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Xia J, Liu T, Wan R, Zhang J, Fu Q. Global burden and trends of the Clostridioides difficile infection-associated diseases from 1990 to 2021: an observational trend study. Ann Med 2025; 57:2451762. [PMID: 39847395 PMCID: PMC11758798 DOI: 10.1080/07853890.2025.2451762] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/17/2024] [Revised: 09/09/2024] [Accepted: 12/09/2024] [Indexed: 01/24/2025] Open
Abstract
BACKGROUND This study was aimed to explore the global burden and trends of Clostridioides difficile infections (CDI) associated diseases. METHODS Data for this study were obtained from the Global Burden of Disease Study 2021. The burden of CDI was assessed using the age-standardized rates of disability-adjusted life years (ASR-DALYs) and deaths (ASDRs). Trends in the burden of CDI were presented using average annual percentage changes (AAPCs). RESULTS The ASR-DALYs for CDI increased from 1.83 (95% UI: 1.53-2.18) per 100,000 in 1990 to 3.46 (95% UI: 3.04-3.96) per 100,000 in 2021, with an AAPC of 2.03% (95% CI: 1.67-2.4%). The ASDRs for CDI rose from 0.10 (95% UI: 0.08-0.11) per 100,000 in 1990 to 0.19 (95% UI: 0.16-0.23) per 100,000 in 2021, with an AAPC of 2.26% (95% CI: 1.74-2.79%). In 2021, higher burdens of ASR-DALYs (10.7 per 100,000) and ASDRs (0.53 per 100,000) were observed in high socio-demographic index (SDI) areas, and among age group over 70 years (31.62/100,000 for ASR-DALYs and 2.45/100,000 for ASDRs). During the COVID-19 pandemic, the global ASR-DALYs and ASDRs slightly decreased. However, in regions with low SDI, low-middle and middle SDI, those rates slightly increased. CONCLUSION The global burden of CDI has significantly increased, particularly in regions with high SDI and among individuals aged 70 years and above. During the COVID-19 pandemic period from 2020 to 2021, the burden of CDI further increased in regions with low, low-middle, and middle SDI. These findings underscore the need for increased attention and intervention, especially in specific countries and populations.
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Affiliation(s)
- Jun Xia
- Department of Neurocritical Care, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei, China
| | - Tan Liu
- Department of Critical Care Medicine, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei, China
| | - Rui Wan
- Department of Critical Care Medicine, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei, China
| | - Jing Zhang
- Department of Neurocritical Care, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei, China
| | - Quanzhu Fu
- Department of Critical Care Medicine, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei, China
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Dobreva E, Donchev D, Stoikov I, Teneva D, Hristova R, Murdjeva M, Vatcheva-Dobrevska R, Ivanov IN. Whole genome sequencing characterization of Clostridioides difficile from Bulgaria during the COVID-19 pandemic. Diagn Microbiol Infect Dis 2025; 111:116703. [PMID: 39862551 DOI: 10.1016/j.diagmicrobio.2025.116703] [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: 08/01/2024] [Revised: 01/14/2025] [Accepted: 01/17/2025] [Indexed: 01/27/2025]
Abstract
Increased incidence of Clostridioides difficile infections were documented in Bulgarian hospitals during COVID-19. WGS was performed on 39 isolates from seven hospitals during 2015-2022. Antimicrobial resistance and toxin genes were inferred from genomes. MLST profiles, cgMLST, and wgMLST phylogeny analyses were performed. Isolates were grouped into eight MLST types as predominant were ST3 (46.15%) and ST1/RT027 (33.33%). ST3 was detected in a single hospital (16/18) and characterized by two toxin variants: tcdA+/tcdB+ (14) and tcdA-/tcdB+ (4). Twelve ST3 strains belonged to the country-specific cgMLST HC2_6485 cluster and ten were identified as a putative outbreak in the infectious disease ward. All the ST1/RT027 isolates were distributed in six hospitals and clustered in an HC2_4711 with strains from neighbouring countries. All C. difficile were susceptible to vancomycin despite the Thr349Ile mutation in vanS in three isolates. We report the first insights into the C. difficile genotype hospital prevalence during the pandemic.
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Affiliation(s)
- Elina Dobreva
- National Reference Laboratory of Control and Monitoring of Antibiotic Resistance (NRL-CMAR), Department Microbiology, National Center of Infectious and Parasitic Diseases (NCIPD), 26 Yanko Sakazov Blvd., Sofia, Bulgaria.
| | - Deyan Donchev
- National Reference Laboratory of Control and Monitoring of Antibiotic Resistance (NRL-CMAR), Department Microbiology, National Center of Infectious and Parasitic Diseases (NCIPD), 26 Yanko Sakazov Blvd., Sofia, Bulgaria
| | - Ivan Stoikov
- National Reference Laboratory of Control and Monitoring of Antibiotic Resistance (NRL-CMAR), Department Microbiology, National Center of Infectious and Parasitic Diseases (NCIPD), 26 Yanko Sakazov Blvd., Sofia, Bulgaria
| | - Deana Teneva
- National Reference Laboratory of Control and Monitoring of Antibiotic Resistance (NRL-CMAR), Department Microbiology, National Center of Infectious and Parasitic Diseases (NCIPD), 26 Yanko Sakazov Blvd., Sofia, Bulgaria
| | - Rumyana Hristova
- National Reference Laboratory of Control and Monitoring of Antibiotic Resistance (NRL-CMAR), Department Microbiology, National Center of Infectious and Parasitic Diseases (NCIPD), 26 Yanko Sakazov Blvd., Sofia, Bulgaria
| | - Marianna Murdjeva
- Laboratory of Microbiology with activities of a Regional tuberculosis laboratory; Hospital for Active Treatment "Sveti Georgi" EAD, 15А Vasil Aprilov Blvd., Plovdiv, Bulgaria
| | - Rossitza Vatcheva-Dobrevska
- Laboratory of Microbiology and Virology, Hospital for Active Treatment "Tsaritsa Yoanna- ISUL", 8 Byalo more Str., Sofia, Bulgaria
| | - Ivan N Ivanov
- National Reference Laboratory of Control and Monitoring of Antibiotic Resistance (NRL-CMAR), Department Microbiology, National Center of Infectious and Parasitic Diseases (NCIPD), 26 Yanko Sakazov Blvd., Sofia, Bulgaria
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Magnusson C, Ölfvingsson E, Hjortswang H, Östholm Å, Serrander L. Improved health-related quality of life in patients with recurrent Clostridioides difficile infection after treatment with faecal microbiota transplantation. Infect Dis (Lond) 2025; 57:239-246. [PMID: 39460926 DOI: 10.1080/23744235.2024.2415694] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/28/2024] [Revised: 08/26/2024] [Accepted: 10/08/2024] [Indexed: 10/28/2024] Open
Abstract
BACKGROUND Clostridioides difficile is a major burden for both healthcare systems and the patients. Faecal microbiota transplantation (FMT) is becoming more common as a treatment since it reduces the risk of recurrent Clostridioides difficile infection (rCDI). OBJECTIVES To evaluate how treatment with FMT is affecting the health-related quality of life (HRQoL) in patients with rCDI. METHODS A prospective observational cohort study was conducted where patients who were offered FMT as a treatment for rCDI were asked to fill in a questionnaire based on the Short Health Scale (SHS) and EuroQol 5-Dimensions 5-Levels (EQ-5D-5L) about their HRQoL before and after treatment. RESULTS Patients with rCDI had poor HRQoL, which improved following FMT. CONCLUSIONS Since FMT cures, reduces the risk of new recurrences of CDI and improves the HRQoL of the patients, it should be offered as a treatment for patients with rCDI. Also, SHS is a useful and reliable instrument for measuring HRQoL in patients with rCDI.
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Affiliation(s)
- Cecilia Magnusson
- Department of Infectious Diseases, Region Jönköping County, Jönköping, and Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden
| | - Elis Ölfvingsson
- Department of Infectious Diseases, Linköping University Hospital, Linköping, and Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden
| | - Henrik Hjortswang
- Department of Gastroenterology and Hepatology, Linköping and Department of Health, Medicine and Caring Sciences, Linköping University, Linköping, Sweden
| | - Åse Östholm
- Department of Infectious Diseases, Linköping University Hospital, Linköping, and Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden
| | - Lena Serrander
- Department of Clinical Microbiology, and Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden
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Liu DA, Chen S, Hu R, Qiu Y, Chen K, Xu Y, Yuan J, Zhang X, Li X. Advances in diagnostic assays for Clostridioides difficile infection in adults. Front Cell Infect Microbiol 2024; 14:1492511. [PMID: 39720791 PMCID: PMC11666450 DOI: 10.3389/fcimb.2024.1492511] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2024] [Accepted: 11/13/2024] [Indexed: 12/26/2024] Open
Abstract
Clostridioides difficile (C. difficile) was a gram-positive anaerobic bacterium in the gut, exhibiting clinical manifestations ranging from mild diarrhoea to fatal pseudomembranous colitis. C. difficile infection (CDI) remains a serious public health problem and accounted for an estimated 360,075 cases in the United States in 2021. It has attracted the utmost attention of the world health organization (WHO). Since publication of a review of the diagnosis of CDI in adults, new clinical diagnostic assays have become available and clinical practice guidelines were updated. This paper presents a comprehensive review of contemporary laboratory diagnostic approaches for CDI in adult patients, with a focus on the utilisation and potential advancements of five sophisticated methodologies, CRISPR in conjunction with nucleic acid amplification tests (NAATs), gene sequencing technology, ultra-high performance liquid chromatography-mass spectrometry, Raman spectroscopy, and real-time cell analysis (RTCA). It can provide new perspectives and ideas for the early diagnosis of CDI in clinical settings.
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Affiliation(s)
- Dong-ang Liu
- Key Laboratory of Pollution Exposure and Health Intervention of Zhejiang Province, Shulan International Medical College, Zhejiang Shuren University, Hangzhou, China
- Key Laboratory of Artificial Organs and Computational Medicine in Zhejiang Province, Shulan International Medical College, Zhejiang Shuren University, Hangzhou, China
| | - Shiyu Chen
- Key Laboratory of Pollution Exposure and Health Intervention of Zhejiang Province, Shulan International Medical College, Zhejiang Shuren University, Hangzhou, China
- Key Laboratory of Artificial Organs and Computational Medicine in Zhejiang Province, Shulan International Medical College, Zhejiang Shuren University, Hangzhou, China
| | - Ruiyao Hu
- Key Laboratory of Pollution Exposure and Health Intervention of Zhejiang Province, Shulan International Medical College, Zhejiang Shuren University, Hangzhou, China
- Key Laboratory of Artificial Organs and Computational Medicine in Zhejiang Province, Shulan International Medical College, Zhejiang Shuren University, Hangzhou, China
| | - Yuting Qiu
- Key Laboratory of Pollution Exposure and Health Intervention of Zhejiang Province, Shulan International Medical College, Zhejiang Shuren University, Hangzhou, China
- Key Laboratory of Artificial Organs and Computational Medicine in Zhejiang Province, Shulan International Medical College, Zhejiang Shuren University, Hangzhou, China
| | - Keyi Chen
- Key Laboratory of Pollution Exposure and Health Intervention of Zhejiang Province, Shulan International Medical College, Zhejiang Shuren University, Hangzhou, China
- Key Laboratory of Artificial Organs and Computational Medicine in Zhejiang Province, Shulan International Medical College, Zhejiang Shuren University, Hangzhou, China
| | - Yue Xu
- Key Laboratory of Pollution Exposure and Health Intervention of Zhejiang Province, Shulan International Medical College, Zhejiang Shuren University, Hangzhou, China
- Key Laboratory of Artificial Organs and Computational Medicine in Zhejiang Province, Shulan International Medical College, Zhejiang Shuren University, Hangzhou, China
| | - Jinghua Yuan
- Key Laboratory of Pollution Exposure and Health Intervention of Zhejiang Province, Shulan International Medical College, Zhejiang Shuren University, Hangzhou, China
- Key Laboratory of Artificial Organs and Computational Medicine in Zhejiang Province, Shulan International Medical College, Zhejiang Shuren University, Hangzhou, China
| | - Xinling Zhang
- Key Laboratory of Pollution Exposure and Health Intervention of Zhejiang Province, Shulan International Medical College, Zhejiang Shuren University, Hangzhou, China
- Key Laboratory of Artificial Organs and Computational Medicine in Zhejiang Province, Shulan International Medical College, Zhejiang Shuren University, Hangzhou, China
| | - Xiaoping Li
- Key Laboratory of Pollution Exposure and Health Intervention of Zhejiang Province, Shulan International Medical College, Zhejiang Shuren University, Hangzhou, China
- Key Laboratory of Artificial Organs and Computational Medicine in Zhejiang Province, Shulan International Medical College, Zhejiang Shuren University, Hangzhou, China
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Miyazaki T, Aoki K, Maeda T, Komori K, Yoshizawa S, Ishii Y, Urita Y, Tateda K. A molecular epidemiological and transmission analysis of Clostridioides difficile using draft whole-genome sequencing in a single hospital. BMC Infect Dis 2024; 24:989. [PMID: 39289598 PMCID: PMC11406711 DOI: 10.1186/s12879-024-09841-9] [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: 04/22/2024] [Accepted: 08/29/2024] [Indexed: 09/19/2024] Open
Abstract
BACKGROUND The nosocomial transmission of toxin-producing Clostridioides difficile is a significant concern in infection control. C. difficile, which resides in human intestines, poses a risk of transmission, especially when patients are in close contact with medical staff. METHODS To investigate the nosocomial transmission of C. difficile in a single center, we analyzed the genetic relationships of the bacteria. This was done using draft whole-genome sequencing (WGS) and examining single nucleotide polymorphisms (SNPs) in core-genome, alongside data regarding the patient's hospital wards and room changes. Our retrospective analysis covered 38 strains, each isolated from a different patient, between April 2014 and January 2015. RESULTS We identified 38 strains that were divided into 11 sequence types (STs). ST81 was the most prevalent (n = 11), followed by ST183 (n = 10) and ST17 (n = 7). A cluster of strains that indicated suspected nosocomial transmission (SNT) was identified through SNP analysis. The draft WGS identified five clusters, with 16 of 38 strains belonging to these clusters. There were two clusters for ST81 (ST81-SNT-1 and ST81-SNT-2), two for ST183 (ST183-SNT-1 and ST183-SNT-2), and one for ST17 (ST17-SNT-1). ST183-SNT-1 was the largest SNT cluster, encompassing five patients who were associated with Wards A, B, and K. The most frequent room changer was a patient labeled Pt08, who changed rooms seven times in Ward B. Patients Pt36 and Pt10, who were also in Ward B, had multiple admissions and discharges during the study period. CONCLUSIONS Additional culture tests and SNP analysis of C. difficile using draft WGS revealed silent transmission within the wards, particularly in cases involving frequent room changes and repeated admissions and discharges. Monitoring C. difficile transmission using WGS-based analysis could serve as a valuable marker in infection control management.
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Affiliation(s)
- Taito Miyazaki
- Infection Control Section, Toho University Omori Medical Center, Tokyo, Japan
- Department of General Medicine and Emergency Care, Toho University School of Medicine, Tokyo, Japan
| | - Kotaro Aoki
- Department of Microbiology and Infectious Diseases, Toho University School of Medicine, 5-21-16 Omori-nishi, Ota-ku, Tokyo, 143-8540, Japan.
| | - Tadashi Maeda
- Department of General Medicine and Emergency Care, Toho University School of Medicine, Tokyo, Japan
| | - Kohji Komori
- Department of Microbiology and Infection Control and Prevention, Toho University Graduate School of Medicine, Tokyo, Japan
| | - Sadako Yoshizawa
- Department of Microbiology and Infectious Diseases, Toho University School of Medicine, 5-21-16 Omori-nishi, Ota-ku, Tokyo, 143-8540, Japan
- Department of Laboratory Medicine, Faculty of Medicine, Toho University School of Medicine, Tokyo, Japan
| | - Yoshikazu Ishii
- Department of Microbiology and Infectious Diseases, Toho University School of Medicine, 5-21-16 Omori-nishi, Ota-ku, Tokyo, 143-8540, Japan
- Center for the Planetary Health and Innovation Science (PHIS), The IDEC Institute, Hiroshima University, Higashi-Hiroshima, Japan
| | - Yoshihisa Urita
- Department of General Medicine and Emergency Care, Toho University School of Medicine, Tokyo, Japan
| | - Kazuhiro Tateda
- Department of Microbiology and Infectious Diseases, Toho University School of Medicine, 5-21-16 Omori-nishi, Ota-ku, Tokyo, 143-8540, Japan
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Fernández-Otal Á, Guío J, Sarasa-Buisan C, Peleato ML, Fillat MF, Lanas Á, Bes MT. Functional characterization of Fur from the strict anaerobe Clostridioides difficile provides insight into its redox-driven regulatory capacity. FEBS J 2024; 291:3604-3627. [PMID: 38775144 DOI: 10.1111/febs.17156] [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: 12/01/2023] [Revised: 02/06/2024] [Accepted: 04/29/2024] [Indexed: 08/15/2024]
Abstract
Clostridioides (formerly Clostridium) difficile is a leading cause of infectious diarrhea associated with antibiotic therapy. The ability of this anaerobic pathogen to acquire enough iron to proliferate under iron limitation conditions imposed by the host largely determines its pathogenicity. However, since high intracellular iron catalyzes formation of deleterious reactive hydroxyl radicals, iron uptake is tightly regulated at the transcriptional level by the ferric uptake regulator Fur. Several studies relate lacking a functional fur gene in C. difficile cells to higher oxidative stress sensitivity, colonization defect and less toxigenicity, although Fur does not appear to directly regulate either oxidative stress response genes or pathogenesis genes. In this work, we report the functional characterization of C. difficile Fur and describe an additional oxidation sensing Fur-mediated mechanism independent of iron, which affects Fur DNA-binding. Using electrophoretic mobility shift assays, we show that Fur binding to the promoters of fur, feoA and fldX genes, identified as iron and Fur-regulated genes in vivo, is specific and does not require co-regulator metal under reducing conditions. Fur treatment with H2O2 produces dose-dependent soluble high molecular weight species unable to bind to target promoters. Moreover, Fur oligomers are dithiotreitol sensitive, highlighting the importance of some interchain disulfide bond(s) for Fur oligomerization, and hence for activity. Additionally, the physiological electron transport chain NADPH-thioredoxin reductase/thioredoxin from Escherichia coli reduces inactive oligomerized C. difficile Fur that recovers activity. In conjunction with available transcriptomic data, these results suggest a previously underappreciated complexity in the control of some members of the Fur regulon that is based on Fur redox properties and might be fundamental for the adaptive response of C. difficile during infection.
