12879-023-08096-0] [Citation(s) in RCA: 66] [Impact Index Per Article: 33.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2022] [Accepted: 02/16/2023] [Indexed: 03/09/2023] Open
Abstract
Clostridioides difficile infection (CDI) affects approximately 500,000 patients annually in the United States, of these around 30,000 will die. CDI carries significant burdens including clinical, social and economic. While healthcare-associated CDI has declined in recent years, community-associated CDI is on the rise. Many patients are also impacted by recurrent C. difficile infections (rCDI); up to 35% of index CDI will recur and of these up to 60% will further recur with multiple recurrences observed. The range of outcomes adversely affected by rCDI is significant and current standard of care does not alter these recurrence rates due to the damaged gut microbiome and subsequent dysbiosis. The clinical landscape of CDI is changing, we discuss the impact of CDI, rCDI, and the wide range of financial, social, and clinical outcomes by which treatments should be evaluated.
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Affiliation(s)
- Paul Feuerstadt
- Division of Digestive Disease, PACT-Gastroenterology Center, Yale University School of Medicine, Hamden, CT, USA
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29
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Chopra T. A profile of the live biotherapeutic product RBX2660 and its role in preventing recurrent Clostridioides difficile infection. Expert Rev Anti Infect Ther 2023; 21:243-253. [PMID: 36756869 DOI: 10.1080/14787210.2023.2171986] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/10/2023]
Abstract
INTRODUCTION Clostridiodes difficile infection (CDI) is a life-threatening illness that has been labelled as an urgent threat by the Centers for Disease prevention (CDC). AREAS COVERED RBX2660, a live biotherapeutic product offers a very promising treatment option for patients with recurrent Clostridiodes difficile infection(rCDI). RBX2660 restores the healthy gut microbiome and shows clinically meaningful benefits for patients suffering from rCDI. Safety, efficacy, and tolerability of RBX2660 have been thoroughly assessed . EXPERT OPINION An FDA-approved, standardized, and accessible microbiota restoration product like RBX2660 would provide a new option for patients in need of treatment for rCDI by breaking the cycle of disease recurrence.
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Affiliation(s)
- Teena Chopra
- Division of Infectious Diseases. Corporate Medical Director, Infection Prevention, Epidemiology, and Antibiotic Stewardship, Detroit Medical Center and Wayne State University, Detroit, Michigan, USA
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30
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Bainum TB, Reveles KR, Hall RG, Cornell K, Alvarez CA. Controversies in the Prevention and Treatment of Clostridioides difficile Infection in Adults: A Narrative Review. Microorganisms 2023; 11:387. [PMID: 36838352 PMCID: PMC9963748 DOI: 10.3390/microorganisms11020387] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2022] [Revised: 01/30/2023] [Accepted: 01/31/2023] [Indexed: 02/05/2023] Open
Abstract
Clostridioides difficile remains a problematic pathogen resulting in significant morbidity and mortality, especially for high-risk groups that include immunocompromised patients. Both the Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America (IDSA/SHEA), as well as the American College of Gastroenterology (ACG) and the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) recently provided guideline updates for C. difficile infection (CDI). In this narrative review, the authors reviewed available literature regarding the prevention or treatment of CDI in adults and focused on disagreements between the IDSA/SHEA and ACG guidelines, as well as articles that have been published since the updates. Several options for primary prophylaxis are available, including probiotics and antibiotics (vancomycin, fidaxomicin). The literature supporting fidaxomicin is currently quite limited. While there are more studies evaluating probiotics and vancomycin, the optimal patient populations and regimens for their use have yet to be defined. While the IDSA/SHEA guidelines discourage metronidazole use for mild CDI episodes, evidence exists that it may remain a reasonable option for these patients. Fidaxomicin has an advantage over vancomycin in reducing recurrences, but its use is limited by cost. Despite this, recent studies suggest fidaxomicin's cost-effectiveness as a first-line therapy, though this is highly dependent on institutional contracts and payment structures. Secondary prophylaxis should focus on non-antimicrobial options to lessen the impact on the microbiome. The oral option of fecal microbiota transplantation (FMT), SER109, and the now FDA-approved RBX2660 represent exciting new options to correct dysbiosis. Bezlotoxumab is another attractive option to prevent recurrences. Further head-to-head studies of newer agents will be needed to guide selection of the optimal therapies for CDI primary and secondary prophylaxis.
