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Kim J, Kim JS, Kim SH, Yoo S, Lee JK, Kim K. Deep learning-based prediction of Clostridioides difficile infection caused by antibiotics using longitudinal electronic health records. NPJ Digit Med 2024; 7:224. [PMID: 39181992 PMCID: PMC11344761 DOI: 10.1038/s41746-024-01215-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2024] [Accepted: 08/02/2024] [Indexed: 08/27/2024] Open
Abstract
Clostridioides difficile infection (CDI) is a major cause of antibiotic-associated diarrhea and colitis. It is recognized as one of the most significant hospital-acquired infections. Although CDI can develop severe complications and spores of Clostridioides difficile can be transmitted by the fecal-oral route, CDI is occasionally overlooked in clinical settings. Thus, it is necessary to monitor high CDI risk groups, particularly those undergoing antibiotic treatment, to prevent complications and spread. We developed and validated a deep learning-based model to predict the occurrence of CDI within 28 days after starting antibiotic treatment using longitudinal electronic health records. For each patient, timelines of vital signs and laboratory tests with a 35-day monitoring period and a patient information vector consisting of age, sex, comorbidities, and medications were constructed. Our model achieved the prediction performance with an area under the receiver operating characteristic curve of 0.952 (95% CI: 0.932-0.973) in internal validation and 0.972 (95% CI: 0.968-0.975) in external validation. Platelet count and body temperature emerged as the most important features. The risk score, the output value of the model, exhibited a consistent increase in the CDI group, while the risk score in the non-CDI group either maintained its initial value or decreased. Using our CDI prediction model, high-risk patients requiring symptom monitoring can be identified. This could help reduce the underdiagnosis of CDI, thereby decreasing transmission and preventing complications.
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Affiliation(s)
- Junmo Kim
- Interdisciplinary Program in Bioengineering, Seoul National University, Seoul, Republic of Korea
| | - Joo Seong Kim
- Division of Gastroenterology, Department of Internal Medicine, Dongguk University Ilsan Hospital, Dongguk University College of Medicine, Goyang, Republic of Korea
| | - Sae-Hoon Kim
- Division of Allergy & Clinical Immunology, Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea
| | - Sooyoung Yoo
- Office of eHealth Research and Businesses, Seoul National University Bundang Hospital, Seongnam, Republic of Korea
| | - Jun Kyu Lee
- Division of Gastroenterology, Department of Internal Medicine, Dongguk University Ilsan Hospital, Dongguk University College of Medicine, Goyang, Republic of Korea.
| | - Kwangsoo Kim
- Department of Transdisciplinary Medicine, Institute of Convergence Medicine with Innovative Technology, Seoul National University Hospital, Seoul, Republic of Korea.
- Department of Medicine, College of Medicine, Seoul National University, Seoul, Republic of Korea.
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Sasaki Y, Yano M, Umehara A, Tagashira Y. Implementation of multifaceted diagnostic stewardship for Clostridioides difficile infection during the COVID-19 pandemic at a small Japanese hospital. ANTIMICROBIAL STEWARDSHIP & HEALTHCARE EPIDEMIOLOGY : ASHE 2024; 4:e96. [PMID: 38836045 PMCID: PMC11149025 DOI: 10.1017/ash.2024.93] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/23/2024] [Revised: 04/19/2024] [Accepted: 04/23/2024] [Indexed: 06/06/2024]
Abstract
Objective Clostridioides difficile infection (CDI) is a common, healthcare-associated infection. However, in Japan, testing for CDI is infrequent, suggesting that its incidence may be underestimated. This study aimed to examine the implementation of a multifaceted, diagnostic stewardship (DS) for CDI in a small Japanese hospital during the coronavirus 2019 pandemic. Design Before-after study. Setting A small Japanese community hospital. Participants Healthcare workers including physicians, nurses, and pharmacists. Interventions A multifaceted intervention including (1) the addition of CD testing criteria to the hospital guidelines; (2) provision of a tutorial on CD testing to physicians, nurses, and pharmacists; (3) assessment by clinical pharmacists and nurses of the need for CD testing in patients with nosocomial diarrhea and issuance of recommendations for CD testing to physicians; (4) reporting of data on the CD testing rate and CDI incidence in the study center. Results The CD testing rate increased before the pandemic (+0.16/10,000 patient-days (PD); P = .28), decreased significantly during the pandemic (-0.79/10,000 PD; P = .02), and then increased significantly immediately after the implementation of the intervention (+29.6/10,000 PD; P < .01). Similarly, the CDI incidence increased significantly before the pandemic (+0.26/10,000 PD; P = .02) and decreased significantly during the pandemic (-0.49/10,000 PD; P = .01). Implementation of the intervention resulted in an immediate and significant increase in the CDI incidence (+6.2/10,000 PD; P < .01). Conclusion Multifaceted DS involving multidisciplinary specialists was effective in improving CD testing, suggesting that appropriate testing can contribute to diagnosing CDI accurately.
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Affiliation(s)
- Yasuhiro Sasaki
- Department of Infection Control, Tama-Nambu Chiiki Hospital, Tokyo, Japan
| | - Masataka Yano
- Department of Infection Control, Tama-Nambu Chiiki Hospital, Tokyo, Japan
| | - Ayumi Umehara
- Department of Infection Control, Tama-Nambu Chiiki Hospital, Tokyo, Japan
| | - Yasuaki Tagashira
- Department of Infection Control, Tama-Nambu Chiiki Hospital, Tokyo, Japan
- Department of Infectious Diseases, Tokyo Medical and Dental University (TMDU), Tokyo, Japan
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Jover-Sáenz A, Ramírez-Hidalgo M, Bellés Bellés A, Ribes Murillo E, Batlle Bosch M, Ribé Miró A, Mari López A, Cayado Cabanillas J, Piqué Palacín N, Garrido-Calvo S, Ortiz Valls M, Gracia Vilas MI, Gros Navés L, Javierre Caudevilla MJ, Montull Navarro L, Bañeres Argiles C, Vaqué Castilla P, Ichart Tomás JJ, Saura Codina M, Andreu Mayor E, Martorell Solé R, Vena Martínez A, Albalad Samper JM, Cano Marrón S, Soler Elcacho C, Rodríguez Garrocho A, Terrer Manrique G, Solé Curcó A, Escuin DDLR, Estadella Servalls MJ, Figueres Farreny AM, Montaña Esteban LM, Sanz Borrell L, Morales Valle A, Pallerola Planes M, Hamadi A, Pujol Aymerich F, Toribio Redondo F, Urgelés Castillón MC, Valgañon Palacios J, Olivart Parejo M, Torres-Puig-gros J. Effects of a Primary Care Antimicrobial Stewardship Program on Meticillin-Resistant Staphylococcus aureus Strains across a Region of Catalunya (Spain) over 5 Years. Antibiotics (Basel) 2024; 13:92. [PMID: 38247651 PMCID: PMC10812605 DOI: 10.3390/antibiotics13010092] [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: 12/20/2023] [Revised: 01/08/2024] [Accepted: 01/15/2024] [Indexed: 01/23/2024] Open
Abstract
Primary care antimicrobial stewardship program (ASP) interventions can reduce the over-prescription of unnecessary antibiotics, but the impact on the reduction in bacterial resistance is less known, and there is a lack of available data. We implemented a prolonged educational counseling ASP in a large regional outpatient setting to assess its feasibility and effectiveness. Over a 5-year post-implementation period, which was compared to a pre-intervention period, a significant reduction in antibiotic prescriptions occurred, particularly those associated with greater harmful effects and resistance selection. There was also a decrease in methicillin-resistant Staphylococcus aureus (MRSA) strains and in their co-resistance to other antibiotics, particularly those with an ecological impact.
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Affiliation(s)
- Alfredo Jover-Sáenz
- Unidad Territorial Infección Nosocomial (UTIN), Hospital Universitari Arnau de Vilanova de Lleida (HUAV), 25198 Lleida, Spain;
| | - María Ramírez-Hidalgo
- Unidad Territorial Infección Nosocomial (UTIN), Hospital Universitari Arnau de Vilanova de Lleida (HUAV), 25198 Lleida, Spain;
| | - Alba Bellés Bellés
- Sección de Microbiología, Hospital Universitari Arnau de Vilanova de Lleida (HUAV), 25198 Lleida, Spain;
| | - Esther Ribes Murillo
- Unidad de Farmacia de Atención Primaria, Institut Català de la Salut (ICS), 25007 Lleida, Spain;
| | - Meritxell Batlle Bosch
- Equipo de Atención Priamaria (EAP) Les Borges Blanques, 25400 Lleida, Spain; (M.B.B.); (A.R.M.)
| | - Anna Ribé Miró
- Equipo de Atención Priamaria (EAP) Les Borges Blanques, 25400 Lleida, Spain; (M.B.B.); (A.R.M.)
| | - Alba Mari López
- EAP Pla d’Urgell, 25001 Lleida, Spain; (A.M.L.); (J.C.C.); (N.P.P.)
| | | | | | | | | | | | | | | | | | | | | | - José Javier Ichart Tomás
- Servicio de Urgencias, Hospital Universitari Arnau de Vilanova de Lleida (HUAV), 25198 Lleida, Spain; (J.J.I.T.); (M.S.C.)
| | - Mireia Saura Codina
- Servicio de Urgencias, Hospital Universitari Arnau de Vilanova de Lleida (HUAV), 25198 Lleida, Spain; (J.J.I.T.); (M.S.C.)
| | | | | | - Ana Vena Martínez
- Servei de Geriatria, Hospital Universitari Santa Maria, 25198 Lleida, Spain;
| | | | - Susana Cano Marrón
- EAP Onze de Setembre, 25005 Lleida, Spain; (S.C.M.); (C.S.E.); (A.R.G.); (G.T.M.)
| | | | | | | | | | | | | | | | | | | | | | | | - Aly Hamadi
- EAP Balaguer, 25600 Lleida, Spain; (M.P.P.); (A.H.)
