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Zhu D, Wozniak KJ, Midani F, Wang S, Sun X, Britton RA. Control of Clostridioides difficile virulence and physiology by the flagellin homeostasis checkpoint FliC-FliW-CsrA in the absence of motility. mBio 2025; 16:e0380124. [PMID: 39882902 PMCID: PMC11898703 DOI: 10.1128/mbio.03801-24] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2024] [Accepted: 01/08/2025] [Indexed: 01/31/2025] Open
Abstract
Mutations affecting Clostridioides difficile flagellin (FliC) have been shown to be hypervirulent in animal models and display increased toxin production and alterations in central metabolism. The regulation of flagellin levels in bacteria is governed by a tripartite regulatory network involving fliC, fliW, and csrA, which creates a feedback system to regulate flagella production. Through genomic analysis of C. difficile clade 5 strains (non-motile), we identified they have jettisoned many of the genes required for flagellum biosynthesis yet retain the major flagellin gene fliC and regulatory gene fliW. We therefore investigated the roles of fliC, fliW, and csrA in the clade 5 ribotype 078 strain C. difficile 1015, which lacks flagella and is non-motile. Analysis of mutations in fliC, fliW, and csrA (and all combinations) on C. difficile pathogenesis indicated that FliW plays a central role in C. difficile virulence as animals infected with strains carrying a deletion of fliW showed decreased survival and increased disease severity. These in vivo findings were supported by in vitro studies showing that mutations impacting the activity of FliW showed increased toxin production. We further identified that FliW can interact with the toxin-positive regulator TcdR, indicating that modulation of toxin production via FliW occurs by sequestering TcdR from activating toxin transcription. Furthermore, disruption of the fliC-fliW-csrA network results in significant changes in carbon source utilization and sporulation. This work highlights that key proteins involved in flagellar biosynthesis retain their regulatory roles in C. difficile pathogenesis and physiology independent of their functions in motility. IMPORTANCE Clostridioides difficile is a leading cause of nosocomial antibiotic-associated diarrhea in developed countries with many known virulence factors. In several pathogens, motility and virulence are intimately linked by regulatory networks that allow coordination of these processes in pathogenesis and physiology. Regulation of C. difficile toxin production by FliC has been demonstrated in vitro and in vivo and has been proposed to link motility and virulence. Here, we show that clinically important, non-motile C. difficile strains have conserved FliC and regulatory partners FliW and CsrA, despite lacking the rest of the machinery to produce functional flagella. Our work highlights a novel role for flagellin outside of its role in motility and FliW in the pathogenesis and physiology of C. difficile.
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Affiliation(s)
- Duolong Zhu
- Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas, USA
- Alkek Center for Metagenomics and Microbiome Research, Baylor College of Medicine, Houston, Texas, USA
| | - Katherine J. Wozniak
- Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas, USA
- Alkek Center for Metagenomics and Microbiome Research, Baylor College of Medicine, Houston, Texas, USA
| | - Firas Midani
- Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas, USA
- Alkek Center for Metagenomics and Microbiome Research, Baylor College of Medicine, Houston, Texas, USA
| | - Shaohui Wang
- Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, Florida, USA
| | - Xingmin Sun
- Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, Florida, USA
| | - Robert A. Britton
- Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas, USA
- Alkek Center for Metagenomics and Microbiome Research, Baylor College of Medicine, Houston, Texas, USA
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Hsia CH, Su HY, Chien YW. Risk Factors for Clostridium difficile Infection in Inpatients: A Four-Year (2017-2020) Retrospective Study. Antibiotics (Basel) 2025; 14:133. [PMID: 40001377 PMCID: PMC11851458 DOI: 10.3390/antibiotics14020133] [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: 01/08/2025] [Revised: 01/26/2025] [Accepted: 01/27/2025] [Indexed: 02/27/2025] Open
Abstract
BACKGROUND Clostridium difficile infection (CDI) impact on healthcare systems is concerning due to high treatment cost and increased hospitalization time. We found that the incidence rate of CDI increased annually at Taipei Medical University Hospital (TMUH). The study aimed to establish monitoring indicators for hospitalized patients receiving antibiotics to prevent CDI occurrences. METHODS A case-control study was conducted to identify the risk factors of CDI among patients who were admitted to TMUH and tested for C. difficile. Patient demographics, patient history, and laboratory data were collected and analyzed. RESULTS Nutrition Risk Screening 2002 score (NRS 2002) in CDI patients was significantly lower than in non-CDI patients (3.1 ± 1.7 vs. 3.5 ± 1.6). The percentage of tube feeding in CDI patients was significantly lower than in non-CDI patients (23.0% vs. 36.7%), whereas parenteral nutrition was higher (8.8% vs. 3.8%). Age (OR = 1.03, p = 0.00), NRS 2002 score (OR =0.86, p = 0.05), comorbidity with cardiovascular disease (OR = 1.73, p = 0.03) or pulmonary disease (OR = 3.72, p = 0.00), patients with tube feeding (OR = 2.02, p = 0.01), and the number of medications (OR = 1.15, p < 0.01) were significant predictors of CDI. CONCLUSION This study revealed that nutritional factors, including NRS 2002 scores and feeding routes, were associated with CDI, emphasizing the importance of nutritional factors as key predictors in managing and preventing CDI.
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Affiliation(s)
- Chu-Hsuan Hsia
- School of Nutrition and Health Sciences, Taipei Medical University, Taipei 11031, Taiwan; (C.-H.H.); (H.-Y.S.)
- Department of Dietetics, Taipei Medical University Hospital, Taipei 11031, Taiwan
- Nutrition Research Center, Taipei Medical University Hospital, Taipei 11031, Taiwan
| | - Hsiu-Yueh Su
- School of Nutrition and Health Sciences, Taipei Medical University, Taipei 11031, Taiwan; (C.-H.H.); (H.-Y.S.)
- Department of Dietetics, Taipei Medical University Hospital, Taipei 11031, Taiwan
- Nutrition Research Center, Taipei Medical University Hospital, Taipei 11031, Taiwan
| | - Yi-Wen Chien
- School of Nutrition and Health Sciences, Taipei Medical University, Taipei 11031, Taiwan; (C.-H.H.); (H.-Y.S.)
- Nutrition Research Center, Taipei Medical University Hospital, Taipei 11031, Taiwan
- TMU Research Center for Digestive Medicine, Taipei Medical University, Taipei 11031, Taiwan
- Graduate Institute of Metabolism and Obesity Sciences, Taipei Medical University, Taipei 11031, Taiwan
- Research Center of Geriatric Nutrition, College of Nutrition, Taipei Medical University, Taipei 11031, Taiwan
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Tiecco G, De Francesco MA, Lenzi A, Pellizzeri S, Rossini F, Sollima A, Signorini L, Castelli F, Caruso A, Quiros-Roldan E. Clostridioides difficile infections caused by hypervirulent strains: a single-centre real-life study. Eur J Clin Microbiol Infect Dis 2025; 44:99-107. [PMID: 39527170 DOI: 10.1007/s10096-024-04982-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: 08/30/2024] [Accepted: 10/31/2024] [Indexed: 11/16/2024]
Abstract
BACKGROUND AND PURPOSE Clostridioides difficile infection (CDI) is a leading cause of healthcare-associated infections worldwide, with hypervirulent strains linked to severe disease and higher mortality. This study aims to analyze the epidemiology of CDI at a tertiary-care hospital in Italy and compare clinical outcomes between patients infected with hypervirulent and non-hypervirulent strains. METHODS A retrospective comparative study was conducted on patients diagnosed with CDI at ASST Spedali Civili di Brescia, Italy, from January 2015 to June 2023. Hypervirulent strains were identified using the GeneXpert assay as positive for cytotoxin gene (tcdB), binary toxin genes (tcdA and tcdB) and a single nucleotide deletion at position 117 in the tcdC gene and compared to a randomized matched control group with non-hypervirulent CDI. Clinical data were collected and analyzed, with multivariate logistic regression employed to identify risk factors for hypervirulent CDI. RESULTS Of 1,059 positive C. difficile specimens, a statistically significant trend between January 2015 to June 2023 was found in the increasing incidence of CDI cases per 1,000 hospital admissions and 10,000 bed-days. Notably, a remarkable increase of hypervirulent strains was recorded in 2021 and 2022 when compared to previous years. A total of 130 patients were analyzed: 62 (47.7%) with hypervirulent CDI and 68 (52.3%) controls. Hypervirulent CDI was associated with higher 30-day mortality (18% vs. 5.8%, p = 0.03). Multivariate analysis showed that hypervirulent CDI significantly increased 30-day mortality risk (OR = 9.915, CI = 2.37-61.05, p = 0.005) and that prior antibiotic therapy was a significant risk factor (OR = 5.49, CI = 1.19-39.96, p = 0.047). DISCUSSION Our epidemiological data, while suggesting a potential resurgence in CDI transmission during COVID-19 pandemic, are derived from a single-center experience with limited generalizability to the broader population. Nonetheless, they highlight the need for strengthened antimicrobial stewardship and national surveillance systems to effectively monitor and manage these strains.
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Affiliation(s)
- Giorgio Tiecco
- Department of Clinical and Experimental Sciences, Unit of Infectious and Tropical Diseases, University of Brescia and ASST Spedali Civili Di Brescia, 25123, Brescia, Italy
| | - Maria Antonia De Francesco
- Institute of Microbiology, Department of Molecular and Translational Medicine, University of Brescia-ASST Spedali Civili, Brescia, Italy
| | - Angelica Lenzi
- Department of Clinical and Experimental Sciences, Unit of Infectious and Tropical Diseases, University of Brescia and ASST Spedali Civili Di Brescia, 25123, Brescia, Italy
| | - Simone Pellizzeri
- Department of Clinical and Experimental Sciences, University of Brescia, 25123, Brescia, Italy
| | - Francesco Rossini
- Department of Clinical and Experimental Sciences, Unit of Infectious and Tropical Diseases, University of Brescia and ASST Spedali Civili Di Brescia, 25123, Brescia, Italy
| | - Alessio Sollima
- Department of Clinical and Experimental Sciences, Unit of Infectious and Tropical Diseases, University of Brescia and ASST Spedali Civili Di Brescia, 25123, Brescia, Italy
| | - Liana Signorini
- Institute of Microbiology, Department of Molecular and Translational Medicine, University of Brescia-ASST Spedali Civili, Brescia, Italy
| | - Francesco Castelli
- Department of Clinical and Experimental Sciences, Unit of Infectious and Tropical Diseases, University of Brescia and ASST Spedali Civili Di Brescia, 25123, Brescia, Italy
| | - Arnaldo Caruso
- Institute of Microbiology, Department of Molecular and Translational Medicine, University of Brescia-ASST Spedali Civili, Brescia, Italy
| | - Eugenia Quiros-Roldan
- Department of Clinical and Experimental Sciences, Unit of Infectious and Tropical Diseases, University of Brescia and ASST Spedali Civili Di Brescia, 25123, Brescia, Italy.
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Vasile CC, Gheorghe LA, Chivu CD, Anghel MAM, Mîinea ȘE, Pițigoi D, Crăciun MD. Clostridioides difficile Infections and Antibiotherapy: Results of Four Years of Observation in a Romanian Tertiary Hospital. Microorganisms 2024; 12:2490. [PMID: 39770693 PMCID: PMC11728022 DOI: 10.3390/microorganisms12122490] [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: 10/30/2024] [Revised: 11/24/2024] [Accepted: 11/27/2024] [Indexed: 01/16/2025] Open
Abstract
Clostridioides difficile infection (CDI) is one of the main causes of morbidity associated with antibiotic use, producing both healthcare-associated infections and community infections. This study aims to describe the epidemiological characteristics, the clinical outcomes, previous antibiotic exposure, and other risk factors of hospitalized patients with CDI in a tertiary infectious disease hospital in Bucharest, Romania. We performed a descriptive analysis based on four-year surveillance data, collected in a tertiary infectious disease hospital in Bucharest, Romania. The annual incidence of CDIs varied from 65.1 cases per 10,000 discharges in 2020 to 211.7 cases per 10,000 discharges in 2023, with a continuously ascending trend. Most of the cases were hospital-acquired cases. There was a high share of antibiotic consumption three months before admission (61.3%). Third-generation cephalosporins, β-lactams with inhibitor combination, and carbapenems were the most used antibiotics, with shares of 46.0%, 25.2%, and 18.6%, respectively. Hospitalization in the previous 12 months and contact with a confirmed CDI case were other frequent factors in the study group, the occurrences of which were recorded as 66.2% and 2.4%, respectively. The surveillance data identified that the annual trend in CDIs is very variable, suggesting the need for continuous and multiannual analysis.
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Affiliation(s)
- Carmen-Cristina Vasile
- Department of Epidemiology, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania; (C.-C.V.); (L.-A.G.); (M.A.M.A.); (Ș.E.M.); (M.-D.C.)
- National Institute for Infectious Diseases “Prof. Dr. Matei Balș”, 021105 Bucharest, Romania
| | - Luisa-Andreea Gheorghe
- Department of Epidemiology, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania; (C.-C.V.); (L.-A.G.); (M.A.M.A.); (Ș.E.M.); (M.-D.C.)
- National Administration of Penitentiaries Bucharest, 023762 Bucharest, Romania
| | - Carmen-Daniela Chivu
- Department of Epidemiology, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania; (C.-C.V.); (L.-A.G.); (M.A.M.A.); (Ș.E.M.); (M.-D.C.)
- Emergency Clinical Hospital for Children “Grigore Alexandrescu”, 011743 Bucharest, Romania
| | - Marta Ana Maria Anghel
- Department of Epidemiology, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania; (C.-C.V.); (L.-A.G.); (M.A.M.A.); (Ș.E.M.); (M.-D.C.)
- National Institute for Infectious Diseases “Prof. Dr. Matei Balș”, 021105 Bucharest, Romania
| | - Ștefan Eduard Mîinea
- Department of Epidemiology, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania; (C.-C.V.); (L.-A.G.); (M.A.M.A.); (Ș.E.M.); (M.-D.C.)
- Medical Directorate, Ministry of Internal Affairs, 010919 Bucharest, Romania
| | - Daniela Pițigoi
- Department of Epidemiology, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania; (C.-C.V.); (L.-A.G.); (M.A.M.A.); (Ș.E.M.); (M.-D.C.)
- National Institute for Infectious Diseases “Prof. Dr. Matei Balș”, 021105 Bucharest, Romania
| | - Maria-Dorina Crăciun
- Department of Epidemiology, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania; (C.-C.V.); (L.-A.G.); (M.A.M.A.); (Ș.E.M.); (M.-D.C.)
- Emergency Clinical Hospital for Children “Grigore Alexandrescu”, 011743 Bucharest, Romania
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5
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Arcay R, Barceló-Nicolau M, Suárez L, Martín L, Reigada R, Höring M, Liebisch G, Garrido C, Cabot G, Vílchez H, Cortés-Lara S, González de Herrero E, López-Causapé C, Oliver A, Barceló-Coblijn G, Mena A. Gut microbiome and plasma lipidome analysis reveals a specific impact of Clostridioides difficile infection on intestinal bacterial communities and sterol metabolism. mBio 2024; 15:e0134724. [PMID: 39189787 PMCID: PMC11481895 DOI: 10.1128/mbio.01347-24] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2024] [Accepted: 07/15/2024] [Indexed: 08/28/2024] Open
Abstract
Clostridioides difficile infection (CDI) causes alterations in the intestinal microbiota, frequently associated with changes in the gut metabolism of bile acids and cholesterol. In addition to the impact on microbiome composition and given the metabolic changes occurring during CDI, our work focuses on the importance to know the effects at the local and systemic levels, both during the infection and its treatment, by paying particular attention to plasma lipid metabolism due to its relationship with CDI pathogenesis. Specific changes, characterized by a loss of microbial richness and diversity and related to a reduction in short-chain acid-producing bacteria and an increase in bile salt hydrolase-producing bacteria, were observed in the gut microbiota of CDI patients, especially in those suffering from recurrent CDI (RCDI). However, gut microbiota showed its ability to restore itself after treatment, resembling healthy individuals, in those patients treated by fecal microbiome transfer (FMT), in contrast with those treated with antibiotics, and displaying increased levels of Eubacterium coprostanoligenes, a cholesterol-reducing anaerobe. Interestingly, changes in plasma lipidome revealed a global depletion in circulating lipids in CDI, with the largest impact on cholesteryl esters. CDI patients also showed a specific and consistent decrease in the levels of lipid species containing linoleic acid-an essential fatty acid-which were only partially recovered after antibiotic treatment. Analysis of the plasma lipidome reflects CDI impact on the gut microbiota and its metabolism, evidencing changes in sterol and fatty acid metabolism that are possibly related to specific alterations observed in gut microbial communities of CDI patients. IMPORTANCE There is increasing evidence about the influence the changes in microbiota and its metabolism has on numerous diseases and infections such as Clostridioides difficile infection (CDI). The knowledge of these changes at local and systemic levels can help us manage this infection to avoid recurrences and apply the best therapies, such as fecal microbiota transfer (FMT). This study shows a better restoration of the gut in FMT-treated patients than in antibiotic-treated patients, resembling healthy controls and showing increased levels of cholesterol-reducing bacteria. Furthermore, it evidences the CDI impact on plasma lipidome. We observed in CDI patients a global depletion in circulating lipids, particularly cholesteryl esters, and a specific decrease in linoleic acid-containing lipids, an essential fatty acid. Our observations could impact CDI management because the lipid content was only partially recovered after treatment, suggesting that continued nutritional support, aiming to restore healthy lipid levels, could be essential for a full recovery.