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Affiliation(s)
- Taryn B. Bainum
- Jerry H. Hodge School of Pharmacy, Texas Tech University Health Sciences Center, Amarillo, TX 79106, USA
| | - Kelly R. Reveles
- College of Pharmacy, The University of Texas at Austin, Austin, TX 78712, USA
- Pharmacotherapy Education and Research Center, University of Texas Health San Antonio, San Antonio, TX 78229, USA
| | - Ronald G. Hall
- Jerry H. Hodge School of Pharmacy, Texas Tech University Health Sciences Center, Amarillo, TX 79106, USA
| | - Kelli Cornell
- Jerry H. Hodge School of Pharmacy, Texas Tech University Health Sciences Center, Amarillo, TX 79106, USA
| | - Carlos A. Alvarez
- Jerry H. Hodge School of Pharmacy, Texas Tech University Health Sciences Center, Amarillo, TX 79106, USA
- Center of Excellence in Real-World Evidence, Texas Tech University Health Sciences Center, Dallas, TX 75235, USA
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31
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Archbald-Pannone L. How do we best manage Clostridioides difficle infections in the elderly? Expert Rev Anti Infect Ther 2023; 21:499-501. [PMID: 36522295 DOI: 10.1080/14787210.2023.2158814] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Affiliation(s)
- Laurie Archbald-Pannone
- Department of Medicine, Division of General, Geriatric, Hospital & Palliative Medicine and Division of Infectious Diseases and International Health University of Virginia, Charlottesville, VA, USA
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32
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Long B, Gottlieb M. Oral fidaxomicin versus vancomycin for Clostridioides difficile infection. Acad Emerg Med 2022; 29:1506-1507. [PMID: 36156832 DOI: 10.1111/acem.14600] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2022] [Accepted: 09/22/2022] [Indexed: 12/14/2022]
Affiliation(s)
- Brit Long
- Department of Emergency Medicine, Brooke Army Medical Center, Fort Sam Houston, Texas, USA
| | - Michael Gottlieb
- Department of Emergency Medicine, Rush University Medical Center, Chicago, Illinois, USA
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33
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Aby ES, Vaughn BP, Enns EA, Rajasingham R. Cost-effectiveness of Fecal Microbiota Transplantation for First Recurrent Clostridioides difficile Infection. Clin Infect Dis 2022; 75:1602-1609. [PMID: 35275989 PMCID: PMC9617579 DOI: 10.1093/cid/ciac207] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2021] [Indexed: 11/14/2022] Open
Abstract
BACKGROUND Both the American College of Gastroenterology and the Infectious Diseases Society of America (IDSA)/Society for Healthcare Epidemiology of America 2021 Clostridioides difficile infection (CDI) guidelines recommend fecal microbiota transplantation (FMT) for persons with multiple recurrent CDI. Emerging data suggest that FMT may have high cure rates when used for first recurrent CDI. The aim of this study was to assess the cost-effectiveness of FMT for first recurrent CDI. METHODS We developed a Markov model to simulate a cohort of patients presenting with initial CDI infection. The model estimated the costs, effectiveness, and cost-effectiveness of different CDI treatment regimens recommended in the 2021 IDSA guidelines, with the additional option of FMT for first recurrent CDI. The model includes stratification by the severity of initial infection, estimates of cure, recurrence, and mortality. Data sources were taken from IDSA guidelines and published literature on treatment outcomes. Outcome measures were quality-adjusted life-years (QALYs), costs, and incremental cost-effectiveness ratios (ICERs). RESULTS When FMT is available for first recurrent CDI, the optimal cost-effective treatment strategy is fidaxomicin for initial nonsevere CDI, vancomycin for initial severe CDI, and FMT for first and subsequent recurrent CDI, with an ICER of $27 135/QALY. In probabilistic sensitivity analysis at a $100 000 cost-effectiveness threshold, FMT for first and subsequent CDI recurrence was cost-effective 90% of the time given parameter uncertainty. CONCLUSIONS FMT is a cost-effective strategy for first recurrent CDI. Prospective evaluation of FMT for first recurrent CDI is warranted to determine the efficacy and risk of recurrence.
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Affiliation(s)
- Elizabeth S Aby
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, University of Minnesota, Minneapolis, Minnesota, USA
| | - Byron P Vaughn
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, University of Minnesota, Minneapolis, Minnesota, USA
| | - Eva A Enns
- Division of Health Policy and Management, School of Public Health, University of Minnesota, Minneapolis, Minnesota, USA
| | - Radha Rajasingham
- Division of Infectious Diseases and International Medicine, Department of Medicine, University of Minnesota, Minneapolis, Minnesota, USA
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Suchman K, Luo Y, Grinspan A. Fecal Microbiota Transplant for Clostridioides Difficile Infection Is Safe and Efficacious in an Immunocompromised Cohort. Dig Dis Sci 2022; 67:4866-4873. [PMID: 35000023 DOI: 10.1007/s10620-021-07347-x] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/15/2021] [Accepted: 11/22/2021] [Indexed: 02/08/2023]
Abstract
BACKGROUND Immunocompromised patients are particularly vulnerable to Clostridioides difficile infection (CDI), hospitalizations and recurrences. Studies have shown that fecal microbiota transplant (FMT) is safe and effective in immunocompromised patients. AIMS To examine the outcomes of FMT for CDI in a diverse cohort of immunocompromised patients stratified by medication class. METHODS We performed a retrospective, long-term follow-up study of FMT in immunocompromised patients, including those undergoing chemotherapy, with inflammatory bowel disease (IBD) on immunomodulators, prior solid organ transplant on immunosuppressants, on chronic steroids 20 mg/day or higher for a minimum of three months, or HIV positive. Primary outcomes included adjusted primary cure rate within 8 weeks, as well as rates of non-response, recurrences, relapses and adverse events. Secondary outcomes included adjusted overall cure rate. Primary cure rate was defined as patients not requiring repeat CDI treatment within 8 weeks after index FMT, and overall cure rate was defined as resolution of CDI symptoms after index FMT or second FMT. RESULTS Our cohort included 77 immunosuppressed patients (53.2% female, median age 39.1 years, range 7-95 years). The majority of our cohort were IBD patients on biologics (62.3%). Adjusting for colectomies and deaths, our primary and overall cure rates were 85.1% and 86.5%, respectively. Twelve patients received FMT for severe or fulminant CDI with a 3-month survival rate of 91.7%. 11.7% of patients experienced serious adverse events following FMT. CONCLUSIONS Our study supports the efficacy and safety of FMT in immunocompromised patients, though future research is needed to further ascertain the potential effects of immunosuppression on FMT outcomes.