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van Prehn J, Crobach MJT, Baktash A, Duszenko N, Kuijper EJ. Diagnostic Guidance for C. difficile Infections. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2024; 1435:33-56. [PMID: 38175470 DOI: 10.1007/978-3-031-42108-2_3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2024]
Abstract
Diagnosis of Clostridioides difficile infection (CDI) can be challenging. First of all, there has been debate on which of the two reference assays, cell cytotoxicity neutralization assay (CCNA) or toxigenic culture (TC), should be considered the gold standard for CDI detection. Although the CCNA suffers most from suboptimal storage conditions and subsequent toxin degradation, TC is reported to falsely increase CDI detection rates as it cannot differentiate CDI patients from patients asymptomatically colonised by toxigenic C. difficile. Several rapid assays are available for CDI detection and fall into three broad categories: (1) enzyme immunoassays for glutamate dehydrogenase, (2) enzyme immunoassays or single-molecule array assays for toxins A/B and (3) nucleic acid amplification tests detecting toxin genes. All three categories have their own limitations, being suboptimal specificity and/or sensitivity or the inability to discern colonised patients from CDI patients. In light of these limitations, multi-step algorithmic testing has been advocated by international guidelines (IDSA/SHEA and ESCMID) in order to optimize diagnostic accuracy. As a result, a survey performed in 2018-2019 in Europe revealed that most of all hospital sites reported using more than one test to diagnose CDI. CDI incidence rates are also influenced by sample selection criteria, as several studies have shown that if not all unformed stool samples are tested for CDI, many cases may be missed due to an absence of clinical suspicion. Since methods for diagnosing CDI remain imperfect, there has been a growing interest in alternative testing strategies like faecal microbiota biomarkers, immune modulating interleukins, cytokines and imaging methods. At the moment, these alternative methods might play an adjunctive role, but they are not suitable to replace conventional CDI testing strategies.
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Affiliation(s)
- Joffrey van Prehn
- Department of Medical Microbiology, Leiden University Centre for Infectious Diseases (LU-CID), Leiden University Medical Centre, Leiden, The Netherlands.
- ESCMID Study Group for C. difficile (ESGCD) and Study Group for Host and Microbiota Interaction (ESGHAMI), Basel, Switzerland.
| | - Monique J T Crobach
- Department of Medical Microbiology, Leiden University Centre for Infectious Diseases (LU-CID), Leiden University Medical Centre, Leiden, The Netherlands
| | - Amoe Baktash
- Department of Medical Microbiology, Leiden University Centre for Infectious Diseases (LU-CID), Leiden University Medical Centre, Leiden, The Netherlands
| | - Nikolas Duszenko
- Department of Medical Microbiology, Leiden University Centre for Infectious Diseases (LU-CID), Leiden University Medical Centre, Leiden, The Netherlands
| | - Ed J Kuijper
- Department of Medical Microbiology, Leiden University Centre for Infectious Diseases (LU-CID), Leiden University Medical Centre, Leiden, The Netherlands
- ESCMID Study Group for C. difficile (ESGCD) and Study Group for Host and Microbiota Interaction (ESGHAMI), Basel, Switzerland
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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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Couturier J, Davies K, Barbut F. Ribotypes and New Virulent Strains Across Europe. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2024; 1435:151-168. [PMID: 38175475 DOI: 10.1007/978-3-031-42108-2_8] [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 (formerly Clostridium) difficile is a major bacterial cause of post-antibiotic diarrhoea. The epidemiology of C. difficile infections (CDIs) has dramatically changed since the early 2000s, with an increasing incidence and severity across Europe. This trend is partly due to the emergence and rapid worldwide spread of the hypervirulent and epidemic PCR ribotype 027. Profiles of patients with CDI have also evolved, with description of community-acquired (CA) infections in patients with no traditional risk factors for CDI. However, epidemiological studies indicated that some European countries have successfully controlled the dissemination of the 027 clone whereas other countries reported the emergence of other virulent or unusual strains. The aims of this review are to summarize the current European CDI epidemiology and to describe the new virulent C. difficile strains circulating in Europe, as well as other potential emerging strains described elsewhere. Standardized typing methods and surveillance programmes are mandatory for a better understanding and monitoring of CDI in Europe.
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Affiliation(s)
- Jeanne Couturier
- National Reference Laboratory for C. difficile, Hôpital Saint-Antoine, Paris, France.
- Université Paris Cité, UMR INSERM 1139, Paris, France.
| | - Kerrie Davies
- Healthcare Associated Infections Research Group, Leeds Teaching Hospitals NHS Trust and University of Leeds, Leeds, UK
- European Society of Clinical Microbiology and Infectious Diseases (ESCMID) study group for Clostridioides difficile (ESGCD), Basel, Switzerland
| | - Frédéric Barbut
- National Reference Laboratory for C. difficile, Hôpital Saint-Antoine, Paris, France
- Université Paris Cité, UMR INSERM 1139, Paris, France
- European Society of Clinical Microbiology and Infectious Diseases (ESCMID) study group for Clostridioides difficile (ESGCD), Basel, Switzerland
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Fridkin SK, Onwubiko UN, Dube W, Robichaux C, Traenkner J, Goodenough D, Angulo FJ, Zamparo JM, Gonzalez E, Khanna S, Myers C, Dumyati G. Determinates of Clostridioides difficile infection (CDI) testing practices among inpatients with diarrhea at selected acute-care hospitals in Rochester, New York, and Atlanta, Georgia, 2020-2021. Infect Control Hosp Epidemiol 2023; 44:1085-1092. [PMID: 36102331 PMCID: PMC10369210 DOI: 10.1017/ice.2022.205] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2022] [Revised: 07/25/2022] [Accepted: 08/01/2022] [Indexed: 11/07/2022]
Abstract
OBJECTIVE We evaluated the impact of test-order frequency per diarrheal episodes on Clostridioides difficile infection (CDI) incidence estimates in a sample of hospitals at 2 CDC Emerging Infections Program (EIP) sites. DESIGN Observational survey. SETTING Inpatients at 5 acute-care hospitals in Rochester, New York, and Atlanta, Georgia, during two 10-workday periods in 2020 and 2021. OUTCOMES We calculated diarrhea incidence, testing frequency, and CDI positivity (defined as any positive NAAT test) across strata. Predictors of CDI testing and positivity were assessed using modified Poisson regression. Population estimates of incidence using modified Emerging Infections Program methodology were compared between sites using the Mantel-Hanzel summary rate ratio. RESULTS Surveillance of 38,365 patient days identified 860 diarrhea cases from 107 patient-care units mapped to 26 unique NHSN defined location types. Incidence of diarrhea was 22.4 of 1,000 patient days (medians, 25.8 for Rochester and 16.2 for Atlanta; P < .01). Similar proportions of diarrhea cases were hospital onset (66%) at both sites. Overall, 35% of patients with diarrhea were tested for CDI, but this differed by site: 21% in Rochester and 49% in Atlanta (P < .01). Regression models identified location type (ie, oncology or critical care) and laxative use predictive of CDI test ordering. Adjusting for these factors, CDI testing was 49% less likely in Rochester than Atlanta (adjusted rate ratio, 0.51; 95% confidence interval [CI], 0.40-0.63). Population estimates in Rochester had a 38% lower incidence of CDI than Atlanta (summary rate ratio, 0.62; 95% CI, 0.54-0.71). CONCLUSION Accounting for patient-specific factors that influence CDI test ordering, differences in testing practices between sites remain and likely contribute to regional differences in surveillance estimates.
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Affiliation(s)
- Scott K. Fridkin
- Division of Infectious Diseases, Department of Medicine, Emory University, Atlanta, Georgia
- Rollins School of Public Health, Emory University, AtlantaGeorgia
| | | | - William Dube
- Division of Infectious Diseases, Department of Medicine, Emory University, Atlanta, Georgia
| | - Chad Robichaux
- Division of Biomedical Informatics, Department of Medicine, Emory University, Atlanta, Georgia
| | - Jessica Traenkner
- Division of Infectious Diseases, Department of Medicine, Emory University, Atlanta, Georgia
| | - Dana Goodenough
- Foundation for Atlanta Veterans’ Education and Research, Decatur, Georgia
- Atlanta Veterans’ Affairs Medical Center, Decatur, Georgia
- Georgia Emerging Infections Program, Atlanta, Georgia
| | - Frederick J. Angulo
- Medical Development and Scientific/Clinical Affairs, Pfizer Vaccines, Collegeville, Pennsylvania
| | - Joann M. Zamparo
- Medical Development and Scientific/Clinical Affairs, Pfizer Vaccines, Collegeville, Pennsylvania
| | - Elisa Gonzalez
- Medical Development and Scientific/Clinical Affairs, Pfizer Vaccines, Collegeville, Pennsylvania
| | - Sahil Khanna
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | - Christopher Myers
- Center for Community Health and Prevention, University of Rochester Medical Center, Rochester, New York
- Infectious Diseases Division, University of Rochester Medical Center, Rochester, New York
| | - Ghinwa Dumyati
- Center for Community Health and Prevention, University of Rochester Medical Center, Rochester, New York
- Infectious Diseases Division, University of Rochester Medical Center, Rochester, New York
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Marcos P, Doyle A, Whyte P, Rogers TR, McElroy M, Fanning S, Frias J, Bolton D. Characterization of Food Chain Clostridioides difficile Isolates in Terms of Ribotype and Antimicrobial Resistance. Microorganisms 2023; 11:1296. [PMID: 37317270 DOI: 10.3390/microorganisms11051296] [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: 03/14/2023] [Revised: 05/12/2023] [Accepted: 05/12/2023] [Indexed: 06/16/2023] Open
Abstract
The aim of this study was to characterize C. difficile isolates from the farm, abattoir, and retail outlets in Ireland in terms of ribotype and antibiotic resistance (vancomycin, erythromycin, metronidazole, moxifloxacin, clindamycin, and rifampicin) using PCR and E-test methods, respectively. The most common ribotype in all stages of the food chain (including retail foods) was 078 and a variant (RT078/4). Less commonly reported (014/0, 002/1, 049, and 205) and novel (RT530, 547, and 683) ribotypes were also detected, but at lower frequencies. Approximately 72% (26/36 tested) of the isolates tested were resistant to at least one antibiotic, with the majority of these (65%; 17/26) displaying a multi-drug (three to five antibiotics) resistant phenotype. It was concluded that ribotype 078, a hypervirulent strain commonly associated with C. difficile infection (CDI) in Ireland, was the most frequent ribotype along the food chain, resistance to clinically important antibiotics was common in C. difficile food chain isolates, and there was no relationship between ribotype and antibiotic resistance profile.