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Affiliation(s)
- Ricardo Arcay
- Microbiology Department, Hospital Universitari Son Espases, Palma, Balearic Islands, Spain
- Institut d’Investigació Sanitària Illes Balears (IdISBa, Health Research Institute of the Balearic Islands), Palma, Balearic Islands, Spain
| | - Maria Barceló-Nicolau
- Institut d’Investigació Sanitària Illes Balears (IdISBa, Health Research Institute of the Balearic Islands), Palma, Balearic Islands, Spain
- Research Unit, University Hospital Son Espases, Palma, Balearic Islands, Spain
| | - Loreto Suárez
- Microbiology Department, Hospital Universitari Son Espases, Palma, Balearic Islands, Spain
- Institut d’Investigació Sanitària Illes Balears (IdISBa, Health Research Institute of the Balearic Islands), Palma, Balearic Islands, Spain
| | - Luisa Martín
- Institut d’Investigació Sanitària Illes Balears (IdISBa, Health Research Institute of the Balearic Islands), Palma, Balearic Islands, Spain
- Internal Medicine Department, Hospital Universitari Son Espases, Palma, Balearic Islands, Spain
| | - Rebeca Reigada
- Institut d’Investigació Sanitària Illes Balears (IdISBa, Health Research Institute of the Balearic Islands), Palma, Balearic Islands, Spain
- Research Unit, University Hospital Son Espases, Palma, Balearic Islands, Spain
| | - Marcus Höring
- Institute of Clinical Chemistry and Laboratory Medicine, University Hospital Regensburg, Regensburg, Bavaria, Germany
| | - Gerhard Liebisch
- Institute of Clinical Chemistry and Laboratory Medicine, University Hospital Regensburg, Regensburg, Bavaria, Germany
| | - Carmen Garrido
- Gastroenterology Department, Hospital Universitari Son Espases, Palma, Balearic Islands, Spain
| | - Gabriel Cabot
- Institut d’Investigació Sanitària Illes Balears (IdISBa, Health Research Institute of the Balearic Islands), Palma, Balearic Islands, Spain
- Research Unit, University Hospital Son Espases, Palma, Balearic Islands, Spain
| | - Helem Vílchez
- Institut d’Investigació Sanitària Illes Balears (IdISBa, Health Research Institute of the Balearic Islands), Palma, Balearic Islands, Spain
- Internal Medicine Department, Hospital Universitari Son Espases, Palma, Balearic Islands, Spain
| | - Sara Cortés-Lara
- Institut d’Investigació Sanitària Illes Balears (IdISBa, Health Research Institute of the Balearic Islands), Palma, Balearic Islands, Spain
- Research Unit, University Hospital Son Espases, Palma, Balearic Islands, Spain
| | - Elisa González de Herrero
- Microbiology Department, Hospital Universitari Son Espases, Palma, Balearic Islands, Spain
- Institut d’Investigació Sanitària Illes Balears (IdISBa, Health Research Institute of the Balearic Islands), Palma, Balearic Islands, Spain
| | - Carla López-Causapé
- Microbiology Department, Hospital Universitari Son Espases, Palma, Balearic Islands, Spain
- Institut d’Investigació Sanitària Illes Balears (IdISBa, Health Research Institute of the Balearic Islands), Palma, Balearic Islands, Spain
- Research Unit, University Hospital Son Espases, Palma, Balearic Islands, Spain
| | - Antonio Oliver
- Microbiology Department, Hospital Universitari Son Espases, Palma, Balearic Islands, Spain
- Institut d’Investigació Sanitària Illes Balears (IdISBa, Health Research Institute of the Balearic Islands), Palma, Balearic Islands, Spain
- Research Unit, University Hospital Son Espases, Palma, Balearic Islands, Spain
| | - Gwendolyn Barceló-Coblijn
- Institut d’Investigació Sanitària Illes Balears (IdISBa, Health Research Institute of the Balearic Islands), Palma, Balearic Islands, Spain
- Research Unit, University Hospital Son Espases, Palma, Balearic Islands, Spain
| | - Ana Mena
- Microbiology Department, Hospital Universitari Son Espases, Palma, Balearic Islands, Spain
- Institut d’Investigació Sanitària Illes Balears (IdISBa, Health Research Institute of the Balearic Islands), Palma, Balearic Islands, Spain
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6
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Jazmati N, Mischnik A, Kern WV, Behnke M, Chakraborty T, Dinkelacker A, Eisenbeis S, Falgenhauer J, Gastmeier P, Häcker G, Imirzalioglu C, Käding N, Kramme E, Peter S, Piepenbrock E, Rupp J, Schneider C, Schwab F, Seifert H, Tacconelli E, Trauth J, Biehl L, Walker SV, Rohde AM. Occurrence and trends of Clostridioides difficile infections in hospitalized patients: a prospective multi-centre cohort study in six German university hospitals, 2016-2020. J Hosp Infect 2024; 151:161-172. [PMID: 38969208 DOI: 10.1016/j.jhin.2024.06.007] [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: 04/16/2024] [Revised: 05/30/2024] [Accepted: 06/09/2024] [Indexed: 07/07/2024]
Abstract
BACKGROUND For Clostridioides difficile infections (CDIs) in Germany no longitudinal multi-centre studies with standardized protocols for diagnosing CDI are available. Recent evaluations of general surveillance databases in Germany indicate a downward trend in CDI rates. We aimed to describe the actual burden and trends of CDI in German university hospitals from 2016 to 2020. METHODS Our study was a prospective multi-centre study covering six German university hospitals. We report the data in total, stratified by year, by medical specialty as well as by CDI severity. Multi-variable regression analyses were performed to assess risk factors for severe CDI. RESULTS We registered 3780 CDI cases among 1,436,352 patients. The median length of stay (LOS) of CDI cases was 20 days (interquartile range 11-37) compared with a general LOS of 4.2 days. In-hospital all-cause mortality in CDI patients was 11.7% (N = 444/3780), while mortality attributed to CDI was 0.4% (N = 16/3761). CDI recurrence rate was comparatively low at 7.2%. The incidence density of severe healthcare-associated healthcare onset (HAHO)-CDI showed a significant decrease from 2.25/10,000 patient days (pd) in 2016 to 1.49/10,000 pd in 2020 (trend calculation P=0.032). CONCLUSIONS Compared with a European point-prevalence study in 2013/2014, where overall CDI incidence density was 11.2 cases/10,000 pd in Germany (EUCLID), we see in our study halved overall CDI rates of 5.6 cases/10,000 pd in 2020. Our study shows current data on the distribution of CDI cases in German university hospitals and thus provides international comparative data on the key indicators of CDI.
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Affiliation(s)
- N Jazmati
- German Centre for Infection Research (DZIF), Germany; Institute for Medical Microbiology, Immunology and Hygiene, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany; Labor Dr. Wisplinghoff, Cologne, Germany.
| | - A Mischnik
- German Centre for Infection Research (DZIF), Germany; Department of Infectious Diseases and Microbiology, University Hospital Schleswig-Holstein/Campus Lübeck, Germany; Division of Infectious Diseases, Department of Medicine II, University Medical Centre and Faculty of Medicine, Albert-Ludwigs-University, Freiburg, Freiburg, Germany
| | - W V Kern
- Division of Infectious Diseases, Department of Medicine II, University Medical Centre and Faculty of Medicine, Albert-Ludwigs-University, Freiburg, Freiburg, Germany
| | - M Behnke
- German Centre for Infection Research (DZIF), Germany; Institute for Hygiene and Environmental Medicine, Charité - University Medicine Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Germany
| | - T Chakraborty
- German Centre for Infection Research (DZIF), Germany; Institute of Medical Microbiology, Justus Liebig University Giessen, Germany
| | - A Dinkelacker
- German Centre for Infection Research (DZIF), Germany; Institute of Medical Microbiology and Hygiene, University of Tübingen, Tübingen, Germany
| | - S Eisenbeis
- German Centre for Infection Research (DZIF), Germany; Division of Infectious Diseases, Department of Internal Medicine 1, University Hospital Tübingen, Tübingen, Germany
| | - J Falgenhauer
- German Centre for Infection Research (DZIF), Germany; Institute of Medical Microbiology, Justus Liebig University Giessen, Germany
| | - P Gastmeier
- German Centre for Infection Research (DZIF), Germany; Institute for Hygiene and Environmental Medicine, Charité - University Medicine Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Germany
| | - G Häcker
- German Centre for Infection Research (DZIF), Germany; Institute for Medical Microbiology and Hygiene, University Medical Centre Freiburg, University of Freiburg, Faculty of Medicine, Freiburg, Germany
| | - C Imirzalioglu
- German Centre for Infection Research (DZIF), Germany; Institute of Medical Microbiology, Justus Liebig University Giessen, Germany
| | - N Käding
- German Centre for Infection Research (DZIF), Germany; Department of Infectious Diseases and Microbiology, University Hospital Schleswig-Holstein/Campus Lübeck, Germany
| | - E Kramme
- German Centre for Infection Research (DZIF), Germany; Department of Infectious Diseases and Microbiology, University Hospital Schleswig-Holstein/Campus Lübeck, Germany
| | - S Peter
- German Centre for Infection Research (DZIF), Germany; Institute of Medical Microbiology and Hygiene, University of Tübingen, Tübingen, Germany
| | - E Piepenbrock
- German Centre for Infection Research (DZIF), Germany; Institute for Medical Microbiology, Immunology and Hygiene, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany
| | - J Rupp
- German Centre for Infection Research (DZIF), Germany; Department of Infectious Diseases and Microbiology, University Hospital Schleswig-Holstein/Campus Lübeck, Germany
| | - C Schneider
- German Centre for Infection Research (DZIF), Germany; Institute for Medical Microbiology and Hygiene, University Medical Centre Freiburg, University of Freiburg, Faculty of Medicine, Freiburg, Germany
| | - F Schwab
- German Centre for Infection Research (DZIF), Germany; Institute for Hygiene and Environmental Medicine, Charité - University Medicine Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Germany
| | - H Seifert
- German Centre for Infection Research (DZIF), Germany; Institute for Medical Microbiology, Immunology and Hygiene, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany; Institute of Translational Research, Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany
| | - E Tacconelli
- German Centre for Infection Research (DZIF), Germany; Division of Infectious Diseases, Department of Internal Medicine 1, University Hospital Tübingen, Tübingen, Germany
| | - J Trauth
- German Centre for Infection Research (DZIF), Germany; Department of Internal Medicine (Infectiology), Uniklinikum Giessen, Germany
| | - L Biehl
- German Centre for Infection Research (DZIF), Germany; Department I of Internal Medicine, University Hospital of Cologne, Germany
| | - S V Walker
- German Centre for Infection Research (DZIF), Germany; Institute for Medical Microbiology, Immunology and Hygiene, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany; RKH Regionale Kliniken Holding und Services GmbH, Institute for Clinical Microbiology and Hospital Hygiene, Hospital Ludwigsburg, Germany
| | - A M Rohde
- German Centre for Infection Research (DZIF), Germany; Institute for Hygiene and Environmental Medicine, Charité - University Medicine Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Germany
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7
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Ilic I, Zivanovic Macuzic I, Ilic M. Mortality Attributable to Clostridioides difficile Infection: The Rising Burden of Disease in European Countries. MEDICINA (KAUNAS, LITHUANIA) 2024; 60:1222. [PMID: 39202503 PMCID: PMC11355982 DOI: 10.3390/medicina60081222] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 07/06/2024] [Revised: 07/19/2024] [Accepted: 07/26/2024] [Indexed: 09/03/2024]
Abstract
Background and Objectives: Clostridioides difficile infection is a major public health issue, being among the main causes of mortality due to healthcare-associated diarrhea. This study aimed to assess the trends in mortality attributable to Clostridioides difficile infections in European countries over a period of 30 years. Materials and Methods: A descriptive epidemiological study was conducted, with the application of an ecological study design, to evaluate the trends in mortality due to Clostridioides difficile infection in the Central, Eastern, and Western European sub-regions from 1990 to 2019. The Global Burden of Disease study database was used. Trends were evaluated with the joinpoint regression analysis. Results: In both sexes, about 76% of all deaths attributable to Clostridioides difficile infections were recorded in the Western European sub-region in 2019. The age-standardized rates of the burden of Clostridioides difficile infection in 2019 were the highest in the Central European sub-region, followed by the Western European sub-region, while the lowest rates were observed in the Eastern European sub-region. A significantly increasing trend in mortality attributable to Clostridioides difficile infection from 1990 to 2019 was recorded both in males (by +2.1% per year) and females (by +2.8% per year). The burden of Clostridioides difficile infection showed increasing trends in most of the European countries, significantly correlating with the country's development, according to the Human Development Index. Conclusions: The rising burden of Clostridioides difficile infection in European countries in the last few decades suggests a need for improving public health measures, with a focus both on the hospital setting and community.
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Affiliation(s)
- Irena Ilic
- Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia
| | - Ivana Zivanovic Macuzic
- Department of Anatomy, Faculty of Medical Sciences, University of Kragujevac, 34000 Kragujevac, Serbia
| | - Milena Ilic
- Department of Epidemiology, Faculty of Medical Sciences, University of Kragujevac, 34000 Kragujevac, Serbia
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8
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Cha JM, Yoon JY, Kwak MS, Lee M, Cho YS. Demographic Characteristics and Economic Burden of Clostridioides difficile Infection in Korea: A Nationwide Population-Based Study after Propensity Score Matching. Antibiotics (Basel) 2024; 13:542. [PMID: 38927208 PMCID: PMC11201190 DOI: 10.3390/antibiotics13060542] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2024] [Revised: 05/29/2024] [Accepted: 06/05/2024] [Indexed: 06/28/2024] Open
Abstract
Clostridioides difficile infection (CDI) poses a considerable threat to global public health. However, there have been insufficient propensity score-matched data on its demographic characteristics and economic burden. Using nationwide claims data, we assessed longitudinal changes in the demographic characteristics and economic burden of CDI between 2011 and 2019 after propensity score matching. We performed a regression analysis to compare the differences in the length of hospital stay and medical costs between patients with CDI and controls (gastroenteritis and colitis). The CDI hospitalization rate increased 2.9-fold between 2011 and 2019. The CDI group had higher comorbidity index scores and was more frequently diagnosed at tertiary hospitals and in the Seoul region than the control group (all p < 0.001). The annual incidence rate of CDI/10,000 persons significantly increased in both sexes and all age groups. The length of hospital stay and medical costs were 3.3-fold and 5.0-fold greater, respectively, in the CDI than in the control group (both p < 0.001). Although the length of hospital stay decreased, total medical costs increased in all age groups and both sexes between 2011 and 2019 (all p < 0.001). When compared with the control group, the CDI-attributable length of hospital stay and medical cost were greater by 15.3 days and KRW 3413 (×103), respectively, after matching. In conclusion, CDI incidence, particularly among the elderly population with comorbidities, has been increasing. In addition, the length of hospital stay and total medical costs of the CDI group were greater than those of the control group.
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Affiliation(s)
- Jae Myung Cha
- Department of Internal Medicine, Kyung Hee University Hospital at Gangdong, Kyung Hee University College of Medicine, Seoul 05278, Republic of Korea; (J.Y.Y.); (M.S.K.); (M.L.)
| | - Jin Young Yoon
- Department of Internal Medicine, Kyung Hee University Hospital at Gangdong, Kyung Hee University College of Medicine, Seoul 05278, Republic of Korea; (J.Y.Y.); (M.S.K.); (M.L.)
| | - Min Seob Kwak
- Department of Internal Medicine, Kyung Hee University Hospital at Gangdong, Kyung Hee University College of Medicine, Seoul 05278, Republic of Korea; (J.Y.Y.); (M.S.K.); (M.L.)
| | - Moonhyung Lee
- Department of Internal Medicine, Kyung Hee University Hospital at Gangdong, Kyung Hee University College of Medicine, Seoul 05278, Republic of Korea; (J.Y.Y.); (M.S.K.); (M.L.)
| | - Young-Seok Cho
- Department of Internal Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea
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9
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Walsh L, Lavelle A, O’Connor PM, Hill C, Ross RP. Comparison of fidaxomicin, thuricin CD, vancomycin and nisin highlights the narrow spectrum nature of thuricin CD. Gut Microbes 2024; 16:2342583. [PMID: 38722061 PMCID: PMC11085969 DOI: 10.1080/19490976.2024.2342583] [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: 12/28/2023] [Accepted: 04/09/2024] [Indexed: 05/12/2024] Open
Abstract
Vancomycin and metronidazole are commonly used treatments for Clostridioides difficile infection (CDI). However, these antibiotics have been associated with high levels of relapse in patients. Fidaxomicin is a new treatment for CDI that is described as a narrow spectrum antibiotic that is minimally active on the commensal bacteria of the gut microbiome. The aim of this study was to compare the effect of fidaxomicin on the human gut microbiome with a number of narrow (thuricin CD) and broad spectrum (vancomycin and nisin) antimicrobials. The spectrum of activity of each antimicrobial was tested against 47 bacterial strains by well-diffusion assay. Minimum inhibitory concentrations (MICs) were calculated against a select number of these strains. Further, a pooled fecal slurry of 6 donors was prepared and incubated for 24 h with 100 µM of each antimicrobial in a mini-fermentation system together with a no-treatment control. Fidaxomicin, vancomycin, and nisin were active against most gram positive bacteria tested in vitro, although fidaxomicin and vancomycin produced larger zones of inhibition compared to nisin. In contrast, the antimicrobial activity of thuricin CD was specific to C. difficile and some Bacillus spp. The MICs showed similar results. Thuricin CD exhibited low MICs (<3.1 µg/mL) for C. difficile and Bacillus firmus, whereas fidaxomicin, vancomycin, and nisin demonstrated lower MICs for all other strains tested when compared to thuricin CD. The narrow spectrum of thuricin CD was also observed in the gut model system. We conclude that the spectrum of activity of fidaxomicin is comparable to that of the broad-spectrum antibiotic vancomycin in vitro and the broad spectrum bacteriocin nisin in a complex community.