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Affiliation(s)
- Kelly Suchman
- Department of Internal Medicine, Northshore Hospital, Barbara and Zucker School of Medicine for Hofstra/Northwell Health, 300 Community Drive, Manhasset, NY, 11030, USA.
| | - Yuying Luo
- The Henry D. Janowitz Division of Gastroenterology, Department of Gastroenterology, Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy Place, New York, NY, 11029, USA
| | - Ari Grinspan
- The Henry D. Janowitz Division of Gastroenterology, Department of Gastroenterology, Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy Place, New York, NY, 11029, USA
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Tashiro S, Mihara T, Sasaki M, Shimamura C, Shimamura R, Suzuki S, Yoshikawa M, Hasegawa T, Enoki Y, Taguchi K, Matsumoto K, Ohge H, Suzuki H, Nakamura A, Mori N, Morinaga Y, Yamagishi Y, Yoshizawa S, Yanagihara K, Mikamo H, Kunishima H. Oral fidaxomicin versus vancomycin for the treatment of Clostridioides difficile infection: A systematic review and meta-analysis of randomized controlled trials. J Infect Chemother 2022; 28:1536-1545. [PMID: 35964806 DOI: 10.1016/j.jiac.2022.08.008] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2022] [Revised: 07/27/2022] [Accepted: 08/04/2022] [Indexed: 11/28/2022]
Abstract
BACKGROUND Fidaxomicin (FDX) has received considerable attention as a novel therapeutic alternative agent to vancomycin (VCM) for Clostridioides difficile infection (CDI). However, the superiority and efficacy profile of FDX are not sufficiently determined by high-quality evidence. This study aimed to clarify the superiority of FDX for CDI treatment through a systematic review and meta-analysis. METHODS We conducted a meta-analysis of randomized controlled trials (RCTs) which evaluated the efficacy and safety of FDX and VCM in patients with CDI. Electronic databases (PubMed, Cochrane Library, Web of Science, and Clinicaltrials.gov) were searched for studies published until October 15, 2021. The primary endpoint was global cure. The secondary endpoints were clinical cure, recurrence, and adverse event. Risk ratios (RRs), risk differences (RDs), and 95% confidence intervals were calculated using Mantel-Haenszel random-effects model. The risk of bias was assessed using Cochrane Handbook for Systematic Reviews of Interventions and Assessment Criteria. RESULTS Six RCTs were included in this meta-analysis. Compared to VCM, FDX was associated with significantly higher global cure rates (RR = 1.18, P < 0.00001; RD = 0.11, 95% CI = 0.07-0.16). In addition, clinical cure rates were comparable between FDX and VCM (P = 0.31). FDX was associated with significantly lower recurrence rates compared to VCM (RR = 0.59, P < 0.0001). In addition, adverse event rates were not significantly different between the drugs (P = 0.41). CONCLUSION FDX achieves significantly higher global cure rates and lower recurrence rates and is comparable to VCM in clinical cure rates and adverse event rates in patients with CDI. Collectively, FDX is superior to VCM as a therapeutic agent for CDI.
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Affiliation(s)
- Sho Tashiro
- Division of Pharmacodynamics, Keio University Faculty of Pharmacy, Tokyo, Japan
| | - Takayuki Mihara
- Division of Pharmacodynamics, Keio University Faculty of Pharmacy, Tokyo, Japan
| | - Moe Sasaki
- Division of Pharmacodynamics, Keio University Faculty of Pharmacy, Tokyo, Japan
| | - Chiaki Shimamura
- Division of Pharmacodynamics, Keio University Faculty of Pharmacy, Tokyo, Japan
| | - Rina Shimamura
- Division of Pharmacodynamics, Keio University Faculty of Pharmacy, Tokyo, Japan
| | - Shiho Suzuki
- Division of Pharmacodynamics, Keio University Faculty of Pharmacy, Tokyo, Japan
| | - Maiko Yoshikawa
- Division of Pharmacodynamics, Keio University Faculty of Pharmacy, Tokyo, Japan
| | - Tatsuki Hasegawa
- Division of Pharmacodynamics, Keio University Faculty of Pharmacy, Tokyo, Japan
| | - Yuki Enoki
- Division of Pharmacodynamics, Keio University Faculty of Pharmacy, Tokyo, Japan.
| | - Kazuaki Taguchi
- Division of Pharmacodynamics, Keio University Faculty of Pharmacy, Tokyo, Japan
| | - Kazuaki Matsumoto
- Division of Pharmacodynamics, Keio University Faculty of Pharmacy, Tokyo, Japan
| | - Hiroki Ohge
- Department of Infectious Diseases, Hiroshima University Hospital, Hiroshima, Japan
| | - Hiromichi Suzuki
- Department of Infectious Diseases, Faculty of Medicine, University of Tsukuba, Ibaraki, Japan
| | - Atsushi Nakamura
- Department of Infection Prevention and Control, Graduate School of Medical Sciences, Nagoya City University, Aichi, Japan
| | - Nobuaki Mori
- Department of General Internal Medicine and Infectious Diseases, National Hospital Organization Tokyo Medical Center, Tokyo, Japan
| | - Yoshitomo Morinaga
- Department of Microbiology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan
| | - Yuka Yamagishi
- Department of Clinical Infectious Diseases, Kochi Medical School, Kochi, Japan
| | - Sadako Yoshizawa
- Department of Clinical Laboratory / Department of Microbiology and Infectious Diseases, Toho University Faculty of Medicine, Tokyo, Japan
| | - Katsunori Yanagihara
- Department of Laboratory Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Hiroshige Mikamo
- Department of Clinical Infectious Diseases, Aichi Medical University Hospital, Aichi, Japan
| | - Hiroyuki Kunishima
- Department of Infectious Diseases, St. Marianna University School of Medicine, Kanagawa, Japan
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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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Bhattar K, Agrawal P. Clostridium difficile Infection During Palliative Capecitabine Chemotherapy: A Case Report. Cureus 2022; 14:e27102. [PMID: 36004012 PMCID: PMC9392427 DOI: 10.7759/cureus.27102] [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] [Accepted: 07/21/2022] [Indexed: 11/17/2022] Open
Abstract
Capecitabine has been used for triple-negative metastatic breast cancers both as monotherapy and in combination with other agents. However, its gastrointestinal side effects are one of the biggest challenges for its patient compliance, and often result in permanent drug withdrawal. There have been reports of it causing enterocolitis (mainly terminal ileitis) and even ischaemic colitis, but it has not frequently been directly associated with Clostridium difficile infection. We describe a case of a 65-year-old woman with triple-negative breast cancer on palliative capecitabine who presented with blood-streaked watery diarrhea and abdominal pain and was diagnosed with chemotherapy-induced severe colitis with superimposed Clostridium difficile infection.