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Affiliation(s)
- Pilar Marcos
- Teagasc Food Research Centre, Ashtown, Dublin 15, D15 KN3K Dublin, Ireland
- School of Veterinary Medicine, University College Dublin, Belfield, Dublin 4, D04 V1W8 Dublin, Ireland
| | - Aoife Doyle
- Department of Clinical Microbiology, Trinity College Dublin, Central Pathology Laboratory, St James's Hospital, Dublin 8, D08 RX0X Dublin, Ireland
- Central Veterinary Research Laboratory, Department of Agriculture, Food and the Marine, Backweston, Celbridge, W23 X3PH Kildare, Ireland
| | - Paul Whyte
- School of Veterinary Medicine, University College Dublin, Belfield, Dublin 4, D04 V1W8 Dublin, Ireland
| | - Thomas R Rogers
- Department of Clinical Microbiology, Trinity College Dublin, Central Pathology Laboratory, St James's Hospital, Dublin 8, D08 RX0X Dublin, Ireland
| | - Máire McElroy
- Central Veterinary Research Laboratory, Department of Agriculture, Food and the Marine, Backweston, Celbridge, W23 X3PH Kildare, Ireland
| | - Seamus Fanning
- UCD-Centre for Food Safety, School of Public Health, Physiotherapy and Sports Science, University College Dublin, Belfield, Dublin 4, D04 V1W8 Dublin, Ireland
| | - Jesus Frias
- Environmental Sustainability and Health Institute, Technological University Dublin, Grangegorman, Dublin 7, D07 H6K8 Dublin, Ireland
| | - Declan Bolton
- Teagasc Food Research Centre, Ashtown, Dublin 15, D15 KN3K Dublin, Ireland
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Muñoz Cuevas C, Asencio Egea MÁ, Franco Huerta M, Huertas Vaquero M, Arias Arias Á, Carranza González R. Case-control study of Clostridioides difficile in a rural health care area. GASTROENTEROLOGIA Y HEPATOLOGIA 2023; 46:1-9. [PMID: 35104606 DOI: 10.1016/j.gastrohep.2022.01.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/20/2021] [Revised: 12/12/2021] [Accepted: 01/20/2022] [Indexed: 01/18/2023]
Abstract
OBJECTIVE To determine the risk and prognostic factors for Clostridioides difficile infection (CDI). PATIENTS AND METHODS Prospective, case-control study with 61 cases and 64 controls, aged ≥2 years with diarrhoea, carried out in Castilla-La Mancha Health Care Area for 14 months. The diagnosis was made by immunochromatography technics (glutamate dehydrogenase and toxin A/B), confirming discordant cases by isothermal amplification. Demographic variables, comorbidities, type of acquisition, previous administration of antibiotics, antacids and immunosuppressants, and evolution were collected. The data were analysed using the chi-square test and the effect of risk and prognostic factors was quantified using an odds ratio with 95% confidence intervals. RESULTS Hospital admission 4 weeks prior to infection, hypoalbuminemia, and previous administration of antibiotics were identified as independent risk factors for CDI. Presenting these 3 factors constitutes nearly 3-fold increase in the risk of becoming infected. A greater number of hospital admissions in the 4-12 weeks prior to CDI were found in the group of nosocomial acquisition. Although there was a greater tendency to recurrence and an unfavourable prognosis among nosocomial cases, these differences were not significant. We found that fever and hospital admission in the 4 weeks prior to infection were unfavourable prognostic factors of CDI. CONCLUSIONS The independent risk factors for CDI were: Hospital admission in the 4 weeks prior to infection, hypoalbuminemia, and previous administration of antibiotics. Fever and hospitalisation in the previous 4 weeks were also identified as prognostic factors of unfavourable evolution.
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Affiliation(s)
- Cristina Muñoz Cuevas
- Laboratorio de Microbiología, Hospital General La Mancha Centro, Ciudad Real, España
| | | | - María Franco Huerta
- Servicio de Medicina Interna, Hospital General La Mancha Centro, Ciudad Real, España
| | - María Huertas Vaquero
- Laboratorio de Microbiología, Hospital General La Mancha Centro, Ciudad Real, España
| | - Ángel Arias Arias
- Unidad de Apoyo a la Investigación, Hospital General La Mancha Centro, Ciudad Real, España
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Angulo FJ, Oliva SP, Carrico R, Furmanek S, Zamparo J, Gonzalez E, Gray S, Ford KD, Swerdlow D, Moïsi JC, Ramirez J. Frequency of stool specimen collection and testing for Clostridioides difficile of hospitalized adults and long-term care facility residents with new-onset diarrhea in Louisville, Kentucky. Int J Infect Dis 2022; 120:196-200. [PMID: 35477052 DOI: 10.1016/j.ijid.2022.04.046] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2021] [Revised: 04/11/2022] [Accepted: 04/20/2022] [Indexed: 01/05/2023] Open
Abstract
OBJECTIVES This study aimed to determine the stool specimen collection and Clostridioides difficile (C. difficile) testing frequency from inpatients and long-term care facility (LTCF) residents with new-onset diarrhea. METHODS A cross-sectional study was conducted in all wards of 9 adult hospitals (3532 beds) and 14 LTCFs (1205 beds) in Louisville, Kentucky to identify new-onset diarrhea (≥3 loose stools in the past 24 h and not present in the preceding 24 h) among Louisville adults via electronic medical record review, nurse interviews, and patient interviews during a 1-2 week observation period in 2018-2019. RESULTS Among Louisville-resident inpatients, 167 patients with 9731 inpatient-days had new-onset diarrhea (1.7/100 inpatient-days). Stool specimens were collected from 32% (53/167); 12 (23%) specimens were laboratory-confirmed for C. difficile infection (CDI) (12.3 cases/10,000 inpatient-days). Among LTCF residents, 63 with 10,402 LTCF resident-days had new-onset diarrhea (0.6/100 LTCF resident-days). Stool specimens were collected from 32% (20/63); 9 (45%) specimens were laboratory-confirmed for CDI (8.6 cases/10,000 LTCF resident-days). CONCLUSIONS New-onset diarrhea was common among inpatients and LTCF residents. Only one-third of patients with new-onset diarrhea had a stool specimen collected and tested for C. difficile-indicative of a potential CDI underdiagnosis-although, further studies are needed to confirm the extent of CDI underdiagnosis.
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Affiliation(s)
- Frederick J Angulo
- Medical Development and Scientific/Clinical Affairs, Pfizer Vaccines, 500 Arcola Road 4024 NE Alameda Street, Collegeville, PA 19426, USA.
| | - Senén Peña Oliva
- Center of Excellence for Research in Infectious Diseases (CERID), Division of Infectious Diseases, School of Medicine, University of Louisville, 501 East Broadway, Suite 100, Louisville, KY 40202, USA
| | - Ruth Carrico
- Center of Excellence for Research in Infectious Diseases (CERID), Division of Infectious Diseases, School of Medicine, University of Louisville, 501 East Broadway, Suite 100, Louisville, KY 40202, USA
| | - Stephen Furmanek
- Center of Excellence for Research in Infectious Diseases (CERID), Division of Infectious Diseases, School of Medicine, University of Louisville, 501 East Broadway, Suite 100, Louisville, KY 40202, USA; Norton Healthcare, Norton Infectious Diseases Institute, Louisville, KY 40202, USA
| | - Joann Zamparo
- Medical Development and Scientific/Clinical Affairs, Pfizer Vaccines, 500 Arcola Road 4024 NE Alameda Street, Collegeville, PA 19426, USA
| | - Elisa Gonzalez
- Medical Development and Scientific/Clinical Affairs, Pfizer Vaccines, 500 Arcola Road 4024 NE Alameda Street, Collegeville, PA 19426, USA
| | - Sharon Gray
- Medical Development and Scientific/Clinical Affairs, Pfizer Vaccines, 500 Arcola Road 4024 NE Alameda Street, Collegeville, PA 19426, USA
| | - Kimbal D Ford
- Medical Development and Scientific/Clinical Affairs, Pfizer Vaccines, 500 Arcola Road 4024 NE Alameda Street, Collegeville, PA 19426, USA
| | - David Swerdlow
- Medical Development and Scientific/Clinical Affairs, Pfizer Vaccines, 500 Arcola Road 4024 NE Alameda Street, Collegeville, PA 19426, USA; Beacon Epidemiology Associates, LLC, Phoenixville, PA 19460, USA
| | - Jennifer C Moïsi
- Medical Development and Scientific/Clinical Affairs, Pfizer Vaccines, 500 Arcola Road 4024 NE Alameda Street, Collegeville, PA 19426, USA
| | - Julio Ramirez
- Center of Excellence for Research in Infectious Diseases (CERID), Division of Infectious Diseases, School of Medicine, University of Louisville, 501 East Broadway, Suite 100, Louisville, KY 40202, USA; Norton Healthcare, Norton Infectious Diseases Institute, Louisville, KY 40202, USA
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11
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López-Cárdenas S, Torres-Martos E, Mora-Delgado J, Sánchez-Calvo JM, Santos-Peña M, Zapata López Á, Dolores López-Prieto M, Pérez-Cortés S, Carlos Alados J. The prognostic value of toxin B and binary toxin in Clostridioides difficile infection. Gut Microbes 2022; 13:1884516. [PMID: 33660568 PMCID: PMC8237967 DOI: 10.1080/19490976.2021.1884516] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023] Open
Abstract
To study the association between detection of the Clostridioides difficile gene encoding the binary toxin (CDT) and direct detection of toxinB (TcdB) from feces with the appearance of serious disease, complications, or recurrence in a prospective series of cases. A total of 220 confirmed cases were included, using a two-step algorithm: an initial study to detect the enzyme, glutamate dehydrogenase (GDH), followed, in cases of positivity, by detection of the tcdB. tcdB-positive patients were investigated for the presence of CDT and TcdB. Outcome variables were severe disease, the modified Illinois C. difficile infection (CDI) prognostic risk index (ZAR score), the appearance of complications (need for colectomy, CDI-related death, or toxic megacolon) and recurrence. Patients who tested positive for the presence of TcdB in feces were found to have greater disease severity than those who tested negative, with a ZAR score of 35.4% vs. 23% (p = .048), a higher recurrence rate (14.6% vs. 5.9%, p = .032), and a tendency for higher number of complications (20.7% vs. 11.5%), although without reaching statistical significance (p = .053). When presence of CDT was analyzed, higher frequencies of severe disease (39.2% vs. 21.2%, p = .005), complications and recurrence (21.6% vs. 10.9%, p = .037 and 14.9% vs. 5.8%, p = .029; respectively) were observed in patients where CDT was detected. TcdB and CDT act as prognostic markers of the appearance of serious disease, complications or recurrence in cases of CDI. Simultaneous detection of both markers, TcdB and CDT, had a greater impact on the prognosis than when they were detected separately.