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Affiliation(s)
- L. Walsh
- School of Microbiology, University College Cork, Cork, Ireland
- APC Microbiome Ireland, University College Cork, Cork, Ireland
| | - A. Lavelle
- School of Microbiology, University College Cork, Cork, Ireland
| | - PM O’Connor
- APC Microbiome Ireland, University College Cork, Cork, Ireland
- Teagasc Food Research Centre, Cork, Ireland
| | - C. Hill
- School of Microbiology, University College Cork, Cork, Ireland
- APC Microbiome Ireland, University College Cork, Cork, Ireland
| | - R. P. Ross
- School of Microbiology, University College Cork, Cork, Ireland
- APC Microbiome Ireland, University College Cork, Cork, Ireland
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10
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Galley NF, Greetham D, Alamán-Zárate MG, Williamson MP, Evans CA, Spittal WD, Buddle JE, Freeman J, Davis GL, Dickman MJ, Wilcox MH, Lovering AL, Fagan RP, Mesnage S. Clostridioides difficile canonical L,D-transpeptidases catalyze a novel type of peptidoglycan cross-links and are not required for beta-lactam resistance. J Biol Chem 2024; 300:105529. [PMID: 38043796 PMCID: PMC10792238 DOI: 10.1016/j.jbc.2023.105529] [Citation(s) in RCA: 5] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2023] [Revised: 11/19/2023] [Accepted: 11/27/2023] [Indexed: 12/05/2023] Open
Abstract
Clostridioides difficile is the leading cause of antibiotic-associated diarrhea worldwide with significant morbidity and mortality. This organism is naturally resistant to several beta-lactam antibiotics that inhibit the polymerization of peptidoglycan, an essential component of the bacteria cell envelope. Previous work has revealed that C. difficile peptidoglycan has an unusual composition. It mostly contains 3-3 cross-links, catalyzed by enzymes called L,D-transpeptidases (Ldts) that are poorly inhibited by beta-lactams. It was therefore hypothesized that peptidoglycan polymerization by these enzymes could underpin antibiotic resistance. Here, we investigated the catalytic activity of the three canonical Ldts encoded by C. difficile (LdtCd1, LdtCd2, and LdtCd3) in vitro and explored their contribution to growth and antibiotic resistance. We show that two of these enzymes catalyze the formation of novel types of peptidoglycan cross-links using meso-diaminopimelic acid both as a donor and an acceptor, also observed in peptidoglycan sacculi. We demonstrate that the simultaneous deletion of these three genes only has a minor impact on both peptidoglycan structure and resistance to beta-lactams. This unexpected result therefore implies that the formation of 3-3 peptidoglycan cross-links in C. difficile is catalyzed by as yet unidentified noncanonical Ldt enzymes.
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Affiliation(s)
- Nicola F Galley
- School of Biosciences, University of Sheffield, Sheffield, UK
| | - Darren Greetham
- School of Biosciences, University of Sheffield, Sheffield, UK
| | | | | | - Caroline A Evans
- Department of Chemical and Biological Engineering, University of Sheffield, Sheffield, UK
| | - William D Spittal
- Department of Microbiology, Leeds Teaching Hospitals NHS Trust, Leeds Institute of Medical Research, University of Leeds, Leeds, UK; Healthcare Associated Infections Research Group, Leeds Institute of Medical Research University of Leeds, Leeds, UK
| | | | - Jane Freeman
- Department of Microbiology, Leeds Teaching Hospitals NHS Trust, Leeds Institute of Medical Research, University of Leeds, Leeds, UK; Healthcare Associated Infections Research Group, Leeds Institute of Medical Research University of Leeds, Leeds, UK
| | - Georgina L Davis
- Department of Microbiology, Leeds Teaching Hospitals NHS Trust, Leeds Institute of Medical Research, University of Leeds, Leeds, UK; Healthcare Associated Infections Research Group, Leeds Institute of Medical Research University of Leeds, Leeds, UK
| | - Mark J Dickman
- Department of Chemical and Biological Engineering, University of Sheffield, Sheffield, UK
| | - Mark H Wilcox
- Department of Microbiology, Leeds Teaching Hospitals NHS Trust, Leeds Institute of Medical Research, University of Leeds, Leeds, UK; Healthcare Associated Infections Research Group, Leeds Institute of Medical Research University of Leeds, Leeds, UK
| | | | - Robert P Fagan
- School of Biosciences, University of Sheffield, Sheffield, UK
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11
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Spigaglia P, Mastrantonio P, Barbanti F. Antibiotic Resistances of Clostridioides difficile. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2024; 1435:169-198. [PMID: 38175476 DOI: 10.1007/978-3-031-42108-2_9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2024]
Abstract
The rapid evolution of antibiotic resistance in Clostridioides difficile and the consequent effects on prevention and treatment of C. difficile infections (CDIs) are a matter of concern for public health. Antibiotic resistance plays an important role in driving C. difficile epidemiology. Emergence of new types is often associated with the emergence of new resistances, and most of the epidemic C. difficile clinical isolates is currently resistant to multiple antibiotics. In particular, it is to worth to note the recent identification of strains with reduced susceptibility to the first-line antibiotics for CDI treatment and/or for relapsing infections. Antibiotic resistance in C. difficile has a multifactorial nature. Acquisition of genetic elements and alterations of the antibiotic target sites, as well as other factors, such as variations in the metabolic pathways or biofilm production, contribute to the survival of this pathogen in the presence of antibiotics. Different transfer mechanisms facilitate the spread of mobile elements among C. difficile strains and between C. difficile and other species. Furthermore, data indicate that both genetic elements and alterations in the antibiotic targets can be maintained in C. difficile regardless of the burden imposed on fitness, and therefore resistances may persist in C. difficile population in absence of antibiotic selective pressure.
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Affiliation(s)
- Patrizia Spigaglia
- Department of Infectious Diseases, Istituto Superiore di Sanità, Rome, Italy.
| | - Paola Mastrantonio
- Department of Infectious Diseases, Istituto Superiore di Sanità, Rome, Italy
| | - Fabrizio Barbanti
- Department of Infectious Diseases, Istituto Superiore di Sanità, Rome, Italy
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12
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Fonseca F, Forrester M, Advinha AM, Coutinho A, Landeira N, Pereira M. Clostridioides difficile Infection in Hospitalized Patients-A Retrospective Epidemiological Study. Healthcare (Basel) 2023; 12:76. [PMID: 38200982 PMCID: PMC10779218 DOI: 10.3390/healthcare12010076] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2023] [Revised: 12/15/2023] [Accepted: 12/22/2023] [Indexed: 01/12/2024] Open
Abstract
Clostridioides difficile infection (CDI) is the main source of healthcare and antibiotic-associated diarrhea in hospital context and long-term care units, showing significant morbidity and mortality. This study aimed to analyze the epidemiological context, describing the severity and outcomes of this event in patients admitted to our hospital, thus confirming the changing global epidemiological trends in comparison with other cohorts. We conducted a single-center, observational, and retrospective study at the Hospital do Espírito Santo (HESE), Évora, in Portugal, analyzing the incidence of CDI in patients meeting eligibility criteria from January to December 2018. During this period, an annual incidence rate of 20.7 cases per 10,000 patients was documented. The studied population average age was 76.4 ± 12.9 years, 83.3% over 65. Most episodes were healthcare-acquired, all occurring in patients presenting multiple risk factors, with recent antibiotic consumption being the most common. Regarding severity, 23.3% of cases were classified as severe episodes. Recurrences affected 16.7% of participants, predominantly female patients over 80 years old, all of whom were healthcare-acquired. Mortality rate was disproportionately high among the older population. Our investigation documented an overall incidence rate of over 10.4-fold the number of cases identified in the year 2000 at the same hospital, more recently and drastically, in community-associated episodes.
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Affiliation(s)
- Frederico Fonseca
- Pharmaceutical Services, Hospital do Espírito Santo, 7000-811 Évora, Portugal; (N.L.); (M.P.)
| | - Mario Forrester
- Sociedade Portuguesa dos Farmacêuticos dos Cuidados de Saúde, 3030-320 Coimbra, Portugal;
- Faculty of Health Sciences, UBI—Universidade da Beira Interior, 6200-506 Covilhã, Portugal
- UFUP—Unidade de Farmacovigilância da Universidade do Porto, 4200-450 Porto, Portugal
| | - Ana Margarida Advinha
- CHRC—Comprehensive Health Research Centre, University of Evora, 7000-811 Évora, Portugal;
- Department of Health and Medical Sciences, School of Health and Human Development, University of Evora, 7000-671 Évora, Portugal
| | - Adriana Coutinho
- Laboratory Services, Microbiology Department, Hospital do Espírito Santo, 7000-811 Évora, Portugal;
| | - Nuno Landeira
- Pharmaceutical Services, Hospital do Espírito Santo, 7000-811 Évora, Portugal; (N.L.); (M.P.)
| | - Maria Pereira
- Pharmaceutical Services, Hospital do Espírito Santo, 7000-811 Évora, Portugal; (N.L.); (M.P.)
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13
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Huang H, Li L, Wu M, Liu Z, Zhao Y, Peng J, Ren X, Chen S. Antibiotics and antibiotic-associated diarrhea: a real-world disproportionality study of the FDA adverse event reporting system from 2004 to 2022. BMC Pharmacol Toxicol 2023; 24:73. [PMID: 38049920 PMCID: PMC10694877 DOI: 10.1186/s40360-023-00710-w] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2023] [Accepted: 11/17/2023] [Indexed: 12/06/2023] Open
Abstract
BACKGROUND Our study aimed to assess the risk signals of antibiotic-associated diarrhea (AAD) caused by various antibiotics using real-world data and provide references for safe clinical applications. METHODS We analyzed data extracted from the FDA Adverse Event Reporting System (FAERS) database, covering the period from the first quarter of 2004 to the third quarter of 2022. We computed the reporting odds ratio (ROR) for each antibiotic or antibiotic class to compare the signal difference. Furthermore, we also examined the differences in the onset times and outcomes of AAD caused by various antibiotics. RESULTS A total of 5,397 reports met the inclusion requirements. Almost all antibiotics, except tobramycin and minocycline (ROR 0.98; 95%CI: 0.64-1.51 and 0.42; 95%CI: 0.16-1.11, respectively), showed a significant correlation with AAD. The analysis of the correlation between different classes of antibiotics and AAD revealed that lincomycins (ROR 29.19; 95%CI: 27.06-31.50), third-generation cephalosporins (ROR 15.96; 95%CI: 14.58-17.47), and first/second generation cephalosporins (ROR 15.29; 95%CI: 13.74-17.01) ranked the top three. The ROR values for antibiotics from the same class of antibiotics also varied greatly, with the ROR values for third-generation cephalosporins ranging from 9.97 to 58.59. There were also differences in ROR values between β-lactamase inhibitors and their corresponding β-lactamase drugs, such as amoxicillin-clavulanate (ROR = 13.31; 95%CI: 12.09-14.65) and amoxicillin (ROR = 6.50; 95%CI: 5.69-7.44). 91.35% of antibiotics have an onset time of less than four weeks. CONCLUSIONS There is a significant correlation between almost all antibiotics and AAD, particularly lincomycins and β-lactam antibiotics, as well as a different correlation within the same class. These findings offer valuable evidence for selecting antibiotics appropriately.
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Affiliation(s)
- Haining Huang
- Department of Clinical Pharmacy, Affiliated Hospital of Jining Medical University, Jining, Shandong, China
| | - Lanfang Li
- Department of Clinical Pharmacy, Affiliated Hospital of Jining Medical University, Jining, Shandong, China
| | - Mingli Wu
- Department of Clinical Pharmacy, Affiliated Hospital of Jining Medical University, Jining, Shandong, China
| | - Zhen Liu
- Department of Clinical Pharmacy, Affiliated Hospital of Jining Medical University, Jining, Shandong, China
| | - Yanyan Zhao
- Department of Clinical Pharmacy, Affiliated Hospital of Jining Medical University, Jining, Shandong, China
| | - Jing Peng
- Department of Clinical Pharmacy, Affiliated Hospital of Jining Medical University, Jining, Shandong, China.
| | - Xiaolei Ren
- Data Center, Affiliated Hospital of Jining Medical University, Jining, Shandong, China.
| | - Shuai Chen
- Department of Pathology, Affiliated Hospital of Jining Medical University, Jining, Shandong, China.
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14
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Zhou Y, He L, Chen C, Zeng H, Day AS, Sergi CM, Fang H, Xie Q, Wu Y. Analysis of risk factors for community-acquired Clostridioides difficile diarrhea in children: a case-control study in Chenzhou, China. Transl Pediatr 2023; 12:2053-2061. [PMID: 38130588 PMCID: PMC10730968 DOI: 10.21037/tp-23-448] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/24/2023] [Accepted: 11/04/2023] [Indexed: 12/23/2023] Open
Abstract
Background Most previous studies on Clostridium difficile infection (CDI) mainly focused on adults with underlying diseases or critical illnesses. However, the number of CDI cases in children has also significantly increased, especially the growth of community-acquired CDI, which has attracted attention. This study was conducted to examine the toxin gene characteristics and the risk factors associated with community-acquired CDI (CA-CDI) in children with diarrhea. Methods Children with diarrhea before admission or within 48 hours of hospitalization were included in the study. Stool samples were collected from children with community-acquired diarrhea who were treated at the Children's Hospital of the First People's Hospital of Chenzhou, China from June of 2021 to June of 2022. Fluorescence real-time polymerase chain reaction was utilized to detect Clostridioides difficile (CD) toxins A (tcdA) and B (tcdB) genes as well as binary toxin gene A (cdtA) and B (cdtB) in the specimens cultured for CD. Each child with CA-CDI was matched with four control children of the same sex, age, and place of residence. Necessary clinical data were extracted from the hospital's electronic medical record system. Then, a multivariate conditional logistic regression analysis was applied to identify potential risk factors for CA-CDI. Results Sixteen (8.3%) of the 193 stool specimens who tested positive for CD were selected for the case group, and their matching 64 control patients were in the study cohort. The breakdown of the CD genotypes of the 16 positive cases were follows: 14 (tcdA+ and tcdB+) (7.25%) and 2 (tcdA+ and tcdB-) (1.04%). The cdtA and cdtB binary toxin genes were negative in all. The results of multivariate conditional logistic regression analysis identified antibiotic use within the previous month [odds ratio (OR) =5.13; 95% confidence interval (CI): 1.65-15.91] and non-breastfeeding (OR =4.89; 95% CI: 1.11-21.53) as independent risk factors for CDI in pediatric patients experiencing community-acquired diarrhea. Conclusions Children who had been treated with antibiotics and not breastfed were more susceptible to CDI. Therefore, in order to prevent and to control the spread of CD infection, being prudent to the aforementioned high-risk factors is strongly advocated in clinical practice.