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Yu H, Alfred T, Nguyen JL, Zhou J, Olsen MA. Incidence, Attributable Mortality, and Healthcare and Out-of-Pocket Costs of Clostridioides difficile Infection in US Medicare Advantage Enrollees. Clin Infect Dis 2022; 76:e1476-e1483. [PMID: 35686435 PMCID: PMC9907506 DOI: 10.1093/cid/ciac467] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2022] [Revised: 05/31/2022] [Accepted: 06/03/2022] [Indexed: 11/15/2022] Open
Abstract
BACKGROUND US attributable Clostridioides difficile infection (CDI) mortality and cost data are primarily from Medicare fee-for-service populations, and little is known about Medicare Advantage Enrollees (MAEs). This study evaluated CDI incidence among MAEs from 2012 to 2019 and determined attributable mortality and costs by comparing MAEs with and without CDI occurring in 2018. METHODS This retrospective cohort study assessed CDI incidence and associated mortality and costs for eligible MAEs ≥65 years of age using the de-identified Optum Clinformatics Data Mart database (Optum; Eden Prairie, Minnesota, USA). Outcomes included mortality, healthcare utilization, and costs, which were assessed via a propensity score-matched cohort using 2018 as the index year. Outcome analyses were stratified by infection acquisition and hospitalization status. RESULTS From 2012 to 2019, overall annual CDI incidence declined from 609 to 442 per 100 000 person-years. Although the incidence of healthcare-associated CDI declined overall (2012, 53.2%; 2019, 47.2%), community-associated CDI increased (2012, 46.8%; 2019, 52.8%). The 1-year attributable mortality was 7.9% (CDI cases, 26.3%; non-CDI controls, 18.4%). At the 2-month follow-up, CDI-associated excess mean total healthcare and out-of-pocket costs were $13 476 and $396, respectively. Total excess mean healthcare costs were greater among hospitalized (healthcare-associated, $28 762; community-associated, $28 330) than nonhospitalized CDI patients ($5704 and $2320, respectively), whereas total excess mean out-of-pocket cost was highest among community-associated hospitalized CDI patients ($970). CONCLUSIONS CDI represents an important public health burden in the MAE population. Preventive strategies and treatments are needed to improve outcomes and reduce costs for healthcare systems and this growing population of older US adults.
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Affiliation(s)
- Holly Yu
- Correspondence: H. Yu, Pfizer Inc, 500 Arcola Road, Collegeville, PA 19426 ()
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Lee SH, Park HK, Kang CD, Choi DH, Park SC, Park JM, Nam SJ, Chae GB, Lee KY, Cho H, Lee SJ. High Dose Intramuscular Vitamin D3 Supplementation Impacts the Gut Microbiota of Patients With Clostridioides Difficile Infection. Front Cell Infect Microbiol 2022; 12:904987. [PMID: 35774395 PMCID: PMC9239168 DOI: 10.3389/fcimb.2022.904987] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2022] [Accepted: 05/10/2022] [Indexed: 11/13/2022] Open
Abstract
Background and Aim Current therapeutic strategies for Clostridioides difficile infections (CDI), including oral vancomycin, metronidazole and fecal microbial transplantation, have limited efficacy and treatment failure may occur in as many as one- third of cases. Recent studies have reported that lower concentrations of 25-hydroxyvitamin D are associated with CDI severity and recurrence. However, there have been no studies on microbiota composition after the administration of vitamin D in patients with CDI. Therefore, our study aimed to compare the microbiota composition between the two groups, including eight CDI-positive patients with vitamin D supplementation and ten CDI-positive patients without vitamin D supplementation by using 16S rRNA microbial profiling. Methods Twenty subjects were enrolled in this prospective randomized controlled study. One subject dropped out due to lack of contact with the guardian after discharge and one subject dropped out due to withdrawal of consent. Thus, 18 patients with CDI and vitamin D insufficiency (vitamin D level < 17 ng/mL) were divided into two groups: CDI with vitamin D supplementation (n = 8) and CDI without vitamin D supplementation (control: n = 10). Subjects with vitamin D insufficiency were randomized to receive 200,000 IU intramuscular cholecalciferol whereas patients in the control group received only oral vancomycin. Stool samples were obtained twice before vancomycin was administered and eight weeks after treatment; the V3-V4 16S rRNA metagenomic sequencing was performed using EzBioCloud. Results The alpha diversity of the gut microbiota in the recovery state was significantly higher than that in the CDI state. Analysis of bacterial relative abundance showed significantly lower Proteobacteria and higher Lachnospiraceae, Ruminococcaceae, Akkermansiaceae, and Bifidobacteriaceae in the recovery state. When comparing the control and vitamin D treatment groups after eight weeks, increase in alpha diversity and, abundance of Lachnospiraceae, and Ruminococcaceae exhibited the same trend in both groups. A significant increase in Bifidobacteriaceae and Christensenellaceae was observed in the vitamin D group; Proteobacteria abundance was significantly lower in the vitamin D treatment group after eight weeks than that in the control group. Conclusion Our study confirmed that the increase in the abundance of beneficial bacteria such as Bifidobacteriaceae, and Christensenellaceae were prominently evident during recovery after administration of a high dose of cholecalciferol. These findings indicate that vitamin D administration may be useful in patients with CDI, and further studies with larger sample sizes are required.