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Affiliation(s)
- Ángela Fernández-Otal
- Department of Biochemistry & Molecular and Cellular Biology, University of Zaragoza, Spain
- Institute for Biocomputation and Physics of Complex Systems (BIFI), Mariano Esquillor (Edif. I+D), Zaragoza, Spain
- Aragon Institute for Health Research (IIS Aragón), Zaragoza, Spain
| | - Jorge Guío
- Department of Biochemistry & Molecular and Cellular Biology, University of Zaragoza, Spain
- Institute for Biocomputation and Physics of Complex Systems (BIFI), Mariano Esquillor (Edif. I+D), Zaragoza, Spain
| | - Cristina Sarasa-Buisan
- Department of Biochemistry & Molecular and Cellular Biology, University of Zaragoza, Spain
- Institute for Biocomputation and Physics of Complex Systems (BIFI), Mariano Esquillor (Edif. I+D), Zaragoza, Spain
| | - M Luisa Peleato
- Department of Biochemistry & Molecular and Cellular Biology, University of Zaragoza, Spain
- Institute for Biocomputation and Physics of Complex Systems (BIFI), Mariano Esquillor (Edif. I+D), Zaragoza, Spain
| | - María F Fillat
- Department of Biochemistry & Molecular and Cellular Biology, University of Zaragoza, Spain
- Institute for Biocomputation and Physics of Complex Systems (BIFI), Mariano Esquillor (Edif. I+D), Zaragoza, Spain
| | - Ángel Lanas
- Aragon Institute for Health Research (IIS Aragón), Zaragoza, Spain
- Digestive Diseases Service, University Clinic Hospital Lozano Blesa, Zaragoza, Spain
- CIBERehd, Madrid, Spain
| | - M Teresa Bes
- Department of Biochemistry & Molecular and Cellular Biology, University of Zaragoza, Spain
- Institute for Biocomputation and Physics of Complex Systems (BIFI), Mariano Esquillor (Edif. I+D), Zaragoza, Spain
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Akhmedov M, Zeynalova P, Fedenko A. Multiple myeloma and infections in the era of novel treatment modalities. Leuk Res 2024; 143:107544. [PMID: 38963989 DOI: 10.1016/j.leukres.2024.107544] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2024] [Revised: 05/14/2024] [Accepted: 06/17/2024] [Indexed: 07/06/2024]
Abstract
Infections are major cause of morbidity and mortality in patients with multiple myeloma. Current treatment landscape of newly-diagnosed multiple myeloma includes different classes of drugs, such as proteasome inhibitors, immunomodulatory drugs, and monoclonal antibodies, all of which are characterized by specific risk and pattern of infectious complications. Additionally, autologous and allogeneic hematopoietic cell transplantation, widely used in the treatment of multiple myeloma, are complex procedures, carrying a significant risk of complications, and mainly infections. Finally, novel treatment modalities such as bispecific T-cell engagers and chimeric antigen receptor T-lymphocytes have been changing the paradigm of myeloma treatment in relapsed-refractory setting. These agents due to unique mechanism of action carry distinct pattern of infectious complications. In this review, an attempt has been made to summarize the incidence, risk factors, and patterns of infections during different stages of myeloma treatment including novel treatment modalities, and to provide evidence underlying the current concept of infectious disease prophylaxis in this category of patients.
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Affiliation(s)
- Mobil Akhmedov
- Department of High-dose Chemotherapy and Bone Marrow Transplantation, P.A. Herzen Moscow Oncology Research Institute, branch of the National Medical Radiology Research Center, Russian Federation; Department of Oncology and Oncosurgery, Russian University of Medicine, Russian Federation.
| | - Pervin Zeynalova
- Department of Oncology, Sechenov University, Russian Federation; Department of Oncology, Lapino Clinical Hospital, Russian Federation
| | - Alexander Fedenko
- Department of High-dose Chemotherapy and Bone Marrow Transplantation, P.A. Herzen Moscow Oncology Research Institute, branch of the National Medical Radiology Research Center, Russian Federation
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Kunishima H, Ichiki K, Ohge H, Sakamoto F, Sato Y, Suzuki H, Nakamura A, Fujimura S, Matsumoto K, Mikamo H, Mizutani T, Morinaga Y, Mori M, Yamagishi Y, Yoshizawa S. Japanese Society for infection prevention and control guide to Clostridioides difficile infection prevention and control. J Infect Chemother 2024; 30:673-715. [PMID: 38714273 DOI: 10.1016/j.jiac.2024.03.018] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2024] [Revised: 03/25/2024] [Accepted: 03/26/2024] [Indexed: 05/09/2024]
Affiliation(s)
- Hiroyuki Kunishima
- Department of Infectious Diseases. St. Marianna University School of Medicine, Japan.
| | - Kaoru Ichiki
- Department of Infection Control and Prevention, Hyogo Medical University Hospital, Japan
| | - Hiroki Ohge
- Department of Infectious Diseases, Hiroshima University Hospital, Japan
| | - Fumie Sakamoto
- Quality Improvement and Safety Center, Itabashi Chuo Medical Center, Japan
| | - Yuka Sato
- Department of Infection Control and Nursing, Graduate School of Nursing, Aichi Medical University, Japan
| | - Hiromichi Suzuki
- Department of Infectious Diseases, University of Tsukuba School of Medicine and Health Sciences, Japan
| | - Atsushi Nakamura
- Department of Infection Prevention and Control, Graduate School of Medical Sciences, Nagoya City University, Japan
| | - Shigeru Fujimura
- Division of Clinical Infectious Diseases and Chemotherapy, Faculty of Pharmaceutical Sciences, Tohoku Medical and Pharmaceutical University, Japan
| | - Kazuaki Matsumoto
- Division of Pharmacodynamics, Faculty of Pharmacy, Keio University, Japan
| | - Hiroshige Mikamo
- Department of Clinical Infectious Diseases, Aichi Medical University, Japan
| | | | - Yoshitomo Morinaga
- Department of Microbiology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Japan
| | - Minako Mori
- Department of Infection Control, Hiroshima University Hospital, Japan
| | - Yuka Yamagishi
- Department of Clinical Infectious Diseases, Kochi Medical School, Kochi University, Japan
| | - Sadako Yoshizawa
- Department of Laboratory Medicine/Department of Microbiology and Infectious Diseases, Faculty of Medicine, Toho University, Japan
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9
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Munteanu C, Schwartz B. Interactions between Dietary Antioxidants, Dietary Fiber and the Gut Microbiome: Their Putative Role in Inflammation and Cancer. Int J Mol Sci 2024; 25:8250. [PMID: 39125822 PMCID: PMC11311432 DOI: 10.3390/ijms25158250] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2024] [Revised: 07/19/2024] [Accepted: 07/25/2024] [Indexed: 08/12/2024] Open
Abstract
The intricate relationship between the gastrointestinal (GI) microbiome and the progression of chronic non-communicable diseases underscores the significance of developing strategies to modulate the GI microbiota for promoting human health. The administration of probiotics and prebiotics represents a good strategy that enhances the population of beneficial bacteria in the intestinal lumen post-consumption, which has a positive impact on human health. In addition, dietary fibers serve as a significant energy source for bacteria inhabiting the cecum and colon. Research articles and reviews sourced from various global databases were systematically analyzed using specific phrases and keywords to investigate these relationships. There is a clear association between dietary fiber intake and improved colon function, gut motility, and reduced colorectal cancer (CRC) risk. Moreover, the state of health is reflected in the reciprocal and bidirectional relationships among food, dietary antioxidants, inflammation, and body composition. They are known for their antioxidant properties and their ability to inhibit angiogenesis, metastasis, and cell proliferation. Additionally, they promote cell survival, modulate immune and inflammatory responses, and inactivate pro-carcinogens. These actions collectively contribute to their role in cancer prevention. In different investigations, antioxidant supplements containing vitamins have been shown to lower the risk of specific cancer types. In contrast, some evidence suggests that taking antioxidant supplements can increase the risk of developing cancer. Ultimately, collaborative efforts among immunologists, clinicians, nutritionists, and dietitians are imperative for designing well-structured nutritional trials to corroborate the clinical efficacy of dietary therapy in managing inflammation and preventing carcinogenesis. This review seeks to explore the interrelationships among dietary antioxidants, dietary fiber, and the gut microbiome, with a particular focus on their potential implications in inflammation and cancer.
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Affiliation(s)
- Camelia Munteanu
- Department of Plant Culture, Faculty of Agriculture, University of Agricultural Sciences and Veterinary Medicine, 400372 Cluj-Napoca, Romania
| | - Betty Schwartz
- The Institute of Biochemistry, Food Science and Nutrition, The School of Nutritional Sciences, Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, Rehovot 7610001, Israel
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Bennett N, Tanamas SK, James R, Ierano C, Malloy MJ, Watson E, Sluggett JK, Dunt D, Thursky K, Worth LJ. Healthcare-associated infections in long-term care facilities: a systematic review and meta-analysis of point prevalence studies. BMJ PUBLIC HEALTH 2024; 2:e000504. [PMID: 40018192 PMCID: PMC11816188 DOI: 10.1136/bmjph-2023-000504] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/17/2023] [Accepted: 05/03/2024] [Indexed: 03/01/2025]
Abstract
Objectives Residents of long-term care facilities (LTCFs) are especially vulnerable to acquiring healthcare-associated infections (HAIs). Our systematic review and meta-analysis estimated the burden of HAIs, identified the most frequent HAIs and explored the impact of facility-level and surveillance methodological differences on HAI burden in LTCFs, as determined by point prevalence studies (PPS). Design Systematic review and meta-analysis. Data sources Bibliographic databases MEDLINE (Ovid), Embase (Ovid) and CINAHL (EBSCOhost) were searched for potentially eligible English-language original research publications. References of short-listed full-text publications, the European Centre for Disease Control and Prevention website and an unpublished 2016-2022 Australian Aged Care PPS report were also checked. Eligibility criteria PPS monitoring HAIs, published and undertaken between January 1991 and June 2023 in LTCFs. Data extraction and synthesis Two reviewers independently screened for eligible PPS and if included, assessed risk of bias for each PPS using the Joanna Briggs Institute (JBI) critical appraisal tool for prevalence studies. Meta-analysis was performed using a generalised linear mixed model. Results 31 publications (including 123 PPS from 33 countries encompassing 709 860 residents) were included. Nine PPS (7.3%) were allocated a JBI quality score greater than 80% while 30 PPS (24.4%) were allocated a score between 70% and 80%. The overall pooled HAI point prevalence was 3.5% (95% CI 3.1% to 4.0%); 3.9% (95% CI 3.2% to 4.7%) when higher bias-risk PPS (<70% quality score) were excluded. Of 120 PPS, the most frequently reported HAIs were urinary tract (UTIs; 38.9%), respiratory tract (RTIs; 33.6%) and skin or soft tissue (SSTIs; 23.7%) infections. HAI point prevalence varied by geographical region (p<0.001), study decade (p<0.001) and HAI surveillance definitions used (p<0.001). There was no difference across facility types (p=0.57) or season (p=0.46). Conclusions HAIs remain a global public health problem and threat to the safety of LTCF residents; effective infection prevention and control strategies to reduce HAIs in LTCFs are still required. Guidance specifically about the prevention and management of UTIs, RTIs and SSTIs should be prioritised. PROSPERO registration number CRD42023406844.
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Affiliation(s)
- Noleen Bennett
- VICNISS Coordinating Centre, Melbourne, Victoria, Australia
- Department of Nursing, Melbourne School of Health Sciences, The University of Melbourne, Melbourne, Victoria, Australia
| | | | - Rodney James
- Department of Infectious Diseases, National Centre for Antimicrobial Stewardship, The University of Melbourne, Melbourne, Victoria, Australia
- Royal Melbourne Hospital Guidance Group, Royal Melbourne Hospital, Melbourne, Victoria, Australia
| | - Courtney Ierano
- Department of Infectious Diseases, National Centre for Antimicrobial Stewardship, The University of Melbourne, Melbourne, Victoria, Australia
- Royal Melbourne Hospital Guidance Group, Royal Melbourne Hospital, Melbourne, Victoria, Australia
| | - Michael J Malloy
- VICNISS Coordinating Centre, Melbourne, Victoria, Australia
- Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Victoria, Australia
| | - Eliza Watson
- VICNISS Coordinating Centre, Melbourne, Victoria, Australia
| | - Janet K Sluggett
- UniSA Allied Health and Human Performance, University of South Australia, Adelaide, South Australia, Australia
- Registry of Senior Australians (ROSA), Healthy Ageing Research Consortium, South Australian Health and Medical Research Institute, Adelaide, South Australia, Australia
| | - David Dunt
- The University of Melbourne, Melbourne, Victoria, Australia
| | - Karin Thursky
- Department of Infectious Diseases, National Centre for Antimicrobial Stewardship, The University of Melbourne, Melbourne, Victoria, Australia
- Royal Melbourne Hospital Guidance Group, Royal Melbourne Hospital, Melbourne, Victoria, Australia
| | - Leon J Worth
- VICNISS Coordinating Centre, Melbourne, Victoria, Australia
- Department of Medicine, The University of Melbourne, Melbourne, Victoria, Australia
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11
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Stoian M, Andone A, Boeriu A, Bândilă SR, Dobru D, Laszlo SȘ, Corău D, Arbănași EM, Russu E, Stoian A. COVID-19 and Clostridioides difficile Coinfection Analysis in the Intensive Care Unit. Antibiotics (Basel) 2024; 13:367. [PMID: 38667043 PMCID: PMC11047694 DOI: 10.3390/antibiotics13040367] [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: 03/25/2024] [Revised: 04/14/2024] [Accepted: 04/16/2024] [Indexed: 04/29/2024] Open
Abstract
Since the emergence of SARS-CoV-2 in late 2019, the global mortality attributable to COVID-19 has reached 6,972,152 deaths according to the World Health Organization (WHO). The association between coinfection with Clostridioides difficile (CDI) and SARS-CoV-2 has limited data in the literature. This retrospective study, conducted at Mureș County Clinical Hospital in Romania, involved 3002 ICU patients. Following stringent inclusion and exclusion criteria, 63 patients were enrolled, with a division into two subgroups-SARS-CoV-2 + CDI patients and CDI patients. Throughout their hospitalization, the patients were closely monitored. Analysis revealed no significant correlation between comorbidities and invasive mechanical ventilation (IMV) or non-invasive mechanical ventilation (NIMV). However, statistically significant associations were noted between renal and hepatic comorbidties (p = 0.009), death and CDI-SARS-CoV-2 coinfection (p = 0.09), flourochinolone treatment and CDI-SARS-CoV-2 infection (p = 0.03), and an association between diabetes mellitus and SARS-CoV-2-CDI infection (p = 0.04), as well as the need for invasive mechanical ventilation (p = 0.04). The patients with CDI treatment were significantly younger and received immuno-modulator or corticotherapy treatment, which was a risk factor for opportunistic agents. Antibiotic and PPI (proton pump inhibitor) treatment were significant risk factors for CDI coinfection, as well as for death, with PPI treatment in combination with antibiotic treatment being a more significant risk factor.
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Affiliation(s)
- Mircea Stoian
- Department of Anesthesiology and Intensive Care, George Emil Palade University of Medicine, Pharmacy, Sciences and Technology of Targu Mures, 540139 Targu Mures, Romania;
| | - Adina Andone
- Gastroenterology Department, George Emil Palade University of Medicine, Pharmacy, Sciences and Technology of Targu Mures, 540142 Targu Mures, Romania; (A.B.); (D.D.)
| | - Alina Boeriu
- Gastroenterology Department, George Emil Palade University of Medicine, Pharmacy, Sciences and Technology of Targu Mures, 540142 Targu Mures, Romania; (A.B.); (D.D.)
| | - Sergio Rareș Bândilă
- Orthopedic Surgery and Traumatology Service, Marina Baixa Hospital, Av. Alcade En Jaume Botella Mayor, 03570 Villajoyosa, Spain;
| | - Daniela Dobru
- Gastroenterology Department, George Emil Palade University of Medicine, Pharmacy, Sciences and Technology of Targu Mures, 540142 Targu Mures, Romania; (A.B.); (D.D.)
| | - Sergiu Ștefan Laszlo
- Intensive Care Unit, Mures, County Hospital, Street Gheorghe Marinescu No 1, 540136 Targu Mures, Romania; (S.Ș.L.); (D.C.)
| | - Dragoș Corău
- Intensive Care Unit, Mures, County Hospital, Street Gheorghe Marinescu No 1, 540136 Targu Mures, Romania; (S.Ș.L.); (D.C.)
| | - Emil Marian Arbănași
- Department of Vascular Surgery, George Emil Palade University of Medicine, Pharmacy, Science and Technology of Targu Mures, 540139 Targu Mures, Romania;
- Clinic of Vascular Surgery, Mures County Emergency Hospital, 540136 Targu Mures, Romania;
- Doctoral School of Medicine and Pharmacy, George Emil Palade University of Medicine, Pharmacy, Sciences and Technology of Targu Mures, 540142 Targu Mures, Romania
| | - Eliza Russu
- Clinic of Vascular Surgery, Mures County Emergency Hospital, 540136 Targu Mures, Romania;
- Doctoral School of Medicine and Pharmacy, George Emil Palade University of Medicine, Pharmacy, Sciences and Technology of Targu Mures, 540142 Targu Mures, Romania
| | - Adina Stoian
- Department of Pathophysiology, George Emil Palade University of Medicine, Pharmacy, Sciences and Technology of Targu Mures, 540136 Targu Mures, Romania;
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12
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Lawrence J, Barrow P, Foster N. Porcine Monocyte DNA Traps Formed during Infection with Pathogenic Clostridioides difficile Strains. Pathogens 2024; 13:228. [PMID: 38535571 PMCID: PMC10975479 DOI: 10.3390/pathogens13030228] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2024] [Revised: 02/21/2024] [Accepted: 02/26/2024] [Indexed: 02/11/2025] Open
Abstract
Clostridioides (Clostridium) difficile is an enteric pathogen of several mammalian species including man, frequently involving nosocomial resurgence, following oral administration of broad-spectrum antibiotics, but also with human-to-human infection occurring, and neonatal pigs with zoonotic transmission. To date, the immune response to C. difficile has mostly focused on neutrophils and cytokine/chemokines, particularly in human infection. The neonatal pig is now recognized as a valuable model for human infection. We show that porcine monocytes respond to C. difficile differently compared with many other bacterial infections. Infection of porcine monocytes with human C. difficile strains CD630 (Ribotype 078) or R20291 (Ribotype 027) for 3 or 24 h post-infection (pi) resulted in a lack of oxidative burst or nitrite ion production when compared to uninfected controls (p > 0.05). The survival dynamics of both CD630 and R20291 in monocytes were similar with intracellular bacterial numbers being similar at 3 h pi and 24 h pi (p > 0.05). However, we show that porcine monocytes entrap C. difficile via extracellular DNA traps. This process began as early as 3 h pi, and at 24 h pi the nuclei appeared to be depleted of DNA, although extracellular DNA was associated with the cell membrane. Our preliminary study also suggests that entrapment of C. difficile by extracellular DNA may occur via a process of monocyte etosis.