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Affiliation(s)
- Yong Zhou
- School of Public Health, Xiangnan University, Chenzhou, China
| | - Liping He
- School of Public Health, Xiangnan University, Chenzhou, China
| | - Cuimei Chen
- School of Public Health, Xiangnan University, Chenzhou, China
| | - Huiwen Zeng
- School of Public Health, Xiangnan University, Chenzhou, China
| | - Andrew S. Day
- Department of Paediatrics, University of Otago Christchurch, Christchurch, New Zealand
| | - Consolato M. Sergi
- Anatomic Pathology Division, Children’s Hospital of Eastern Ontario, University of Ottawa, Ottawa, ON, Canada
- Department of Laboratory Medicine and Pathology, Stollery Children’s Hospital, Edmonton, AB, Canada
| | - Huilong Fang
- School of Public Health, Xiangnan University, Chenzhou, China
| | - Qun Xie
- School of Public Health, Xiangnan University, Chenzhou, China
| | - Yuan Wu
- National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China
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15
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Alhameed AF, Saferuddin N, Alturkistani T, Al Musawa M, Damfu N, Alattas M. Vancomycin vs metronidazole use for the treatment of Clostridioides difficile infection in a tertiary care hospital in Saudi Arabia. Heliyon 2023; 9:e22053. [PMID: 38027991 PMCID: PMC10663888 DOI: 10.1016/j.heliyon.2023.e22053] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2023] [Revised: 11/02/2023] [Accepted: 11/02/2023] [Indexed: 12/01/2023] Open
Abstract
Background The 2017 Infectious Diseases Society of America (IDSA) Clostridioides difficile infection (CDI) guidelines recommendation for oral vancomycin as preferred treatment was based on studies conducted in North America, Australia, and Europe. According to recent published data, metronidazole remains a reasonable option. No studies have been conducted in Saudi Arabia to compare prescribing patterns before and after the release of the guidelines. Due to low CDI burden in Saudi Arabia, the aim is to assess the effectiveness and outcomes of vancomycin vs metronidazole treatment options. Methods This was a retrospective cohort study conducted in a tertiary care hospital in Jeddah which was approved by the Institutional Review Board (IRB 2020-53). Data was collected from January 2017 to April 2020. Eligible patients were adults (>18 years old) diagnosed with CDI who either received oral metronidazole (500 mg 3 times daily) or oral vancomycin (125-500 mg 4 times daily). Patients who received a combination of treatment or who were diagnosed with fulminant CDI were excluded. Demographic data were collected. The primary outcome was to assess treatment response to initial therapy with oral metronidazole versus oral vancomycin. Secondary outcomes included assessing early treatment response, time to discharge after diagnosis, proportion of patients with a positive VRE surveillance culture within 6 months of diagnosis, 30-day recurrence and 30-day all-cause mortality. Chi-square or Fisher's exact test were used to examine differences in categorical variables while student t-test or Mann-Whitney test, were used to examine differences in continuous variables. P value < 0.05 was considered as significant. Results A total of 166 patients were included in the analysis. Demographic characteristics were not significantly different between the two groups. There was no difference in treatment response between vancomycin and metronidazole (96.4 % versus 94.3 %, p = 0.682). However, compared with metronidazole, vancomycin treatment was significantly associated with better early response (94.0 % versus 77.8 %, p = 0.008). Other outcomes were not significantly different between the two drug groups for time to discharge after diagnosis (P = 0.522), 30-day recurrence (P > 0.99) and 30-day all-cause mortality (P = 0.782). Of note, the vancomycin versus metronidazole use before the 2017 IDSA guidelines (26 % versus 74 %) was completely reversed after the release of the guidelines (83.3 % versus 16.7 %), p < 0.001). Conclusion The results of this study demonstrate that vancomycin and metronidazole have comparable outcomes in regards to treatment response for non-fulminant CDI. The study also reveals the high and quick impact of international guidelines on local prescription patterns. Further studies are needed in Saudi Arabia to guide the treatment of CDI.
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Affiliation(s)
- Abrar F. Alhameed
- Pharmaceutical Care Division, King Faisal Specialist Hospital and Research Centre, Madinah, Saudi Arabia
- Pharmaceutical Care Division, King Faisal Specialist Hospital and Research Centre, Jeddah, Saudi Arabia
| | - Nada Saferuddin
- Pharmaceutical Care Division, King Faisal Specialist Hospital and Research Centre, Jeddah, Saudi Arabia
| | - Tariq Alturkistani
- Pharmaceutical Care Division, King Faisal Specialist Hospital and Research Centre, Jeddah, Saudi Arabia
| | - Mohammed Al Musawa
- Pharmaceutical Care Division, King Faisal Specialist Hospital and Research Centre, Jeddah, Saudi Arabia
| | - Nader Damfu
- Pharmaceutical Care Department, King Abdul Aziz Medical City, Jeddah, Saudi Arabia
| | - Majda Alattas
- Pharmaceutical Care Division, King Faisal Specialist Hospital and Research Centre, Jeddah, Saudi Arabia
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Cui Y, Zhang C, Jia Q, Gong X, Tan Y, Hua X, Jian W, Yang S, Hayer K, Raja Idris RK, Zhang Y, Wu Y, Tu Z. An epidemiological surveillance study (2021-2022): detection of a high diversity of Clostridioides difficile isolates in one tertiary hospital in Chongqing, Southwest China. BMC Infect Dis 2023; 23:703. [PMID: 37858038 PMCID: PMC10588108 DOI: 10.1186/s12879-023-08666-2] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2023] [Accepted: 10/03/2023] [Indexed: 10/21/2023] Open
Abstract
BACKGROUND Clostridioides difficile is a bacterium that causes antibiotic-associated infectious diarrhea and pseudomembranous enterocolitis. The impact of C. difficile infection (CDI) in China has gained significant attention in recent years. However, little epidemiological data are available from Chongqing, a city located in Southwest China. This study aimed to investigate the epidemiological pattern of CDI and explore the drug resistance of C. difficile isolates in Chongqing. METHODS A case-control study was conducted to investigate the clinical infection characteristics and susceptibility factors of C. difficile. The features of the C. difficile isolates were evaluated by testing for toxin genes and using multi-locus sequence typing (MLST). The susceptibility of strains to nine antibiotics was determined using agar dilution technique. RESULTS Out of 2084 diarrhea patients, 90 were tested positive for the isolation of toxigenic C. difficile strains, resulting in a CDI prevalence rate of 4.32%. Tetracycline, cephalosporins, hepatobiliary disease, and gastrointestinal disorders were identified as independent risk factors for CDI incidence. The 90 strains were classified into 21 sequence types (ST), with ST3 being the most frequent (n = 25, 27.78%), followed by ST2 (n = 10, 11.11%) and ST37 (n = 9, 10%). Three different toxin types were identified: 69 (76.67%) were A+B+CDT-, 12 (13.33%) were A-B+CDT-, and 9 (10%) were A+B+CDT+. Although substantial resistance to erythromycin (73.33%), moxifloxacin (62.22%), and clindamycin (82.22%), none of the isolates exhibited resistance to vancomycin, tigecycline, or metronidazole. Furthermore, different toxin types displayed varying anti-microbial characteristics. CONCLUSIONS The strains identified in Chongqing, Southwest China, exhibited high genetic diversity. Enhance full awareness of high-risk patients with HA-CDI infection, particularly those with gastrointestinal and hepatocellular diseases, and emphasize caution in the use of tetracycline and capecitabine. These findings suggest that a potential epidemic of CDI may occur in the future, emphasizing the need for timely monitoring.
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Affiliation(s)
- Yihong Cui
- Department of Pathogen Biology, College of Basic Medical Science, Chongqing Medical University, 400016, Chongqing, China
| | - Chuanming Zhang
- Department of Laboratory Medicine, The First Affiliated Hospital of Chongqing Medical University, 400016, Chongqing, China
| | - Qianying Jia
- Department of Infectious Diseases, The First Affiliated Hospital of Chongqing Medical University, 400016, Chongqing, China
| | - Xue Gong
- Department of Pathogen Biology, College of Basic Medical Science, Chongqing Medical University, 400016, Chongqing, China
| | - Yu Tan
- Department of Pathogen Biology, College of Basic Medical Science, Chongqing Medical University, 400016, Chongqing, China
| | - Xinping Hua
- Department of Pathogen Biology, College of Basic Medical Science, Chongqing Medical University, 400016, Chongqing, China
| | - Wenwen Jian
- Department of Pathogen Biology, College of Basic Medical Science, Chongqing Medical University, 400016, Chongqing, China
| | - Shenglin Yang
- Department of Pathogen Biology, College of Basic Medical Science, Chongqing Medical University, 400016, Chongqing, China
| | - Kim Hayer
- Leicester Medical School, University of Leicester, LE1 7RH, Leicester, UK
| | | | - Yi Zhang
- International Medical College, Chongqing Medical University, 400016, Chongqing, China
| | - Yuan Wu
- State Key Laboratory of Infectious Disease Prevention and Control, National Insti for Communicable Disease Control and Prevention, Chinese Center for Disease Prevention and Control, 102206, Beijing, China
| | - Zeng Tu
- Department of Pathogen Biology, College of Basic Medical Science, Chongqing Medical University, 400016, Chongqing, China.
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Carling PC, Parry MF, Olmstead R. Environmental approaches to controlling Clostridioides difficile infection in healthcare settings. Antimicrob Resist Infect Control 2023; 12:94. [PMID: 37679758 PMCID: PMC10483842 DOI: 10.1186/s13756-023-01295-z] [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: 05/14/2023] [Accepted: 08/25/2023] [Indexed: 09/09/2023] Open
Abstract
As today's most prevalent and costly healthcare-associated infection, hospital-onset Clostridioides difficile infection (HO-CDI) represents a major threat to patient safety world-wide. This review will discuss how new insights into the epidemiology of CDI have quantified the prevalence of C. difficile (CD) spore contamination of the patient-zone as well as the role of asymptomatically colonized patients who unavoidable contaminate their near and distant environments with resilient spores. Clarification of the epidemiology of CD in parallel with the development of a new generation of sporicidal agents which can be used on a daily basis without damaging surfaces, equipment, or the environment, led to the research discussed in this review. These advances underscore the potential for significantly mitigating HO-CDI when combined with ongoing programs for optimizing the thoroughness of cleaning as well as disinfection. The consequence of this paradigm-shift in environmental hygiene practice, particularly when combined with advances in hand hygiene practice, has the potential for significantly improving patient safety in hospitals globally by mitigating the acquisition of CD spores and, quite plausibly, other environmentally transmitted healthcare-associated pathogens.
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Marshall A, McGrath JW, Mitchell M, Fanning S, McMullan G. One size does not fit all - Trehalose metabolism by Clostridioides difficile is variable across the five phylogenetic lineages. Microb Genom 2023; 9:001110. [PMID: 37768179 PMCID: PMC10569727 DOI: 10.1099/mgen.0.001110] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2023] [Accepted: 09/19/2023] [Indexed: 09/29/2023] Open
Abstract
Clostridioides difficile, the leading cause of antibiotic-associated diarrhoea worldwide, is a genetically diverse species which can metabolise a number of nutrient sources upon colonising a dysbiotic gut environment. Trehalose, a disaccharide sugar consisting of two glucose molecules bonded by an α 1,1-glycosidic bond, has been hypothesised to be involved in the emergence of C. difficile hypervirulence due to its increased utilisation by the RT027 and RT078 strains. Here, growth in trehalose as the sole carbon source was shown to be non-uniform across representative C. difficile strains, even though the genes for its metabolism were induced. Growth in trehalose reduced the expression of genes associated with toxin production and sporulation in the C. difficile R20291 (RT027) and M120 (RT078) strains in vitro, suggesting an inhibitory effect on virulence factors. Interestingly, the R20291 TreR transcriptional regulatory protein appeared to possess an activator function as its DNA-binding ability was increased in the presence of its effector, trehalose-6-phosphate. Using RNA-sequencing analysis, we report the identification of a putative trehalose metabolism pathway which is induced during growth in trehalose: this has not been previously described within the C. difficile species. These data demonstrate the metabolic diversity exhibited by C. difficile which warrants further investigation to elucidate the molecular basis of trehalose metabolism within this important gut pathogen.
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Affiliation(s)
- Andrew Marshall
- School of Biological Sciences, Queen’s University Belfast, 19 Chlorine Gardens, Belfast, BT9 5DL, UK
| | - John W. McGrath
- School of Biological Sciences, Queen’s University Belfast, 19 Chlorine Gardens, Belfast, BT9 5DL, UK
| | - Molly Mitchell
- University College Dublin-Centre for Food Safety University College Dublin, Dublin, Ireland
| | - Séamus Fanning
- University College Dublin-Centre for Food Safety University College Dublin, Dublin, Ireland
| | - Geoff McMullan
- School of Biological Sciences, Queen’s University Belfast, 19 Chlorine Gardens, Belfast, BT9 5DL, UK
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Skjøt-Arkil H, Rune Nanthan K, Chen M, Rosenvinge FS. Carrier prevalence of Clostridioides difficile in emergency departments and the association of prior antibiotic consumption: a combined cross-sectional and nested case-control study. J Antimicrob Chemother 2023:dkad213. [PMID: 37409612 DOI: 10.1093/jac/dkad213] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2023] [Accepted: 06/25/2023] [Indexed: 07/07/2023] Open
Abstract
INTRODUCTION Clostridioides difficile infection is an urgent public health threat, and the incidence has been increasing over the last decades. Knowledge of the prevalence of C. difficile in acutely admitted patients and risk factors for colonization with C. difficile assists emergency departments (EDs) in prioritizing preventive initiatives. This national study aimed to describe prevalence and risk factors for C. difficile carriers acutely admitted to EDs, focusing on the impact of earlier antibiotic prescription. METHODS We conducted a nationwide analytic cross-sectional study with prospective data collection combined with a nested case-control study with retrospective data collection. All adults visiting one of eight Danish EDs were interviewed and examined for C. difficile. Using a national register, we collected the antibiotic history within the 2 years prior to enrolment. The primary outcome was the prevalence of C. difficile colonization, and secondary outcomes were related to risk factors and prior antibiotic prescription. Multivariate analyses examined the association between earlier antibiotic prescription and C. difficile colonization. RESULTS Of 5019 participants, 89 were colonized with C. difficile (prevalence of 1.8%). A significant and exposure-dependent association was found for penicillins [DDD/person-year(PY) > 20; OR 4.93 (95% CI 2.22-10.97)] and fluoroquinolones [DDD/PY > 20; OR 8.81 (95% CI 2.54-30.55)], but not macrolides. Timing of the prescription did not affect the association. CONCLUSIONS One out of 55 patients visiting a Danish ED were colonized with C. difficile. Risk factors for colonization included high age, comorbidity and prior prescription of fluoroquinolones and penicillins.
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Affiliation(s)
- Helene Skjøt-Arkil
- Department of Regional Health Research at University of Southern Denmark, Aabenraa, Denmark
- Emergency Department at University Hospital of Southern Denmark, Aabenraa, Denmark
| | - Kumanan Rune Nanthan
- Emergency Department at University Hospital of Southern Denmark, Aabenraa, Denmark
| | - Ming Chen
- Department of Microbiology at University Hospital of Southern Denmark, Aabenraa, Denmark
| | - Flemming S Rosenvinge
- Department of Clinical Microbiology at Odense University Hospital, and Research Unit of Clinical Microbiology at University of Southern Denmark, Odense, Denmark
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Armstrong EP, Malone DC, Franic DM, Pham SV, Gratie D, Amin A. Patient Experiences with Clostridioides difficile Infection and Its Treatment: A Systematic Literature Review. Infect Dis Ther 2023:10.1007/s40121-023-00833-x. [PMID: 37395984 PMCID: PMC10390453 DOI: 10.1007/s40121-023-00833-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2023] [Accepted: 06/01/2023] [Indexed: 07/04/2023] Open
Abstract
INTRODUCTION Clostridioides difficile infection (CDI) is a globally recognized cause of morbidity and mortality with devastating effects on health-related quality of life (HRQoL). The objective of this study was to conduct the first systematic literature review (SLR) to assess the humanistic burden of CDI on patient experiences, including HRQoL and related constructs, and attitudes towards treatment alternatives. METHODS An SLR was conducted to identify peer-reviewed articles that assessed CDI, including recurrent CDI (rCDI), and patient-reported outcomes or HRQoL. PubMed, Embase, and the Cochrane Collaboration abstracting services were used to conduct literature searches from 2010 to 2021 in the English language. This SLR was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) criteria. RESULTS Of 511 identified articles, 21 met study inclusion criteria. The SLR showed CDI has a devastating impact on patients' overall HRQoL that continues well beyond infection clearance. The impact of CDI on physical, emotional, social, and professional well-being rivaled abdominal symptoms of uncontrollable diarrhea, being worse for patients with rCDI. Patients with CDI feel isolated, depressed, lonely, and continue to be frightened of recurrences as well as being contagious to others. Most believe that they will never be free of CDI. CONCLUSION CDI and rCDI are debilitating conditions affecting physical, psychological, social, and professional functioning of patients' HRQoL, even long after the event has occurred. The results of this SLR suggest that CDI is a devastating condition in need of better prevention strategies, improved psychological support, and treatments that address the microbiome disruption to break the cycle of recurrence. Additional safe and effective therapies are needed to address this unmet medical need.
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Affiliation(s)
- Edward P Armstrong
- Strategic Therapeutics and University of Arizona College of Pharmacy, Tucson, AZ, USA
| | - Daniel C Malone
- Strategic Therapeutics and University of Utah College of Pharmacy, Salt Lake City, UT, USA
| | - Duska M Franic
- Evidence Institute AESARA, P.O. Box 4266, Chapel Hill, NC, 27515, USA.
| | - Sissi V Pham
- Evidence Institute AESARA, P.O. Box 4266, Chapel Hill, NC, 27515, USA
| | - Dan Gratie
- Evidence Institute AESARA, P.O. Box 4266, Chapel Hill, NC, 27515, USA
| | - Alpesh Amin
- Medicine, Business, Public Health, Nursing Science, & Biomedical Engineering, Hospitalist Program, University of California, Irvine, Irvine, CA, USA
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21
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Naz F, Petri WA. Host Immunity and Immunization Strategies for Clostridioides difficile Infection. Clin Microbiol Rev 2023; 36:e0015722. [PMID: 37162338 PMCID: PMC10283484 DOI: 10.1128/cmr.00157-22] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/11/2023] Open
Abstract
Clostridioides difficile infection (CDI) represents a significant challenge to public health. C. difficile-associated mortality and morbidity have led the U.S. CDC to designate it as an urgent threat. Moreover, recurrence or relapses can occur in up to a third of CDI patients, due in part to antibiotics being the primary treatment for CDI and the major cause of the disease. In this review, we summarize the current knowledge of innate immune responses, adaptive immune responses, and the link between innate and adaptive immune responses of the host against CDI. The other major determinants of CDI, such as C. difficile toxins, the host microbiota, and related treatments, are also described. Finally, we discuss the known therapeutic approaches and the current status of immunization strategies for CDI, which might help to bridge the knowledge gap in the generation of therapy against CDI.