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Affiliation(s)
- Salvador López-Cárdenas
- Unit of Infectious Diseases and Clinical Microbiology. Jerez De La Frontera University Hospital, Jerez De La Frontera, Cádiz, Spain,CONTACT Juan Mora Delgado Unit of Infectious Diseases and Clinical Microbiology. Jerez De La Frontera University Hospital, Jerez De La Frontera, Cádiz, Spain
| | - Eva Torres-Martos
- Unit of Infectious Diseases and Clinical Microbiology. Jerez De La Frontera University Hospital, Jerez De La Frontera, Cádiz, Spain
| | - Juan Mora-Delgado
- Unit of Infectious Diseases and Clinical Microbiology. Jerez De La Frontera University Hospital, Jerez De La Frontera, Cádiz, Spain
| | - Juan Manuel Sánchez-Calvo
- Unit of Infectious Diseases and Clinical Microbiology. Jerez De La Frontera University Hospital, Jerez De La Frontera, Cádiz, Spain
| | - Marta Santos-Peña
- Unit of Infectious Diseases and Clinical Microbiology. Jerez De La Frontera University Hospital, Jerez De La Frontera, Cádiz, Spain
| | - Ángel Zapata López
- Unit of Infectious Diseases and Clinical Microbiology. Jerez De La Frontera University Hospital, Jerez De La Frontera, Cádiz, Spain
| | - María Dolores López-Prieto
- Unit of Infectious Diseases and Clinical Microbiology. Jerez De La Frontera University Hospital, Jerez De La Frontera, Cádiz, Spain
| | - Salvador Pérez-Cortés
- Unit of Infectious Diseases and Clinical Microbiology. Jerez De La Frontera University Hospital, Jerez De La Frontera, Cádiz, Spain
| | - Juan Carlos Alados
- Unit of Infectious Diseases and Clinical Microbiology. Jerez De La Frontera University Hospital, Jerez De La Frontera, Cádiz, Spain
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12
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Wickramage I, Spigaglia P, Sun X. Mechanisms of antibiotic resistance of Clostridioides difficile. J Antimicrob Chemother 2021; 76:3077-3090. [PMID: 34297842 DOI: 10.1093/jac/dkab231] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Clostridioides difficile (CD) is one of the top five urgent antibiotic resistance threats in USA. There is a worldwide increase in MDR of CD, with emergence of novel strains which are often more virulent and MDR. Antibiotic resistance in CD is constantly evolving with acquisition of novel resistance mechanisms, which can be transferred between different species of bacteria and among different CD strains present in the clinical setting, community, and environment. Therefore, understanding the antibiotic resistance mechanisms of CD is important to guide optimal antibiotic stewardship policies and to identify novel therapeutic targets to combat CD as well as other bacteria. Epidemiology of CD is driven by the evolution of antibiotic resistance. Prevalence of different CD strains and their characteristic resistomes show distinct global geographical patterns. Understanding epidemiologically driven and strain-specific characteristics of antibiotic resistance is important for effective epidemiological surveillance of antibiotic resistance and to curb the inter-strain and -species spread of the CD resistome. CD has developed resistance to antibiotics with diverse mechanisms such as drug alteration, modification of the antibiotic target site and extrusion of drugs via efflux pumps. In this review, we summarized the most recent advancements in the understanding of mechanisms of antibiotic resistance in CD and analysed the antibiotic resistance factors present in genomes of a few representative well known, epidemic and MDR CD strains found predominantly in different regions of the world.
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Affiliation(s)
- Ishani Wickramage
- Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, 12901 Bruce B. Down Blvd, Tampa, FL 33612, USA
| | - Patrizia Spigaglia
- Department of Infectious Diseases, Istituto Superiore di Sanità, Rome, Italy
| | - Xingmin Sun
- Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, 12901 Bruce B. Down Blvd, Tampa, FL 33612, USA
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13
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Cataldo MA, Granata G, D'Arezzo S, Tonziello G, Vulcano A, De Giuli C, Meledandri M, Di Caro A, Petrosillo N. Hospitalized patients with diarrhea: Rate of Clostridioides difficile infection underdiagnosis and drivers of clinical suspicion. Anaerobe 2021; 70:102380. [PMID: 33971317 DOI: 10.1016/j.anaerobe.2021.102380] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2021] [Revised: 04/30/2021] [Accepted: 05/02/2021] [Indexed: 02/08/2023]
Abstract
OBJECTIVES Clostridioides difficile infection (CDI) represents a challenging issue, with an evolving epidemiology. Main objectives of our study were: to assess the frequency of diarrhea of overall etiology, including CDI, as a cause of hospital admission or occurring during hospital stay;- to determine the rate of underdiagnosis of community-acquired (CA-), health care associated (HCA)- and hospital onset (HO-) CDI, and explore factors associated with its clinical suspicion by physicians. METHODS A prospective cohort study included all hospitalized patients with diarrhea at two acute-care hospitals. C. difficile (CD) tests were performed on every stool samples, irrespective of the treating physician request. Factors associated with the likelihood of CD test request by physicians were assessed. RESULTS We enrolled 871 (6%) patients with diarrhea. CD test performed on all diarrheic stool samples was positive in 228 cases (26%); 37, 106, 85 cases of CA- (14%), HCA- (42%) and HO- diarrhea (24%), respectively. Treating physicians did not request CD test in 207 (24%) diarrhea cases. The rate of CDI underdiagnosis was 11% (24/228); it was higher in CA-CDI (27%, 10/37). Logistic regression analysis identified age >65 years (RR 1.1; 95 CI 1.06-1.2) and hospitalizations in the previous 3 months (RR 1.2; 95% CI 1.1-1.3) as independent factors associated with the likelihood of requesting the CD test by the physician. These risk factors differed by epidemiological classification of diarrhea and by hospital. CONCLUSIONS Our study confirmed the relevance of CDI underdiagnosis and provided new insights in the factors underlying the lack of CDI clinical suspicion.
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Affiliation(s)
- Maria Adriana Cataldo
- National Institute for Infectious Diseases "Lazzaro Spallanzani", Via Portuense, 292-00149, Rome, Italy.
| | - Guido Granata
- National Institute for Infectious Diseases "Lazzaro Spallanzani", Via Portuense, 292-00149, Rome, Italy
| | - Silvia D'Arezzo
- National Institute for Infectious Diseases "Lazzaro Spallanzani", Via Portuense, 292-00149, Rome, Italy
| | - Gilda Tonziello
- National Institute for Infectious Diseases "Lazzaro Spallanzani", Via Portuense, 292-00149, Rome, Italy
| | - Antonella Vulcano
- National Institute for Infectious Diseases "Lazzaro Spallanzani", Via Portuense, 292-00149, Rome, Italy
| | - Chiara De Giuli
- National Institute for Infectious Diseases "Lazzaro Spallanzani", Via Portuense, 292-00149, Rome, Italy
| | | | - Antonino Di Caro
- National Institute for Infectious Diseases "Lazzaro Spallanzani", Via Portuense, 292-00149, Rome, Italy
| | - Nicola Petrosillo
- National Institute for Infectious Diseases "Lazzaro Spallanzani", Via Portuense, 292-00149, Rome, Italy
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14
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Bouza E, Cobo J, Rodríguez-Hernández MJ, Salavert M, Horcajada JP, Iribarren JA, Obi E, Lozano V, Maratia S, Cuesta M, Uría E, Limón E. Economic burden of recurrent Clostridioides difficile infection in adults admitted to Spanish hospitals. A multicentre retrospective observational study. REVISTA ESPANOLA DE QUIMIOTERAPIA : PUBLICACION OFICIAL DE LA SOCIEDAD ESPANOLA DE QUIMIOTERAPIA 2021; 34:126-135. [PMID: 33618513 PMCID: PMC8019457 DOI: 10.37201/req/135.2020] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/17/2020] [Revised: 12/09/2020] [Accepted: 01/07/2021] [Indexed: 12/21/2022]
Abstract
OBJECTIVE Clostridioides difficile infection (CDI) is associated with increased hospital stays and mortality and a high likelihood of rehospitalization, leading to increased health resource use and costs. The objective was to estimate the economic burden of recurrent CDI (rCDI). METHODS Observational, retrospective study carried out in six hospitals. Adults aged ≥18 years with ≥1 confirmed diagnosis (primary or secondary) of rCDI between January 2010 and May 2018 were included. rCDI-related resource use included days of hospital stay (emergency room, ward, isolation and ICU), tests and treatments. For patients with primary diagnosis of rCDI, the complete hospital stay was attributed to rCDI. When diagnosis of rCDI was secondary, hospital stay attributed to rCDI was estimated using 1:1 propensity score matching as the difference in hospital stay compared to controls. Controls were hospitalizations without CDI recorded in the Spanish National Hospital Discharge Database. The cost was calculated by multiplying the natural resource units by the unit cost. Costs (euros) were updated to 2019. RESULTS We included 282 rCDI episodes (188 as primary diagnosis): 66.31% of patients were aged ≥65 years and 57.80% were female. The mean hospital stay (SD) was 17.18 (23.27) days: 86.17% of rCDI episodes were isolated for a mean (SD) of 10.30 (9.97) days. The total mean cost (95%-CI) per episode was €10,877 (9,499-12,777), of which the hospital stay accounted for 92.56. CONCLUSIONS There is high cost and resource use associated with rCDI, highlighting the importance of preventing rCDI to the Spanish National Health System.
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Affiliation(s)
| | | | | | | | | | | | | | - V Lozano
- Virginia Lozano, Merck Sharp-Dohme, Calle de Josefa Valcárcel, 38, 28027, Madrid, Spain.
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15
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Jaqueti Aroca J, Molina Esteban LM, García-Arata I, García-Martínez J, Cano De Torres I, Prieto Menchero S. Significance of a polymerase chain reaction method in the detection of Clostridioides difficile. REVISTA ESPANOLA DE QUIMIOTERAPIA 2021; 34:141-144. [PMID: 33601876 PMCID: PMC8019460 DOI: 10.37201/req/010.2020] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 11/10/2022]
Abstract
OBJECTIVE Clostridioides difficile (CD) is the most common cause of nosocomial diarrhea. Detection of CD toxin in patients' faecal samples is the traditional rapid method for the diagnosis of CD infection. Various testing algorithms have been proposed: an initial screening test using a rapid test, and a confirmatory test (cytotoxicity neutralization assay, toxigenic culture, nucleic acid amplification test) for discordant results. The aim of this study was to evaluate the effectiveness of a two-step algorithm using an immunochromatographic test followed of a polymerase chain reaction (PCR). METHODS The specimens have been tested according to the following schedule: 1) Step one: All samples were tested for detection of glutamate dehydrogenase antigen (GDH) and toxin A/B using the C. diff QUIK CHEK Complete test. All GDH and toxins positive results were considered CD positives; 2) Step two: When the results were discrepant (only GDH+ or toxins+), the samples were confirmed using the PCR test BD MAX Cdiff. All PCR positive results were considered CD positives. RESULTS A total of 2,138 specimens were initially tested. 139 were positive for GDH and toxins. 160 discrepant results (148 GDH+ and 12 toxins+) were tested by PCR, 117 were positive (107/148 GDH+ and 10/12 toxins+). CONCLUSIONS The implementation of a PCR method showed an increase de 117 positive results (73.1% of discrepant). Considering the sensitivity of C.diff QUIK CHEK (instructions of manufacturer), the GDH discrepant results may be false negatives, y the samples PCR and toxins positives may be real positives results.