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Affiliation(s)
- Jade Lawrence
- School of Veterinary Medicine and Science, University of Nottingham, Nottingham LE12 5RD, UK;
| | - Paul Barrow
- School of Veterinary Medicine, University of Surrey, Daphne Jackson Road, Guildford GU2 7AL, UK;
| | - Neil Foster
- Department of Veterinary and Animal Science, SRUC Aberdeen, Craibstone Campus, Aberdeen AB21 9YA, UK
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13
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van Prehn J, van Werkhoven CH, Skinner AM, Guery B, Dubberke ER, Kuijper EJ. Which trial do we need? A sequential multiple assignment randomized trial to determine the optimal Clostridioides difficile treatment sequence. Clin Microbiol Infect 2024; 30:165-169. [PMID: 37652123 DOI: 10.1016/j.cmi.2023.08.023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2023] [Revised: 08/23/2023] [Accepted: 08/24/2023] [Indexed: 09/02/2023]
Affiliation(s)
- Joffrey van Prehn
- Department of Medical Microbiology, Centre for Infectious Diseases, Leiden University Medical Center, Leiden, the Netherlands; ESCMID (European Society of Clinical Microbiology and Infectious Diseases) Study Group for Clostridioides Difficile (ESGCD), Basel, Switzerland; ESCMID (European Society of Clinical Microbiology and Infectious Diseases) Study Group for Host and Microbiota Interaction (ESGHAMI), Basel, Switzerland.
| | - Cornelis H van Werkhoven
- Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands
| | - Andrew M Skinner
- Department of Research and Medicine, Edward Hines Jr Veterans Administration Hospital, Hines, IL, USA; Loyola University Medical Center, Department of Medicine, Maywood, IL, USA
| | - Benoit Guery
- ESCMID (European Society of Clinical Microbiology and Infectious Diseases) Study Group for Clostridioides Difficile (ESGCD), Basel, Switzerland; ESCMID (European Society of Clinical Microbiology and Infectious Diseases) Study Group for Host and Microbiota Interaction (ESGHAMI), Basel, Switzerland; Department of Medicine, Infectious Diseases Service, University Hospital and University of Lausanne, Lausanne, Switzerland
| | - Erik R Dubberke
- ESCMID (European Society of Clinical Microbiology and Infectious Diseases) Study Group for Clostridioides Difficile (ESGCD), Basel, Switzerland; Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA
| | - Ed J Kuijper
- Department of Medical Microbiology, Centre for Infectious Diseases, Leiden University Medical Center, Leiden, the Netherlands; ESCMID (European Society of Clinical Microbiology and Infectious Diseases) Study Group for Clostridioides Difficile (ESGCD), Basel, Switzerland; ESCMID (European Society of Clinical Microbiology and Infectious Diseases) Study Group for Host and Microbiota Interaction (ESGHAMI), Basel, Switzerland
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14
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Reigadas E, Vázquez-Cuesta S, Bouza E. Economic Burden of Clostridioides difficile Infection in European Countries. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2024; 1435:1-12. [PMID: 38175468 DOI: 10.1007/978-3-031-42108-2_1] [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
Clostridioides difficile infection (CDI) remains a considerable challenge to healthcare systems worldwide. Although CDI represents a significant burden on healthcare systems in Europe, few studies have attempted to estimate the consumption of resources associated with CDI in Europe. The reported extra costs attributable to CDI vary widely according to the definitions, design, and methodologies used, making comparisons difficult to perform. In this chapter, the economic burden of healthcare facility-associated CDI in Europe will be assessed, as will other less explored areas such as the economic burden of recurrent CDI, community-acquired CDI, pediatric CDI, and CDI in outbreaks.
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Affiliation(s)
- Elena Reigadas
- Department of Clinical Microbiology and Infectious Diseases, Hospital General Universitario Gregorio Marañón, Madrid, Spain
- Medicine Department, School of Medicine, Universidad Complutense de Madrid (UCM), Madrid, Spain
- Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain
| | | | - Emilio Bouza
- Department of Clinical Microbiology and Infectious Diseases, Hospital General Universitario Gregorio Marañón, Madrid, Spain
- Medicine Department, School of Medicine, Universidad Complutense de Madrid (UCM), Madrid, Spain
- Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain
- CIBER de Enfermedades Respiratorias (CIBERES CB06/06/0058), Madrid, Spain
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15
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Coia CW, Banks AL, Cottom L, Fitzpatrick F. The Need for European Surveillance of CDI. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2024; 1435:13-31. [PMID: 38175469 DOI: 10.1007/978-3-031-42108-2_2] [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
Since the turn of the millennium, the epidemiology of Clostridioides difficile infection (CDI) has continued to challenge. Changes in clinical presentation, severity of disease, descriptions of new risk factors and the occurrence of outbreaks all emphasised the importance of early diagnosis and standardised surveillance systems. However, a lack of consensus on case definitions, clinical guidelines and optimal laboratory diagnostics across Europe has led to the underestimation of CDI and impeded comparison between countries. These inconsistencies have prevented the true burden of disease from being appreciated.Acceptance that a multi-country CDI surveillance program and optimised diagnostic strategies are required has built the foundations for a more robust, unified surveillance. The concerted efforts of the European Centre for Disease Prevention and Control (ECDC) CDI networks led to the development of the European surveillance protocol and an over-arching long-term CDI surveillance strategy for 2014-2020, which has been followed by the development of surveillance systems in at least 20 European countries. However, surveillance activities in individual countries have slowed during the COVID-19 pandemic as resources were diverted to the global health crisis. A renewed and strengthened focus on CDI surveillance and prevention is therefore urgently needed post COVID-19.
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Affiliation(s)
- Camilla Wiuff Coia
- Department of Bacteria, Parasites and Fungi, Statens Serum Institut, Copenhagen, Denmark.
| | - A-Lan Banks
- St. Helens & Knowsley Teaching Hospitals NHS Trust Whiston Hospital, Prescot, Merseyside, UK
| | - Laura Cottom
- Department of Clinical Microbiology, Glasgow Royal Infirmary, Greater Glasgow & Clyde, Glasgow, UK
| | - Fidelma Fitzpatrick
- Departments of Clinical Microbiology, The Royal College of Surgeons in Ireland, and Beaumont Hospital, Dublin, Ireland
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16
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Normington C, Chilton CH, Buckley AM. Clostridioides difficile infections; new treatments and future perspectives. Curr Opin Gastroenterol 2024; 40:7-13. [PMID: 37942659 PMCID: PMC10715702 DOI: 10.1097/mog.0000000000000989] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/10/2023]
Abstract
PURPOSE OF REVIEW As a significant cause of global morbidity and mortality, Clostridioides difficile infections (CDIs) are listed by the Centres for Disease Control and prevention as one of the top 5 urgent threats in the USA. CDI occurs from gut microbiome dysbiosis, typically through antibiotic-mediated disruption; however, antibiotics are the treatment of choice, which can result in recurrent infections. Here, we highlight new treatments available and provide a perspective on different classes of future treatments. RECENT FINDINGS Due to the reduced risk of disease recurrence, the microbiome-sparing antibiotic Fidaxomicin has been recommended as the first-line treatment for C. difficile infection. Based on the success of faecal microbiota transplantations (FMT) in treating CDI recurrence, defined microbiome biotherapeutics offer a safer and more tightly controlled alterative as an adjunct to antibiotic therapy. Given the association between antibiotic-mediated dysbiosis of the intestinal microbiota and the recurrence of CDI, future prospective therapies aim to reduce the dependence on antibiotics for the treatment of CDI. SUMMARY With current first-in-line antibiotic therapy options associated with high levels of recurrent CDI, the availability of new generation targeted therapeutics can really impact treatment success. There are still unknowns about the long-term implications of these new CDI therapeutics, but efforts to expand the CDI treatment toolbox can offer multiple solutions for clinicians to treat this multifaceted infectious disease to reduce patient suffering.
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Affiliation(s)
- Charmaine Normington
- Healthcare Associated Infections Research Group, School of Medicine, Faculty of Health and Medicine, University of Leeds
- Leeds Teaching Hospital Trust, Leeds General Infirmary
| | - Caroline H. Chilton
- Healthcare Associated Infections Research Group, School of Medicine, Faculty of Health and Medicine, University of Leeds
- Leeds Teaching Hospital Trust, Leeds General Infirmary
| | - Anthony M. Buckley
- Microbiome and Nutritional Sciences Group, School of Food Science & Nutrition, Faculty of Environment, University of Leeds, Leeds, UK
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17
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Coia JE, Kuijper EJ, Fitzpatrick F. The ESCMID Study Group for Clostridioides difficile: History, Role, and Perspectives. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2024; 1435:351-362. [PMID: 38175483 DOI: 10.1007/978-3-031-42108-2_16] [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
Clostridioides difficile (C. difficile) is a major nosocomial pathogen but is also increasingly recognised as an important diarrhoeal pathogen in the community, not always associated with antibiotics. The European Society of Clinical Microbiology and Infectious Diseases (ESCMID) Study Group for C. difficile (ESGCD) is a group of clinicians, scientists, and others from many European countries and further afield, who share a common interest in C. difficile. The aims of the Study Group are centred around raising the profile of C. difficile infection (CDI) in humans and animals, fostering collaboration amongst centres in different European countries and providing a forum for discussing and disseminating information. One of the principal aims of the Study Group is to raise awareness of C. difficile infections in Europe. ESGCD has a particular interest in the development and dissemination of European guidance on prevention, diagnosis, and treatment of CDI. This chapter will discuss the organisation of ESGCD within the ESCMID Study Group structure, the origins of the Study Group, the aims, and objectives of the group, and will highlight some of the past and present activities of ESGCD in relation to these.
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Affiliation(s)
- John E Coia
- Institute for Regional Health Research (IRS), University of Southern Denmark (SDU), Esbjerg, Denmark.
- ESCMID Study Group for C. difficile (ESGCD), Basel, Switzerland.
- ESCMID Study Group for Nosocomial Infections (ESGNI), Basel, Switzerland.
| | - Ed J Kuijper
- ESCMID Study Group for C. difficile (ESGCD), Basel, Switzerland
- Department of Medical Microbiology, Center of Infectious Diseases, Leiden University Medical Center, Leiden, The Netherlands
- ESCMID Study Group for Host and Microbiota Interaction (ESGHAMI), Basel, Switzerland
| | - Fidelma Fitzpatrick
- ESCMID Study Group for C. difficile (ESGCD), Basel, Switzerland
- ESCMID Study Group for Host and Microbiota Interaction (ESGHAMI), Basel, Switzerland
- Department of Clinical Microbiology, The Royal College of Surgeons in Ireland and Beaumont Hospital, Dublin, Ireland
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18
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Vehreschild MJGT, Schreiber S, von Müller L, Epple HJ, Weinke T, Manthey C, Oh J, Wahler S, Stallmach A. Trends in the epidemiology of Clostridioides difficile infection in Germany. Infection 2023; 51:1695-1702. [PMID: 37162717 PMCID: PMC10170422 DOI: 10.1007/s15010-023-02044-5] [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: 04/16/2023] [Accepted: 04/25/2023] [Indexed: 05/11/2023]
Abstract
PURPOSES Despite reports of a declining incidence over the last decade, Clostridioides difficile infection (CDI) is still considered the most important healthcare-associated causes of diarrhea worldwide. In Germany, several measures have been taken to observe, report, and influence this development. This report aims to analyze the development of hospital coding for CDI in Germany over the last decade and to use it to estimate the public health burden caused by CDI. METHODS Reports from the Institute for Hospital Remuneration Systems, German Federal Statistical Office (DESTATIS), the Robert-Koch-Institute (RKI), Saxonian authorities and hospital quality reports during 2010-2021 were examined for CDI coding and assessed in a structured expert consultation. Analysis was performed using 2019 versions of Microsoft Excel® and Microsoft Access®. RESULTS Peaks of 32,203 cases with a primary diagnosis (PD) of CDI and 78,648 cases with a secondary diagnosis (SD) of CDI were observed in 2015. The number of cases had decreased to 15,412 PD cases (- 52.1%) and 40,188 SD cases (- 48.9%) by 2021. These results were paralleled by a similar decline in notifiable severe cases. However, average duration of hospitalization of the cases remained constant during this period. CONCLUSIONS Hospital coding of CDI and notification to authorities has approximately halved from 2015 to 2021. Potential influential factors include hospital hygiene campaigns, implementation of antibiotic stewardship programs, social distancing due to the COVID-19 pandemic, and a decrease in more pathogenic subtypes of bacteria. Further research is necessary to validate the multiple possible drivers for this development.
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Affiliation(s)
| | - Stefan Schreiber
- Department Medicine I, University Hospital Schleswig-Holstein, Christian-Albrechts-University, Rosalind-Franklin-Str. 12, 24105 Kiel, Germany
| | - Lutz von Müller
- Christophorus-Kliniken GmbH, Südring 41, 48653 Coesfeld, Germany
| | - Hans-Jörg Epple
- Charité, Universitätsmedizin Berlin, Campus Benjamin Franklin, Antibiotic Stewardship, Hindenburgdamm 30, 12203 Berlin, Germany
| | - Thomas Weinke
- Ernst Von Bergmann Klinikum gGmbH, Charlottenstraße 72, 14467 Potsdam, Germany
| | - Carolin Manthey
- Gemeinschaftspraxis Innere Medizin (GIM), Pferdebachstr. 29, 58455 Witten, Germany
| | - Jun Oh
- Universitätsklinikum Hamburg-Eppendorf, Martinistraße 52, 20246 Hamburg, Germany
| | - Steffen Wahler
- St. Bernward GmbH, Friedrich-Kirsten-Str. 40, 22391 Hamburg, Germany
| | - Andreas Stallmach
- Klinik Für Innere Medizin IV, Universitätsklinikum Jena, Am Klinikum 1, 07747 Jena, Germany
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19
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Ferar K, Hall TO, Crawford DC, Rowley R, Satterfield BA, Li R, Gragert L, Karlson EW, de Andrade M, Kullo IJ, McCarty CA, Kho A, Hayes MG, Ritchie MD, Crane PK, Mirel DB, Carlson C, Connolly JJ, Hakonarson H, Crenshaw AT, Carrell D, Luo Y, Dikilitas O, Denny JC, Jarvik GP, Crosslin DR. Genetic variation in the human leukocyte antigen region confers susceptibility to Clostridioides difficile infection. Sci Rep 2023; 13:18532. [PMID: 37898691 PMCID: PMC10613277 DOI: 10.1038/s41598-023-45649-4] [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: 12/30/2022] [Accepted: 10/22/2023] [Indexed: 10/30/2023] Open
Abstract
Clostridioides difficile (C. diff.) infection (CDI) is a leading cause of hospital acquired diarrhea in North America and Europe and a major cause of morbidity and mortality. Known risk factors do not fully explain CDI susceptibility, and genetic susceptibility is suggested by the fact that some patients with colons that are colonized with C. diff. do not develop any infection while others develop severe or recurrent infections. To identify common genetic variants associated with CDI, we performed a genome-wide association analysis in 19,861 participants (1349 cases; 18,512 controls) from the Electronic Medical Records and Genomics (eMERGE) Network. Using logistic regression, we found strong evidence for genetic variation in the DRB locus of the MHC (HLA) II region that predisposes individuals to CDI (P > 1.0 × 10-14; OR 1.56). Altered transcriptional regulation in the HLA region may play a role in conferring susceptibility to this opportunistic enteric pathogen.
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Affiliation(s)
- Kathleen Ferar
- Department of Biomedical Informatics and Medical Education, University of Washington, Seattle, WA, USA.
| | - Taryn O Hall
- Optum Genomics, UnitedHealth Group, Minnetonka, MN, USA
| | - Dana C Crawford
- Department of Population and Quantitative Health Sciences, Cleveland Institute for Computational Biology, Case Western Reserve University, Cleveland, OH, USA
- Department of Genetics and Genome Sciences, Cleveland Institute for Computational Biology, Case Western Reserve University, Cleveland, OH, USA
| | - Robb Rowley
- National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA
| | | | - Rongling Li
- National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA
| | - Loren Gragert
- Division of Biomedical Informatics and Genomics, John W. Deming Department of Medicine, Tulane University School of Medicine, New Orleans, LA, USA
| | | | - Mariza de Andrade
- Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN, USA
| | - Iftikhar J Kullo
- Department of Cardiovascular Diseases, Mayo Clinic, Rochester, MN, USA
| | - Catherine A McCarty
- University of Minnesota Medical School, Duluth, MN, USA
- Center for Human Genetics, Marshfield Clinic Research Foundation, Marshfield, WI, USA
| | - Abel Kho
- Divisions of General Internal Medicine and Preventive Medicine, Northwestern University, Chicago, IL, USA
| | - M Geoffrey Hayes
- Division of Endocrinology, Metabolism, and Molecular Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
| | - Marylyn D Ritchie
- Department of Biochemistry and Molecular Biology, Center for Systems Genomics, Pennsylvania State University, University Park, PA, USA
| | - Paul K Crane
- Division of General Internal Medicine, University of Washington, Seattle, WA, USA
| | | | - Christopher Carlson
- Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
| | - John J Connolly
- Center for Applied Genomics, The Children's Hospital of Philadelphia, Philadelphia, PA, USA
| | - Hakon Hakonarson
- Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA, USA
| | | | - David Carrell
- Kaiser Permanente Washington Health Research Institute, Seattle, WA, USA
| | - Yuan Luo
- Northwestern University Feinberg School of Medicine, Chicago, IL, USA
| | - Ozan Dikilitas
- Department of Cardiovascular Diseases, Mayo Clinic, Rochester, MN, USA
| | - Joshua C Denny
- Department of Biomedical Informatics, Vanderbilt University, Nashville, TN, USA
| | - Gail P Jarvik
- Department of Medicine (Medical Genetics), University of Washington Medical Center, Seattle, WA, USA
| | - David R Crosslin
- Division of Biomedical Informatics and Genomics, John W. Deming Department of Medicine, Tulane University School of Medicine, New Orleans, LA, USA.