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Affiliation(s)
- Farha Naz
- Division of Infectious Diseases and International Health, University of Virginia School of Medicine, Charlottesville, Virginia, USA
| | - William A. Petri
- Division of Infectious Diseases and International Health, University of Virginia School of Medicine, Charlottesville, Virginia, USA
- Department of Pathology, University of Virginia School of Medicine, Charlottesville, Virginia, USA
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22
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Miqdad MA, Kosaraju K, Mohamad A, Hulwi H, Rais U, Taleb M, Aloreibi T. Clostridium difficile Infection: Risk and Poor Prognostic Factors at a Tertiary Hospital in the Eastern Region of Saudi Arabia. Cureus 2023; 15:e39193. [PMID: 37378089 PMCID: PMC10291994 DOI: 10.7759/cureus.39193] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/18/2023] [Indexed: 06/29/2023] Open
Abstract
BACKGROUND Clostridium difficile (C. difficile) is a common cause of hospital-acquired diarrhea. It is associated with significantly higher mortality and morbidity in addition to the cost-effectiveness burden on the healthcare system. The primary risk factors for C. difficile infection (CDI) are past C. difficile exposure, proton pump inhibitors, and antibiotic usage. These risk factors are also associated with poor prognosis. OBJECTIVE This study was performed in Dr. Sulaiman Al Habib Tertiary Hospital in the Eastern Region of Saudi Arabia. The aim was to evaluate the risk and prognostic factors of CDI and their association with the outcomes of hospital stay, such as complications, length of stay (LOS), and treatment duration. PATIENTS AND METHODS This is a retrospective cohort study for all patients who tested for C. difficile in the medical department. The target population was all adult patients ≥16 years with positive stool toxins for C. difficile between April 2019 and July 2022. The main outcome measures are risk and poor prognostic factors for CDI. RESULTS C. difficle infection patients were included in the study; 12 (52.2%) were female, and 11 (47.8%) were male. The mean age of the patients was 58.3 (SD: 21.5) years; 13 (56.5%) patients were below 65 years, and 10 were above 65 years. Only four patients were without comorbidities, and 19 (82.6%) patients had various comorbidities. Importantly, hypertension was the most common comorbidity in 47.8% of the patients. Furthermore, advanced age significantly impacted the hospital LOS as the mean age among patients who stayed at the hospital less than four days and those who stayed ≥4 days was 49.08 (19.7) and 68.36 (19.5), respectively (P = .028). CONCLUSION Advanced age was the most frequent poor prognostic factor among our inpatient participants with positive CDI. It was significantly associated with longer hospital LOS, more complications, and longer treatment duration.
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Affiliation(s)
- Mohammed A Miqdad
- Internal Medicine, Dr. Sulaiman Al Habib Medical Group, Khobar, SAU
- Tele-Geriatric Research Fellowship, Michigan State University, Michigan, USA
| | | | - Abdullah Mohamad
- Internal Medicine, Dr. Sulaiman Al Habib Medical Group, Khobar, SAU
| | - Hasan Hulwi
- Internal Medicine, Dr. Sulaiman Al Habib Medical Group, Khobar, SAU
| | - Ubaid Rais
- Pharmacology, Dr. Sulaiman Al Habib Medical Group, Khobar, SAU
| | - Mohammad Taleb
- Internal Medicine, Dr. Sulaiman Al Habib Medical Group, Khobar, SAU
| | - Talal Aloreibi
- Infectious Diseases, Dr. Sulaiman Al Habib Medical Group, Khobar, SAU
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23
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Tsekouras N, Meletis E, Kostoulas P, Labronikou G, Athanasakopoulou Z, Christodoulopoulos G, Billinis C, Papatsiros VG. Detection of Enterotoxigenic Escherichia coli and Clostridia in the Aetiology of Neonatal Piglet Diarrhoea: Important Factors for Their Prevention. Life (Basel) 2023; 13:life13051092. [PMID: 37240738 DOI: 10.3390/life13051092] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2023] [Revised: 04/13/2023] [Accepted: 04/23/2023] [Indexed: 05/28/2023] Open
Abstract
This study aimed to research the involvement of enterotoxigenic E. coli (ETEC) and C. difficile or C. perfringens type C in the aetiology of neonatal piglet diarrhoea in Greece and to identify preventive factors for them. A total of 78 pooled faecal samples were collected randomly from 234 suckling piglets (1-4 days of age) with diarrhoea from 26 pig farms (3 piglets × 3 litters × 26 farms = 234 piglets = 78 faecal pool samples). The collected samples were initially screened for the presence of E. coli and C. difficile or C. perfringens via cultivation on MacConkey and anaerobic blood agar, respectively. Subsequently, the samples were pooled on ELUTE cards. From samples tested, 69.23% of those in the farms were ETEC F4-positive, 30.77% were ETEC F5-positive, 61.54% ETEC were F6-positive, 42.31% were ETEC F4- and E. coli enterotoxin LT-positive, 19.23% were ETEC F5- and LT-positive, 42.31% were ETEC F6- and LT-positive, while LT was found in 57.69% of those in the farms. C. difficile was involved in many cases and identified as an emerging neonatal diarrhoea etiological agent. Specifically, Toxin A of C. difficile was found in 84.62% and Toxin B in 88.46% of those in the farms. Antibiotic administration to sows in combination with probiotics or acidifiers was revealed to reduce the detection of antigens of ETEC and the enterotoxin LT of E. coli.
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Affiliation(s)
- Nikolaos Tsekouras
- Clinic of Medicine, Faculty of Veterinary Science, University of Thessaly, 43100 Karditsa, Greece
| | - Eleftherios Meletis
- Faculty of Public and Integrated Health, University of Thessaly, 43100 Karditsa, Greece
| | - Polychronis Kostoulas
- Faculty of Public and Integrated Health, University of Thessaly, 43100 Karditsa, Greece
| | | | - Zoi Athanasakopoulou
- Department of Microbiology and Parasitology, Faculty of Veterinary Science, University of Thessaly, 43100 Karditsa, Greece
| | - Georgios Christodoulopoulos
- Department of Animal Science, Agricultural University of Athens, 75 Iera Odos Street, Botanikos, 11855 Athens, Greece
| | - Charalambos Billinis
- Faculty of Public and Integrated Health, University of Thessaly, 43100 Karditsa, Greece
- Department of Microbiology and Parasitology, Faculty of Veterinary Science, University of Thessaly, 43100 Karditsa, Greece
| | - Vasileios G Papatsiros
- Clinic of Medicine, Faculty of Veterinary Science, University of Thessaly, 43100 Karditsa, Greece
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Wang S, Ju X, Heuler J, Zhang K, Duan Z, Warnakulasuriya Patabendige HML, Zhao S, Sun X. Recombinant Fusion Protein Vaccine Containing Clostridioides difficile FliC and FliD Protects Mice against C. difficile Infection. Infect Immun 2023; 91:e0016922. [PMID: 36939332 PMCID: PMC10112125 DOI: 10.1128/iai.00169-22] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2022] [Accepted: 02/09/2023] [Indexed: 03/21/2023] Open
Abstract
Bacterial flagella are involved in infection through their roles in host cell adhesion, cell invasion, auto-agglutination, colonization, the formation of biofilms, and the regulation and secretion of nonflagellar bacterial proteins that are involved in the virulence process. In this study, we constructed a fusion protein vaccine (FliCD) containing the Clostridioides difficile flagellar proteins FliC and FliD. The immunization of mice with FliCD induced potent IgG and IgA antibody responses against FliCD, protected mice against C. difficile infection (CDI), and decreased the C. difficile spore and toxin levels in the feces after infection. Additionally, the anti-FliCD serum inhibited the binding of C. difficile vegetative cells to HCT8 cells. These results suggest that FliCD may represent an effective vaccine candidate against CDI.
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Affiliation(s)
- Shaohui Wang
- Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, Florida, USA
| | - Xianghong Ju
- Department of Infectious Diseases and Global Health, Tufts University Cummings School of Veterinary Medicine, North Grafton, Massachusetts, USA
| | - Joshua Heuler
- Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, Florida, USA
| | - Keshan Zhang
- Department of Infectious Diseases and Global Health, Tufts University Cummings School of Veterinary Medicine, North Grafton, Massachusetts, USA
| | - Zhibian Duan
- Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, Florida, USA
| | | | - Song Zhao
- Department of Infectious Diseases and Global Health, Tufts University Cummings School of Veterinary Medicine, North Grafton, Massachusetts, USA
| | - Xingmin Sun
- Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, Florida, USA
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25
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Comparcini D, Simonetti V, Segala FV, Di Gennaro F, Bavaro DF, Pompeo MA, Saracino A, Cicolini G. Nurses’ Knowledge, Attitudes and Practices on the Management of Clostridioides difficile Infection: A Cross-Sectional Study. Antibiotics (Basel) 2023; 12:antibiotics12030529. [PMID: 36978396 PMCID: PMC10044176 DOI: 10.3390/antibiotics12030529] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2023] [Revised: 03/02/2023] [Accepted: 03/04/2023] [Indexed: 03/09/2023] Open
Abstract
Clostridioides difficile is, worldwide, the leading cause of hospital-acquired infection. Outbreaks are largely related to antibiotic exposure and contact contamination, but little is known about C. difficle infection (CDI) awareness in the nurse population. We conducted a cross-sectional survey to study Italian nurses, based on CDI guidelines. We recruited 200 nurses working in 14 Italian hospitals. Using a one-way analysis of variance of knowledge scores, female nurses (mean 9.67 (standard deviation ± 1.63), p = 0.03), and nurses with a higher level of university education (mean 9.79 (SD ± 1.67), p = 0.04) were demonstrated to have better knowledge about CDI. In addition, 92.5% (n = 184) of the sample declared that they did not have specific postgraduate training about CDI. Seventy-four percent (n = 149) of the respondents declared that they used procedures, protocols and guidelines about CDI in their workplace, but only 46.5% (n = 93) reported using C. difficile-specific bundles during their daily practice. In conclusion, our study highlights a lack of knowledge concerning CDI clinical guidelines among Italian nurses.
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Affiliation(s)
- Dania Comparcini
- CdL Infermieristica di Ancona, Facoltà Medicina e Chirurgia, Università Politecnica delle Marche (Univpm), 60121 Ancona, Italy
| | - Valentina Simonetti
- Dipartimento di Medicina e Chirurgia, LUM “Giuseppe Degennaro”, 70121 Bari, Italy
| | - Francesco Vladimiro Segala
- Department of Precision and Regenerative Medicine and Ionian Area—(DiMePRe-J), University of Bari “Aldo Moro”, 70121 Bari, Italy
- Correspondence:
| | - Francesco Di Gennaro
- Department of Precision and Regenerative Medicine and Ionian Area—(DiMePRe-J), University of Bari “Aldo Moro”, 70121 Bari, Italy
| | - Davide Fiore Bavaro
- Department of Precision and Regenerative Medicine and Ionian Area—(DiMePRe-J), University of Bari “Aldo Moro”, 70121 Bari, Italy
| | | | - Annalisa Saracino
- Department of Precision and Regenerative Medicine and Ionian Area—(DiMePRe-J), University of Bari “Aldo Moro”, 70121 Bari, Italy
| | - Giancarlo Cicolini
- Department of Precision and Regenerative Medicine and Ionian Area—(DiMePRe-J), University of Bari “Aldo Moro”, 70121 Bari, Italy
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26
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Prayag PS, Patwardhan SA, Panchakshari SP, Prayag AP. Clostridium difficile in Oncology Patients—Review of Diagnosis and Management in the Indian Setting. Indian J Med Paediatr Oncol 2023. [DOI: 10.1055/s-0042-1760316] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/05/2023] Open
Abstract
Abstract
Clostridoides (formerly Clostridium) difficile (C. difficile) is a toxin-producing, gram-positive anaerobic bacillus, commonly implicated in antibiotic-associated diarrhea and pseudomembranous colitis. The true burden of C. difficile infection is unclear in India, as it is likely underdiagnosed and underreported. Its incidence is much higher in oncology patients where it can contribute significantly to morbidity and mortality. There are several challenges in the Indian setting, including lack of uniform availability of testing infrastructure, as well as therapy. Oncology patients further present with a unique set of challenges. This article will review the approach to diagnosis and management of C. difficile-associated diarrhea in India, with a focus on oncology patients.
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Affiliation(s)
- Parikshit S Prayag
- Department of Infectious Diseases, Deenanath Mangeshkar Hospital, Pune, Maharashtra, India
| | - Sampada A Patwardhan
- Department of Microbiology, Deenanath Mangeshkar Hospital, Pune, Maharashtra, India
| | - Shweta P Panchakshari
- Department of Infectious Diseases, Deenanath Mangeshkar Hospital, Pune, Maharashtra, India
| | - Amrita P Prayag
- Department of Research, Deenanath Mangeshkar Hospital, Pune, Maharashtra, India
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Bustin KA, Abbas A, Wang X, Abt MC, Zackular JP, Matthews ML. Characterizing metabolic drivers of Clostridioides difficile infection with activity-based hydrazine probes. Front Pharmacol 2023; 14:1074619. [PMID: 36778002 PMCID: PMC9908766 DOI: 10.3389/fphar.2023.1074619] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2022] [Accepted: 01/05/2023] [Indexed: 01/27/2023] Open
Abstract
Many enzymes require post-translational modifications or cofactor machinery for primary function. As these catalytically essential moieties are highly regulated, they act as dual sensors and chemical handles for context-dependent metabolic activity. Clostridioides difficile is a major nosocomial pathogen that infects the colon. Energy generating metabolism, particularly through amino acid Stickland fermentation, is central to colonization and persistence of this pathogen during infection. Here using activity-based protein profiling (ABPP), we revealed Stickland enzyme activity is a biomarker for C. difficile infection (CDI) and annotated two such cofactor-dependent Stickland reductases. We structurally characterized the cysteine-derived pyruvoyl cofactors of D-proline and glycine reductase in C. difficile cultures and showed through cofactor monitoring that their activity is regulated by their respective amino acid substrates. Proline reductase was consistently active in toxigenic C. difficile, confirming the enzyme to be a major metabolic driver of CDI. Further, activity-based hydrazine probes were shown to be active site-directed inhibitors of proline reductase. As such, this enzyme activity, via its druggable cofactor modality, is a promising therapeutic target that could allow for the repopulation of bacteria that compete with C. difficile for proline and therefore restore colonization resistance against C. difficile in the gut.
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Affiliation(s)
- Katelyn A. Bustin
- Department of Chemistry, University of Pennsylvania, Philadelphia, PA, United States
| | - Arwa Abbas
- Division of Protective Immunity, Children’s Hospital of Pennsylvania, Philadelphia, PA, United States
| | - Xie Wang
- Department of Chemistry, University of Pennsylvania, Philadelphia, PA, United States
| | - Michael C. Abt
- Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States
| | - Joseph P. Zackular
- Division of Protective Immunity, Children’s Hospital of Pennsylvania, Philadelphia, PA, United States
- Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States
| | - Megan L. Matthews
- Department of Chemistry, University of Pennsylvania, Philadelphia, PA, United States
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Muñoz Cuevas C, Asencio Egea MÁ, Franco Huerta M, Huertas Vaquero M, Arias Arias Á, Carranza González R. Case-control study of Clostridioides difficile in a rural health care area. GASTROENTEROLOGIA Y HEPATOLOGIA 2023; 46:1-9. [PMID: 35104606 DOI: 10.1016/j.gastrohep.2022.01.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/20/2021] [Revised: 12/12/2021] [Accepted: 01/20/2022] [Indexed: 01/18/2023]
Abstract
OBJECTIVE To determine the risk and prognostic factors for Clostridioides difficile infection (CDI). PATIENTS AND METHODS Prospective, case-control study with 61 cases and 64 controls, aged ≥2 years with diarrhoea, carried out in Castilla-La Mancha Health Care Area for 14 months. The diagnosis was made by immunochromatography technics (glutamate dehydrogenase and toxin A/B), confirming discordant cases by isothermal amplification. Demographic variables, comorbidities, type of acquisition, previous administration of antibiotics, antacids and immunosuppressants, and evolution were collected. The data were analysed using the chi-square test and the effect of risk and prognostic factors was quantified using an odds ratio with 95% confidence intervals. RESULTS Hospital admission 4 weeks prior to infection, hypoalbuminemia, and previous administration of antibiotics were identified as independent risk factors for CDI. Presenting these 3 factors constitutes nearly 3-fold increase in the risk of becoming infected. A greater number of hospital admissions in the 4-12 weeks prior to CDI were found in the group of nosocomial acquisition. Although there was a greater tendency to recurrence and an unfavourable prognosis among nosocomial cases, these differences were not significant. We found that fever and hospital admission in the 4 weeks prior to infection were unfavourable prognostic factors of CDI. CONCLUSIONS The independent risk factors for CDI were: Hospital admission in the 4 weeks prior to infection, hypoalbuminemia, and previous administration of antibiotics. Fever and hospitalisation in the previous 4 weeks were also identified as prognostic factors of unfavourable evolution.