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Affiliation(s)
- J Jaqueti Aroca
- Jerónimo Jaqueti Aroca, Laboratorio Clínico, Hospital Universitario de Fuenlabrada, Camino del Molino, 2. 28942 Madrid, Spain.
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16
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Kampouri E, Croxatto A, Prod’hom G, Guery B. Clostridioides difficile Infection, Still a Long Way to Go. J Clin Med 2021; 10:jcm10030389. [PMID: 33498428 PMCID: PMC7864166 DOI: 10.3390/jcm10030389] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2020] [Revised: 01/12/2021] [Accepted: 01/14/2021] [Indexed: 12/11/2022] Open
Abstract
Clostridioides difficile is an increasingly common pathogen both within and outside the hospital and is responsible for a large clinical spectrum from asymptomatic carriage to complicated infection associated with a high mortality. While diagnostic methods have considerably progressed over the years, the optimal diagnostic algorithm is still debated and there is no single diagnostic test that can be used as a standalone test. More importantly, the heterogeneity in diagnostic practices between centers along with the lack of robust surveillance systems in all countries and an important degree of underdiagnosis due to lack of clinical suspicion in the community, hinder a more accurate evaluation of the burden of disease. Our improved understanding of the physiopathology of CDI has allowed some significant progress in the treatment of CDI, including a broader use of fidaxomicine, the use of fecal microbiota transplantation for multiples recurrences and newer approaches including antibodies, vaccines and new molecules, already developed or in the pipeline. However, the management of CDI recurrences and severe infections remain challenging and the main question remains: how to best target these often expensive treatments to the right population. In this review we discuss current diagnostic approaches, treatment and potential prevention strategies, with a special focus on recent advances in the field as well as areas of uncertainty and unmet needs and how to address them.
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Affiliation(s)
- Eleftheria Kampouri
- Infectious Diseases Service, Department of Medicine, University Hospital and University of Lausanne, 1011 Lausanne, Switzerland;
| | - Antony Croxatto
- Institute of Microbiology, Department of Medical Laboratory and Pathology, University Hospital and University of Lausanne, 1011 Lausanne, Switzerland; (A.C.); (G.P.)
| | - Guy Prod’hom
- Institute of Microbiology, Department of Medical Laboratory and Pathology, University Hospital and University of Lausanne, 1011 Lausanne, Switzerland; (A.C.); (G.P.)
| | - Benoit Guery
- Infectious Diseases Service, Department of Medicine, University Hospital and University of Lausanne, 1011 Lausanne, Switzerland;
- Correspondence: ; Tel.: +41-21-314-1643
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17
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Clostridioides difficile Infection: A Room for Multifaceted Interventions. J Clin Med 2020; 9:jcm9124114. [PMID: 33419243 PMCID: PMC7767249 DOI: 10.3390/jcm9124114] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2020] [Accepted: 12/17/2020] [Indexed: 12/17/2022] Open
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18
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Martínez-Meléndez A, Morfin-Otero R, Villarreal-Treviño L, Baines SD, Camacho-Ortíz A, Garza-González E. Molecular epidemiology of predominant and emerging Clostridioides difficile ribotypes. J Microbiol Methods 2020; 175:105974. [PMID: 32531232 DOI: 10.1016/j.mimet.2020.105974] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2020] [Revised: 06/05/2020] [Accepted: 06/05/2020] [Indexed: 12/18/2022]
Abstract
There has been an increase in the incidence and severity of Clostridioides difficile infection (CDI) worldwide, and strategies to control, monitor, and diminish the associated morbidity and mortality have been developed. Several typing methods have been used for typing of isolates and studying the epidemiology of CDI; serotyping was the first typing method, but then was replaced by pulsed-field gel electrophoresis (PFGE). PCR ribotyping is now the gold standard method; however, multi locus sequence typing (MLST) schemes have been developed. New sequencing technologies have allowed comparing whole bacterial genomes to address genetic relatedness with a high level of resolution and discriminatory power to distinguish between closely related strains. Here, we review the most frequent C. difficile ribotypes reported worldwide, with a focus on their epidemiology and genetic characteristics.
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Affiliation(s)
- Adrián Martínez-Meléndez
- Universidad Autónoma de Nuevo León, Facultad de Ciencias Químicas, Pedro de Alba S/N, Ciudad Universitaria, CP 66450 San Nicolás de los Garza, Nuevo Leon, Mexico
| | - Rayo Morfin-Otero
- Hospital Civil de Guadalajara "Fray Antonio Alcalde" e Instituto de Patología Infecciosa y Experimental, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara. Sierra Mojada 950, Col. Independencia, CP 44350 Guadalajara, Jalisco, Mexico
| | - Licet Villarreal-Treviño
- Universidad Autónoma de Nuevo León, Facultad de Ciencias Biológicas, Departamento de Microbiología e Inmunología, Pedro de Alba S/N, Ciudad Universitaria, CP 66450 San Nicolás de los Garza, Nuevo Leon, Mexico
| | - Simon D Baines
- University of Hertfordshire, School of Life and Medical Sciences, Department of Biological and Environmental Sciences, Hatfield AL10 9AB, UK
| | - Adrián Camacho-Ortíz
- Universidad Autónoma de Nuevo León, Hospital Universitario "Dr. José Eleuterio González", Servicio de Infectología. Av. Francisco I. Madero Pte. S/N y Av. José E. González. Col. Mitras Centro, CP 64460 Monterrey, Nuevo Leon, Mexico
| | - Elvira Garza-González
- Universidad Autónoma de Nuevo León, Hospital Universitario "Dr. José Eleuterio González", Servicio de Infectología. Av. Francisco I. Madero Pte. S/N y Av. José E. González. Col. Mitras Centro, CP 64460 Monterrey, Nuevo Leon, Mexico.
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19
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Sambri V, Gateau C, Zannoli S, Dirani G, Couturier J, Op den Buijs I, Roymans R, Hallet E, Arnold M, Zumoberhaus A, Steiner S, van de Bovenkamp J, Altwegg M, Berlinger L, Barbut F. Diagnosing Clostridioides difficile infections with molecular diagnostics: multicenter evaluation of revogene C. difficile assay. Eur J Clin Microbiol Infect Dis 2020; 39:1169-1175. [PMID: 32062723 PMCID: PMC7225180 DOI: 10.1007/s10096-020-03829-4] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2019] [Accepted: 01/22/2020] [Indexed: 01/05/2023]
Abstract
Clostridioides difficile infections are a significant threat to our healthcare system, and rapid and accurate diagnostics are crucial to implement the necessary infection prevention and control measurements. Nucleic acid amplification tests are such reliable diagnostic tools for the detection of toxigenic Clostridioides difficile strains directly from stool specimens. In this multicenter evaluation, we determined the performance of the revogene C. difficile assay. The analysis was conducted on prospective stool specimens collected from six different sites in Europe. The performance of the revogene C. difficile assay was compared to the different routine diagnostic methods and, for a subset of the specimens, against toxigenic culture. In total, 2621 valid stool specimens were tested, and the revogene C. difficile assay displayed a sensitivity/specificity of 97.1% [93.3-99.0] and 98.9% [98.5-99.3] for identification of Clostridioides difficile infection. Discrepancy analysis using additional methods improved this performance to 98.8% [95.8-99.9] and 99.6% [99.2-99.8], respectively. In comparison to toxigenic culture, the revogene C. difficile assay displayed a sensitivity/specificity of 93.0% [86.1-97.1] and 99.5% [98.7-99.9], respectively. These results indicate that the revogene C. difficile assay is a robust and reliable aid in the diagnosis of Clostridioides difficile infections.
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Affiliation(s)
- Vittorio Sambri
- Operative unit of Clinical Microbiology, Regional Reference Centre for Microbiological Emergencies, S. Orsola-Malpighi University Hospital, Bologna, Italy.
- Unit of Microbiology, The Great Romagna Hub Laboratory, Pievesestina, FC, Italy.
- DIMES, University of Bologna, Bologna, Italy.
| | - Cécile Gateau
- National Reference Laboratory for C. difficile, Hôpital Saint-Antoine, Assistance Publique-Hôpitaux de Paris, INSERM U-1139, University Paris Descartes, Paris, France
| | - Silvia Zannoli
- Operative unit of Clinical Microbiology, Regional Reference Centre for Microbiological Emergencies, S. Orsola-Malpighi University Hospital, Bologna, Italy
| | - Giorgio Dirani
- Operative unit of Clinical Microbiology, Regional Reference Centre for Microbiological Emergencies, S. Orsola-Malpighi University Hospital, Bologna, Italy
| | - Jeanne Couturier
- National Reference Laboratory for C. difficile, Hôpital Saint-Antoine, Assistance Publique-Hôpitaux de Paris, INSERM U-1139, University Paris Descartes, Paris, France
| | | | - René Roymans
- Laboratory of Medical Microbiology, Stichting PAMM, Veldhoven, Netherlands
| | - Emma Hallet
- Great Western Hospital, Swindon, UK
- Royal Devon and Exeter Hospital, Exeter, UK
| | | | | | | | | | | | | | - Frédéric Barbut
- National Reference Laboratory for C. difficile, Hôpital Saint-Antoine, Assistance Publique-Hôpitaux de Paris, INSERM U-1139, University Paris Descartes, Paris, France
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20
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Wu Q, Savidge TC. Systems approaches for the clinical diagnosis of Clostridioides difficile infection. Transl Res 2020; 220:57-67. [PMID: 32272094 DOI: 10.1016/j.trsl.2020.03.006] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/17/2020] [Revised: 03/02/2020] [Accepted: 03/09/2020] [Indexed: 12/18/2022]
Abstract
Clostridioides difficile infection (CDI) is an urgent threat to global public health. Patient susceptibility to C. difficile is highly dependent on host immune status and gut dysbiosis resulting in loss of protective microbiota consortia that prevent spore germination, pathogen colonization, and disease pathogenesis. Recent clinical studies highlight the problems of differentiating symptomatic CDI from asymptomatic C. difficile carriage in patients with diarrhea. In this review, we consider how integration of microbiome and host immune systems biology data may aid in the clinical diagnosis of CDI when validated against gold standard testing and combined with standard microbiology laboratory assays.