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20
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de-la-Rosa-Martinez D, Bobadilla Del Valle M, Esteban-Kenel V, Zinser Peniche P, Ponce De León Garduño A, Cornejo Juárez P, Sánchez Cruz MN, Camacho-Ortiz A, Vilar-Compte D. Molecular characterization and genotyping of isolates from cancer patients with Clostridioides difficile infection or asymptomatic colonization. J Med Microbiol 2023; 72. [PMID: 37624363 DOI: 10.1099/jmm.0.001748] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/26/2023] Open
Abstract
Introduction. Cancer patients with Clostridioides difficile infection (CDI) are at a higher risk for adverse outcomes. In addition, a high prevalence of Clostridioides difficile asymptomatic colonization (CDAC) has been reported in this vulnerable population.Gap Statement. The molecular characteristics and potential role of CDAC in healthcare-related transmission in the cancer population have been poorly explored.Aim. We aimed to compare the molecular and genotypic characteristics of C. difficile isolates from cancer patients with CDAC and CDI.Method. We conducted a prospective cohort study of cancer patients with CDAC or CDI from a referral centre. Molecular characterization, typification and tcdC gene expression of isolates were performed.Results. The hospital-onset and community-onset healthcare facility-associated CDI rates were 4.5 cases/10 000 patient-days and 1.4 cases/1 000 admissions during the study period. Fifty-one C. difficile strains were isolated: 37 (72 %) and 14 (28 %) from patients with CDI or CDAC, respectively. All isolates from symptomatic patients were tcdA+/tcdB+, and four (10 %) were ctdA+/ctdB+. In the CDAC group, 10 (71 %) isolates were toxigenic, and none were ctdA+/ctdB+. The Δ18 in-frame tcdC deletion and two transition mutations were found in five isolates. After bacterial typing, 60 % of toxigenic isolates from asymptomatic carriers were clonal to those from patients with C. difficile-associated diarrhoea. No NAP1/027/BI strains were detected.Conclusions. We found a clonal association between C. difficile isolates from patients with CDAC and CDI. Studies are needed to evaluate the potential role of asymptomatic carriers in the dynamics of nosocomial transmission to support infection control measures and reduce the burden of CDI in high-risk groups.
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Affiliation(s)
- Daniel de-la-Rosa-Martinez
- Plan de Estudios Combinados en Medicina (PECEM), Faculty of Medicine, Universidad Nacional Autonoma de Mexico, México City, Mexico
- Departament of Infectious Diseases, Instituto Nacional de Cancerología, Mexico City, Mexico
| | - Miriam Bobadilla Del Valle
- Laboratory of Clinical Microbiology, Departament of Infectious Diseases, Instituto Nacional de Ciencias Medicas y Nutrición, Mexico City, Mexico
| | - Veronica Esteban-Kenel
- Laboratory of Clinical Microbiology, Departament of Infectious Diseases, Instituto Nacional de Ciencias Medicas y Nutrición, Mexico City, Mexico
| | - Paola Zinser Peniche
- Departament of Infectious Diseases, Instituto Nacional de Cancerología, Mexico City, Mexico
| | - Alfredo Ponce De León Garduño
- Laboratory of Clinical Microbiology, Departament of Infectious Diseases, Instituto Nacional de Ciencias Medicas y Nutrición, Mexico City, Mexico
| | | | - María Nancy Sánchez Cruz
- Laboratory of Clinical Microbiology, Departament of Infectious Diseases, Instituto Nacional de Ciencias Medicas y Nutrición, Mexico City, Mexico
| | - Adrian Camacho-Ortiz
- Department of Infectious Diseases, Department of Internal Medicine, Hospital Universitario Dr. Jose Eleuterio Gonzalez, Universidad Autónoma de Nuevo León, Monterrey, Mexico
| | - Diana Vilar-Compte
- Departament of Infectious Diseases, Instituto Nacional de Cancerología, Mexico City, Mexico
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21
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Jolivet S, Couturier J, Grohs P, Vilfaillot A, Zahar JR, Frange P, Casetta A, Moulin V, Lawrence C, Baune P, Bourgeois C, Bouffier A, Laussucq C, Sienzonit L, Picard S, Podglajen I, Kassis-Chikhani N, Barbut F. Prevalence and risk factors of toxigenic Clostridioides difficile asymptomatic carriage in 11 French hospitals. Front Med (Lausanne) 2023; 10:1221363. [PMID: 37547619 PMCID: PMC10402895 DOI: 10.3389/fmed.2023.1221363] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2023] [Accepted: 06/28/2023] [Indexed: 08/08/2023] Open
Abstract
Clostridioides difficile infection (CDI) incidence has increased over the last 20 years. Studies suggest that asymptomatic carriers may be an important reservoir of C. difficile in healthcare settings. We conducted a point prevalence study to estimate the toxigenic C. difficile asymptomatic carriage rate and the associated risk factors in patients >3 years old. Between September 16, 2019 and January 15, 2020, all patients hospitalized in 11 healthcare facilities in the Paris urban area were included in the study. They were screened on the day of the survey for toxigenic C. difficile carriage by rectal swab and interviewed. Isolates were characterized by PCR ribotyping and multiplex PCR targeting toxin genes. A logistic regression model was used to determine the risk factors associated with toxigenic C. difficile asymptomatic carriage using uni- and multivariate analysis in the subpopulation of patients >3 years old. During the study period, 2,389 patients were included and screened. The median age was 62 years (interquartile range 35-78 years) and 1,153 were male (48.3%). Nineteen patients had a previous CDI (0.9%). Overall, 185/2389 patients were positive for C. difficile (7.7%), including 93 toxigenic strains (3.9%): 77 (82.8%) were asymptomatic (prevalence 3.2%) whereas 12 (12.9%) were diarrheic. Prevalences of toxigenic C. difficile were 3.5% in patients >3 years old and 7.0% in ≤3 years old subjects, respectively. Toxigenic strains mainly belonged to PCR ribotypes 106 (n = 14, 15.0%), 014 (n = 12, 12.9%), and 020 (n = 10, 10.8%). Among toxigenic strains, 6 (6.4%) produced the binary toxin. In multivariate analysis, two factors were positively associated with toxigenic C. difficile asymptomatic carriage in patients >3 years old: multidrug-resistant organisms co-carriage [adjusted Odd Ratio (aOR) 2.3, CI 95% 1.2-4.7, p = 0.02] and previous CDI (aOR 5.8, CI 95% 1.2-28.6, p = 0.03). Conversely, consumption of raw milk products were associated with reduced risk of toxigenic C. difficile colonization (aOR 0.5, CI 95% 0.2-0.9, p = 0.01). We showed that there was a low prevalence of asymptomatic toxigenic C. difficile carriage in hospitalized patients. Consumption of raw milk prevents toxigenic C. difficile colonization, probably due to the barrier effect of milk-associated bacteria.
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Affiliation(s)
- Sarah Jolivet
- Unité de prévention du risque infectieux, Hôpital Saint Antoine, Paris, France
| | - Jeanne Couturier
- Laboratoire de microbiologie de l’environnement, Hôpital Saint Antoine, Paris, France
- National Reference Laboratory for Clostridioides difficile, Paris, France
| | - Patrick Grohs
- Laboratoire de microbiologie, Hôpital Européen Georges Pompidou, Paris, France
| | - Aurélie Vilfaillot
- Unité de Recherche Clinique, Hôpital Européen Georges Pompidou, Paris, France
- INSERM Centre d’Investigation Clinique 1418, Paris, France
| | - Jean-Ralph Zahar
- Unité de Prévention du Risque infectieux, Hôpitaux Avicenne, Bobigny/Jean Verdier, Bondy/René Muret, Sevran, France
| | - Pierre Frange
- Équipe de Prévention du Risque infectieux, Laboratoire de microbiologie clinique, Hôpital Necker – Enfants malades, Groupe hospitalier Assistance Publique – Hôpitaux de Paris (APHP) Centre – Université Paris Cité, Paris, France
| | - Anne Casetta
- Équipe de Prévention du Risque infectieux, Hôpital Cochin, Paris, France
| | - Véronique Moulin
- Équipe de Prévention du Risque infectieux, Hôpitaux Corentin Celton/Vaugirard, Issy-les-Moulineaux, France
| | - Christine Lawrence
- Équipe de Prévention du Risque infectieux, GHU Paris-Saclay site R. Poincaré, Garches, France
| | - Patricia Baune
- Équipe de Prévention du Risque infectieux, Hôpital Paul Brousse, Villejuif, France
| | - Cléo Bourgeois
- Unité de Recherche Clinique, Hôpital Européen Georges Pompidou, Paris, France
- INSERM Centre d’Investigation Clinique 1418, Paris, France
| | - Axel Bouffier
- Unité de Recherche Clinique, Hôpital Européen Georges Pompidou, Paris, France
- INSERM Centre d’Investigation Clinique 1418, Paris, France
| | - Claudine Laussucq
- Laboratoire de microbiologie, Hôpital Européen Georges Pompidou, Paris, France
| | - Lydia Sienzonit
- Laboratoire de microbiologie, Hôpital Européen Georges Pompidou, Paris, France
| | - Simon Picard
- Laboratoire de microbiologie, Hôpital Européen Georges Pompidou, Paris, France
| | - Isabelle Podglajen
- Laboratoire de microbiologie, Hôpital Européen Georges Pompidou, Paris, France
| | - Najiby Kassis-Chikhani
- Équipe de Prévention du Risque infectieux, Hôpital Européen Georges Pompidou, Paris, France
| | - Frédéric Barbut
- Unité de prévention du risque infectieux, Hôpital Saint Antoine, Paris, France
- Laboratoire de microbiologie de l’environnement, Hôpital Saint Antoine, Paris, France
- National Reference Laboratory for Clostridioides difficile, Paris, France
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22
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Spigaglia P, Barbanti F, Faccini S, Vescovi M, Criscuolo EM, Ceruti R, Gaspano C, Rosignoli C. Clostridioides difficile in Pigs and Dairy Cattle in Northern Italy: Prevalence, Characterization and Comparison between Animal and Human Strains. Microorganisms 2023; 11:1738. [PMID: 37512910 PMCID: PMC10383565 DOI: 10.3390/microorganisms11071738] [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: 04/14/2023] [Revised: 06/21/2023] [Accepted: 06/29/2023] [Indexed: 07/30/2023] Open
Abstract
It has been observed that novel strains of Clostridioides difficile can rapidly emerge and move between animal and human hosts. The aim of this study was to investigate the prevalence of C. difficile in pigs and dairy cattle in northern Italy and to characterize and compare C. difficile animal strains with those from patients from the same geographical area. The C. difficile strains were isolated from animals from farms and slaughterhouses (cross-sectional studies) and from neonatal animals with enteric disorders in routine diagnostic investigations (passive surveillance). Samples positive for C. difficile were found in 87% of the pig farms and in 40% of the cattle farms involved in the cross-sectional studies, with a 20% prevalence among suckling piglets and 6.7% prevalence in neonatal calves, with no significant difference between animals with and without diarrheal symptoms. The prevalence of C. difficile in older animal categories was significantly lower. This result suggests that young age is an important risk factor for C. difficile colonization. In cross-sectional studies at slaughterhouses, in both the heavy pigs and dairy cows examined, only 2% of the intestinal content samples were positive for C. difficile and no contamination was found on the surface of the carcasses. Considering passive surveillance, the prevalence rates of positive samples were 29% in piglets and 1.4% in calves. Overall, 267 strains of animal origin and 97 from humans were collected. In total, 39 ribotypes (RTs) were identified, with RT 078 and RT 018 being predominant among animals and humans, respectively. Several RTs overlapped between animals and patients. In particular, RT 569 was identified as an emergent type in our country. Resistance to erythromycin and moxifloxacin was widely diffused among C. difficile strains, regardless of origin. This study supports C. difficile as a pathogen of one-health importance and highlights the need for a collaborative approach between physicians and veterinarians to control and prevent infections that are able to cross species and geographical barriers.
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Affiliation(s)
- Patrizia Spigaglia
- Dipartimento di Malattie Infettive, Istituto Superiore di Sanità, 00161 Roma, Italy
| | - Fabrizio Barbanti
- Dipartimento di Malattie Infettive, Istituto Superiore di Sanità, 00161 Roma, Italy
| | - Silvia Faccini
- Istituto Zooprofilattico Sperimentale della Lombardia e dell'Emilia Romagna "B. Ubertini", Sede Territoriale di Mantova, 46100 Mantova, Italy
| | - Mariella Vescovi
- Istituto Zooprofilattico Sperimentale della Lombardia e dell'Emilia Romagna "B. Ubertini", Sede Territoriale di Mantova, 46100 Mantova, Italy
| | | | - Rossella Ceruti
- Servizio di Medicina di Laboratorio, ASST Ospedale "Carlo Poma", 46100 Mantova, Italy
| | - Clara Gaspano
- Servizio di Medicina di Laboratorio, ASST Ospedale "Carlo Poma", 46100 Mantova, Italy
| | - Carlo Rosignoli
- Istituto Zooprofilattico Sperimentale della Lombardia e dell'Emilia Romagna "B. Ubertini", Sede Territoriale di Mantova, 46100 Mantova, Italy
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23
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Williamson CHD, Roe CC, Terriquez J, Hornstra H, Lucero S, Nunnally AE, Vazquez AJ, Vinocur J, Plude C, Nienstadt L, Stone NE, Celona KR, Wagner DM, Keim P, Sahl JW. A local-scale One Health genomic surveillance of Clostridioides difficile demonstrates highly related strains from humans, canines, and the environment. Microb Genom 2023; 9. [PMID: 37347682 DOI: 10.1099/mgen.0.001046] [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] [Indexed: 06/24/2023] Open
Abstract
Although infections caused by Clostridioides difficile have historically been attributed to hospital acquisition, growing evidence supports the role of community acquisition in C. difficile infection (CDI). Symptoms of CDI can range from mild, self-resolving diarrhoea to toxic megacolon, pseudomembranous colitis, and death. In this study, we sampled C. difficile from clinical, environmental, and canine reservoirs in Flagstaff, Arizona, USA, to understand the distribution and transmission of the pathogen in a One Health framework; Flagstaff is a medium-sized, geographically isolated city with a single hospital system, making it an ideal site to characterize genomic overlap between sequenced C. difficile isolates across reservoirs. An analysis of 562 genomes from Flagstaff isolates identified 65 sequence types (STs), with eight STs being found across all three reservoirs and another nine found across two reservoirs. A screen of toxin genes in the pathogenicity locus identified nine STs where all isolates lost the toxin genes needed for CDI manifestation (tcdB, tcdA), demonstrating the widespread distribution of non-toxigenic C. difficile (NTCD) isolates in all three reservoirs; 15 NTCD genomes were sequenced from symptomatic, clinical samples, including two from mixed infections that contained both tcdB+ and tcdB- isolates. A comparative single nucleotide polymorphism (SNP) analysis of clinically derived isolates identified 78 genomes falling within clusters separated by ≤2 SNPs, indicating that ~19 % of clinical isolates are associated with potential healthcare-associated transmission clusters; only symptomatic cases were sampled in this study, and we did not sample asymptomatic transmission. Using this same SNP threshold, we identified genomic overlap between canine and soil isolates, as well as putative transmission between environmental and human reservoirs. The core genome of isolates sequenced in this study plus a representative set of public C. difficile genomes (n=136), was 2690 coding region sequences, which constitutes ~70 % of an individual C. difficile genome; this number is significantly higher than has been published in some other studies, suggesting that genome data quality is important in understanding the minimal number of genes needed by C. difficile. This study demonstrates the close genomic overlap among isolates sampled across reservoirs, which was facilitated by maximizing the genomic search space used for comprehensive identification of potential transmission events. Understanding the distribution of toxigenic and non-toxigenic C. difficile across reservoirs has implications for surveillance sampling strategies, characterizing routes of infections, and implementing mitigation measures to limit human infection.
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Affiliation(s)
| | - Chandler C Roe
- The Pathogen and Microbiome Institute, Northern Arizona University, Flagstaff, AZ, USA
| | | | - Heidie Hornstra
- The Pathogen and Microbiome Institute, Northern Arizona University, Flagstaff, AZ, USA
| | - Samantha Lucero
- The Pathogen and Microbiome Institute, Northern Arizona University, Flagstaff, AZ, USA
| | - Amalee E Nunnally
- The Pathogen and Microbiome Institute, Northern Arizona University, Flagstaff, AZ, USA
| | - Adam J Vazquez
- The Pathogen and Microbiome Institute, Northern Arizona University, Flagstaff, AZ, USA
| | | | | | | | - Nathan E Stone
- The Pathogen and Microbiome Institute, Northern Arizona University, Flagstaff, AZ, USA
| | - Kimberly R Celona
- The Pathogen and Microbiome Institute, Northern Arizona University, Flagstaff, AZ, USA
| | - David M Wagner
- The Pathogen and Microbiome Institute, Northern Arizona University, Flagstaff, AZ, USA
| | - Paul Keim
- The Pathogen and Microbiome Institute, Northern Arizona University, Flagstaff, AZ, USA
| | - Jason W Sahl
- The Pathogen and Microbiome Institute, Northern Arizona University, Flagstaff, AZ, USA
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24
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Hu X, Dong R, Huang S, Zeng Y, Zhan W, Gao X, Tian D, Peng J, Xu J, Wang T, Zhang Y, Wang X, Zhang X, Liu J, Guang B, Yang T. CDBN-YGXZ, a Novel Small-Molecule Drug, Shows Efficacy against Clostridioides difficile Infection and Recurrence in Mouse and Hamster Infection Models. Antimicrob Agents Chemother 2023; 67:e0170422. [PMID: 37052498 PMCID: PMC10190532 DOI: 10.1128/aac.01704-22] [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: 12/22/2022] [Accepted: 03/01/2023] [Indexed: 04/14/2023] Open
Abstract
Clostridioides difficile infection (CDI) causes severe diarrhea and colitis, leading to significant morbidity, mortality, and high medical costs worldwide. Oral vancomycin, a first-line treatment for CDI, is associated with a high risk of recurrence, necessitating novel therapies for primary and recurrent CDI. A novel small-molecule compound, CDBN-YGXZ, was synthesized by modifying the benzene ring of nitazoxanide with lauric acid. The mechanism of action of CDBN-YGXZ was validated using a pyruvate:ferredoxin/flavodoxin oxidoreductase (PFOR) inhibition assay. The efficacy of CDBN-YGXZ was evaluated using the MIC test and CDI infection model in mice and hamsters. Furthermore, metagenomics was used to reveal the underlying reasons for the effective reduction or prevention of CDI after CDBN-YGXZ treatment. The inhibitory activity against PFOR induced by CDBN-YGXZ. MIC tests showed that the in vitro activity of CDBN-YGXZ against C. difficile ranging from 0.1 to 1.5 μg/mL. In the mouse and hamster CDI models, CDBN-YGXZ provided protection during both treatment and relapse, while vancomycin treatment resulted in severe relapse and significant clinical scores. Compared with global effects on the indigenous gut microbiota induced by vancomycin, CDBN-YGXZ treatment had a mild influence on gut microbes, thus resulting in the disappearance or reduction of CDI recurrence. CDBN-YGXZ displayed potent activity against C. difficile in vitro and in vivo, reducing or preventing relapse in infected animals, which could merit further development as a potential drug candidate for treating CDI.