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Affiliation(s)
- Cristina Muñoz Cuevas
- Laboratorio de Microbiología, Hospital General La Mancha Centro, Ciudad Real, España
| | | | - María Franco Huerta
- Servicio de Medicina Interna, Hospital General La Mancha Centro, Ciudad Real, España
| | - María Huertas Vaquero
- Laboratorio de Microbiología, Hospital General La Mancha Centro, Ciudad Real, España
| | - Ángel Arias Arias
- Unidad de Apoyo a la Investigación, Hospital General La Mancha Centro, Ciudad Real, España
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Nale JY, Thanki AM, Rashid SJ, Shan J, Vinner GK, Dowah ASA, Cheng JKJ, Sicheritz-Pontén T, Clokie MRJ. Diversity, Dynamics and Therapeutic Application of Clostridioides difficile Bacteriophages. Viruses 2022; 14:v14122772. [PMID: 36560776 PMCID: PMC9784644 DOI: 10.3390/v14122772] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2022] [Revised: 12/08/2022] [Accepted: 12/08/2022] [Indexed: 12/15/2022] Open
Abstract
Clostridioides difficile causes antibiotic-induced diarrhoea and pseudomembranous colitis in humans and animals. Current conventional treatment relies solely on antibiotics, but C. difficile infection (CDI) cases remain persistently high with concomitant increased recurrence often due to the emergence of antibiotic-resistant strains. Antibiotics used in treatment also induce gut microbial imbalance; therefore, novel therapeutics with improved target specificity are being investigated. Bacteriophages (phages) kill bacteria with precision, hence are alternative therapeutics for the targeted eradication of the pathogen. Here, we review current progress in C. difficile phage research. We discuss tested strategies of isolating C. difficile phages directly, and via enrichment methods from various sample types and through antibiotic induction to mediate prophage release. We also summarise phenotypic phage data that reveal their morphological, genetic diversity, and various ways they impact their host physiology and pathogenicity during infection and lysogeny. Furthermore, we describe the therapeutic development of phages through efficacy testing in different in vitro, ex vivo and in vivo infection models. We also discuss genetic modification of phages to prevent horizontal gene transfer and improve lysis efficacy and formulation to enhance stability and delivery of the phages. The goal of this review is to provide a more in-depth understanding of C. difficile phages and theoretical and practical knowledge on pre-clinical, therapeutic evaluation of the safety and effectiveness of phage therapy for CDI.
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Affiliation(s)
- Janet Y. Nale
- Centre for Epidemiology and Planetary Health, Department of Veterinary and Animal Science, Scotland’s Rural College, Inverness IV2 5NA, UK
- Department of Genetics and Genome Biology, University of Leicester, Leicester LE1 7RH, UK
| | - Anisha M. Thanki
- Department of Genetics and Genome Biology, University of Leicester, Leicester LE1 7RH, UK
| | - Srwa J. Rashid
- Department of Genetics and Genome Biology, University of Leicester, Leicester LE1 7RH, UK
| | - Jinyu Shan
- Department of Genetics and Genome Biology, University of Leicester, Leicester LE1 7RH, UK
| | - Gurinder K. Vinner
- Department of Genetics and Genome Biology, University of Leicester, Leicester LE1 7RH, UK
| | - Ahmed S. A. Dowah
- Department of Genetics and Genome Biology, University of Leicester, Leicester LE1 7RH, UK
- School of Pharmacy, University of Lincoln, Lincoln LN6 7TS, UK
| | | | - Thomas Sicheritz-Pontén
- Center for Evolutionary Hologenomics, The Globe Institute, University of Copenhagen, 1353 Copenhagen, Denmark
- Centre of Excellence for Omics-Driven Computational Biodiscovery, AIMST University, Bedong 08100, Kedah, Malaysia
| | - Martha R. J. Clokie
- Department of Genetics and Genome Biology, University of Leicester, Leicester LE1 7RH, UK
- Correspondence:
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Park SO, Yeo I. Trends in Clostridioides difficile prevalence, mortality, severity, and age composition during 2003-2014, the national inpatient sample database in the US. Ann Med 2022; 54:1851-1858. [PMID: 35786103 PMCID: PMC9258430 DOI: 10.1080/07853890.2022.2092893] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
BACKGROUND Clostridioides difficile (formerly known as Clostridium difficile) infection (CDI) is one of the most prevalent healthcare-associated infections in the United States (US). In the early 2000s, CDI emerged as a great threat with increasing prevalence, mortality, and severity, especially in advanced age. We investigated the US national trends in in-hospital CDI prevalence, mortality, severity, and age composition from 2003 to 2014. METHODS We identified the patients with CDI using the national inpatient sample data from 2003 to 2014. We performed Poisson regression model and Kendall's tau-b correlation test for our analyses. RESULTS Adjusted overall CDI prevalence did not significantly change during 2003-2014. In-hospital mortality of overall CDI did not significantly change during 2003-2008, then significantly decreased during 2008-2014. Severity of overall CDI significantly increased during 2003-2008, then decreased during 2008-2014. The proportions of patients with age ≥ 65 years decreased in CDI prevalence, mortality, and severity during 2003-2014. CONCLUSIONS Compared to the earlier years 2003-2008, overall CDI outcome improved in the later years 2008-2014. Younger patients increasingly contributed to CDI prevalence, mortality, and severity during 2003-2014. More studies to understand underlying driving forces of changes in CDI trends are warranted to mitigate CDI.
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Affiliation(s)
- Sun O Park
- Division of Infectious Diseases, Department of Medicine, Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, NY, USA
| | - Ilhwan Yeo
- Department of Medicine, New York Presbyterian, Queens, NY, USA
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31
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Kichloo A, El-Amir Z, Dahiya DS, Al-Haddad M, Singh J, Singh G, Corpuz C, Shaka H. Rate and predictors of 30-day readmission for clostridiodes difficile: a United States analysis. Ann Med 2022; 54:150-158. [PMID: 34989297 PMCID: PMC8741240 DOI: 10.1080/07853890.2021.2023211] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND Clostridiodes difficile is a leading cause of healthcare-associated diarrhea. In this study, we aimed to identify the rates and predictors for 30-day readmissions of Clostridiodes difficile Enterocolitis (CDE) in the United States. METHODS We conducted a retrospective study of the Nationwide Readmissions Database to identify adult hospitalizations with a principal diagnosis of CDE for 2018. Individuals <18 years old and elective hospitalizations were excluded. Primary outcomes included readmission rate and the top ten principal diagnosis on readmission, while the secondary outcomes were inpatient mortality, hospital costs and independent predictors of 30-day all-cause readmissions. Furthermore, we devised a scoring system to estimate the risk of CDE readmissions. Stata® Version 16 was used for statistical analysis and p-values ≤0.05 were statistically significant. RESULTS We identified 94,668 index hospitalizations and 18,296 readmissions at 30-days for CDE in 2018. The 30-day all-cause readmission rate was 25.7%. On readmission, CDE was the most common principal diagnosis (25.7%), followed by unspecified sepsis, and acute renal failure. A female predominance was also noted for index and 30-day readmissions of CDE. Compared to index admissions, we noted higher odds of inpatient mortality [4.4 vs 1.4%, Odds Ratio (OR):3.32, 95% Confidence Interval (CI):2.87-3.84, p < 0.001], longer mean length of stay (LOS) [6.4 vs 5.6 days, Mean Difference (MD):0.9, 95% CI:0.7-1.0, p < 0.001), and higher mean total hospital charge (THC) [$56,015 vs $40,871, MD:15,144, 95% CI:13,260-17,027, p < 0.001] for 30-day readmissions of CDE. Independent predictors for 30-day all-cause readmissions of CDE included discharged against medical advice (AMA) [Adjusd Hazard Ratio (aHR):2.01, 95% CI:1.73-2.53, p < 0.001], diabetes mellitus (DM) [aHR:1.22, 95% CI:1.16-1.29, p < 0.001], and chronic kidney disease (CKD) [aHR:1.29, 95% CI:1.21-1.37, p < 0.001]. CONCLUSION The all-cause 30-day readmission rate and inpatient mortality for CDE was 25.7% and 4.4%, respectively. Discharge AMA, DM and CKD were independent predictors for 30-day all-cause readmissions of CDE.KEY MESSAGEThe 30-day all-cause readmission rate for Clostridiodes difficile Enterocolitis was noted to be 21.4% in 2018.Independent predictors of 30-day all-cause readmissions for Clostridiodes difficile Enterocolitis include diabetes mellitus, discharged against medical advice and chronic kidney disease.Readmissions of Clostridiodes difficile Enterocolitis had higher mortality rates, healthcare cost and length of hospital stay compared to index admissions.
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Affiliation(s)
- Asim Kichloo
- Department of Internal Medicine, Central Michigan University College of Medicine, Saginaw, MI, USA.,Department of Internal Medicine, Samaritan Medical Center, Watertown, NY, USA
| | - Zain El-Amir
- Department of Internal Medicine, Central Michigan University College of Medicine, Saginaw, MI, USA
| | - Dushyant Singh Dahiya
- Department of Internal Medicine, Central Michigan University College of Medicine, Saginaw, MI, USA
| | - Mohammad Al-Haddad
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Jagmeet Singh
- Department of Nephrology, Guthrie Robert Packer Hospital, Sayre, PA, USA
| | - Gurdeep Singh
- Department of Medicine and Endocrinology, Our Lady of Lourdes Memorial Hospital, Binghamton, NY, USA
| | - Carlos Corpuz
- Department of Internal Medicine, John H. Stronger Jr. Hospital of Cook County, Chicago, IL, USA
| | - Hafeez Shaka
- Department of Internal Medicine, John H. Stronger Jr. Hospital of Cook County, Chicago, IL, USA
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Jabłońska-Trypuć A, Makuła M, Włodarczyk-Makuła M, Wołejko E, Wydro U, Serra-Majem L, Wiater J. Inanimate Surfaces as a Source of Hospital Infections Caused by Fungi, Bacteria and Viruses with Particular Emphasis on SARS-CoV-2. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2022; 19:8121. [PMID: 35805776 PMCID: PMC9265696 DOI: 10.3390/ijerph19138121] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/09/2022] [Revised: 06/28/2022] [Accepted: 06/30/2022] [Indexed: 02/01/2023]
Abstract
The carriers of nosocomial infections are the hands of medical personnel and inanimate surfaces. Both hands and surfaces may be contaminated as a result of contact with the patient, their body fluids, and touching contaminated surfaces in the patient's surroundings. Visually clean inanimate surfaces are an important source of pathogens. Microorganisms have properties thanks to which they can survive in unfavorable conditions, from a few days to several months. Bacteria, viruses and fungi are able to transmit from inanimate surfaces to the skin of the patient and the medical staff. These pathogens include SARS-CoV-2, which can survive on various types of inanimate surfaces, being a potential source of infection. By following the recommendations related to washing and disinfecting hands and surfaces, and using appropriate washing and disinfecting agents with a broad biocidal spectrum, high material compatibility and the shortest duration of action, we contribute to breaking the chain of nosocomial infections.
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Affiliation(s)
- Agata Jabłońska-Trypuć
- Department of Chemistry, Biology and Biotechnology, Faculty of Civil Engineering and Environmental Sciences, Bialystok University of Technology, Wiejska 45E Street, 15-351 Białystok, Poland; (E.W.); (U.W.)
| | - Marcin Makuła
- Faculty of Medical Sciences in Zabrze, Medical University of Silesia, Traugutta sq.2, 41-800 Zabrze, Poland;
| | - Maria Włodarczyk-Makuła
- Faculty of Infrastructure and Environment, Częstochowa University of Technology, 69 Dabrowskiego Str., 42-201 Częstochowa, Poland;
| | - Elżbieta Wołejko
- Department of Chemistry, Biology and Biotechnology, Faculty of Civil Engineering and Environmental Sciences, Bialystok University of Technology, Wiejska 45E Street, 15-351 Białystok, Poland; (E.W.); (U.W.)
| | - Urszula Wydro
- Department of Chemistry, Biology and Biotechnology, Faculty of Civil Engineering and Environmental Sciences, Bialystok University of Technology, Wiejska 45E Street, 15-351 Białystok, Poland; (E.W.); (U.W.)
| | - Lluis Serra-Majem
- Research Institute of Biomedical and Health Sciences, University of Las Palmas de Gran Canaria, 35001 Las Palmas de Gran Canaria, Spain;
| | - Józefa Wiater
- Department of Agri-Food Engineering and Environmental Management, Faculty of Civil Engineering and Environmental Sciences, Bialystok University of Technology, Wiejska 45E Street, 15-351 Białystok, Poland;
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Wang S, Zhu D, Sun X. Development of an Effective Nontoxigenic Clostridioides difficile-Based Oral Vaccine against C. difficile Infection. Microbiol Spectr 2022; 10:e0026322. [PMID: 35583336 PMCID: PMC9241731 DOI: 10.1128/spectrum.00263-22] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2022] [Accepted: 04/21/2022] [Indexed: 11/20/2022] Open
Abstract
The symptoms of Clostridioides difficile infection (CDI) are largely attributed to two C. difficile toxins, TcdA and TcdB. Significant efforts have been devoted to developing vaccines targeting both toxins through parenteral immunization routes. Recently, we generated a novel chimeric protein (designated Tcd169), comprised of the glucosyltransferase domain (GT), the cysteine protease domain (CPD), and the receptor binding domain (RBD) of TcdB, and the RBD of TcdA. Parenteral immunizations with Tcd169 provide mice effective protection against infection with a ribotype (RT) 027 C. difficile strain. In this study, we expressed Tcd169 in a nontoxigenic C. difficile CCUG37785 strain (designated NTCD), resulting in strain NTCD_Tcd169 to develop an oral vaccine that can target both C. difficile toxins and colonization/adhesion factors. Oral immunizations with NTCD_Tcd169 spores induced systematic and mucosal antibody responses against, not only both toxins, but also C. difficile flagellins (FliC/FliD). Intriguingly yet importantly, anti-Tcd169 sera raised against Tcd169 protein were significantly cross-reactive with FliC/FliD and two surface layer proteins (SlpA and Cwp2). Oral immunizations with NTCD_Tcd169 spores provided mice effective protection against infection with a hypervirulent RT027 C. difficile strain R20291and significantly reduced R20291spore numbers in feces compared with NTCD or PBS immunized mice. These results imply that the genetically modified, nontoxigenic C. difficile strain expressing Tcd169 may represent a novel mucosal vaccine candidate against CDI. IMPORTANCE Clostridioides difficile is an enteric pathogen, and symptoms of C. difficile infection (CDI) are mainly by two exotoxins TcdA and TcdB. Active vaccination is cost-effective approach to prevent CDI and high rates of recurrence. Ideally, vaccines should target both C. difficile toxins and cell/spore colonization. In this study, we expressed immunodominant fragments of TcdA and TcdB (i.e., Tcd169) in a nontoxigenic C. difficile CCUG37785 strain, generating a promising oral/mucosal vaccine candidate against CDI, by targeting both toxins and colonization of pathogenic C. difficile strains. Importantly, anti-Tcd169 sera raised against Tcd169 protein were significantly cross-reactive with FliC/FliD and two surface layer proteins (SlpA and Cwp2), and all of which are involved in C. difficile adhesion/colonization in vitro and in vivo.
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Affiliation(s)
- Shaohui Wang
- Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, Florida, USA
| | - Duolong Zhu
- Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, Florida, USA
| | - Xingmin Sun
- Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, Florida, USA
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Kim N, Lee SY, Park J, Lee J. Comparative Evaluation of Three Immunoassays for the Simultaneous Detection of Clostridioides difficile Glutamate Dehydrogenase and Toxin A/B. Microorganisms 2022; 10:947. [PMID: 35630390 PMCID: PMC9145049 DOI: 10.3390/microorganisms10050947] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2022] [Revised: 04/23/2022] [Accepted: 04/28/2022] [Indexed: 11/20/2022] Open
Abstract
BACKGROUND In the medical laboratory, a step-by-step workflow for Clostridioides difficile infection (CDI) detection using glutamate dehydrogenase (GDH) and toxin A/B assays for initial screening, along with a nucleic acid amplification test (NAAT), has been recommended recently. In this study, we evaluated these three immunoassays for the simultaneous detection of GDH and Clostridioides difficile (CD) toxin A/B. METHODS A total of 304 stool samples were tested for the presence of GDH antigen and CD toxin A/B using VIDAS C. difficile GDH and toxin A/B (CDAB), RIDASCREEN C. difficile GDH and toxin A/B (RIDA), and C. DIFF QUIK CHEK COMPLETE according to the manufacturers' recommendations. As complementary reference methods for GDH and toxin A/B detection in the three immunoassays, CD cultures using ChromID C. difficile agar and the Xpert C. difficile assay, respectively, were tested. RESULTS All three GDH assays showed overall substantial agreement with the CD culture. All three toxin A/B assays showed overall moderate agreement with the Xpert C. difficile assay. In comparison with consensus results, VIDAS GDH and QCC GDH showed almost perfect agreement, whereas RIDA GDH showed inferior but substantial agreement. All three toxin A/B assays showed almost perfect agreement. CONCLUSIONS Since the QCC GDH and toxin A/B assay is relatively more sensitive and specific than the other two immunoassays for discriminating toxigenic or non-toxigenic CDI, QCC is very helpful for the simultaneous identification of GDH and CD toxin A/B in the initial step of the two-round workflow for diagnosing CDI.