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Affiliation(s)
- Qinglong Wu
- Department of Pathology and Immunology, Baylor College of Medicine, Houston, Texas; Texas Children's Microbiome Center, Department of Pathology, Texas Children's Hospital, Houston, Texas
| | - Tor C Savidge
- Department of Pathology and Immunology, Baylor College of Medicine, Houston, Texas; Texas Children's Microbiome Center, Department of Pathology, Texas Children's Hospital, Houston, Texas.
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Bouza E, Aguado JM, Alcalá L, Almirante B, Alonso-Fernández P, Borges M, Cobo J, Guardiola J, Horcajada JP, Maseda E, Mensa J, Merchante N, Muñoz P, Pérez Sáenz JL, Pujol M, Reigadas E, Salavert M, Barberán J. Recommendations for the diagnosis and treatment of Clostridioides difficile infection: An official clinical practice guideline of the Spanish Society of Chemotherapy (SEQ), Spanish Society of Internal Medicine (SEMI) and the working group of Postoperative Infection of the Spanish Society of Anesthesia and Reanimation (SEDAR). REVISTA ESPANOLA DE QUIMIOTERAPIA : PUBLICACION OFICIAL DE LA SOCIEDAD ESPANOLA DE QUIMIOTERAPIA 2020; 33:151-175. [PMID: 32080996 PMCID: PMC7111242 DOI: 10.37201/req/2065.2020] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/02/2020] [Accepted: 01/26/2020] [Indexed: 12/12/2022]
Abstract
This document gathers the opinion of a multidisciplinary forum of experts on different aspects of the diagnosis and treatment of Clostridioides difficile infection (CDI) in Spain. It has been structured around a series of questions that the attendees considered relevant and in which a consensus opinion was reached. The main messages were as follows: CDI should be suspected in patients older than 2 years of age in the presence of diarrhea, paralytic ileus and unexplained leukocytosis, even in the absence of classical risk factors. With a few exceptions, a single stool sample is sufficient for diagnosis, which can be sent to the laboratory with or without transportation media for enteropathogenic bacteria. In the absence of diarrhoea, rectal swabs may be valid. The microbiology laboratory should include C. difficile among the pathogens routinely searched in patients with diarrhoea. Laboratory tests in different order and sequence schemes include GDH detection, presence of toxins, molecular tests and toxigenic culture. Immediate determination of sensitivity to drugs such as vancomycin, metronidazole or fidaxomycin is not required. The evolution of toxin persistence is not a suitable test for follow up. Laboratory diagnosis of CDI should be rapid and results reported and interpreted to clinicians immediately. In addition to the basic support of all diarrheic episodes, CDI treatment requires the suppression of antiperistaltic agents, proton pump inhibitors and antibiotics, where possible. Oral vancomycin and fidaxomycin are the antibacterials of choice in treatment, intravenous metronidazole being restricted for patients in whom the presence of the above drugs in the intestinal lumen cannot be assured. Fecal material transplantation is the treatment of choice for patients with multiple recurrences but uncertainties persist regarding its standardization and safety. Bezlotoxumab is a monoclonal antibody to C. difficile toxin B that should be administered to patients at high risk of recurrence. Surgery is becoming less and less necessary and prevention with vaccines is under research. Probiotics have so far not been shown to be therapeutically or preventively effective. The therapeutic strategy should be based, rather than on the number of episodes, on the severity of the episodes and on their potential to recur. Some data point to the efficacy of oral vancomycin prophylaxis in patients who reccur CDI when systemic antibiotics are required again.
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Affiliation(s)
- E Bouza
- Emilio Bouza MD, PhD, Instituto de Investigación Sanitaria Gregorio Marañón, Servicio de Microbiología Clínica y E. Infecciosas C/ Dr. Esquerdo, 46 - 28007 Madrid, Spain.
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Novakova E, Stefkovicova M, Kopilec MG, Novak M, Kotlebova N, Kuijper E, Krutova M. The emergence of Clostridium difficile ribotypes 027 and 176 with a predominance of the Clostridium difficile ribotype 001 recognized in Slovakia following the European standardized Clostridium difficile infection surveillance of 2016. Int J Infect Dis 2020; 90:111-115. [PMID: 31707136 PMCID: PMC6912155 DOI: 10.1016/j.ijid.2019.10.038] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2019] [Revised: 10/25/2019] [Accepted: 10/29/2019] [Indexed: 12/26/2022] Open
Abstract
AIM To obtain standardized epidemiological data for Clostridium difficile infection (CDI) in Slovakia. METHODS Between October and December 2016, 36 hospitals in Slovakia used the European Centre for Disease Prevention and Control (ECDC) Clostridium difficile infection (CDI) surveillance protocol. RESULTS The overall mean CDI incidence density was 2.8 (95% confidence interval 1.9-3.9) cases per 10 000 patient-days. Of 332 CDI cases, 273 (84.9%) were healthcare-associated, 45 (15.1%) were community-associated, and 14 (4.2%) were cases of recurrent CDI. A complicated course of CDI was reported in 14.8% of cases (n=51). CDI outcome data were available for 95.5% of cases (n=317). Of the 35 patients (11.1%) who died, 34 did so within 30 days after their CDI diagnosis. Of the 78 isolates obtained from 12 hospitals, 46 belonged to PCR ribotype 001 (59.0%; 11 hospitals) and 23 belonged to ribotype 176 (29.5%; six hospitals). A total of 73 isolates (93.6%) showed reduced susceptibility to moxifloxacin (ribotypes 001 and 176; p< 0.01). A reduced susceptibility to metronidazole was observed in 13 isolates that subsequently proved to be metronidazole-susceptible when, after thawing, they were retested using the agar dilution method. No reduced susceptibility to vancomycin was found. CONCLUSIONS These results show the emergence of C. difficile ribotypes 027 and 176 with a predominance of ribotype 001 in Slovakia in 2016. Given that an almost homogeneous reduced susceptibility to moxifloxacin was detected in C. difficile isolates, this stresses the importance of reducing fluoroquinolone prescriptions in Slovak healthcare settings.
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Affiliation(s)
- Elena Novakova
- Department of Microbiology and Immunology, Comenius University, Jessenius Faculty of Medicine in Martin, Slovakia
| | - Maria Stefkovicova
- Department of Epidemiology, Regional Public Health Authority, Trenčín, Slovakia; Department of Laboratory Medicine and Public Health, Faculty of Health Care, Alexander Dubcek University, Trenčín, Slovakia
| | | | - Martin Novak
- Department of Public Health, Comenius University, Jessenius Faculty of Medicine in Martin, Slovakia
| | - Nina Kotlebova
- Department of Microbiology and Immunology, Comenius University, Jessenius Faculty of Medicine in Martin, Slovakia
| | - Ed Kuijper
- Department of Medical Microbiology, Leiden University Medical Centre, Leiden, The Netherlands
| | - Marcela Krutova
- Department of Medical Microbiology, Charles University in Prague, 2nd Faculty of Medicine and Motol University Hospital, Prague, Czech Republic.
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23
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Piatti G, Bruzzone M, Fontana V, Ceppi M. Analysis of Routine and Integrative Data from Clostridioides difficile Infection Diagnosis and the Consequent Observations. Open Microbiol J 2019. [DOI: 10.2174/1874285801913010343] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Abstract
Background:Clostridioides difficileInfection (CDI) is an acute disease that needs a fast proper treatment. Unfortunately, the diagnosis, and above all the understanding of the results, remain arduous.Objective:This study analyzed routine and integrative results of all fecal samples from patients over time. Our aim was to understand the dynamics of CDI infection and the meaning of “difficult to interpret” results, to make physicians better understand the various tools they can use.Methods:We evaluated routine results obtained from 815 diarrheal stools with Enzyme Immunoassay (EIA) that detectsC. difficileGlutamate Dehydrogenase (GDH) antigen and toxin B. We also reanalyzed a part of samples using integrative tests: a Real-time polymerase chain reaction (RT-PCR) forC. difficiletoxin B gene (tcdB) and the automated immunoassay VIDASC. difficilesystem for GDH and toxins A/B.Results:EIA GDH positivity increased through multiple testing over time, with aPvalue <0.001, depicting a sort of bacterial growth curve. Eighty-five percent of GDH positive/toxin B negative,i.e., discrepant, samples PCR weretcdBpositive, 61.5% of discrepanttcdBpositive samples were VIDAS toxins A/B positive, and 44.4% of GDH EIA negative stools were VIDAS GDH positive.Conclusion:The results confirmed the low sensitivity of the EIA system forC. difficileGDH and toxins, questioned the use of the latter for concluding any CDI diagnostic algorithm, and led us to indicate the algorithm beginning with tcdB molecular research, and continuing in positive cases with VIDAS CD GDH method, as the most effective for CDI.
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Imwattana K, Knight DR, Kullin B, Collins DA, Putsathit P, Kiratisin P, Riley TV. Antimicrobial resistance in Clostridium difficile ribotype 017. Expert Rev Anti Infect Ther 2019; 18:17-25. [PMID: 31800331 DOI: 10.1080/14787210.2020.1701436] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Introduction: Antimicrobial resistance (AMR) played an important role in the initial outbreaks of Clostridium difficile infection (CDI) in the 1970s. C. difficile ribotype (RT) 017 has emerged as the major strain of C. difficile in Asia, where antimicrobial use is poorly regulated. This strain has also caused CDI outbreaks around the world for almost 30 years. Many of these outbreaks were associated with clindamycin and fluoroquinolone resistance. AMR and selective pressure is likely to be responsible for the success of this RT and may drive future outbreaks.Areas covered: This narrative review summarizes the prevalence and mechanisms of AMR in C. difficile RT 017 and transmission of these AMR mechanisms. To address these topics, reports of outbreaks due to C. difficile RT 017, epidemiologic studies with antimicrobial susceptibility results, studies on resistance mechanisms found in C. difficile and related publications available through Pubmed until September 2019 were collated and the findings discussed.Expert opinion: Primary prevention is the key to control CDI. This should be achieved by developing antimicrobial stewardship in medical, veterinary and agricultural practices. AMR is the key factor that drives CDI outbreaks, and methods for the early detection of AMR can facilitate the control of outbreaks.