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Affiliation(s)
- Xiaojun Hu
- School of Pharmacy, Chengdu Medical College, Chengdu, Sichuan Province, China
| | - Renhan Dong
- Chengdu Biobel Biotechnology Co., Ltd., Chengdu, Sichuan Province, China
| | - Sheng Huang
- School of Pharmacy, Chengdu Medical College, Chengdu, Sichuan Province, China
| | - Yisheng Zeng
- School of Pharmacy, Chengdu Medical College, Chengdu, Sichuan Province, China
| | - Wei Zhan
- Chengdu Biobel Biotechnology Co., Ltd., Chengdu, Sichuan Province, China
| | - Xiaofang Gao
- School of Pharmacy, Chengdu Medical College, Chengdu, Sichuan Province, China
| | - Dong Tian
- School of Pharmacy, Chengdu Medical College, Chengdu, Sichuan Province, China
| | - Jian Peng
- School of Pharmacy, Chengdu Medical College, Chengdu, Sichuan Province, China
| | - Jiewei Xu
- School of Pharmacy, Chengdu Medical College, Chengdu, Sichuan Province, China
| | - Ting Wang
- School of Pharmacy, Chengdu Medical College, Chengdu, Sichuan Province, China
| | - Yaying Zhang
- School of Pharmacy, Chengdu Medical College, Chengdu, Sichuan Province, China
| | - Xiaohui Wang
- Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
| | - Xiaoxia Zhang
- Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
| | - Jin Liu
- School of Pharmacy, Chengdu Medical College, Chengdu, Sichuan Province, China
| | - Bing Guang
- School of Pharmacy, Chengdu Medical College, Chengdu, Sichuan Province, China
- Chengdu Biobel Biotechnology Co., Ltd., Chengdu, Sichuan Province, China
| | - Tai Yang
- School of Pharmacy, Chengdu Medical College, Chengdu, Sichuan Province, China
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25
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Pal R, Athamneh AI, Deshpande R, Ramirez JAR, Adu KT, Muthuirulan P, Pawar S, Biazzo M, Apidianakis Y, Sundekilde UK, de la Fuente-Nunez C, Martens MG, Tegos GP, Seleem MN. Probiotics: insights and new opportunities for Clostridioides difficile intervention. Crit Rev Microbiol 2023; 49:414-434. [PMID: 35574602 PMCID: PMC9743071 DOI: 10.1080/1040841x.2022.2072705] [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] [Received: 12/16/2021] [Revised: 04/17/2022] [Accepted: 04/28/2022] [Indexed: 02/08/2023]
Abstract
Clostridioides difficile infection (CDI) is a life-threatening disease caused by the Gram-positive, opportunistic intestinal pathogen C. difficile. Despite the availability of antimicrobial drugs to treat CDI, such as vancomycin, metronidazole, and fidaxomicin, recurrence of infection remains a significant clinical challenge. The use of live commensal microorganisms, or probiotics, is one of the most investigated non-antibiotic therapeutic options to balance gastrointestinal (GI) microbiota and subsequently tackle dysbiosis. In this review, we will discuss major commensal probiotic strains that have the potential to prevent and/or treat CDI and its recurrence, reassess the efficacy of probiotics supplementation as a CDI intervention, delve into lessons learned from probiotic modulation of the immune system, explore avenues like genome-scale metabolic network reconstructions, genome sequencing, and multi-omics to identify novel strains and understand their functionality, and discuss the current regulatory framework, challenges, and future directions.
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Affiliation(s)
- Rusha Pal
- Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA, 24061, USA
| | - Ahmad I.M. Athamneh
- Department of Comparative Pathobiology, College of Veterinary Medicine, Purdue University, West Lafayette, IN 47907, USA
| | | | - Jose A. R Ramirez
- ProbioWorld Consulting Group, James Cook University, 4811, Queensland, Australia
| | - Kayode T. Adu
- ProbioWorld Consulting Group, James Cook University, 4811, Queensland, Australia
- Cann Group, Walter and Eliza Hall Institute, La Trobe University, Victoria 3083, Australia
| | | | - Shrikant Pawar
- The Anlyan Center Yale Center for Genomic Analysis, Yale School of Medicine, New Haven CT USA
| | - Manuele Biazzo
- The Bioarte Ltd Laboratories at Life Science Park, San Gwann, Malta
| | | | | | - Cesar de la Fuente-Nunez
- Machine Biology Group, Departments of Psychiatry and Microbiology, Institute for Biomedical Informatics, Institute for Translational Medicine and Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America
- Departments of Bioengineering and Chemical and Biomolecular Engineering, School of Engineering and Applied Science, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America
- Penn Institute for Computational Science, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America
| | - Mark G. Martens
- Reading Hospital, Tower Health, West Reading, PA 19611, USA
- Drexel University College of Medicine, Philadelphia, PA, 19129, USA
| | - George P. Tegos
- Drexel University College of Medicine, Philadelphia, PA, 19129, USA
| | - Mohamed N. Seleem
- Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA, 24061, USA
- Center for Emerging, Zoonotic and Arthropod-borne Pathogens, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, USA
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26
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Epidemiology of Clostridioides difficile Infections in Germany, 2010-2019: A Review from Four Public Databases. Infect Dis Ther 2023; 12:1057-1072. [PMID: 36897556 PMCID: PMC10000342 DOI: 10.1007/s40121-023-00785-2] [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: 01/17/2023] [Accepted: 02/22/2023] [Indexed: 03/11/2023] Open
Abstract
INTRODUCTION Clostridioides difficile infection (CDI) is a recognized global threat especially for vulnerable populations. It is of particular concern to healthcare providers as it is found in both hospital and community settings, with severe courses, frequent recurrence, high mortality and substantial financial impact on the healthcare system. The CDI burden in Germany has been described and compared by analysing data from four different public databases. METHODS Data on hospital burden of CDI have been extracted, compared, and discussed from four public databases for the years 2010-2019. Hospital days due to CDI were compared to established vaccine preventable diseases, such as influenza and herpes zoster, and also to CDI hospitalisations in the United States (US). RESULTS All four databases reported comparable incidences and trends. Beginning in 2010, population-based hospitalised CDI incidence increased to a peak of > 137/100,000 in 2013. Then, incidence declined to 81/100,000 in 2019. Hospitalised patients with CDI were predominantly > 50 years of age. The population-based incidence of severe CDI was between 1.4 and 8.4/100,000 per year. Recurrence rates were between 5.9 to 6.5%. More than 1,000 CDI deaths occurred each year, with a peak of 2,666 deaths in 2015. Cumulative CDI patient days (PD) were between 204,596 and 355,466 each year, which exceeded cumulated PD for influenza and herpes zoster in most years, though year-to-year differences were observed. Finally, hospitalized CDI incidence was higher in Germany than in the US, where the disease is well recognized as a public health threat. CONCLUSIONS All four public sources documented a decline in CDI cases since 2013, but the disease burden remains substantial and warrants continued attention as a severe public health challenge.
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27
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The Environment, Farm Animals and Foods as Sources of Clostridioides difficile Infection in Humans. Foods 2023; 12:foods12051094. [PMID: 36900611 PMCID: PMC10000743 DOI: 10.3390/foods12051094] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2022] [Revised: 02/21/2023] [Accepted: 02/28/2023] [Indexed: 03/08/2023] Open
Abstract
The recent discovery of the same Clostridioides difficile ribotypes associated with human infection in a broad range of environments, animals and foods, coupled with an ever-increasing rate of community-acquired infections, suggests this pathogen may be foodborne. The objective of this review was to examine the evidence supporting this hypothesis. A review of the literature found that forty-three different ribotypes, including six hypervirulent strains, have been detected in meat and vegetable food products, all of which carry the genes encoding pathogenesis. Of these, nine ribotypes (002, 003, 012, 014, 027, 029, 070, 078 and 126) have been isolated from patients with confirmed community-associated C. difficile infection (CDI). A meta-analysis of this data suggested there is a higher risk of exposure to all ribotypes when consuming shellfish or pork, with the latter being the main foodborne route for ribotypes 027 and 078, the hypervirulent strains that cause most human illnesses. Managing the risk of foodborne CDI is difficult as there are multiple routes of transmission from the farming and processing environment to humans. Moreover, the endospores are resistant to most physical and chemical treatments. The most effective current strategy is, therefore, to limit the use of broad-spectrum antibiotics while advising potentially vulnerable patients to avoid high-risk foods such as shellfish and pork.
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Incidence and Risk Factors for Clostridioides difficile Infections in Non-COVID and COVID-19 Patients: Experience from a Tertiary Care Hospital. Microorganisms 2023; 11:microorganisms11020435. [PMID: 36838400 PMCID: PMC9964032 DOI: 10.3390/microorganisms11020435] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2023] [Revised: 01/30/2023] [Accepted: 01/31/2023] [Indexed: 02/11/2023] Open
Abstract
(1) Background: The aim of this study was to assess the incidence and the risk factors for healthcare-associated Clostridioides difficile infection (HA-CDI) in patients with COVID-19 and without this infection. (2) Methods: A single-center, prospective observational study was conducted at the University Clinical Hospital Center in Belgrade, Serbia, from January 2019 to December 2021. The entire hospital was a COVID-dedicated hospital for 12 months during the study period. The incidence density rates and risk factors for HA-CDI in patients with and without COVID-19 are presented. (3) Results: The incidence rates of HA-CDIs were three times higher in patients with COVID-19. The HA-CDI-COVID-patients were younger (69.9 ± 12.6 vs. 72.5 ± 11.6; p = 0.017), admitted from another hospital (20.5% vs. 2.9; p < 0.001), had antimicrobial therapy before CDI (99.1% vs. 91.3%, p < 0.001), received two or more antibiotics (p = 0.030) during a longer period (p = 0.035), received proton pump inhibitors (95.9% vs. 50.0%, p < 0.001) during a longer period (p = 0.012) and steroids (32.8% vs. 20.4%, p < 0.001). During the last month before their current hospitalization, a higher percentage of patients without COVID-19 disease were hospitalized in our hospital (p < 0.001). Independent predictors for HA-CDIs in patients with COVID-19 were admission from another hospital (p = 0.003), the length of antibiotic administration (0.020), and the use of steroids in therapy (p < 0.001). The HA-CDI predictors in the non-COVID patients were older age (p = 0.017), advanced-stage renal failure (p = 0.005), chemotherapy (p = 0.003), and a low albumin level (0.005). (4) Conclusion: Higher incidence rates of HAI-CDIs in COVID-19 patients did not occur due to reduced infection control precautions and hygiene measures but due to antibiotic therapy and therapy with other drugs used during the pandemic.
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Stead S, Vogt L, Antons D, Salge TO, Gecht J, Klasen M, Sopka S. Hospital resource endowments and nosocomial infections: longitudinal evidence from the English National Health Service on Clostridioides difficile between 2011 and 2019. J Hosp Infect 2023; 134:129-137. [PMID: 36750139 DOI: 10.1016/j.jhin.2023.01.014] [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: 10/27/2022] [Revised: 01/30/2023] [Accepted: 01/30/2023] [Indexed: 02/07/2023]
Abstract
OBJECTIVES To identify key factors associated with Clostridioides difficile infections (CDIs) in healthcare at the hospital organization level. DESIGN Longitudinal study covering the period 2011-2019. Hospital reports were analysed to determine the number of CDIs and several hospital-related environmental factors: financial resources (i.e., cleaning expenditure), spatial resources (i.e., number of single rooms with a private bathroom), human resources (i.e., number of physicians and nursing staff) and cultural resources (i.e., error reporting climate). The relationships between the environmental factors and CDIs were analysed in a hybrid within- and between-hospital random-effect model. SETTING A total of 129 general hospital Trusts operating in the English National Health Service (NHS). PARTICIPANTS All inpatients in 129 general hospital trusts of the NHS in the years 2011-2019, covering 120,629 cases of CDI. MAIN OUTCOME MEASURE Annual number of CDIs per hospital trust. RESULTS Single rooms were associated with fewer CDIs at the within-hospital level, but not at the between-hospital level. Similarly, more nursing staff was associated with fewer CDIs at the within-hospital level, but not at the between-hospital level. This effect was not observed for physician staffing. A different picture emerged for the protective effect of cultural resources, with a weakly significant effect of between-hospital differences, but no within-hospital effect. Financial resources were not associated with CDIs either between hospitals or within them over time. CONCLUSIONS The present study identified hospital resources with a beneficial influence on CDI rates. Healthcare organizations can use this knowledge for active CDI prevention.
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Affiliation(s)
- S Stead
- Institute for Technology and Innovation Management, RWTH Aachen University, Aachen, Germany
| | - L Vogt
- Department of Anaesthesiology, Medical Faculty, University Hospital RWTH Aachen, Aachen, Germany; AIXTRA - Interdisciplinary Center for Training and Patient Safety, Medical Faculty RWTH Aachen, Aachen, Germany.
| | - D Antons
- Institute for Technology and Innovation Management, RWTH Aachen University, Aachen, Germany
| | - T O Salge
- Institute for Technology and Innovation Management, RWTH Aachen University, Aachen, Germany
| | - J Gecht
- Department of Anaesthesiology, Medical Faculty, University Hospital RWTH Aachen, Aachen, Germany; AIXTRA - Interdisciplinary Center for Training and Patient Safety, Medical Faculty RWTH Aachen, Aachen, Germany
| | - M Klasen
- Department of Anaesthesiology, Medical Faculty, University Hospital RWTH Aachen, Aachen, Germany; AIXTRA - Interdisciplinary Center for Training and Patient Safety, Medical Faculty RWTH Aachen, Aachen, Germany
| | - S Sopka
- Department of Anaesthesiology, Medical Faculty, University Hospital RWTH Aachen, Aachen, Germany; AIXTRA - Interdisciplinary Center for Training and Patient Safety, Medical Faculty RWTH Aachen, Aachen, Germany
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Stojanovic P, Harmanus C, Kuijper EJ. Community-onset Clostridioides difficile infection in south Serbia. Anaerobe 2023; 79:102669. [PMID: 36455757 DOI: 10.1016/j.anaerobe.2022.102669] [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: 09/01/2022] [Revised: 11/15/2022] [Accepted: 11/20/2022] [Indexed: 11/30/2022]
Abstract
BACKGROUND Data from the past decade indicates that Clostridioides difficile infection (CDI) is not only a nosocomial infection but is also increasingly recognized as a disease in the community. OBJECTIVE We aimed to study community-onset (CO) CDI in the various age groups in south Serbia with its clinical characteristics, risk factors and microbiological characterization. METHODS The study group included 93 patients with CO-CDI (median age 62). The control group consisted of 186 patients with community-onset diarrhea and stool samples negative tested for CDI. RESULTS Of all CDI cases diagnosed with a community onset, 74.19% had a previous contact with a healthcare facility in the previous 12 weeks, but 34.40% have no record on hospitalization in the previous 12 months. Using a multivariate statistical regression model, the following risk factors for CO-CDI development were found; antacid usage (OR = 0.267, 95%C.I.:0.10-0.291, p < 0.01), chronic kidney disease (OR = 0.234, 95%C.I.:0.10-0.51, p < 0.01) and antibiotic use during the prior 2 months (OR = 0.061, 95%C.I.:0.02-0.17, p < 0.01), especially tetracycline's (OR = 0.146, 95% C.I.:0.07-0.22, p < 0.01) and cephalosporin's (OR = 0.110, 95%C.I.:0.14-0.42, p < 0.01). The most common ribotypes (RTs) detected in patients with CO-CDI were RT001 (32.3%) and RT027 (24.7%). All tested toxin producing C. difficile isolates were sensitive to metronidazole, vancomycin and tigecycline. A high rate of resistance to moxifloxacin (73.11%) and rifampicin (23.65%) was found. CONCLUSION Patients with CO-CDI had frequently contact with healthcare facility in the previous 12 weeks. Restriction of antacid usage and of high-risk antibiotics in the community may help reduce the incidence of CO-CDI.
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Affiliation(s)
- Predrag Stojanovic
- Faculty of Medicine, University of Niš, Zorana Đinđića 50, 18000, Niš, Serbia; Institute for Public Health Nis, Center of Microbiology, 18000, Niš, Serbia(1).
| | - Celine Harmanus
- Department of Medical Microbiology, Center for Infectious Diseases, National Expertise Center for Clostridioides difficile infections, National Institute of Public Health and the Environment, Leiden University Medical Center, PO Box 9600, 2300RC, Leiden, the Netherlands
| | - Ed J Kuijper
- Department of Medical Microbiology, Center for Infectious Diseases, National Expertise Center for Clostridioides difficile infections, National Institute of Public Health and the Environment, Leiden University Medical Center, PO Box 9600, 2300RC, Leiden, the Netherlands
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Santhanam P, Egberg M, Kappelman MD. Higher mortality rates associated with Clostridioides difficile infection in hospitalized children with cystic fibrosis. Pediatr Pulmonol 2023; 58:484-491. [PMID: 36349995 DOI: 10.1002/ppul.26214] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/06/2022] [Revised: 08/18/2022] [Accepted: 09/28/2022] [Indexed: 11/10/2022]
Abstract
OBJECTIVE(S) To determine the association of Clostridioides difficile Infection (CDI) with in-hospital mortality, Length of Stay (LOS), and hospital charges among pediatric Cystic Fibrosis (CF) hospitalizations using a large nationally representative pediatric hospital database. STUDY DESIGN We identified Cystic Fibrosis-related hospitalizations during the years 1997 to 2016 in the Kids' Inpatient Database (KID) and compared in-hospital mortality, LOS, and hospital charges among hospitalizations with and without a coexisting diagnosis of C. difficile using logistic regression models for mortality and general linear models with gamma distribution and logarithmic transformation for LOS and hospital charges. We also evaluated temporal trends in the proportion of CF hospitalizations with concomitant CDI using data published triennially RESULTS: We analyzed 21,616 pediatric CF hospitalizations between the years 1997 to 2016 and found a total of 240 (1.1%) hospitalizations with concurrent CDI diagnosis. Adjusted analyses demonstrated an association of CDI with increased mortality (OR 5.2, 95% CI 2.5-10.7), longer LOS (46.5% increment, 95% CI 36.0-57.1), and higher charges (65.8% increment, 95% CI 53.5-78.1) for all comparisons. The proportion of CF hospitalizations with CDI increased over time from 0.64% in 1997 to 1.73% in 2016 (p < 0.001). CONCLUSION(S) As CDI is associated with excess mortality, LOS, and cost in children hospitalized for CF, a healthy level of suspicion for CDI may be needed in patients with CF in the appropriate clinical context. Efforts to prevent, diagnose, and treat CDI may improve hospital outcomes among children with CF.