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Affiliation(s)
- Sang Hoon Lee
- Department of Internal Medicine, Kangwon National University Hospital, Kangwon National University School of Medicine, Chuncheon, South Korea
| | - Han-Ki Park
- Division of Allergy and Clinical Immunology, Department of Internal Medicine, School of Medicine, Kyungpook National University Chilgok Hospital, Kyungpook National University, Daegu, South Korea
| | - Chang Don Kang
- Department of Internal Medicine, Kangwon National University Hospital, Kangwon National University School of Medicine, Chuncheon, South Korea
| | - Dae Hee Choi
- Department of Internal Medicine, Kangwon National University Hospital, Kangwon National University School of Medicine, Chuncheon, South Korea
| | - Sung Chul Park
- Department of Internal Medicine, Kangwon National University Hospital, Kangwon National University School of Medicine, Chuncheon, South Korea
| | - Jin Myung Park
- Department of Internal Medicine, Kangwon National University Hospital, Kangwon National University School of Medicine, Chuncheon, South Korea
| | - Seung-Joo Nam
- Department of Internal Medicine, Kangwon National University Hospital, Kangwon National University School of Medicine, Chuncheon, South Korea
| | - Gi Bong Chae
- Department of Surgery, Kangwon National University Hospital, Kangwon NationalUniversity School of Medicine, Chuncheon, South Korea
| | - Kyoung yul Lee
- Department of Pathology, Kangwon National University School of Medicine, Chuncheon, South Korea
| | - Hyunseok Cho
- Department of Hospital Medicine, Kangwon National University School of Medicine, Chuncheon, South Korea
| | - Sung Joon Lee
- Department of Internal Medicine, Kangwon National University Hospital, Kangwon National University School of Medicine, Chuncheon, South Korea
- *Correspondence: Sung Joon Lee, ; orcid.org/0000-0002-6451-0400
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Olmedo M, Kestler M, Valerio M, Padilla B, Rodríguez González C, Chamarro E, Machado M, Álvarez-Uría A, Alcalá L, Muñoz P, Bouza E. Bezlotoxumab in the treatment of Clostridioides difficile infections: a real-life experience. REVISTA ESPANOLA DE QUIMIOTERAPIA : PUBLICACION OFICIAL DE LA SOCIEDAD ESPANOLA DE QUIMIOTERAPIA 2022; 35:279-283. [PMID: 35279984 PMCID: PMC9134882 DOI: 10.37201/req/120.2021] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 08/24/2021] [Revised: 12/15/2021] [Accepted: 01/15/2022] [Indexed: 12/02/2022]
Abstract
OBJECTIVE Following the approval of bezlotoxumab in 2017, studies evaluating its effectiveness in prevention of Clostridioides difficile infection under "real-life" conditions are scarce. METHODS We conducted a retrospective study developed in a large tertiary care hospital describing the use and outcomes of patients with Clostridioides difficile infection (CDI) treated with bezlotoxumab. RESULTS A total of 16 patients were include, all of whom had an episode of CDI with high probability of recurrence and 14 of them had some kind of immunosuppression. Bezlotoxumab was effective in the prevention of CDI recurrence in 11 of the 14 cases in which follow up was possible, without significant side effects. CONCLUSIONS Bezlotoxumab was well tolerated and the incidence of recurrent CDI in a high-risk population for recurrence was only 21.4%.
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Affiliation(s)
- M Olmedo
- María Olmedo, Department of Clinical Microbiology and Infectious Diseases, Hospital General Universitario Gregorio Marañón, Madrid, Spain.
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Alonso CD, Maron G, Kamboj M, Carpenter PA, Gurunathan A, Mullane KM, Dubberke ER. American Society for Transplantation and Cellular Therapy Series: #5-Management of Clostridioides difficile Infection in Hematopoietic Cell Transplant Recipients. Transplant Cell Ther 2022; 28:225-232. [PMID: 35202891 DOI: 10.1016/j.jtct.2022.02.013] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2022] [Accepted: 02/14/2022] [Indexed: 12/17/2022]
Abstract
The Practice Guidelines Committee of the American Society for Transplantation and Cellular Therapy partnered with its Transplant Infectious Disease Special Interest Group to update its 2009 compendium-style infectious disease guidelines for hematopoietic cell transplantation (HCT). A completely new approach was taken with the goal of better serving clinical providers by publishing each standalone topic in the infectious disease series as a concise format of frequently asked questions (FAQ), tables, and figures. Adult and pediatric infectious disease and HCT content experts developed and then answered FAQs and finalized topics with harmonized recommendations that were made by assigning an A through E strength of recommendation paired with a level of supporting evidence graded I through III. This fifth guideline in the series focuses on Clostridioides difficile infection with FAQs that address the prevalence, incidence, clinical features, colonization versus infection, clinical complications, diagnostic considerations, pharmacological therapies for episodic or recurrent infection, and the roles of prophylactic antibiotics, probiotics, and fecal microbiota transplantation.