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Affiliation(s)
- Korakrit Imwattana
- School of Biomedical Sciences, The University of Western Australia, Crawley, Australia.,Department of Microbiology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Daniel R Knight
- Medical, Molecular and Forensic Sciences, Murdoch University, Murdoch, Australia
| | - Brian Kullin
- Department of Molecular and Cell Biology, University of Cape Town, Cape Town, South Africa
| | - Deirdre A Collins
- School of Medical and Health Sciences, Edith Cowan University, Joondalup, Australia
| | - Papanin Putsathit
- School of Medical and Health Sciences, Edith Cowan University, Joondalup, Australia
| | - Pattarachai Kiratisin
- Department of Microbiology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Thomas V Riley
- School of Biomedical Sciences, The University of Western Australia, Crawley, Australia.,Medical, Molecular and Forensic Sciences, Murdoch University, Murdoch, Australia.,School of Medical and Health Sciences, Edith Cowan University, Joondalup, Australia.,PathWest Laboratory Medicine, Queen Elizabeth II Medical Centre, Nedlands, Australia
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25
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García-Fernández S, Frentrup M, Steglich M, Gonzaga A, Cobo M, López-Fresneña N, Cobo J, Morosini MI, Cantón R, Del Campo R, Nübel U. Whole-genome sequencing reveals nosocomial Clostridioides difficile transmission and a previously unsuspected epidemic scenario. Sci Rep 2019; 9:6959. [PMID: 31061423 PMCID: PMC6502822 DOI: 10.1038/s41598-019-43464-4] [Citation(s) in RCA: 27] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2019] [Accepted: 04/25/2019] [Indexed: 12/19/2022] Open
Abstract
To trace the routes and frequencies of transmission of Clostridioides difficile in a tertiary-care hospital in Madrid (Spain), we sequenced the genomes from all C. difficile isolates collected over 36 months (2014-2016) that were indistinguishable from any other isolate by PCR ribotyping. From a total of 589 C. difficile infection cases, we cultivated and PCR-ribotyped 367 C. difficile isolates (62%), of which 265 were genome-sequenced. Based on close relatedness of successively collected isolates (≤2 SNPs difference in their genomes), whole-genome sequencing revealed a total of 17 independent, putative transmission clusters, caused by various C. difficile strains and each containing 2 to 18 cases, none of which had been detected previously by standard epidemiological surveillance. Proportions of linked isolates varied widely among PCR ribotypes, from 3% (1/36) for ribotype 014/020 to 60% (12/20) for ribotype 027, suggesting differential aptitudes for nosocomial spread. Remarkably, only a minority (17%) of transmission recipients had direct ward contact to their presumed donors and specific C. difficile genome types frequently went undetectable for several months before re-emerging later, suggesting reservoirs for the pathogen outside of symptomatic patients. Taken together, our analysis based on genome sequencing suggested considerable within-hospital epidemic spread of C. difficile, even though epidemiological data initially had been inconspicuous.
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Affiliation(s)
- Sergio García-Fernández
- Servicio de Microbiología, Hospital Universitario Ramón y Cajal, and Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Madrid, Spain.,Red Española de Investigación en Patología Infecciosa (REIPI), Madrid, Spain
| | | | - Matthias Steglich
- Leibniz Institute DSMZ, Braunschweig, Germany.,German Center of Infection Research (DZIF), Braunschweig, Germany
| | | | - Marta Cobo
- Servicio de Microbiología, Hospital Universitario Ramón y Cajal, and Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Madrid, Spain
| | - Nieves López-Fresneña
- Servicio de Medicina Preventiva, Hospital Universitario Ramón y Cajal, Madrid, Spain
| | - Javier Cobo
- Red Española de Investigación en Patología Infecciosa (REIPI), Madrid, Spain.,Servicio de Enfermedades Infecciosas, and Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Madrid, Spain
| | - María-Isabel Morosini
- Servicio de Microbiología, Hospital Universitario Ramón y Cajal, and Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Madrid, Spain.,Red Española de Investigación en Patología Infecciosa (REIPI), Madrid, Spain
| | - Rafael Cantón
- Servicio de Microbiología, Hospital Universitario Ramón y Cajal, and Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Madrid, Spain.,Red Española de Investigación en Patología Infecciosa (REIPI), Madrid, Spain
| | - Rosa Del Campo
- Servicio de Microbiología, Hospital Universitario Ramón y Cajal, and Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Madrid, Spain.,Red Española de Investigación en Patología Infecciosa (REIPI), Madrid, Spain
| | - Ulrich Nübel
- Leibniz Institute DSMZ, Braunschweig, Germany. .,German Center of Infection Research (DZIF), Braunschweig, Germany. .,Braunschweig Integrated Center of Systems Biology (BRICS), Technical University, Braunschweig, Germany.
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26
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Rubio-Terrés C, Aguado JM, Almirante B, Cobo J, Grau S, Salavert M, González Antona Sánchez E, López Gutiérrez C, Rubio-Rodríguez D. Extended-pulsed fidaxomicin versus vancomycin in patients 60 years and older with Clostridium difficile infection: cost-effectiveness analysis in Spain. Eur J Clin Microbiol Infect Dis 2019; 38:1105-1111. [PMID: 30989419 PMCID: PMC6520320 DOI: 10.1007/s10096-019-03503-4] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2018] [Accepted: 02/04/2019] [Indexed: 01/13/2023]
Abstract
The cost of treating Clostridium difficile infection (CDI) in Spain is substantial. Findings from the randomised, controlled, open-label, phase 3b/4 EXTEND study showed that an extended-pulsed fidaxomicin (EPFX) regimen was associated with improved sustained clinical cure and reduced recurrence of CDI versus vancomycin in patients aged 60 years and older. We assessed the cost-effectiveness of EPFX versus vancomycin for the treatment of CDI in patients aged 60 years and older from the perspective of the National Health System (NHS) in Spain. We used a Markov model with six health states and 1-year time horizon. Health resources, their unit costs and utilities were based on published sources. Key efficacy data and transition probabilities were obtained from the EXTEND study and published sources. A panel of Spanish clinical experts validated all model assumptions. In the analysis, 0.638 and 0.594 quality-adjusted life years (QALYs) per patient were obtained with EPFX and vancomycin, respectively, with a gain of 0.044 QALYs with EPFX. The cost per patient treated with EPFX and vancomycin was estimated to be €10,046 and €10,693, respectively, with a saving of €647 per patient treated with EPFX. For willingness-to-pay thresholds of €20,000, €25,000 and €30,000 per QALY gained, the probability that EPFX was the most cost-effective treatment was 99.3%, 99.5% and 99.9%, respectively. According to our economic model and the assumptions based on the Spanish NHS, EPFX is cost-effective compared with vancomycin for the first-line treatment of CDI in patients aged 60 years and older.
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Affiliation(s)
| | - José María Aguado
- Department of Infectious Diseases, Hospital Universitario 12 de Octubre, Madrid, Spain
| | - Benito Almirante
- Department of Infectious Diseases, Hospital Universitario Vall d'Hebron, Barcelona, Spain
| | - Javier Cobo
- Department of Infectious Diseases, Hospital Universitario Ramón y Cajal/IRYCIS, Madrid, Spain
| | - Santiago Grau
- Department of Pharmacy, Hospital del Mar, Barcelona, Spain
| | - Miguel Salavert
- Department of Infectious Diseases, Hospital Universitario La Fe, Valencia, Spain
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27
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Suárez-Bode L, Barrón R, Pérez JL, Mena A. Increasing prevalence of the epidemic ribotype 106 in healthcare facility-associated and community-associated Clostridioides difficile infection. Anaerobe 2018; 55:124-129. [PMID: 30550807 DOI: 10.1016/j.anaerobe.2018.12.002] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2018] [Revised: 12/08/2018] [Accepted: 12/10/2018] [Indexed: 02/08/2023]
Abstract
Clostridioides difficile is the leading cause of nosocomial diarrhea and antibiotics associated diarrhea, but it is also an increasingly common cause of community diarrhea. In recent years we have observed a progressive increase in the incidence of C. difficile infection (CDI) both at the hospital and community setting that could be explained by the dynamic epidemiology of C. difficile. The present study analyzes changes in the epidemiology of CDI for two years comparing healthcare facility-associated (HCFA) and community-associated (CA) CDI epidemiology, observed in a single laboratory setting. All new episodes of CDI diagnosed during the years 2015-2016 were included in the study and classified as HFCA-, CA- or indeterminate CDI. Isolates were characterized by ribotyping and antimicrobial susceptibility was also determined. A total of 272 primary episodes of different patients were included in the study and classified 55.5% as CA-, 32% as HO-HCFA, 6.25% as CO-HCFA and 6.25% as indeterminate CDI. Overall, ribotype 106 was the most prevalent and also, many patients who suffered recurrent episodes were associated with this ribotype (29%). In fact, ribotype 106 showed a significantly higher recurrence rate than other ribotypes (26% vs 11%, p = 0.03). Moreover, 46% of the moxifloxacin resistant isolates were ribotype 106. No significant differences of antimicrobial resistance were observed between HCFA- and CA-CDI isolates, although fluoroquinolone resistance rates were slightly higher in HCFA-CDI isolates (25% vs 18.5%), and fluoroquinolone resistant ribotypes 106 and 126 were more frequently associated to CA-CDI and ribotype 078 to HCFA-CDI. The increasing incidence of CDI in our health care area is partially explained by the growing prevalence of the epidemic ribotype 106, both in HFCA- and CA-CDI, probably favored by the higher resistance and recurrence rate associated to ribotype 106 isolates.
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Affiliation(s)
- Loreto Suárez-Bode
- Microbiology Department, Hospital Universitari Son Espases and Instituto de Investigación Sanitaria Illes Balears (IdISBa), Palma de Mallorca, Spain
| | - Rubén Barrón
- Microbiology Department, Hospital Universitari Son Espases and Instituto de Investigación Sanitaria Illes Balears (IdISBa), Palma de Mallorca, Spain
| | - José L Pérez
- Microbiology Department, Hospital Universitari Son Espases and Instituto de Investigación Sanitaria Illes Balears (IdISBa), Palma de Mallorca, Spain
| | - Ana Mena
- Microbiology Department, Hospital Universitari Son Espases and Instituto de Investigación Sanitaria Illes Balears (IdISBa), Palma de Mallorca, Spain.
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Muñoz-Miralles J, Trindade BC, Castro-Córdova P, Bergin IL, Kirk LA, Gil F, Aronoff DM, Paredes-Sabja D. Indomethacin increases severity of Clostridium difficile infection in mouse model. Future Microbiol 2018; 13:1271-1281. [PMID: 30238771 PMCID: PMC6190216 DOI: 10.2217/fmb-2017-0311] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2017] [Accepted: 05/10/2018] [Indexed: 01/05/2023] Open
Abstract
AIM To evaluate the effect on the nonsteroidal anti-inflammatory drug indomethacin on Clostridium difficile infection (CDI) severity. MATERIALS & METHODS Indomethacin was administered in two different mouse models of antibiotic-associated CDI in two different facilities, using a low and high dose of indomethacin. RESULTS Indomethacin administration caused weight loss, increased the signs of severe infection and worsened histopathological damage, leading to 100% mortality during CDI. Indomethacin-treated, antibiotic-exposed mice infected with C. difficile had enhanced intestinal inflammation with increased expression of KC, IL-1β and IL-22 compared with infected mice unexposed to indomethacin. CONCLUSION These results demonstrate a negative impact of nonsteroidal anti-inflammatory drugs on antibiotic-associated CDI in mice and suggest that targeting the synthesis or signaling of prostaglandins might be an approach to ameliorating the severity of CDI.