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Affiliation(s)
- Prathipa Santhanam
- Division of Pediatric Gastroenterology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
| | - Matthew Egberg
- Division of Pediatric Gastroenterology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.,Multidisciplinary Center for Inflammatory Bowel Diseases, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.,Center for Gastrointestinal Biology and Disease, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
| | - Michael D Kappelman
- Division of Pediatric Gastroenterology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.,Multidisciplinary Center for Inflammatory Bowel Diseases, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.,Center for Gastrointestinal Biology and Disease, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
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Legenza L, Coetzee R, Rose WE, Esack T, Crombie K, Mina M, Safdar N, Barnett SG. Application of consolidated framework for implementation research to improve Clostridioides difficile infection management in district hospitals. Res Social Adm Pharm 2022; 18:4100-4111. [PMID: 35981939 PMCID: PMC9891768 DOI: 10.1016/j.sapharm.2022.07.046] [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: 08/27/2021] [Revised: 06/08/2022] [Accepted: 07/26/2022] [Indexed: 02/03/2023]
Abstract
BACKGROUND Clostridioides difficile infection (CDI) contributes the global threats of drug resistant infections, healthcare acquired infections and antimicrobial resistance. Yet CDI knowledge among healthcare providers in low-resource settings is limited and CDI testing, treatment, and infection prevention measures are often delayed. OBJECTIVES to develop a CDI intervention informed by the local context within South African public district level hospitals, and analyze the CDI intervention and implementation process. METHODS A CDI checklist intervention was designed and implemented at three district level hospitals in the Western Cape, South Africa that volunteered to participate. Data collection included a retrospective medical records review of patients hospitalized with C. difficile test orders during the 90 days post-implementation. Patient outcomes and checklist components (e.g. antibiotics) were collected. Qualitative interviews (n = 14) and focus groups (n = 6) were conducted with healthcare providers on-site. The Consolidated Framework for Implementation Research (CFIR) and the Framework for Reporting Adaptations and Modifications to Evidence-based Implementation Strategies (FRAME-IS) were applied to collected data and observations in order to identify drivers and barriers to implementation and understand differences in uptake. RESULTS One of the three hospitals displayed high intervention uptake. Highly relevant CFIR constructs linked to intervention uptake included tension for change, strong peer intervention champions, champions in influential leadership positions, and the intervention's simplicity (CFIR construct: complexity). Tension for change, a recognized need to improve CDI identification and treatment, at the high uptake hospital was also supported by an academic partnership for antimicrobial stewardship. CONCLUSIONS This research provides a straight-forward health systems strengthening intervention for CDI that is both needed and uncomplicated, in an understudied low resource setting. Intervention uptake was highest in the hospital with tension for change, influential champions, and existing academic partnerships. Implementation in settings with fewer academic connections requires further testing of collaborative implementation strategies and proactive adaptations.
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Affiliation(s)
- Laurel Legenza
- University of Wisconsin-Madison School of Pharmacy, 777 Highland Ave, Madison, WI, 53705, United States; University of the Western Cape School of Pharmacy, Robert Sobukwe, Cape Town, 7535, South Africa.
| | - Renier Coetzee
- University of the Western Cape School of Pharmacy, Robert Sobukwe, Cape Town, 7535, South Africa; University of the Western Cape School of Public Health, Robert Sobukwe, Cape Town, 7535, South Africa
| | - Warren E Rose
- University of Wisconsin-Madison School of Pharmacy, 777 Highland Ave, Madison, WI, 53705, United States
| | - Tasneem Esack
- Victoria Hospital, Wynberg, Cape Town, 7800, South Africa
| | - Kenneth Crombie
- University of Cape Town, Rondebosch, Cape Town, 7700, South Africa
| | - Megan Mina
- University of Cape Town, Rondebosch, Cape Town, 7700, South Africa; General Justice Gizenga Mpanza Regional Hospital, KwaDukuza, KwaZulu-Natal, 4450, South Africa
| | - Nasia Safdar
- University of Wisconsin School of Medicine and Public Health, 750 Highland Ave, Madison, WI, 53726, United States
| | - Susanne G Barnett
- University of Wisconsin-Madison School of Pharmacy, 777 Highland Ave, Madison, WI, 53705, United States
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Persson S, Nielsen HL, Coia JE, Engberg J, Olesen BS, Engsbro AL, Petersen AM, Holt HM, Lemming L, Marmolin ES, Søndergaard TS, Andersen LP, Jensen MBF, Wiuff C, Sørensen G, Nielsen SH, Nielsen EM. Sentinel surveillance and epidemiology of Clostridioides difficile in Denmark, 2016 to 2019. Euro Surveill 2022; 27:2200244. [PMID: 36695439 PMCID: PMC9732923 DOI: 10.2807/1560-7917.es.2022.27.49.2200244] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2022] [Accepted: 07/06/2022] [Indexed: 12/13/2022] Open
Abstract
BackgroundSince 2008, Danish national surveillance of Clostridioides difficile has focused on binary toxin-positive strains in order to monitor epidemic types such as PCR ribotype (RT) 027 and 078. Additional surveillance is needed to provide a more unbiased representation of all strains from the clinical reservoir.AimSetting up a new sentinel surveillance scheme for an improved understanding of type distribution relative to time, geography and epidemiology, here presenting data from 2016 to 2019.MethodsFor 2─4 weeks in spring and autumn each year between 2016 and 2019, all 10 Danish Departments of Clinical Microbiology collected faecal samples containing toxigenic C. difficile. Isolates were typed at the national reference laboratory at Statens Serum Institut. The typing method in 2016-17 used tandem-repeat-sequence typing, while the typing method in 2018-19 was whole genome sequencing.ResultsDuring the study period, the sentinel surveillance scheme included ca 14-15% of all Danish cases of C. difficile infections. Binary toxin-negative strains accounted for 75% and 16 of the 20 most prevalent types. The most common sequence types (ST) were ST2/13 (RT014/020) (19.5%), ST1 (RT027) (10.8%), ST11 (RT078) (6.7%), ST8 (RT002) (6.6%) and ST6 (RT005/117) (5.1%). The data also highlighted geographical differences, mostly related to ST1 and temporal decline of ST1 (p = 0.0008) and the increase of ST103 (p = 0.002), ST17 (p = 0.004) and ST37 (p = 0.003), the latter three binary toxin-negative.ConclusionSentinel surveillance allowed nationwide monitoring of geographical differences and temporal changes in C. difficile infections in Denmark, including emerging types, regardless of binary toxin status.
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Affiliation(s)
- Søren Persson
- Department of Bacteria, Parasites and Fungi, Statens Serum Institut, Copenhagen, Denmark
| | - Hans Linde Nielsen
- Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
- Department of Clinical Microbiology, Aalborg University Hospital, Aalborg, Denmark
| | - John Eugenio Coia
- Department of Regional Health Research IRS, University of Southern Denmark, Esbjerg, Denmark
- Department of Clinical Microbiology, Esbjerg Hospital, University of Southern Denmark, Esbjerg, Denmark
| | - Jørgen Engberg
- Department of Clinical Microbiology, Zealand University Hospital, Køge, Denmark
| | - Bente Scharvik Olesen
- Department of Clinical Microbiology, Copenhagen University Hospital - Herlev and Gentofte, Herlev, Denmark
| | - Anne Line Engsbro
- Department of Clinical Microbiology, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark
| | - Andreas Munk Petersen
- Department of Gastroenterology, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark
- Department of Clinical Microbiology, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark
| | - Hanne Marie Holt
- Department of Clinical Microbiology, Odense University Hospital, Odense, Denmark
| | - Lars Lemming
- Department of Clinical Microbiology, Aarhus University Hospital, Aarhus, Denmark
| | | | | | - Leif Percival Andersen
- Department of Clinical Microbiology, Copenhagen University Hospital (Rigshospitalet), Copenhagen, Denmark
| | | | - Camilla Wiuff
- Department of Clinical Microbiology, Esbjerg Hospital, University of Southern Denmark, Esbjerg, Denmark
| | - Gitte Sørensen
- Department of Bacteria, Parasites and Fungi, Statens Serum Institut, Copenhagen, Denmark
| | | | - Eva Møller Nielsen
- Department of Bacteria, Parasites and Fungi, Statens Serum Institut, Copenhagen, Denmark
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Magnusson C, Mernelius S, Bengnér M, Norén T, Serrander L, Forshell S, Matussek A. Characterization of a Clostridioides difficile outbreak caused by PCR ribotype 046, associated with increased mortality. Emerg Microbes Infect 2022; 11:850-859. [PMID: 35240942 PMCID: PMC8942542 DOI: 10.1080/22221751.2022.2049981] [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] [Indexed: 11/16/2022]
Abstract
This study describes a large nosocomial outbreak of Clostridioides difficile infections (CDI) dominated by ribotype (RT) 046 in a Swedish hospital. The present study aimed to examine the pathogenicity of this RT, explore epidemiological links by whole genome sequencing (WGS), and evaluate different interventions implemented to stop the outbreak. Clinical isolates (n = 366) collected during and after the outbreak were ribotyped and 246 isolates were subjected to WGS. Medical records of patients infected with the seven most common RTs were evaluated. RT046 was spread effectively throughout the hospital and was the most common among the 44 different RTs found (114/366 isolates). Infection with RT046 was associated with higher mortality compared to other strains (20.2% to 7.8%), although there were no differences in concomitant disease, age or antibiotic treatment. To control the outbreak, several measures were successfully implemented.
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Affiliation(s)
- Cecilia Magnusson
- Department of Infectious Diseases, Region Jönköping County, Jönköping and Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden
| | - Sara Mernelius
- Laboratory Medicine, Region Jönköping County, Jönköping and Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden
| | - Malin Bengnér
- Office for control of Communicable Diseases, Region Jönköping County, Jönköping, Sweden
| | - Torbjörn Norén
- Faculty of Medicine and Health, Department of Laboratory Medicine, National Reference Laboratory for Clostridioides difficile, Clinical Microbiology, Örebro University, Örebro, Sweden
| | - Lena Serrander
- Division of Clinical Microbiology, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden
| | - Sophie Forshell
- Department of Infectious Diseases, Region Jönköping County, Jönköping and Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden
| | - Andreas Matussek
- Laboratory Medicine, Region Jönköping County, Jönköping and Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden.,Division of Laboratory Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.,Division of Laboratory Medicine, Oslo University Hospital, Oslo, Norway
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Kiersnowska ZM, Lemiech-Mirowska E, Michałkiewicz M, Sierocka A, Marczak M. Detection and Analysis of Clostridioides difficile Spores in a Hospital Environment. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2022; 19:15670. [PMID: 36497742 PMCID: PMC9740219 DOI: 10.3390/ijerph192315670] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 10/07/2022] [Revised: 11/19/2022] [Accepted: 11/22/2022] [Indexed: 06/17/2023]
Abstract
Clostridioides difficile, due to its long survival time in a hospital environment, is considered to be one of the most frequent factors in healthcare-associated infections. Patient care requires not only rapid and accurate diagnosis, but also knowledge of individual risk factors for infections, e.g., with C. difficile, in various clinical conditions. The goal of this study was to analyse the degree of contamination of a hospital environment with C. difficile spores. Culturing was performed using C diff Banana BrothTM medium, which enables germination of the spores of these bacteria. Samples were collected from inanimate objects within a hospital environment in a specialist hospital in Poland. The results of the study demonstrated the presence of 18 positive samples of Clostridioides spp. (15.4%). Of these, C. difficile spores were detected in six samples, Clostridioides perfringens in eight samples, Clostridioides sporogenes in two samples and Clostridioides innocuum and Clostridioides baratii in one sample each. Among the six samples of C. difficile, a total of four strains which produce the B toxin were cultured. The binary toxin related to ribotype 027 was not detected in our study. Nosocomial infection risk management is a significant problem, mainly concerning the issues of hygiene maintenance, cleaning policy and quality control, and awareness of infection risk.
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Affiliation(s)
- Zofia Maria Kiersnowska
- Department of Management and Logistics in Healthcare, Medical University of Lodz, 90-419 Lodz, Poland
| | - Ewelina Lemiech-Mirowska
- Department of Management and Logistics in Healthcare, Medical University of Lodz, 90-419 Lodz, Poland
| | - Michał Michałkiewicz
- Institute of Environmental Engineering and Building Installations, Faculty of Environmental Engineering and Energy, Poznan University of Technology, 60-965 Poznan, Poland
| | - Aleksandra Sierocka
- Department of Management and Logistics in Healthcare, Medical University of Lodz, 90-419 Lodz, Poland
| | - Michał Marczak
- Department of Management and Logistics in Healthcare, Medical University of Lodz, 90-419 Lodz, Poland
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Tsai CS, Cheng YL, Chen JS, Tsai PJ, Tsai BY, Hsu BM, Huang IH. Hypervirulent Clostridioides difficile RT078 lineage isolates from the river: A potential reservoir for environmental transmission. JOURNAL OF MICROBIOLOGY, IMMUNOLOGY, AND INFECTION = WEI MIAN YU GAN RAN ZA ZHI 2022; 55:977-981. [PMID: 35739056 DOI: 10.1016/j.jmii.2022.05.002] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/10/2021] [Revised: 03/27/2022] [Accepted: 05/12/2022] [Indexed: 06/15/2023]
Abstract
This is the first report to discover Clostridiodes difficile (C. difficile) ribotype RT126 and RT598 (both ribotypes belong to RT078-lineage) in a river water system in southern Taiwan. Fluoroquinolone resistance was also found. The connection between clinical isolates and those from the environment needs further investigation.
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Affiliation(s)
- Chin-Shiang Tsai
- Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Department of Internal Medicine, National Cheng Kung University Hospital, Dou-Liou Branch, College of Medicine, National Cheng Kung University, Yunlin, Taiwan; Department of Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Ya-Lien Cheng
- Department of Microbiology and Immunology, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Jung-Sheng Chen
- Department of Medical Research, E-Da Hospital, Kaohsiung City, Taiwan
| | - Pei-Jane Tsai
- Department of Medical Laboratory Science and Biotechnology, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Bo-Yang Tsai
- Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Bing-Mu Hsu
- Department of Earth and Environmental Sciences, National Chung Cheng University, Chiayi, Taiwan
| | - I-Hsiu Huang
- Department of Biochemistry and Microbiology, Oklahoma State University Center for Health Sciences, USA.
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Gonzalez CA, Van Rysselberghe NL, Maschhoff C, Gardner MJ. Clostridium difficile colitis portends poor outcomes in lower extremity orthopaedic trauma surgery. Injury 2022; 53:3458-3463. [PMID: 36002345 DOI: 10.1016/j.injury.2022.08.026] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/23/2022] [Revised: 07/26/2022] [Accepted: 08/10/2022] [Indexed: 02/02/2023]
Abstract
INTRODUCTION Clostridium difficile is the most common cause of healthcare-associated infectious diarrhea and colitis, and carries the potential for high morbidity, particularly in frail patient populations. The purpose of this study was to utilize a large nationally representative database in order to report 1.) the incidence of CDC in patients with operative lower extremity fractures, 2.) risk factors for the development of CDC, 3.) the association of CDC with length of stay (LOS), readmission, and 30-day mortality rates. METHODS The ACS-NSQIP (2015-2019) was queried for patients who underwent surgical fixation of lower extremity fractures. A backward elimination multivariate regression model was used to identify risk factors for CDC. Chi squared and multivariate regression that controlled for preoperative variables and comorbidities were used to compare outcomes in patients with and without CDC. RESULTS 95,532 patients were included, 681 (0.71%) of whom developed CDC. Risk factors for CDC were advanced age, ASA class ≥ 3, smoking, dialysis, anemia, hypoalbuminemia, preoperative SIRS, preoperative wound infections, preoperative sepsis, and the use of spinal anesthesia or MAC/IV sedation. Patients with CDC had significantly increased 30-day mortality rates (10.6% vs 4.4%; OR 1.80, 95% CI 1.41-2.31), readmission (34.2% vs 7.5%; OR 5.13, 95% CI 4.36-6.05, and length of stay (7.5 days vs 5.3 days) compared to patients without CDC. CONCLUSION The incidence of CDC in lower extremity orthopedic trauma patients was 0.71%. An occurrence of CDC was associated with approximately a 2.5 times increase in 30-day mortality, five times the readmission rate, and a longer hospital stay compared to patients without CDC. Mitigating the spread of c. diff through improved antibiotic stewardship and prompt treatment of CDC is paramount to decreasing the burden this infection imposes on orthopedic trauma patients and the healthcare system.