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Affiliation(s)
- Namsu Kim
- Department of Laboratory Medicine, Jeonbuk National University Medical School and Hospital, Jeonju 54907, Korea; (N.K.); (S.Y.L.)
- Research Institute of Clinical Medicine of Jeonbuk National University-Biomedical Research Institute of Jeonbuk National University Hospital, Jeonju 54907, Korea
| | - Seung Yeob Lee
- Department of Laboratory Medicine, Jeonbuk National University Medical School and Hospital, Jeonju 54907, Korea; (N.K.); (S.Y.L.)
- Research Institute of Clinical Medicine of Jeonbuk National University-Biomedical Research Institute of Jeonbuk National University Hospital, Jeonju 54907, Korea
| | - Joonhong Park
- Department of Laboratory Medicine, Jeonbuk National University Medical School and Hospital, Jeonju 54907, Korea; (N.K.); (S.Y.L.)
- Research Institute of Clinical Medicine of Jeonbuk National University-Biomedical Research Institute of Jeonbuk National University Hospital, Jeonju 54907, Korea
| | - Jaehyeon Lee
- Department of Laboratory Medicine, Jeonbuk National University Medical School and Hospital, Jeonju 54907, Korea; (N.K.); (S.Y.L.)
- Research Institute of Clinical Medicine of Jeonbuk National University-Biomedical Research Institute of Jeonbuk National University Hospital, Jeonju 54907, Korea
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Human α-Defensin-6 Neutralizes Clostridioides difficile Toxins TcdA and TcdB by Direct Binding. Int J Mol Sci 2022; 23:ijms23094509. [PMID: 35562899 PMCID: PMC9101188 DOI: 10.3390/ijms23094509] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2022] [Revised: 04/14/2022] [Accepted: 04/14/2022] [Indexed: 02/04/2023] Open
Abstract
Rising incidences and mortalities have drawn attention to Clostridioides difficile infections (CDIs) in recent years. The main virulence factors of this bacterium are the exotoxins TcdA and TcdB, which glucosylate Rho-GTPases and thereby inhibit Rho/actin-mediated processes in cells. This results in cell rounding, gut barrier disruption and characteristic clinical symptoms. So far, treatment of CDIs is limited and mainly restricted to some antibiotics, often leading to a vicious circle of antibiotic-induced disease recurrence. Here, we demonstrate the protective effect of the human antimicrobial peptide α-defensin-6 against TcdA, TcdB and the combination of both toxins in vitro and in vivo and unravel the underlying molecular mechanism. The defensin prevented toxin-mediated glucosylation of Rho-GTPases in cells and protected human cells, model epithelial barriers as well as zebrafish embryos from toxic effects. In vitro analyses revealed direct binding to TcdB in an SPR approach and the rapid formation of TcdB/α-defensin-6 complexes, as analyzed with fluorescent TcdB by time-lapse microscopy. In conclusion, the results imply that α-defensin-6 rapidly sequesters the toxin into complexes, which prevents its cytotoxic activity. These findings extend the understanding of how human peptides neutralize bacterial protein toxins and might be a starting point for the development of novel therapeutic options against CDIs.
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Jo J, Gonzales-Luna AJ, Lancaster CK, McPherson JK, Begum K, Jahangir Alam M, Garey KW. Multi-country surveillance of Clostridioides difficile demonstrates high prevalence of spores in non-healthcare environmental settings. Anaerobe 2022; 75:102543. [DOI: 10.1016/j.anaerobe.2022.102543] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2021] [Revised: 01/27/2022] [Accepted: 02/23/2022] [Indexed: 01/05/2023]
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Flock G, Yin HB, Chen CH, Pellissery AJ, Venkitanarayanan K. Survivability of Clostridioides difficile spores in fermented pork summer sausage during refrigerated storage. Vet World 2022; 15:162-167. [PMID: 35369600 PMCID: PMC8924379 DOI: 10.14202/vetworld.2022.162-167] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2021] [Accepted: 12/23/2021] [Indexed: 01/05/2023] Open
Abstract
Background and Aim: Clostridioides difficile is a spore-forming pathogen that causes serious enteric disease in humans. Strains have been isolated from food animals and meat, including pork, which suggest a potential for foodborne transmission. Pork summer sausage is a popular fermented meat product, which is consumed cooked or cooked to a lower internal temperature due to acidification of the product. The effect of acidity and cooking on the viability of C. difficile spores in a fermented meat product has not been determined. Therefore, the aim was to study the survivability of C. difficile spores in fermented pork summer sausage. Materials and Methods: Fermented pork sausages were prepared according to a commercial recipe with or without starter culture and C. difficile spores followed by fermentation at 37°C for ~12 h under 85% relative humidity until pH 5.0 was reached and further processed as cooked (>57°C) or uncooked (≤57°C) and stored at 4°C. C. difficile spores in sausages were enumerated at 1 h following inoculation and on days 0, 1, 7, 14, 21, 30, 60, and 90 of storage. Results: It was observed that C. difficile spore viability in control unfermented treatment was significantly different on day 0 from the fermented, fermented cooked, and control unfermented cooked treatments (p<0.05); however, there was no significant difference among the latter three treatment groups throughout 90 days of storage (p>0.05). On day 90 of storage, the unfermented control sausages yielded ~4.0 log colony-forming unit (CFU)/g of C. difficile spores compared to ~3.5 log CFU/g recovered from fermented samples and the unfermented cooked control samples identifying spore viability in all treatment groups. Conclusion: C. difficile spores were found to survive the acidity and cooking of fermented pork summer sausage and storage at 4°C for 3 months, thereby highlighting the need for effective intervention strategies to reduce the risk of C. difficile contamination in pork products.
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Affiliation(s)
- Genevieve Flock
- Combat Capabilities Development Command Soldier Center, Soldier Sustainment Directorate, Combat Feeding Division, Natick 01760, Massachusetts, United States
| | - Hsin-Bai Yin
- Department of Agriculture, USDA Agricultural Research Service, Beltsville, Maryland 20705, United States
| | - Chi-Hung Chen
- Department of Agriculture, USDA Agricultural Research Service, Beltsville, Maryland 20705, United States
| | - Abraham Joseph Pellissery
- Department of Animal Science, University of Connecticut, College of Agriculture Health and Natural Resources, Mansfield 06269, Connecticut, United States
| | - Kumar Venkitanarayanan
- Department of Animal Science, University of Connecticut, College of Agriculture Health and Natural Resources, Mansfield 06269, Connecticut, United States
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Nibbering B, Gerding DN, Kuijper EJ, Zwittink RD, Smits WK. Host Immune Responses to Clostridioides difficile: Toxins and Beyond. Front Microbiol 2022; 12:804949. [PMID: 34992590 PMCID: PMC8724541 DOI: 10.3389/fmicb.2021.804949] [Citation(s) in RCA: 23] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2021] [Accepted: 11/22/2021] [Indexed: 12/17/2022] Open
Abstract
Clostridioides difficile is often resistant to the actions of antibiotics to treat other bacterial infections and the resulting C. difficile infection (CDI) is among the leading causes of nosocomial infectious diarrhea worldwide. The primary virulence mechanism contributing to CDI is the production of toxins. Treatment failures and recurrence of CDI have urged the medical community to search for novel treatment options. Strains that do not produce toxins, so called non-toxigenic C. difficile, have been known to colonize the colon and protect the host against CDI. In this review, a comprehensive description and comparison of the immune responses to toxigenic C. difficile and non-toxigenic adherence, and colonization factors, here called non-toxin proteins, is provided. This revealed a number of similarities between the host immune responses to toxigenic C. difficile and non-toxin proteins, such as the influx of granulocytes and the type of T-cell response. Differences may reflect genuine variation between the responses to toxigenic or non-toxigenic C. difficile or gaps in the current knowledge with respect to the immune response toward non-toxigenic C. difficile. Toxin-based and non-toxin-based immunization studies have been evaluated to further explore the role of B cells and reveal that plasma cells are important in protection against CDI. Since the success of toxin-based interventions in humans to date is limited, it is vital that future research will focus on the immune responses to non-toxin proteins and in particular non-toxigenic strains.
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Affiliation(s)
- Britt Nibbering
- Center for Microbiome Analyses and Therapeutics, Leiden University Medical Center, Leiden, Netherlands.,Department of Medical Microbiology, Leiden University Medical Center, Leiden, Netherlands
| | - Dale N Gerding
- Department of Veterans Affairs, Research Service, Edward Hines Jr. VA Hospital, Hines, IL, United States
| | - Ed J Kuijper
- Center for Microbiome Analyses and Therapeutics, Leiden University Medical Center, Leiden, Netherlands.,Department of Medical Microbiology, Leiden University Medical Center, Leiden, Netherlands
| | - Romy D Zwittink
- Center for Microbiome Analyses and Therapeutics, Leiden University Medical Center, Leiden, Netherlands.,Department of Medical Microbiology, Leiden University Medical Center, Leiden, Netherlands
| | - Wiep Klaas Smits
- Center for Microbiome Analyses and Therapeutics, Leiden University Medical Center, Leiden, Netherlands.,Department of Medical Microbiology, Leiden University Medical Center, Leiden, Netherlands
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Machine Learning Approaches to Investigate Clostridioides difficile Infection and Outcomes: A Systematic Review. Int J Med Inform 2022; 160:104706. [DOI: 10.1016/j.ijmedinf.2022.104706] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2021] [Revised: 12/21/2021] [Accepted: 01/22/2022] [Indexed: 11/20/2022]
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Zhu D, Wang S, Sun X. FliW and CsrA Govern Flagellin (FliC) Synthesis and Play Pleiotropic Roles in Virulence and Physiology of Clostridioides difficile R20291. Front Microbiol 2021; 12:735616. [PMID: 34675903 PMCID: PMC8523840 DOI: 10.3389/fmicb.2021.735616] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2021] [Accepted: 09/13/2021] [Indexed: 02/04/2023] Open
Abstract
Clostridioides difficile flagellin FliC is associated with toxin gene expression, bacterial colonization, and virulence, and is also involved in pleiotropic gene regulation during in vivo infection. However, how fliC expression is regulated in C. difficile remains unclear. In Bacillus subtilis, flagellin homeostasis and motility are coregulated by flagellar assembly factor (FliW), flagellin Hag (FliC homolog), and Carbon storage regulator A (CsrA), which is referred to as partner-switching mechanism "FliW-CsrA-Hag." In this study, we characterized FliW and CsrA functions by deleting or overexpressing fliW, csrA, and fliW-csrA in C. difficile R20291. We showed that fliW deletion, csrA overexpression in R20291, and csrA complementation in R20291ΔWA (fliW-csrA codeletion mutant) dramatically decreased FliC production, but not fliC gene transcription. Suppression of fliC translation by csrA overexpression can be relieved mostly when fliW was coexpressed, and no significant difference in FliC production was detected when only fliW was complemented in R20291ΔWA. Further, loss of fliW led to increased biofilm formation, cell adhesion, toxin production, and pathogenicity in a mouse model of C. difficile infection (CDI), while fliW-csrA codeletion decreased toxin production and mortality in vivo. Our data suggest that CsrA negatively modulates fliC expression and FliW indirectly affects fliC expression through inhibition of CsrA post-transcriptional regulation. In light of "FliW-CsrA-Hag" switch coregulation mechanism reported in B. subtilis, our data also suggest that "FliW-CsrA-fliC/FliC" can regulate many facets of C. difficile R20291 pathogenicity. These findings further aid us in understanding the virulence regulation in C. difficile.
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Affiliation(s)
| | | | - Xingmin Sun
- Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL, United States
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Elfassy A, Kalina WV, French R, Nguyen H, Tan C, Sebastian S, Wilcox MH, Davies K, Kutzler MA, Jansen KU, Anderson A, Pride MW. Development and clinical validation of an automated cell cytotoxicity neutralization assay for detecting Clostridioides difficile toxins in clinically relevant stools samples. Anaerobe 2021; 71:102415. [PMID: 34298152 DOI: 10.1016/j.anaerobe.2021.102415] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2021] [Revised: 07/14/2021] [Accepted: 07/16/2021] [Indexed: 01/05/2023]
Abstract
OBJECTIVES To improve the diagnostic accuracy of Clostridioides difficile infection, current U.S. and E.U. guidelines recommend multistep testing that detects the presence of C. difficile and toxin in clinically relevant stool samples to confirm active disease. An accepted gold standard to detect C. difficile toxins is the cell cytotoxicity neutralization assay (CCNA). Although highly sensitive, the traditional CCNA has limitations. One such limitation is the subjective interpretation of an analyst to recognize cytopathic effects in cultured cells exposed to a fecal sample containing toxin. To overcome this limitation, an automated CCNA was developed that replaces most human pipetting steps with robotics and incorporates CellTiterGlo® for a semi-quantitative, non-subjective measure of cell viability instead of microscopy. METHODS To determine sample positivity and control for non-specific cytopathic effects, two thresholds were defined and validated by evaluating the sample with/without antitoxin antisera (sample-antitoxin/sample + antitoxin): 1) a >70% cell viability threshold was validated with samples containing anti-toxin, and 2) a >1.2-fold difference cut-off where sample results above the cut-off are considered positive. RESULTS Assay validation demonstrated excellent accuracy, precision, and sample linearity with an LOD of 126.9 pg/mL toxin-B in stool. The positivity cut-offs were clinically validated by comparing 322 diarrheal stool sample results with those run in a predicate, microscopic readout-based CCNA. The automated CCNA demonstrated 96% sensitivity and 100% specificity compared with the predicate CCNA. CONCLUSIONS Overall, the automated CCNA provides a specific, sensitive, and reproducible tool to support determination of CDI epidemiology or the efficacy of interventions such as vaccines.
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Affiliation(s)
- Arik Elfassy
- Pfizer Vaccines Research and Development, Pearl River, NY, USA; Current Affiliation: Elusys Therapeutics, Parsippany, NJ, USA
| | - Warren V Kalina
- Pfizer Vaccines Research and Development, Pearl River, NY, USA
| | - Roger French
- Pfizer Vaccines Research and Development, Pearl River, NY, USA
| | - Ha Nguyen
- Pfizer Vaccines Research and Development, Pearl River, NY, USA
| | - Charles Tan
- Pfizer Vaccines Research and Development, Pearl River, NY, USA
| | - Shite Sebastian
- Pfizer Vaccines Research and Development, Pearl River, NY, USA; Current Affiliation: Affinivax, Lexington, MA, USA
| | - Mark H Wilcox
- Leeds Teaching Hospitals NHS Trust and University of Leeds, Leeds, United Kingdom
| | - Kerrie Davies
- Leeds Teaching Hospitals NHS Trust and University of Leeds, Leeds, United Kingdom
| | | | | | | | - Michael W Pride
- Pfizer Vaccines Research and Development, Pearl River, NY, USA.
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Clostridioides difficile Infection in Patients with Chronic Kidney Disease: A Systematic Review. BIOMED RESEARCH INTERNATIONAL 2021; 2021:5466656. [PMID: 34557546 PMCID: PMC8455215 DOI: 10.1155/2021/5466656] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/18/2021] [Accepted: 08/24/2021] [Indexed: 11/17/2022]
Abstract
Clostridioides difficile infection (CDI) is a health issue of utmost significance in Europe and North America, due to its high prevalence, morbidity, and mortality rate. The clinical spectrum of CDI is broad, ranging from asymptomatic to deadly fulminant colitis. When associated with chronic kidney disease (CKD), CDI is more prevalent and more severe than in the general population, due to specific risk factors such as impaired immune system, intestinal dysmotility, high antibiotic use leading to disturbed microbiota, frequent hospitalization, and PPI use. We performed a systematic review on the issue of prevention and treatment of CDI in the CKD population, analysing the suitable randomized controlled cohort studies published between 2000 and 2021. The results show that the most important aspect of prevention is isolation and disinfection with chlorine-based solution and hydrogen peroxide vapour to stop the spread of bacteria. In terms of prevention, using Lactobacillus plantarum (LP299v) proved to be more efficient than disinfection measures in transplant patients, leading to higher cure rates and less recurrent episodes of CDI. Treatment with oral fidaxomycin is more effective than with oral vancomycin for the initial episode of CDI in CKD patients. Faecal microbiota transplantation (FMT) is more effective than vancomycin in recurrent CDI in CKD patients. More large-sample RCTs are necessary to conclude on the best treatment and prevention strategy of CDI in CKD patients.
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Zhu D, Patabendige HMLW, Tomlinson BR, Wang S, Hussain S, Flores D, He Y, Shaw LN, Sun X. Cwl0971, a novel peptidoglycan hydrolase, plays pleiotropic roles in Clostridioides difficile R20291. Environ Microbiol 2021; 23:5222-5238. [PMID: 33893759 PMCID: PMC11217927 DOI: 10.1111/1462-2920.15529] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2020] [Accepted: 04/12/2021] [Indexed: 02/04/2023]
Abstract
Clostridioides difficile is a Gram-positive, spore-forming, toxin-producing anaerobe that can cause nosocomial antibiotic-associated intestinal disease. Although the production of toxin A (TcdA) and toxin B (TcdB) contribute to the main pathogenesis of C. difficile, the mechanism of TcdA and TcdB release from cell remains unclear. In this study, we identified and characterized a new cell wall hydrolase Cwl0971 (CDR20291_0971) from C. difficile R20291, which is involved in bacterial autolysis. The gene 0971 deletion mutant (R20291Δ0971) generated with CRISPR-AsCpfI exhibited significantly delayed cell autolysis and increased cell viability compared to R20291, and the purified Cwl0971 exhibited hydrolase activity for Bacillus subtilis cell wall. Meanwhile, 0971 gene deletion impaired TcdA and TcdB release due to the decreased cell autolysis in the stationary/late phase of cell growth. Moreover, sporulation of the mutant strain decreased significantly compared to the wild type strain. In vivo, the defect of Cwl0971 decreased fitness over the parent strain in a mouse infection model. Collectively, Cwl0971 is involved in cell wall lysis and cell viability, which affects toxin release, sporulation, germination, and pathogenicity of R20291, indicating that Cwl0971 could be an attractive target for C. difficile infection therapeutics and prophylactics.