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Affiliation(s)
- Carolyn D Alonso
- Division of Infectious Diseases, Beth Israel Deaconess Medical Center, Boston, Massachusetts; Harvard Medical School, Boston, Massachusetts.
| | - Gabriela Maron
- Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, Tennessee
| | - Mini Kamboj
- Division of Infectious Diseases, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Paul A Carpenter
- Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington
| | | | - Kathleen M Mullane
- Section of Infectious Diseases and Global Health, University of Chicago Medicine, Chicago, Illinois
| | - Erik R Dubberke
- Washington University School of Medicine, St. Louis, Missouri
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Hammeken LH, Baunwall SMD, Dahlerup JF, Hvas CL, Ehlers LH. Health-related quality of life in patients with recurrent Clostridioides difficile infections. Therap Adv Gastroenterol 2022; 15:17562848221078441. [PMID: 35463939 PMCID: PMC9019313 DOI: 10.1177/17562848221078441] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/20/2021] [Accepted: 01/19/2022] [Indexed: 02/04/2023] Open
Abstract
BACKGROUND The health-related quality of life (HrQoL) can be substantially affected in patients with recurrent Clostridioides difficile infection (rCDI) but the impact of effective treatment of the infection remains unclear. This study aimed to evaluate the HrQoL in patients with rCDI and estimate the gain in HrQoL associated with effective treatment of rCDI. METHODS Patients' HrQoL was estimated based on EuroQol 5-Dimensions 3-Levels (EQ-5D-3L) questionnaires obtained from a Danish randomised controlled trial (RCT). In the RCT, 64 patients with rCDI were randomised to receive either vancomycin (n = 16), fidaxomicin (n = 24) or faecal microbiota transplantation (FMT) preceded by vancomycin (n = 24). The primary outcome in the RCT was rCDI resolution. Patients were closely monitored during the RCT, and rescue FMT was offered to those who failed their primary treatment. Patients' HrQoL was measured at baseline and at 8- and 26-weeks follow-up. Linear regression analyses conditional on the differences between baseline and follow-up measurements were used to assess statistical significance (p < 0.05). RESULTS Within 26 weeks of follow-up, 13 (81%) patients treated with vancomycin, 12 (50%) patients treated with fidaxomicin, and 3 (13%) patients treated with FMT had a subsequent recurrence and received a rescue FMT. The average HrQoL for untreated patients with rCDI was 0.675. After receiving effective treatment, this value increased by 0.139 to 0.813 (p < 0.001) at week 8 and by 0.098 to 0.773 (p = 0.003) at week 26 of follow-up compared with baseline. CONCLUSION The HrQoL was adversely affected in patients with an active episode of rCDI but increased substantially after receiving an effective treatment algorithm in which rescue FMT was provided in case of a primary treatment failure. TRIAL REGISTRATION The RCT was preregistered at EudraCT (j.no. 2015-003004-24, https://www.clinicaltrialsregister.eu/ctr-search/trial/2015-003004-24/results) and at ClinicalTrials.gov (study identifier NCT02743234, https://clinicaltrials.gov/ct2/show/NCT02743234).
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Affiliation(s)
| | - Simon M. D. Baunwall
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark
| | - Jens F. Dahlerup
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark
| | - Christian L. Hvas
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark
| | - Lars H. Ehlers
- Danish Center for Healthcare Improvements, Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
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Yokoyama Y, Shiota A, Asai N, Koizumi Y, Yamagishi Y, Sakanashi D, Nakamura A, Suematsu H, Ohnishi M, Mikamo H. Risk factors of first recurrence of Clostridioides difficile infection. Anaerobe 2022; 75:102556. [PMID: 35395406 DOI: 10.1016/j.anaerobe.2022.102556] [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: 06/13/2021] [Revised: 03/30/2022] [Accepted: 04/02/2022] [Indexed: 11/17/2022]
Abstract
OBJECTIVES Clostridioides difficile infection (CDI) often recurs. Approximately 25% of patients have recurrences after the initial treatment, and patients who have relapsed once are more likely to relapse. We aimed to identify the risk factors for initial CDI recurrence. METHODS We performed a retrospective survey of patient backgrounds and treatment-related factors. Risk factors were analyzed using single and multiple logistic regression analyses. RESULTS A total of 134 patients were included in the study. Prophylactic probiotic use and nasogastric tube feeding were independent risk factors for the initial recurrence of CDI. Patients using prophylactic probiotics had significantly higher recurrence rates than those not using prophylactic probiotics. CONCLUSION Prophylactic probiotic use and nasogastric tube placement may be risk factors for the initial recurrence of CDI. It is noteworthy that CDI that occurs during the use of prophylactic probiotics may be prone to recurrence.
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Affiliation(s)
- Yuki Yokoyama
- Department of Clinical Infectious Diseases, Aichi Medical University Graduate School of Medicine, Japan; Department of Pharmacy, Aichi Medical University Hospital, Aichi, Japan
| | - Arufumi Shiota
- Department of Pharmacy, Aichi Medical University Hospital, Aichi, Japan; Department of Infection Control and Prevention, Aichi Medical University Hospital, Japan; Department of Clinical Infectious Diseases, Aichi Medical University Hospital, Japan
| | - Nobuhiro Asai
- Department of Infection Control and Prevention, Aichi Medical University Hospital, Japan; Department of Clinical Infectious Diseases, Aichi Medical University Hospital, Japan
| | - Yusuke Koizumi
- Department of Clinical Infectious Diseases, Aichi Medical University Hospital, Japan
| | - Yuka Yamagishi
- Department of Clinical Infectious Diseases, Aichi Medical University Graduate School of Medicine, Japan; Department of Infection Control and Prevention, Aichi Medical University Hospital, Japan; Department of Clinical Infectious Diseases, Aichi Medical University Hospital, Japan
| | - Daisuke Sakanashi
- Department of Infection Control and Prevention, Aichi Medical University Hospital, Japan
| | - Akiko Nakamura
- Department of Infection Control and Prevention, Aichi Medical University Hospital, Japan
| | - Hiroyuki Suematsu
- Department of Infection Control and Prevention, Aichi Medical University Hospital, Japan
| | - Masafumi Ohnishi
- Department of Pharmacy, Aichi Medical University Hospital, Aichi, Japan
| | - Hiroshige Mikamo
- Department of Clinical Infectious Diseases, Aichi Medical University Graduate School of Medicine, Japan; Department of Infection Control and Prevention, Aichi Medical University Hospital, Japan; Department of Clinical Infectious Diseases, Aichi Medical University Hospital, Japan.