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Affiliation(s)
- Christian A Gonzalez
- University of Nevada, Reno School of Medicine, 1664N Virginia St Reno, NV 89557, USA.
| | | | | | - Michael J Gardner
- Department of Orthopaedic Surgery, Stanford University, Stanford, CA, USA
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Singh S, Newton-Foot M, Nel P, Pienaar C. Comparison of commercial assays and two-step approach to detect Clostridioides difficile in South Africa. Afr J Lab Med 2022; 11:1809. [PMID: 36263391 PMCID: PMC9575369 DOI: 10.4102/ajlm.v11i1.1809] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2021] [Accepted: 05/26/2022] [Indexed: 11/06/2022] Open
Abstract
Background Clostridioides difficile is the number one cause of hospital-acquired diarrhoea. Accurate diagnosis of C. difficile is of utmost importance as it guides patient management and infection control practices. Studies evaluating the performance of commercially available nucleic acid amplification tests (NAATs) versus algorithms are lacking in resource-limited settings. Objective This study assessed the performance of three commercially available tests and a two-step approach for the diagnosis of C. difficile infection using toxigenic culture (TC) as the gold standard. Methods Two hundred and twenty-three non-duplicate loose stool samples were submitted to the National Health Laboratory Service Microbiology Laboratory at Tygerberg Hospital, Cape Town, South Africa, from October 2017 to October 2018. The samples were tested in parallel using the C. DIFF QUIK CHEK COMPLETE enzyme immunoassay (EIA) and two NAATs (Xpert C. difficile and BD MAX Cdiff), and the results were compared to TC. The performance of a two-step approach consisting of the C. DIFF QUIK CHEK COMPLETE followed by the Xpert C. difficile was also determined. Results Of 223 faecal specimens tested, 37 (16.6%) were TC-positive. The sensitivity and specificity of the C. DIFF QUIK CHEK COMPLETE were 54.1% and 98.9%; Xpert C. difficile, 86.4% and 96.8%; BD MAX Cdiff, 89.2% and 96.8%; and two-step approach, 89.2% and 96.2%. Conclusion The C. DIFF QUIK CHEK COMPLETE, in a two-step approach with the Xpert C. difficile, performed similarly to the NAATs on their own and offer advantages in terms of cost and workflow in low-resource settings.
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Affiliation(s)
- Sarishna Singh
- National Health Laboratory Service Tygerberg Academic Laboratory, Division of Medical Microbiology, Tygerberg Hospital, Tygerberg, South Africa,Division of Medical Microbiology, Department of Pathology, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa
| | - Mae Newton-Foot
- National Health Laboratory Service Tygerberg Academic Laboratory, Division of Medical Microbiology, Tygerberg Hospital, Tygerberg, South Africa,Division of Medical Microbiology, Department of Pathology, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa
| | - Pieter Nel
- National Health Laboratory Service Tygerberg Academic Laboratory, Division of Medical Microbiology, Tygerberg Hospital, Tygerberg, South Africa,Division of Medical Microbiology, Department of Pathology, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa
| | - Colette Pienaar
- National Health Laboratory Service Tygerberg Academic Laboratory, Division of Medical Microbiology, Tygerberg Hospital, Tygerberg, South Africa,Division of Medical Microbiology, Department of Pathology, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa
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Perić A, Rančić N, Dragojević-Simić V, Milenković B, Ljubenović N, Rakonjac B, Begović-Kuprešanin V, Šuljagić V. Association between Antibiotic Use and Hospital-Onset Clostridioides difficile Infection in University Tertiary Hospital in Serbia, 2011–2021: An Ecological Analysis. Antibiotics (Basel) 2022; 11:antibiotics11091178. [PMID: 36139957 PMCID: PMC9495030 DOI: 10.3390/antibiotics11091178] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2022] [Revised: 08/24/2022] [Accepted: 08/26/2022] [Indexed: 11/16/2022] Open
Abstract
This ecological study is the largest to date examining the association between rates of antibiotic use (AU) and hospital-onset (HO) Clostridioides difficile infection (CDI) in a tertiary university hospital in Serbia. There was no clear trend in the incidence of HO-CDI over time. Total utilization of antibacterials for systemic use increased from 38.57 DDD/100 bed-days (BD) in 2011 to 56.39 DDD/100 BD in 2021. The most commonly used antibiotics were third-generation cephalosporins, especially ceftriaxone, with maximum consumption in 2021 (19.14 DDD/100 BD). The share of the Access group in the total utilization of antibiotics ranged from 29.95% to 42.96% during the observed period. The utilization of the Reserve group of antibiotics indicated a statistically significant increasing trend (p = 0.034). A statistically significant difference in the consumption of medium-risk antibiotics from 2011 to 2021 was shown for penicillins and a combination of sulfamethoxazole and trimethoprim. The consumption of cefotaxime showed a statistically significant negative association with the rate of HO-CDI (r = −0.647; p = 0.031). Ampicillin and the combination of amoxicilline with clavulanic acid have shown a negative statistically significant correlation with the ID of HO-CDI (r = −0.773 and r = −0.821, respectively). Moreover, there was a statistically significant negative correlation between consumption of “medium-risk antibiotics” and the rate of HO-CDI (r = −0.677). The next challenging step for the hospital multidisciplinary team for antimicrobials is to modify the antibiotic list according to the Access, Watch, and Reserve classification, in such a way that at least 60% of the AU should be from the Access group, according to the World Health Organization recommendation.
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Affiliation(s)
- Aneta Perić
- Department for Pharmacy, Military Medical Academy, 11000 Belgrade, Serbia
- Medical Faculty, Military Medical Academy, University of Defence, 11000 Belgrade, Serbia
| | - Nemanja Rančić
- Medical Faculty, Military Medical Academy, University of Defence, 11000 Belgrade, Serbia
- Centre for Clinical Pharmacology, Military Medical Academy, 11000 Belgrade, Serbia
- Correspondence:
| | - Viktorija Dragojević-Simić
- Medical Faculty, Military Medical Academy, University of Defence, 11000 Belgrade, Serbia
- Centre for Clinical Pharmacology, Military Medical Academy, 11000 Belgrade, Serbia
| | - Bojana Milenković
- Department for Pharmacy, Military Medical Academy, 11000 Belgrade, Serbia
| | - Nenad Ljubenović
- Institute of Epidemiology, Military Medical Academy, 11000 Belgrade, Serbia
| | - Bojan Rakonjac
- Institute of Medical Microbiology, Military Medical Academy, 11000 Belgrade, Serbia
| | - Vesna Begović-Kuprešanin
- Medical Faculty, Military Medical Academy, University of Defence, 11000 Belgrade, Serbia
- Clinic for Infectious and Tropic Diseases, Military Medical Academy, 11000 Belgrade, Serbia
| | - Vesna Šuljagić
- Medical Faculty, Military Medical Academy, University of Defence, 11000 Belgrade, Serbia
- Department of Healthcare-Related Infection Control, Military Medical Academy, 11000 Belgrade, Serbia
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Schnizlein MK, Young VB. Capturing the environment of the Clostridioides difficile infection cycle. Nat Rev Gastroenterol Hepatol 2022; 19:508-520. [PMID: 35468953 DOI: 10.1038/s41575-022-00610-0] [Citation(s) in RCA: 37] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 03/21/2022] [Indexed: 12/11/2022]
Abstract
Clostridioides difficile (formerly Clostridium difficile) infection is a substantial health and economic burden worldwide. Great strides have been made over the past several years in characterizing the physiology of C. difficile infection, particularly regarding how gut microorganisms and their host work together to provide colonization resistance. As mammalian hosts and their indigenous gut microbiota have co-evolved, they have formed a complex yet stable relationship that prevents invading microorganisms from establishing themselves. In this Review, we discuss the latest advances in our understanding of C. difficile physiology that have contributed to its success as a pathogen, including its versatile survival factors and ability to adapt to unique niches. Using discoveries regarding microorganism-host and microorganism-microorganism interactions that constitute colonization resistance, we place C. difficile within the fiercely competitive gut environment. A comprehensive understanding of these relationships is required to continue the development of precision medicine-based treatments for C. difficile infection.
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Affiliation(s)
- Matthew K Schnizlein
- Department of Microbiology and Immunology, University of Michigan, Ann Arbor, MI, USA
| | - Vincent B Young
- Department of Microbiology and Immunology, University of Michigan, Ann Arbor, MI, USA.
- Department of Internal Medicine/Division of Infectious Diseases, University of Michigan Medical School, Ann Arbor, MI, USA.
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Lin M, Li Z, Lin Q, Wang P, Liu W, Yuan J, Hong Z, Chen Y. Development and Clinical Application of a Rapid and Visual Loop-Mediated Isothermal Amplification Test for tetM gene in Clostridioides difficile Strains Cultured from Feces. Int J Infect Dis 2022; 122:676-684. [PMID: 35843495 DOI: 10.1016/j.ijid.2022.07.032] [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: 01/20/2022] [Revised: 04/23/2022] [Accepted: 07/09/2022] [Indexed: 10/17/2022] Open
Abstract
OBJECTIVES To develop a rapid and visual loop-mediated isothermal amplification (LAMP) assay targeting the tetM gene in Clostridioides difficile (C. difficile) strains cultured from feces. METHODS Primers were designed to recognize the tetM gene in C. difficile by LAMP, using turbidity and visual detection. The sensitivity and specificity of LAMP primers was determined. Besides, We conducted both LAMP and polymerase chain reaction (PCR) for the tcdA, tcdB, cdtA, cdtB, ermB, tetM genes in 300 toxigenic C. difficile strains cultured from feces. RESULTS The target DNA was amplified and visualized within 60 minutes at a temperature of 62°C. A total of 26 bacterial strains were found negative for tetM, which manifested high specificity of the primers. The detection limit of LAMP was 36.1 pg/µl, which was 100-fold more sensitive than PCR. The positive rate of tetM in toxigenic C. difficile strains cultured from feces was 93.3% by both LAMP and PCR. The proportion of toxin types in those C. difficile strains was 95.7% for A+B+CDT-, 4% for A-B+CDT-, and 0.3% for A+B+CDT+, respectively. CONCLUSIONS This is the first study examining tetM gene in C. difficile strains cultured from feces by LAMP. Its high specificity and sensitivity, as well as visual detection, make the new assay a powerful diagnostic tool for rapid testing.
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Affiliation(s)
- Minyi Lin
- Department of Infectious Diseases, The Fifth Affiliated Hospital, Sun Yat-Sen University, 52 East Meihua Road, Zhuhai, 519000, China
| | - Zitong Li
- Department of Gastroenterology, Guangdong Provincial Key Laboratory of Gastroenterology, State Key Laboratory of Organ Failure Research, Nanfang Hospital, Southern Medical University, 1838 North Guangzhou Ave. Guangzhou, China
| | - Qianyun Lin
- Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, No. 95, Yong An Road, Xi Cheng District, Beijing, 100050, China
| | - Pu Wang
- Department of Gastroenterology, Guangdong Provincial Key Laboratory of Gastroenterology, State Key Laboratory of Organ Failure Research, Nanfang Hospital, Southern Medical University, 1838 North Guangzhou Ave. Guangzhou, China
| | - Wei Liu
- Institute of Disease Control and Prevention, Academy of Military Medical Sciences, 20 Dongda Street, Fengtai District, Beijing, 100071, China
| | - Jing Yuan
- Institute of Disease Control and Prevention, Academy of Military Medical Sciences, 20 Dongda Street, Fengtai District, Beijing, 100071, China
| | - Zhongsi Hong
- Department of Infectious Diseases, The Fifth Affiliated Hospital, Sun Yat-Sen University, 52 East Meihua Road, Zhuhai, 519000, China.
| | - Ye Chen
- Department of Gastroenterology, Integrative Microecology Center, Shenzhen Hospital, Southern Medical University, 1333 New Lake Road, Shenzhen, 518100, China.
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Towards Development of a Non-Toxigenic Clostridioides difficile Oral Spore Vaccine against Toxigenic C. difficile. Pharmaceutics 2022; 14:pharmaceutics14051086. [PMID: 35631671 PMCID: PMC9146386 DOI: 10.3390/pharmaceutics14051086] [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: 04/18/2022] [Revised: 05/12/2022] [Accepted: 05/16/2022] [Indexed: 11/24/2022] Open
Abstract
Clostridioides difficile is an opportunistic gut pathogen which causes severe colitis, leading to significant morbidity and mortality due to its toxins, TcdA and TcdB. Two intra-muscular toxoid vaccines entered Phase III trials and strongly induced toxin-neutralising antibodies systemically but failed to provide local protection in the colon from primary C. difficile infection (CDI). Alternatively, by immunising orally, the ileum (main immune inductive site) can be directly targeted to confer protection in the large intestine. The gut commensal, non-toxigenic C. difficile (NTCD) was previously tested in animal models as an oral vaccine for natural delivery of an engineered toxin chimera to the small intestine and successfully induced toxin-neutralising antibodies. We investigated whether NTCD could be further exploited to induce antibodies that block the adherence of C. difficile to epithelial cells to target the first stage of pathogenesis. In NTCD strain T7, the colonisation factor, CD0873, and a domain of TcdB were overexpressed. Following oral immunisation of hamsters with spores of recombinant strain, T7-0873 or T7-TcdB, intestinal and systemic responses were investigated. Vaccination with T7-0873 successfully induced intestinal antibodies that significantly reduced adhesion of toxigenic C. difficile to Caco-2 cells, and these responses were mirrored in sera. Additional engineering of NTCD is now warranted to further develop this vaccine.
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Subirats J, Sharpe H, Topp E. Fate of Clostridia and other spore-forming Firmicute bacteria during feedstock anaerobic digestion and aerobic composting. JOURNAL OF ENVIRONMENTAL MANAGEMENT 2022; 309:114643. [PMID: 35151135 DOI: 10.1016/j.jenvman.2022.114643] [Citation(s) in RCA: 28] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/05/2021] [Revised: 01/26/2022] [Accepted: 01/30/2022] [Indexed: 06/14/2023]
Abstract
Pathogenic spore-forming Firmicutes are commonly present in animal and human wastes that are used as fertilizers in crop production. Pre-treatments of organic waste prior to land application offer the potential to abate enteric microorganisms, and therefore reduce the risk of contamination of crops or adjacent water resources with pathogens carried in these materials. The inactivation and reduction of gram-positive spore formers such as Clostridium spp., Clostridioides spp. and Bacillus spp. from animal and human waste can be challenging given the recalcitrance of the spores these bacteria produce. Given the significance of these organisms to human and animal health, information concerning spore-forming bacteria inactivation during anaerobic digestion (AD) and aerobic composting (AC) is required as the basis for recommending safe organic waste management practices. In this review, an assessment of the inactivation of spore-forming Firmicutes during AD and AC was conducted to provide guidance for practical management of organic matrices of animal or human origin. Temperature and pH may be the main factors contributing to the inactivation of spore-forming Firmicutes during batch lab-scale AD (log reduction <0.5-5 log). In continuous digesters, wet AD systems do not effectively inactivate spore-forming Firmicutes even under thermopholic conditions (log reduction -1.09 - 0.98), but dry AD systems could be a feasible management practice to inactivate spore-forming Firmicutes from organic materials with high solid content (log reduction 1.77-3.1). In contrast, composting is an effective treatment to abate spore-forming Firmicutes (log reduction 1.7-6.5) when thermophilic conditions last at least six consecutive days. Temperature, moisture content and composting scale are the key operating conditions influencing the inactivation of spore-forming Firmicutes during composting. Where possible, undertaking AD with subsequent composting to ensure the biosafety of digestate before its downstream processing and recycling is recommended to abate recalcitrant bacteria in digestate.
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Affiliation(s)
- Jessica Subirats
- Agriculture and Agri-Food Canada, London Research and Development Centre, London, Ontario, Canada; Department of Biology, University of Western Ontario, London, Ontario, Canada.
| | - Hannah Sharpe
- Agriculture and Agri-Food Canada, London Research and Development Centre, London, Ontario, Canada; Department of Biology, University of Western Ontario, London, Ontario, Canada
| | - Edward Topp
- Agriculture and Agri-Food Canada, London Research and Development Centre, London, Ontario, Canada; Department of Biology, University of Western Ontario, London, Ontario, Canada.
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Wang S, Heuler J, Wickramage I, Sun X. Genomic and Phenotypic Characterization of the Nontoxigenic Clostridioides difficile Strain CCUG37785 and Demonstration of Its Therapeutic Potential for the Prevention of C. difficile Infection. Microbiol Spectr 2022; 10:e0178821. [PMID: 35315695 PMCID: PMC9045287 DOI: 10.1128/spectrum.01788-21] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2021] [Accepted: 02/19/2022] [Indexed: 01/05/2023] Open
Abstract
Symptoms of Clostridioides difficile infection (CDI) are attributed largely to two toxins, TcdA and TcdB. About 17-23% of C. difficile isolates produce binary toxin, which enhances C. difficile pathogenesis. Previously, we engineered the nontoxigenic C. difficile strain CCUG37785 (designated as CCUG37785) to express immunogenic fragments of TcdA and TcdB as an oral mucosal CDI vaccine candidate. In this study, we performed genomic and phenotypic analyses of CCUG37785 and evaluated its potential use for preventing and treating CDI. Whole genome sequencing showed that CCUG37785 is ribotype ST3 and lacks toxin genes. Comparative analyses of PaLoc and CdtLoc loci of CCUG37785 revealed 115-bp and 68-bp conserved fragments in these regions, respectively. Phenotypic comparisons between CCUG37785 and C. difficile R20291 (an epidemic hypervirulent BI/NAPI/027 strain, designated as R20291) found that CCUG37785 exhibited significantly higher adhesion and sporulation, significantly lower spore germination and biofilm formation, and comparable motility to R20291. We also showed that oral inoculation of CCUG37785 spores prior to infection with R20291 spores provided mice almost full protection against developing CDI. However, oral inoculation of CCUG37785 spores after infection with R20291 spores only provided minor protection against CDI. Further analysis showed that mice pretreated with CCUG37785 spores secreted significantly less R20291 spores, while mice treated with CCUG37785 spores after infection with R20291 secreted a comparable amount of R20291 spores to mice infected with R20291 spores only. Our data both highlight the potential use of CCUG37785 for the prevention of primary and recurrent CDI in humans and support its use as an oral mucosal vaccine carrier against CDI. IMPORTANCE Clostridioides difficile infection (CDI) symptoms range from diarrhea to intestinal inflammation/lesion and death and are mainly caused by two exotoxins, TcdA and TcdB. Active vaccination provides the attractive opportunity to prevent CDI and recurrence. No vaccine against CDI is currently licensed. Tremendous efforts have been devoted to developing vaccines targeting both toxins. However, ideally, vaccines should target both toxins and C. difficile cells/spores that transmit the disease and cause recurrence. Furthermore, C. difficile is an enteric pathogen, and mucosal/oral immunization would be particularly useful to protect the host against CDI considering that the gut is the main site of disease onset and progression. Data in our current study not only highlight the potential use of CCUG37785 to prevent primary and recurrent CDI in humans but also further support its use as an oral mucosal vaccine carrier 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
| | - Joshua Heuler
- Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, Florida, USA
| | - Ishani Wickramage
- 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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A short communication article: A Clostridioides difficile surveillance study of Canadian retail meat samples from 2016-2018. Anaerobe 2022; 74:102551. [PMID: 35341959 DOI: 10.1016/j.anaerobe.2022.102551] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2021] [Revised: 03/14/2022] [Accepted: 03/17/2022] [Indexed: 12/12/2022]
Abstract
In this study, we isolated and molecularly characterized 10 (1.6%) C. difficile isolates from 644 commercially available raw meat samples. Molecular typing by PFGE and ribotyping revealed NAP and ribotypes commonly associated with human clinical cases, suggesting retail meat could be a possible source of transmission warranting further investigation.