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Affiliation(s)
- Duolong Zhu
- Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, Florida
| | | | - Brooke Rene Tomlinson
- Department of Cell Biology, Microbiology and Molecular Biology, University of South Florida, Tampa, Florida
| | - Shaohui Wang
- Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, Florida
| | - Syed Hussain
- Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, Florida
| | - Domenica Flores
- Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, Florida
| | - Yongqun He
- Department of Microbiology and Immunology, and Center for Computational Medicine and Bioinformatics, Unit for Laboratory Animal Medicine, University of Michigan Medical School, Ann Arbor, Michigan
| | - Lindsey N. Shaw
- Department of Cell Biology, Microbiology and Molecular Biology, University of South Florida, Tampa, Florida
| | - Xingmin Sun
- Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, Florida
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Cardiolipin-Containing Lipid Membranes Attract the Bacterial Cell Division Protein DivIVA. Int J Mol Sci 2021; 22:ijms22158350. [PMID: 34361115 PMCID: PMC8348161 DOI: 10.3390/ijms22158350] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2021] [Revised: 07/28/2021] [Accepted: 08/01/2021] [Indexed: 02/04/2023] Open
Abstract
DivIVA is a protein initially identified as a spatial regulator of cell division in the model organism Bacillus subtilis, but its homologues are present in many other Gram-positive bacteria, including Clostridia species. Besides its role as topological regulator of the Min system during bacterial cell division, DivIVA is involved in chromosome segregation during sporulation, genetic competence, and cell wall synthesis. DivIVA localizes to regions of high membrane curvature, such as the cell poles and cell division site, where it recruits distinct binding partners. Previously, it was suggested that negative curvature sensing is the main mechanism by which DivIVA binds to these specific regions. Here, we show that Clostridioides difficile DivIVA binds preferably to membranes containing negatively charged phospholipids, especially cardiolipin. Strikingly, we observed that upon binding, DivIVA modifies the lipid distribution and induces changes to lipid bilayers containing cardiolipin. Our observations indicate that DivIVA might play a more complex and so far unknown active role during the formation of the cell division septal membrane.
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Noori M, Ghalavand Z, Azimirad M, Yadegar A, Eslami G, Krutova M, Brajerova M, Goudarzi M, Zali MR. Genetic diversity and phylogenetic analysis of the surface layer protein A gene (slpA) among Clostridioides difficile clinical isolates from Tehran, Iran. Anaerobe 2021; 70:102403. [PMID: 34111549 DOI: 10.1016/j.anaerobe.2021.102403] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2020] [Revised: 05/24/2021] [Accepted: 06/04/2021] [Indexed: 12/15/2022]
Abstract
Clostridioides difficile is the most common causative agent of healthcare-associated diarrhea. C. difficile strains produce a crystalline surface layer protein (SlpA), encoded by the slpA gene. Previous studies have shown that SlpA varies among C. difficile strains. In this study, we used the SlpA sequence-based typing system (SlpAST) for the molecular genotyping of C. difficile clinical isolates identified in Iran; the PCR ribotypes (RTs) and toxin profiles of the isolates were also characterized. Forty-eight C. difficile isolates were obtained from diarrheal patients, and characterized by capillary electrophoresis (CE) PCR ribotyping and the detection of toxin genes. In addition, the genetic diversity of the slpA gene was investigated by Sanger sequencing. The most common RTs were RT126 (20.8%), followed by RT001 (12.5%) and RT084 (10.4%). The intact PaLoc arrangement representing cdu2+/tcdR+/tcdB+/tcdE+/tcdA+/tcdC+/cdd3+ profile was the predominant pattern and cdtA and cdtB genes were found in one-third of the isolates. Using the SlpA genotyping, 12 main genotypes and 16 subtypes were identified. The SlpA type 078-1 was the most prevalent genotype (20.8%), and identified within the isolates of RT126. The yok-1, gr-1, cr-1 and kr-3 genotypes were detected in 14.5%, 12.5%, 12.5% and 8.3% of isolates, respectively. Almost all the isolates with the same RT were clustered in similar SlpA sequence types. In comparison to PCR ribotyping, SlpAST, as a simple and highly reproducible sequenced-based technique, can discriminate well between C. difficile isolates. This typing method appears to be a valuable tool for the epidemiological study of C. difficile isolates worldwide.
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Affiliation(s)
- Maryam Noori
- Department of Microbiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Zohreh Ghalavand
- Department of Microbiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Masoumeh Azimirad
- Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Abbas Yadegar
- Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
| | - Gita Eslami
- Department of Microbiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
| | - Marcela Krutova
- Department of Medical Microbiology, Charles University, 2nd Faculty of Medicine and Motol University Hospital, Prague, Czech Republic
| | - Marie Brajerova
- Department of Medical Microbiology, Charles University, 2nd Faculty of Medicine and Motol University Hospital, Prague, Czech Republic
| | - Mehdi Goudarzi
- Department of Microbiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mohammad Reza Zali
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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AlJindan R, AlEraky DM, Borgio JF, AbdulAzeez S, Abdalhamid B, Mahmoud N, Farhat M. Diagnostic deficiencies of C. difficile infection among patients in a tertiary hospital in Saudi Arabia: A laboratory-based case series. Saudi J Biol Sci 2021; 28:4472-4477. [PMID: 34354432 PMCID: PMC8324924 DOI: 10.1016/j.sjbs.2021.04.044] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2021] [Revised: 04/16/2021] [Accepted: 04/17/2021] [Indexed: 12/19/2022] Open
Abstract
Clostridioides difficile infection (CDI) has become a threatening public health problem in the developed world. In the kingdom of Saudi Arabia, prevalence of CDI is still unknown due to limited surveillance protocols and diagnostic resources. We used a two-step procedure to study and confirm C. difficile cases. We also studied toxin profiles of these isolates. Stool samples were collected from symptomatic patients and clinically suspected of CDI for almost 12 months. Isolates were confirmed by culture method followed by 16S rRNA sequencing. Multiplex PCR was performed for the identification of toxin A, toxin B and binary toxin genes and compared to Gene Expert results. Out of the 47 collected samples, 27 were successfully grown on culture media. 18 samples were confirmed as C. difficile by both culture and 16S rRNA sequencing. Interestingly, the rest of the isolates (9 species) belonged to different genera. Our results showed 95% of samples were positive for both toxin A and B (tcdA, tcdB) and all samples exhibited the toxin gene regulator tcdC. All samples were confirmed negative for the binary toxin gene ctdB and 11% of the isolates were positive for ctdA gene. Interestingly, one isolate harbored the binary toxin gene (cdtA +) and tested negative for both toxins A and B. We believe that combining the standard culture method with molecular techniques can make the detection of C. difficile more accurate.
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Affiliation(s)
- Reem AlJindan
- Department of Microbiology, College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia
| | - Doaa M AlEraky
- Department of Biomedical Dental Science, Microbiology and Immunology Division, Collage of Dentistry, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia
| | - J. Francis Borgio
- Department of Genetic Research, Institute for Research and Medical Consultations (IRMC), Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia
- Department of Epidemic Diseases Research, Institute for Research and Medical Consultations (IRMC), Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia
| | - Sayed AbdulAzeez
- Department of Genetic Research, Institute for Research and Medical Consultations (IRMC), Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia
| | - Baha Abdalhamid
- Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, Nebraska, USA
| | - Nehal Mahmoud
- Department of Microbiology, College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia
| | - Maha Farhat
- Department of Biochemistry, College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia
- Corresponding author.
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Potent Acid Suppression With Vonoprazan vs Proton Pump Inhibitors Does Not Have Higher Association With Clostridioides difficile Infection. Am J Gastroenterol 2021; 116:1632-1637. [PMID: 33989224 DOI: 10.14309/ajg.0000000000001309] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/19/2020] [Accepted: 04/12/2021] [Indexed: 12/11/2022]
Abstract
INTRODUCTION Proton pump inhibitors (PPIs) are associated with the onset of Clostridioides difficile infection (CDI). Although a new potassium-competitive acid blocker, vonoprazan, consistently shows a more potent acid inhibitory effect in comparison to PPIs, the risk of CDI in vonoprazan-treated patients relative to those treated with PPIs is unknown. In this retrospective case-control study, using a nationwide hospital-based administrative database in Japan, we investigated the association of the onset of CDI in patients treated with vonoprazan. METHODS A CDI case was defined as a case in which a patient was diagnosed and treated for CDI. For each CDI case, 3 non-CDI patients were extracted as controls. Information on the usage of acid suppressants in the 2 months before the onset of CDI and other confounding factors was collected. Relative associations of gastric acid suppressants with the onset of CDI were estimated. RESULTS A total of 4,466 CDI cases and 13,220 of non-CDI controls were extracted. A multivariate conditional regression analysis revealed that PPI or vonoprazan use was modestly, but significantly associated with CDI (odds ratio [95% confidence interval]: PPI, 1.3 [1.2-1.4]; vonoprazan, 1.4 [1.2-1.7]). With PPI users as a reference, vonoprazan did not show a stronger association with CDI (odds ratio [95% confidence interval]: 1.07 [0.91-1.26]). DISCUSSION We found a significant positive association between vonoprazan use and CDI; however, the magnitude of the association was not beyond that in PPI users. This is the first report on any potential adverse effects of vonoprazan.
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Jiang Y, Sarpong EM, Sears P, Obi EN. Budget Impact Analysis of Fidaxomicin Versus Vancomycin for the Treatment of Clostridioides difficile Infection in the United States. Infect Dis Ther 2021; 11:111-126. [PMID: 34292496 DOI: 10.1007/s40121-021-00480-0] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2020] [Accepted: 06/10/2021] [Indexed: 11/30/2022] Open
Abstract
INTRODUCTION Fidaxomicin is as effective as vancomycin in treating Clostridioides difficile infection (CDI) but more effective at preventing recurrence. However, because fidaxomicin is more costly than vancomycin, its overall value in managing CDI is not well understood. This study assessed the budget impact of introducing fidaxomicin versus vancomycin for the treatment of adults with CDI from a hospital perspective in the US. METHODS A cohort-based decision analytic model was developed over a 1-year horizon. A hospital with 10,000 annual hospitalizations was simulated. The model considered two adult populations: patients with no prior CDI episode and patients with one prior CDI episode. Two scenarios were assessed per population: 15% fidaxomicin/85% vancomycin use and 100% vancomycin use. Model inputs were obtained from published sources and expert opinion. Model outcomes included cost, payment, and revenue at the hospital level, per treated CDI patient, and per admitted patient. Budget impact was calculated as the difference in revenue between scenarios. One-way sensitivity analyses tested the effects of varying model inputs on the budget impact. RESULTS In patients with no prior CDI episode, treatment with fidaxomicin resulted in potential savings over 1 year of $1105 at the hospital level, $14 per treated CDI patient, and $0.11 per admitted patient. In patients with one prior CDI episode, fidaxomicin use was associated with potential savings over 1 year of $1150 at the hospital level, $74 per treated CDI patient, and $0.12 per admitted patient. Savings were driven by a reduced rate of CDI recurrence with fidaxomicin treatment and uptake of fidaxomicin. Sensitivity analyses indicated savings when inputs were varied in most scenarios. CONCLUSION Budgetary savings can be achieved with fidaxomicin due to reduced CDI recurrence as a result of a superior sustained clinical response. Our results support considering the broader benefits of fidaxomicin, beyond its cost, when making formulary inclusion decisions.
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Affiliation(s)
- Yiling Jiang
- Merck Sharp & Dohme (UK) Ltd., 120 Moorgate, London, EC2Y 9AL, UK.
| | - Eric M Sarpong
- Merck & Co., Inc., 200 Galloping Hill Road, Kenilworth, NJ, 07033, USA
| | - Pamela Sears
- Merck & Co., Inc., 200 Galloping Hill Road, Kenilworth, NJ, 07033, USA
| | - Engels N Obi
- Merck & Co., Inc., 200 Galloping Hill Road, Kenilworth, NJ, 07033, USA
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Costs Associated with the Treatment of Clostridioides Difficile Infections. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2021; 18:ijerph18147647. [PMID: 34300098 PMCID: PMC8307892 DOI: 10.3390/ijerph18147647] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/28/2021] [Revised: 07/14/2021] [Accepted: 07/17/2021] [Indexed: 12/25/2022]
Abstract
Background: Clostridioides difficile, as the main cause of infectious diarrhoea in hospitalised patients, is a considerable challenge for medical personnel (hospital environment) who have direct contact with the patient, as well as being of interest to public health specialists. Financial issues related to the occurrence of the above-mentioned micro-organism are being increasingly raised. Due to the scale of the phenomenon, we are beginning to pay attention to the significant system costs caused by the diagnosis and treatment of CDI infection and its complications. Studies indicate that the nosocomial infection of C. difficile complicates hospitalisation, by increasing the cost by more than half and extending patient’s stay by an average of 3.6 days. Material and methods: The aim of this study was to attempt to calculate the estimated costs associated with the prolonged hospitalisation of patients with nosocomial CDI infection, using the example of a hospital in Lodz. A total of 53 completed hospitalisations of patients treated in the period of January–August 2018 were analysed, during which hospital Clostridioides difficile infection was identified. For the purposes of this study, statistical data collected in the hospital’s IT system were also analysed, covering 44,868 hospitalisations in the Jan–Aug 2018 period, during which no hospital infection occurred. They was a control group, in which the analysed cases were compared. The obtained data in the study determined how long each patient with Clostridioides difficile infection stayed in the hospital (from the moment infection was diagnosed until the day of hospital discharge), and which diagnosis related groups (DRG) (according to National Health Fund guidelines) were assigned. The average length of patient stay without infection within a given DRG group in each hospital ward was also determined. The collected materials became the initial point for the final analysis of hospital costs and the length of hospital stay caused by Clostridioides difficile infection. Results: Clostridioides difficile infection extended the hospital stay by an average of almost 12 days. The average cost of prolonged hospitalisation due to CDI infection (according to the average cost per person-day) was about PLN 7148 (1664 EUR), which gave a total value of about PLN 378,860.6 (88,240.5 EUR) in the examined period. At the same time, the average expenditure from the National Health Fund for hospitalisation due to CDI infections increased by about PLN 6627 (1542.8 EUR), which in the analysed period translated into over PLN 351,232.0 (81,505.5 EUR) (according to settlements with the National Health Fund). The outcome indicates that there is a clear relation between CDI and the anticipated length of hospitalisation of patients without an infection.
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McSharry S, Koolman L, Whyte P, Bolton D. Investigation of the Effectiveness of Disinfectants Used in Meat-Processing Facilities to Control Clostridium sporogenes and Clostridioides difficile Spores. Foods 2021; 10:foods10061436. [PMID: 34205779 PMCID: PMC8234884 DOI: 10.3390/foods10061436] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2021] [Revised: 05/28/2021] [Accepted: 06/17/2021] [Indexed: 11/26/2022] Open
Abstract
Spore-forming bacteria are a major concern for the food industry as they cause both spoilage and food safety issues. Moreover, as they are more resistant than vegetative cells, their removal from the food processing environment may be difficult to achieve. This study investigated the efficacy of the ten most commonly used disinfectant agents (assigned 1–10), used at the recommended concentrations in the meat industry, for their ability to eliminate Clostridium sporogenes and Clostridioides difficile spores. Test-tube based suspension assays suggested that disinfectants 2 (10% v/v preparation of a mixture of hydrogen peroxide (10–30%), acetic acid (1–10%) and peracetic acid (1–10%)), 7 (4% w/v preparation of a mixture of peroxymonosulphate (30–50%), sulphamic acid (1–10%) and troclosene sodium (1–10%)) and 10 (2% v/v preparation of a mixture of glutaraldehyde (10–30%), benzalkonium chloride (1–10%)) were the most effective formulations. D-values for these ranged from 2.1 to 8.4 min at 20 °C for the target spores. Based on these findings, it is recommended that these disinfectants are used to control Clostridium spores in the meat plant environment.
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Affiliation(s)
- Siobhán McSharry
- Teagasc Food Research Centre, Ashtown, 15 Dublin, Ireland; (S.M.); (L.K.)
- School of Veterinary Medicine, University College Dublin, Belfield, 4 Dublin, Ireland;
| | - Leonard Koolman
- Teagasc Food Research Centre, Ashtown, 15 Dublin, Ireland; (S.M.); (L.K.)
| | - Paul Whyte
- School of Veterinary Medicine, University College Dublin, Belfield, 4 Dublin, Ireland;
| | - Declan Bolton
- Teagasc Food Research Centre, Ashtown, 15 Dublin, Ireland; (S.M.); (L.K.)
- Correspondence: ; Tel.: +353-0-1-805-9539
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