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Sehgal K, Zandvakili I, Tariq R, Pardi DS, Khanna S. Systematic Review and Meta-Analysis: Efficacy of Vancomycin Taper and Pulse Regimens in Clostridioides difficile Infection. Expert Rev Anti Infect Ther 2022; 20:577-583. [PMID: 34693838 DOI: 10.1080/14787210.2022.1997588] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2021] [Accepted: 10/18/2021] [Indexed: 12/29/2022]
Abstract
BACKGROUND Vancomycin is the drug of choice for treating Clostridioides difficile infection (CDI). We compare CDI resolution with vancomycin taper, pulse, and taper-and-pulse regimens. METHODS We searched for Medline, Embase, Cochrane, and Scopus through October 9th, 2020. Taper regimen was defined as dose reduction over time; pulse was a regimen less frequent than daily. Studies assessing CDI resolution rates were included. Meta-analyses for resolution rates were performed using weighted proportion ratios (WPR). RESULTS Ten studies with 675 patients treated with vancomycin regimens were included. Resolution rates were 83% (212/266, 95% CI 69-94%, I2 = 85%) for taper-and-pulse, 68% (264/383, 95% CI 57-78%, I2 = 72%) for taper alone, and 54% (11/26 95% CI 0-100%, I2 = 86%) for pulse alone regimens. Taper-and-pulse was superior to taper alone (WPR 83% vs 68%, p < 0.0001) and pulse alone (WPR 83% vs 54%, p < 0.0004), no significant difference between taper alone or pulse alone (WPR 68% vs 54%, p = 0.1). CONCLUSIONS Limitations of our analysis are a small number of included studies and heterogeneity. Vancomycin taper-and-pulse seems superior to pulse alone or taper alone for recurrent CDI. A randomized controlled trial comparing vancomycin taper-and-pulse to fidaxomicin and microbiome restoration is needed.
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Affiliation(s)
- Kanika Sehgal
- Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, MN
| | - Inuk Zandvakili
- Division of Gastroenterology, University of Pennsylvania, Philadelphia, PA
| | - Raseen Tariq
- Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, MN
- Department of Internal Medicine, Rochester Regional Health, Rochester, NY
| | - Darrell S Pardi
- Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, MN
| | - Sahil Khanna
- Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, MN
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Johnson S, Gerding DN, Li X, Reda DJ, Donskey CJ, Gupta K, Goetz MB, Climo MW, Gordin FM, Ringer R, Johnson N, Johnson M, Calais LA, Goldberg AM, Ge L, Haegerich T. Defining optimal treatment for recurrent Clostridioides difficile infection (OpTION study): A randomized, double-blind comparison of three antibiotic regimens for patients with a first or second recurrence. Contemp Clin Trials 2022; 116:106756. [DOI: 10.1016/j.cct.2022.106756] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2022] [Revised: 04/01/2022] [Accepted: 04/04/2022] [Indexed: 11/26/2022]
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Marcela K, de Meij GT, Fidelma F, Richard DJ, Mark WH, Ed KJ. How to: Clostridioides difficile infection in children. Clin Microbiol Infect 2022; 28:1085-1090. [DOI: 10.1016/j.cmi.2022.03.001] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2021] [Revised: 02/07/2022] [Accepted: 03/01/2022] [Indexed: 12/12/2022]
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Watts AE, Sninsky JA, Richey MM, Donovan K, Dougherty MK, McGill SK. Family Stool Donation Predicts Failure of Fecal Microbiota Transplant for Clostridioides difficile Infection. GASTRO HEP ADVANCES 2022; 1:141-146. [PMID: 39131119 PMCID: PMC11307599 DOI: 10.1016/j.gastha.2021.11.007] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/06/2021] [Accepted: 11/15/2021] [Indexed: 08/13/2024]
Abstract
Background and Aims Fecal microbiota transplant (FMT) via colonoscopy is highly effective treatment for Clostridioides difficile infection (CDI). We aimed to determine baseline patient characteristics that predict failure to respond to colonoscopy-based FMT. Methods We evaluated adult patients who received FMT for CDI not responding to standard therapies at a single tertiary center between 2014 and 2018 in this retrospective cohort study. We defined clinical success as formed stool or C difficile-negative diarrhea at 2 months after FMT. If patients required a second FMT, follow-up was extended 2 months after repeat infusion. We performed multivariate logistic regression and a random forest model to identify variables predictive of response to FMT. Results Clinical success was attained in 87.3% of 103 patients who underwent FMT for CDI. In the multivariate model, the odds of FMT failure for family donation compared with stool bank were odds ratio 4.13 (1.00-7.01 P = .049). Diarrhea while taking anti-CDI antibiotics was common (37.8% of patients) and did not predict failure (odds ratio 0.64, 0.19-2.11 P = .46) in the univariate model. A machine learning model to predict response using clinical factors only achieved a sensitivity of 70%, specificity of 77%, and negative predictive value of 96%. Conclusion Colonoscopy-based FMT was highly effective for CDI, even in a population where immunosuppression and proton pump inhibitor use were common. Family stool donation was associated with FMT failure, compared with the use of a stool bank. The study suggests that the use of a stool bank may not only improve access to FMT but also its efficacy.