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Ciortescu I, Drug VL, Bărboi OB, Pleșca D, Livadariu R, Ionescu L. Uncommon Association of Mckittrick-Wheelock Syndrome and Clostridioides difficile Infection in Acute Renal Failure. Diagnostics (Basel) 2022; 12:diagnostics12040784. [PMID: 35453832 PMCID: PMC9026323 DOI: 10.3390/diagnostics12040784] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2021] [Revised: 02/26/2022] [Accepted: 03/21/2022] [Indexed: 11/16/2022] Open
Abstract
We present the case of a 71-year-old male who suffered an episode of acute renal failure caused by the uncommon association of two different diseases (Clostridioides difficile infection and McKittrick-Wheelock syndrome). He presented with hypovolemic shock, severe hypokalemia, hyponatremia, metabolic acidosis and acute renal failure; consequences of secretory diarrhea caused by a giant rectal tumor revealed from colonoscopy. The biopsy results revealed tubulo-villous adenoma with low/high grade dysplasia. After correction of electrolyte imbalances and azotemia, the patient underwent surgical resection with full subsequent recovery. In the literature review, including papers published from which January 1945 to April 2021, we found only one case-report of acute renal failure associated with Clostridioides difficile infection and McKittrick-Wheelock syndrome.
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Affiliation(s)
- Irina Ciortescu
- Medical I Department, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania; (I.C.); (V.-L.D.)
- Institute of Gastroenterology and Hepatology, Saint Spiridon Hospital, 700111 Iasi, Romania;
| | - Vasile-Liviu Drug
- Medical I Department, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania; (I.C.); (V.-L.D.)
- Institute of Gastroenterology and Hepatology, Saint Spiridon Hospital, 700111 Iasi, Romania;
| | - Oana-Bogdana Bărboi
- Medical I Department, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania; (I.C.); (V.-L.D.)
- Institute of Gastroenterology and Hepatology, Saint Spiridon Hospital, 700111 Iasi, Romania;
- Correspondence:
| | - Denis Pleșca
- Institute of Gastroenterology and Hepatology, Saint Spiridon Hospital, 700111 Iasi, Romania;
| | - Roxana Livadariu
- 1st Surgery Department, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania; (R.L.); (L.I.)
- 3rd Surgery Department, Saint Spiridon Hospital, 700115 Iasi, Romania
| | - Lidia Ionescu
- 1st Surgery Department, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania; (R.L.); (L.I.)
- 3rd Surgery Department, Saint Spiridon Hospital, 700115 Iasi, Romania
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Milenković B, Šuljagić V, Perić A, Dragojević-Simić V, Tarabar O, Milanović M, Putić V, Tomić D, Miljković B, Vezmar Kovačević S. Outcomes of Clostridioides difficile infection in adult cancer and non-cancer patients hospitalised in a tertiary hospital: a prospective cohort study. Eur J Hosp Pharm 2022; 29:e15-e22. [PMID: 33579720 PMCID: PMC8899674 DOI: 10.1136/ejhpharm-2020-002574] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2020] [Revised: 01/12/2021] [Accepted: 01/26/2021] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Clostridioides difficile infection (CDI) is one of the most common healthcare-associated (HA) infections. Cancer patients, particularly haemato-oncological patients, have an increased risk for CDI due to more risk factors compared with non-cancer patients. The aim of this study was to investigate differences in outcomes associated with HA CDI in patients with solid and haematological malignancies compared with patients with no underlying malignant disease in a tertiary healthcare centre in Serbia. METHODS A prospective cohort study was conducted including adult patients diagnosed with an initial episode of HA CDI. Their demographic and clinical characteristics associated with risk factors for CDI were documented. Outcomes such as all-cause 30-day mortality, cure of infection, diarrhoea relaps and recurrence of disease were followed. Patients were assigned to cancer and non-cancer groups. Within the cancer group, patients were divided into the solid tumour subgroup and haematological malignancy subgroup. RESULTS During a 7-year period, HA CDI was observed in 28 (5.1%) patients with haematological malignancy, 101 (18.3%) patients with solid tumours and 424 (76.7%) non-cancer patients. Older age (OR 1.04, 95% CI 1.02 to 1.07, p<0.001), admission to the intensive care unit (ICU) (OR 2.61, 95% CI 1.37 to 4.95, p=0.003), mechanical ventilation (OR 5.19, 95% CI 2.78 to 9.71, p<0.001) and use of antibiotics prior to CDI (OR 1.04, 95% CI 1.02 to 1.06, p=0.02) were associated with increased mortality. Compared with patients with solid tumours, patients with haematological malignancy were younger (65 vs 57 years, p=0.015), did not require ICU admission (25.0% vs 0%) or mechanical ventilation (8.9% vs 0%) and were treated longer with antibiotics prior to CDI (14 vs 24 days, p=0.002). CONCLUSIONS Patients with haematological malignancy were exposed to different risk factors for CDI associated with mortality compared with patients with solid tumours and non-cancer patients. Older age, ICU stay and mechanical ventilation, but not presence or type of cancer, predicted the all-cause 30-day mortality.
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Affiliation(s)
| | - Vesna Šuljagić
- Medical Faculty University of Defence, Belgrade, Serbia
- Section for Prevention and Control of Nosocomial Infections, Military Medical Academy, Belgrade, Serbia
| | - Aneta Perić
- Department of Pharmacy, Military Medical Academy, Belgrade, Serbia
- Medical Faculty University of Defence, Belgrade, Serbia
| | - Viktorija Dragojević-Simić
- Medical Faculty University of Defence, Belgrade, Serbia
- Center for Clinical Pharmacology, Military Medical Academy, Belgrade, Serbia
| | - Olivera Tarabar
- Medical Faculty University of Defence, Belgrade, Serbia
- Clinic for Haematology, Military Medical Academy, Belgrade, Serbia
| | - Milomir Milanović
- Medical Faculty University of Defence, Belgrade, Serbia
- Clinic for Infectious and Tropic Diseases, Military Medical Academy, Belgrade, Serbia
| | - Vesna Putić
- Department of Pharmacy, Military Medical Academy, Belgrade, Serbia
- Medical Faculty University of Defence, Belgrade, Serbia
| | - Diana Tomić
- Institute of Microbiology, Military Medical Academy, Belgrade, Serbia
| | - Branislava Miljković
- Department of Pharmacokinetics and Clinical Pharmacy, Faculty of Pharmacy University of Belgrade, Belgrade, Serbia
| | - Sandra Vezmar Kovačević
- Department of Pharmacokinetics and Clinical Pharmacy, Faculty of Pharmacy University of Belgrade, Belgrade, Serbia
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Papanikolopoulou A, Maltezou HC, Gargalianos-Kakolyris P, Pangalis A, Pantazis N, Pantos C, Tountas Y, Tsakris A, Kantzanou M. Association between consumption of antibiotics, infection control interventions and Clostridioides difficile infections: Analysis of six-year time-series data in a tertiary-care hospital in Greece. Infect Dis Health 2022; 27:119-128. [PMID: 35153189 DOI: 10.1016/j.idh.2022.01.002] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2021] [Revised: 12/21/2021] [Accepted: 01/16/2022] [Indexed: 12/15/2022]
Abstract
BACKGROUND To investigate the association between Clostridioides difficile infection (CDI), antibiotic use, and infection control interventions, during an antibiotic stewardship program (ASP) implemented in a tertiary-care hospital in Greece from 2013 to 2018. METHODS Analysis was applied for the following monthly indices: 1. consumption of antibiotics; 2. use of hand hygiene disinfectant solutions; 3. percentage of isolations of patients either with multidrug-resistant (MDR) bacteria, or CDI, or admitted from another hospital; and 4. percentage of patients with CDI divided into two groups: community-acquired CDI (CACDI) and hospital-associated CDI (HACDI) (onset ≤72 h and >72 h after admission, respectively). RESULTS During the study, a significant reduction in CACDI rate from 0.3%/admissions [95% CI 0.1-0.6] to 0.1%/admissions [95% CI 0.0-0.3] (p-value = 0.035) was observed in adults ICU, while CDI rates were stable in the rest of the hospital. Antibiotic consumption showed a significant reduction in total hospital, from 91.7 DDDs [95% CI 89.7-93.7] to 80.1 DDDs [95% CI 79.1-81.1] (p-value<0.001), except adults ICU. Non-advanced antibiotics correlated with decreased CDI rates in Adults Clinic Departments and ICU. Isolation of patients one and two months earlier correlated with decreased CACDI rates per 20% [95% CI 0.64-1.00, p-value = 0.046] and HACDI per 23% [95% CI 0.60-1.00, p-value = 0.050] in Adults Clinic Departments. Consumption of disinfectant solutions current month correlated with decreased rate for CACDI per 33% [95% CI 0.49-0.91, p-value = 0.011] and HACDI per 38% [95% CI 0.40-0.98, p-value = 0.040] in total Hospital Clinics. CONCLUSION Rational antibiotic prescribing during ASP along with multipronged intervention strategy focusing on hand hygiene and patient isolation measures prevent and control CDI outbreaks in the hospital setting.
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Affiliation(s)
| | - Helena C Maltezou
- Directorate of Research, Studies and Documentation, National Public Health Organization, Athens, 15123 Greece.
| | | | - Anastasia Pangalis
- Biopathology Department, Athens Medical Center, Marousi, Athens, 15125 Greece
| | - Nikos Pantazis
- Department of Hygiene, Epidemiology and Medical Statistics, Faculty of Medicine, School of Health Sciences, National and Kapodistrian University of Athens, Athens, 15772 Greece
| | - Constantinos Pantos
- Department of Pharmacology, School of Medicine, National and Kapodistrian University of Athens, Athens, 15772 Greece
| | - Yannis Tountas
- Department of Hygiene, Epidemiology and Medical Statistics, Faculty of Medicine, School of Health Sciences, National and Kapodistrian University of Athens, Athens, 15772 Greece
| | - Athanasios Tsakris
- Department of Microbiology, School of Medicine, National and Kapodistrian University of Athens, Athens, 15772 Greece
| | - Maria Kantzanou
- Department of Hygiene, Epidemiology and Medical Statistics, Faculty of Medicine, School of Health Sciences, National and Kapodistrian University of Athens, Athens, 15772 Greece
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49
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Spigaglia P. Clostridioides difficile infection (CDI) during the COVID-19 pandemic. Anaerobe 2022; 74:102518. [PMID: 35063599 PMCID: PMC8767936 DOI: 10.1016/j.anaerobe.2022.102518] [Citation(s) in RCA: 36] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2021] [Revised: 01/08/2022] [Accepted: 01/14/2022] [Indexed: 02/07/2023]
Abstract
The ongoing coronavirus disease (COVID-19) pandemic has dramatically tested healthcare systems around the world, with serious repercussions on the measures of prevention and control of hospital-acquired infections (HAIs). Among HAIs, Clostridioides difficile infection (CDI) represents one of the most important global public health threats. Although the full impact of the COVID-19 pandemic on CDI remains undetermined, depending on the development of the pandemic in the coming months, in this review literature studies of the last three years have been considered in order to depict the current situation, and make some considerations about possible future developments. If on the one hand, a general reduction in CDI incidence has been reported in several settings, mainly due to the extraordinary reinforcement of infection prevention measures, on the other hand, the critical circumstances experienced in many hospitals have limited the effectiveness of these measures, particularly in the intensive care units (ICUs), increasing the possibility of the occurrence of hospital-acquired CDI (HA-CDI). New concerns have arisen from the decrease in C. difficile testing and the increased use of broad-spectrum antibiotics reported during the pandemic. In particular, overuse of antibiotics and disinfectants may lead to a selection of resistant C. difficile strains not only in hospitals but also in the community. Furthermore, patients infected with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and patients that have survived COVID-19 may represent a new group of frail patients potentially at a higher risk of CDI, a group that could potentially increase in size due to SARS-CoV-2 evolution. In the dramatic COVID-19 era, the multifactorial nature of CDI has emerged more clearly than before, highlighting the necessity of a strong refocus on efforts to improve prevention strategies and to integrate CDI surveillance in a One Health prospective in order to curtail the public health threat posed by this infection in the next future.
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50
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van Prehn J, Reigadas E, Vogelzang EH, Bouza E, Hristea A, Guery B, Krutova M, Norén T, Allerberger F, Coia JE, Goorhuis A, van Rossen TM, Ooijevaar RE, Burns K, Scharvik Olesen BR, Tschudin-Sutter S, Wilcox MH, Vehreschild MJGT, Fitzpatrick F, Kuijper EJ. European Society of Clinical Microbiology and Infectious Diseases: 2021 update on the treatment guidance document for Clostridioides difficile infection in adults. Clin Microbiol Infect 2021; 27 Suppl 2:S1-S21. [PMID: 34678515 DOI: 10.1016/j.cmi.2021.09.038] [Citation(s) in RCA: 301] [Impact Index Per Article: 75.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2021] [Revised: 09/23/2021] [Accepted: 09/30/2021] [Indexed: 12/13/2022]
Abstract
SCOPE In 2009, the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) published the first treatment guidance document for Clostridioides difficile infection (CDI). This document was updated in 2014. The growing literature on CDI antimicrobial treatment and novel treatment approaches, such as faecal microbiota transplantation (FMT) and toxin-binding monoclonal antibodies, prompted the ESCMID study group on C. difficile (ESGCD) to update the 2014 treatment guidance document for CDI in adults. METHODS AND QUESTIONS Key questions on CDI treatment were formulated by the guideline committee and included: What is the best treatment for initial, severe, severe-complicated, refractory, recurrent and multiple recurrent CDI? What is the best treatment when no oral therapy is possible? Can prognostic factors identify patients at risk for severe and recurrent CDI and is there a place for CDI prophylaxis? Outcome measures for treatment strategy were: clinical cure, recurrence and sustained cure. For studies on surgical interventions and severe-complicated CDI the outcome was mortality. Appraisal of available literature and drafting of recommendations was performed by the guideline drafting group. The total body of evidence for the recommendations on CDI treatment consists of the literature described in the previous guidelines, supplemented with a systematic literature search on randomized clinical trials and observational studies from 2012 and onwards. The Grades of Recommendation Assessment, Development and Evaluation (GRADE) system was used to grade the strength of our recommendations and the quality of the evidence. The guideline committee was invited to comment on the recommendations. The guideline draft was sent to external experts and a patients' representative for review. Full ESCMID endorsement was obtained after a public consultation procedure. RECOMMENDATIONS Important changes compared with previous guideline include but are not limited to: metronidazole is no longer recommended for treatment of CDI when fidaxomicin or vancomycin are available, fidaxomicin is the preferred agent for treatment of initial CDI and the first recurrence of CDI when available and feasible, FMT or bezlotoxumab in addition to standard of care antibiotics (SoC) are preferred for treatment of a second or further recurrence of CDI, bezlotoxumab in addition to SoC is recommended for the first recurrence of CDI when fidaxomicin was used to manage the initial CDI episode, and bezlotoxumab is considered as an ancillary treatment to vancomycin for a CDI episode with high risk of recurrence when fidaxomicin is not available. Contrary to the previous guideline, in the current guideline emphasis is placed on risk for recurrence as a factor that determines treatment strategy for the individual patient, rather than the disease severity.
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Affiliation(s)
- Joffrey van Prehn
- Department of Medical Microbiology, Centre for Infectious Diseases, Leiden University Medical Center, Leiden, the Netherlands
| | - Elena Reigadas
- Department of Clinical Microbiology and Infectious Diseases, Hospital General Universitario Gregorio Marañón, Madrid, Spain
| | - Erik H Vogelzang
- Department of Medical Microbiology and Infection Control, Amsterdam University Medical Center, Location VUmc, Amsterdam, the Netherlands
| | - Emilio Bouza
- Department of Clinical Microbiology and Infectious Diseases, Hospital General Universitario Gregorio Marañón, Madrid, Spain
| | - Adriana Hristea
- University of Medicine and Pharmacy Carol Davila, National Institute for Infectious Diseases Prof Dr Matei Bals, Romania
| | - Benoit Guery
- Infectious Diseases Specialist, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland
| | - Marcela Krutova
- Department of Medical Microbiology, Charles University in Prague and Motol University Hospital, Czech Republic
| | - Torbjorn Norén
- Faculty of Medicine and Health, Department of Laboratory Medicine, National Reference Laboratory for Clostridioides difficile, Clinical Microbiology, Örebro University Hospital, Örebro, Sweden
| | | | - John E Coia
- Department of Clinical Microbiology, Hospital South West Jutland and Department of Regional Health Research IRS, University of Southern Denmark, Esbjerg, Denmark
| | - Abraham Goorhuis
- Department of Infectious Diseases, Amsterdam University Medical Centers, Academic Medical Center, Amsterdam, the Netherlands
| | - Tessel M van Rossen
- Department of Medical Microbiology and Infection Control, Amsterdam University Medical Center, Location VUmc, Amsterdam, the Netherlands
| | - Rogier E Ooijevaar
- Department of Gastroenterology, Amsterdam University Medical Center, Location VUmc, Amsterdam, the Netherlands
| | - Karen Burns
- Departments of Clinical Microbiology, Beaumont Hospital & Royal College of Surgeons in Ireland, Dublin, Ireland
| | | | - Sarah Tschudin-Sutter
- Department of Infectious Diseases and Infection Control, University Hospital Basel, University Basel, Universitatsspital, Basel, Switzerland
| | - Mark H Wilcox
- Department of Microbiology, Old Medical, School Leeds General Infirmary, Leeds Teaching Hospitals & University of Leeds, Leeds, United Kingdom
| | - Maria J G T Vehreschild
- German Centre for Infection Research (DZIF), Partner Site Bonn-Cologne, Cologne, Germany; Department of Internal Medicine, Infectious Diseases, University Hospital Frankfurt, Goethe University Frankfurt, Frankfurt am Main, Germany
| | - Fidelma Fitzpatrick
- Department of Clinical Microbiology, Beaumont Hospital, Dublin, Ireland; Department of Clinical Microbiology, Royal College of Surgeons in Ireland, Dublin, Ireland
| | - Ed J Kuijper
- Department of Medical Microbiology, Centre for Infectious Diseases, Leiden University Medical Center, Leiden, the Netherlands; National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands.
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