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Affiliation(s)
- Ariel E. Watts
- Division of Gastrointestinal Biology and Disease, Department of Medicine, University of North Carolina Chapel Hill, Chapel Hill, North Carolina
| | - Jared A. Sninsky
- Division of Gastrointestinal Biology and Disease, Department of Medicine, University of North Carolina Chapel Hill, Chapel Hill, North Carolina
| | - Morgan M. Richey
- Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
| | - Kevin Donovan
- Department of Biostatistics, University of North Carolina Chapel Hill, Chapel Hill, North Carolina
| | - Michael K. Dougherty
- Division of Gastrointestinal Biology and Disease, Department of Medicine, University of North Carolina Chapel Hill, Chapel Hill, North Carolina
| | - Sarah K. McGill
- Division of Gastrointestinal Biology and Disease, Department of Medicine, University of North Carolina Chapel Hill, Chapel Hill, North Carolina
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Askar SF, Kenney RM, Tariq Z, Conner R, Williams J, Ramesh M, Alangaden GJ. Bezlotoxumab for Prevention of Recurrent Clostridioides difficile Infection With a Focus on Immunocompromised Patients. J Pharm Pract 2022; 36:584-587. [PMID: 35090351 DOI: 10.1177/08971900221074929] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
OBJECTIVES Approximately 25% of patients with Clostridioides difficile infection (CDI) will experience recurrence, which is greater in immunocompromised patients. We report experience with an institutional guideline targeting high-risk immunocompromised patients. METHODS This was a retrospective cohort of consecutive patients with CDI who met institutional criteria for bezlotoxumab due to high risk for recurrent CDI between June 1, 2017, and November 30, 2018. The primary endpoint of recurrent CDI within 12 weeks was compared between patients who received the standard of care (SoC) plus or minus bezlotoxumab. RESULTS Twenty-three patients received bezlotoxumab infusion plus SoC and were compared to 30 SoC patients. 84% of patients were immunocompromised and 54.7% were transplant recipients. The primary endpoint occurred in 13% of bezlotoxumab patients compared to 23.3% of SoC patients. No serious adverse effects were identified. CONCLUSION Bezlotoxumab was associated with a meaningful reduction in recurrent CDI in this cohort largely comprising immunocompromised and transplant patients. Larger studies are warranted to evaluate bezlotoxumab in this population.
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Affiliation(s)
- Sally F Askar
- Department of Internal Medicine, 24016Henry Ford Hospital, Detroit, MI, USA
| | - Rachel M Kenney
- Department of Pharmacy Services, 24016Henry Ford Hospital, Detroit, MI, USA
| | - Zain Tariq
- Division of Infectious Diseases, 24016Henry Ford Hospital, Detroit, MI, USA
| | - Ruth Conner
- Division of Infectious Diseases, 24016Henry Ford Hospital, Detroit, MI, USA
| | - Jonathan Williams
- Division of Infectious Diseases, 24016Henry Ford Hospital, Detroit, MI, USA
| | - Mayur Ramesh
- Division of Infectious Diseases, 24016Henry Ford Hospital, Detroit, MI, USA
| | - George J Alangaden
- Division of Infectious Diseases, 24016Henry Ford Hospital, Detroit, MI, USA
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Giles J, Roberts A. Clostridioides difficile: Current overview and future perspectives. ADVANCES IN PROTEIN CHEMISTRY AND STRUCTURAL BIOLOGY 2022; 129:215-245. [PMID: 35305720 DOI: 10.1016/bs.apcsb.2021.11.003] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/14/2023]
Abstract
The most common world-wide cause of antibiotic-associated infectious diarrhea and colitis is the toxin producing bacterium, Clostridioides difficile (C. difficile). Here we review the background and characteristics of the bacterium and the toxins produced together with the epidemiology and the complex pathogenesis that leads to a broad clinical spectrum of disease. The review describes the difficulties faced in obtaining a quick and accurate diagnosis despite the range of sensitive and specific diagnostic tools available. We also discuss the problem of disease recurrence and the importance of disease prevention. The high rates of infection recurrence mean that treatment strategies are constantly under review and we outline the diverse treatment options that are currently in use and explore the emerging treatment options of pulsed antibiotic use, microbial replacement therapies and the use of monoclonal antibodies. We summarize the future direction of treatment strategies which include the development of novel antibiotics, the administration of oral polyclonal antibody formulations, the use of vaccines, the administration of competitive non-toxigenic spores and the neutralization of antibiotics at the microbiota level. Future successful treatments will likely involve a combination of therapies to provide the most effective and robust approach to C. difficile management.
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Affiliation(s)
- Joanna Giles
- MicroPharm Ltd, Newcastle Emlyn, United Kingdom.
| | - April Roberts
- Toxins Group, National Infection Service, Public Health England, Porton Down, United Kingdom
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Cheng F, Huang Z, Li Z, Wei W. Efficacy and Safety of Fecal Microbiota Transplant for recurrent
Clostridium Difficile Infection in Inflammatory Bowel Disease Patients: A Systematic Review and Meta-Analysis. REVISTA ESPANOLA DE ENFERMEDADES DIGESTIVAS 2022; 114:543-549. [DOI: 10.17235/reed.2022.8814/2022] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
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