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Affiliation(s)
- Juan Muñoz-Miralles
- Millennium Nucleus in the Biology of Intestinal Microbiota, Facultad de Ciencias de la Vida, Universidad Andrés Bello, 8370186 Santiago, Chile
- Microbiota-Host Interactions & Clostridia Research Group, Departamento de Ciencias Biológicas, Facultad de Ciencias de la Vida, Universidad Andrés Bello, 8370186 Santiago, Chile
| | - Bruno C Trindade
- Department of Pathology, The University of Massachusetts Medical School, Worcester, 01605 MA, USA
| | - Pablo Castro-Córdova
- Millennium Nucleus in the Biology of Intestinal Microbiota, Facultad de Ciencias de la Vida, Universidad Andrés Bello, 8370186 Santiago, Chile
- Microbiota-Host Interactions & Clostridia Research Group, Departamento de Ciencias Biológicas, Facultad de Ciencias de la Vida, Universidad Andrés Bello, 8370186 Santiago, Chile
| | - Ingrid L Bergin
- The Unit for Laboratory Animal Medicine, The University of Michigan, Ann Arbor, 48109 MI, USA
| | - Leslie A Kirk
- The Unit for Laboratory Animal Medicine, The University of Michigan, Ann Arbor, 48109 MI, USA
| | - Fernando Gil
- Millennium Nucleus in the Biology of Intestinal Microbiota, Facultad de Ciencias de la Vida, Universidad Andrés Bello, 8370186 Santiago, Chile
- Microbiota-Host Interactions & Clostridia Research Group, Departamento de Ciencias Biológicas, Facultad de Ciencias de la Vida, Universidad Andrés Bello, 8370186 Santiago, Chile
| | - David M Aronoff
- Department of Medicine, Division of Infectious Diseases, Vanderbilt University Medical Center, Nashville, 37232 TN, USA
| | - Daniel Paredes-Sabja
- Millennium Nucleus in the Biology of Intestinal Microbiota, Facultad de Ciencias de la Vida, Universidad Andrés Bello, 8370186 Santiago, Chile
- Microbiota-Host Interactions & Clostridia Research Group, Departamento de Ciencias Biológicas, Facultad de Ciencias de la Vida, Universidad Andrés Bello, 8370186 Santiago, Chile
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Goret J, Blanchi J, Floch P, Peuchant O, Chrisment D, Sanchez R, Biessy H, Lemarié R, Leyssene D, Loutfi B, Mimouni S, Flao T, Bébéar C, Mégraud F. Impact of the introduction of a nucleic acid amplification test for Clostridium difficile diagnosis on stool rejection policies. Gut Pathog 2018; 10:19. [PMID: 29854009 PMCID: PMC5975266 DOI: 10.1186/s13099-018-0245-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/01/2018] [Accepted: 05/19/2018] [Indexed: 12/02/2022] Open
Abstract
Background The change from non-molecular to nucleic acid amplification tests (NAATs) is known to increase the detection of Clostridium difficile infection (CDI); however, the impact on stool rejection policies in clinical laboratories is unclear. The current guidelines have reinforced the importance of respecting strict conditions for performing tests on stool samples for CDI diagnosis. The purpose of this study was to estimate whether the implementation of molecular tests has resulted in changes in stool rejection policies between clinical laboratories that introduced NAATs and those that did not. Results A survey was conducted to evaluate the change in the number of stool samples rejected and the rejection criteria among 12 hospital laboratories in southwestern France before and after the switch from non-molecular tests to NAATs using retrospective data from June 1 till September 30, 2013 and the same period 2014. Four laboratories introduced NAATs as a second or third step in the process. A total of 1378 and 1297 stools samples were collected in 2013 and 2014, respectively. The mean number of rejected stool samples significantly increased (p < 0.001, Chi square test), with a total of 99 (7.1%) and 147 (11.3%) specimens rejected in 2013 and 2014, respectively. Notably, these laboratories had more stringent criteria and were no longer testing the stool samples of patients with CDI-positive results within 7 days. In contrast, there was a significant decrease in the rate of rejected stool samples (p < 0.001, Chi square test) in the five laboratories that did not adopt NAATs and a less stringent stool rejection policy. Conclusion Nucleic acid amplification test implementation improved compliance with recommended stool rejection policies. Laboratories should follow the recommended laboratory algorithm for the CDI diagnosis combined with the correct stool rejection policy. Electronic supplementary material The online version of this article (10.1186/s13099-018-0245-x) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- J Goret
- 1Laboratoire de Bactériologie, C.H.U. de Bordeaux, Groupe Hospitalier Pellegrin, Place Amélie Raba Léon, 33076 Bordeaux Cedex, France
| | - J Blanchi
- 1Laboratoire de Bactériologie, C.H.U. de Bordeaux, Groupe Hospitalier Pellegrin, Place Amélie Raba Léon, 33076 Bordeaux Cedex, France
| | - P Floch
- 2C.H.U. de Bordeaux, Hôpital Haut-Lévèque, Pessac, France
| | - O Peuchant
- 2C.H.U. de Bordeaux, Hôpital Haut-Lévèque, Pessac, France
| | | | - R Sanchez
- C.H. de Périgueux, Périgueux, France
| | - H Biessy
- G.H. de La Rochelle-Ré-Aunis, La Rochelle, France
| | - R Lemarié
- G.H. de La Rochelle-Ré-Aunis, La Rochelle, France
| | - D Leyssene
- C. H. de la Côte Basque, Bayonne, France
| | - B Loutfi
- C.H. Mont de Marsan, Mont de Marsan, France
| | | | - T Flao
- C.H.I.C Marmande-Tonneins, Marmande, France
| | - C Bébéar
- 1Laboratoire de Bactériologie, C.H.U. de Bordeaux, Groupe Hospitalier Pellegrin, Place Amélie Raba Léon, 33076 Bordeaux Cedex, France
| | - F Mégraud
- 1Laboratoire de Bactériologie, C.H.U. de Bordeaux, Groupe Hospitalier Pellegrin, Place Amélie Raba Léon, 33076 Bordeaux Cedex, France
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Riley TV, Collins DA, Karunakaran R, Kahar MA, Adnan A, Hassan SA, Zainul NH, Rustam FRM, Wahab ZA, Ramli R, Lee YY, Hassan H. High Prevalence of Toxigenic and Nontoxigenic Clostridium difficile Strains in Malaysia. J Clin Microbiol 2018; 56:e00170-18. [PMID: 29563206 PMCID: PMC5971540 DOI: 10.1128/jcm.00170-18] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2018] [Accepted: 03/19/2018] [Indexed: 12/30/2022] Open
Abstract
Accumulating evidence shows a high prevalence of Clostridium difficile in Southeast Asia associated with a range of clinical presentations. However, severe infections are rarely reported. We investigated C. difficile infection (CDI) across four hospitals in Kuala Lumpur and Kota Bharu, Malaysia. Enzyme immunoassays for glutamate dehydrogenase (GDH) and toxin A or B were performed on diarrheal stool specimens collected from patients in 2015 and 2016. Specimens were also cultured and isolates of C. difficile characterized by PCR ribotyping and detection of toxin genes. In total, 437 specimens were collected and fecal toxin was detected in 3.0%. A further 16.2% of specimens were GDH positive and toxin negative. After culture, toxigenic strains were isolated from 10.3% and nontoxigenic strains from 12.4% of specimens. The most prevalent PCR ribotypes (RTs) were RT 017 (20.0%) and RT 043 (10.0%). The high prevalence of RT 017 and nontoxigenic strains in Malaysia and in neighboring Thailand and Indonesia suggests that they localize to the region of Southeast Asia, with an implication that they may mediate the burden of CDI in the region.
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Affiliation(s)
- Thomas V Riley
- School of Pathology and Laboratory Medicine, University of Western Australia, Crawley, Australia
- Department of Microbiology, PathWest Laboratory Medicine, Nedlands, Australia
- School of Veterinary and Life Sciences, Murdoch University, Murdoch, Australia
| | - Deirdre A Collins
- School of Pathology and Laboratory Medicine, University of Western Australia, Crawley, Australia
| | - Rina Karunakaran
- Department of Medical Microbiology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
| | - Maria Abdul Kahar
- Department of Medical Microbiology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
| | - Ariza Adnan
- Department of Medical Microbiology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
| | - Siti Asma Hassan
- School of Medical Sciences, Universiti Sains Malaysia, Kota Bharu, Malaysia
| | | | | | - Z Abd Wahab
- Sungai Buloh Hospital, Sungai Buloh, Malaysia
| | - Ramliza Ramli
- Department of Microbiology and Immunology, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia
| | - Yeong Yeh Lee
- School of Medical Sciences, Universiti Sains Malaysia, Kota Bharu, Malaysia
| | - Hamimah Hassan
- Department of Medical Microbiology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
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Gateau C, Couturier J, Coia J, Barbut F. How to: diagnose infection caused by Clostridium difficile. Clin Microbiol Infect 2018; 24:463-468. [DOI: 10.1016/j.cmi.2017.12.005] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2017] [Revised: 11/30/2017] [Accepted: 12/07/2017] [Indexed: 01/05/2023]
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González-Abad MJ, Alonso Sanz M. Recuperación de episodios de infección por Clostridium difficile tras la aplicación de un documento de consenso. An Pediatr (Barc) 2018; 88:226-227. [DOI: 10.1016/j.anpedi.2017.05.012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2017] [Revised: 05/23/2017] [Accepted: 05/25/2017] [Indexed: 11/27/2022] Open
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Gutiérrez-Pizarraya A, Martín-Villén L, Alcalá-Hernández L, Marín Arriaza M, Balandín-Moreno B, Aragón-González C, Ferreres-Franco J, Chiveli Monleón MÁ, Anguita-Alonso P, Bouza-Santiago E, Garnacho-Montero J. Epidemiology and risk factors for Clostridium difficile infection in critically ill patients in Spain: The PROCRID study. Enferm Infecc Microbiol Clin 2018; 36:218-221. [DOI: 10.1016/j.eimc.2017.01.007] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2016] [Revised: 01/30/2017] [Accepted: 01/30/2017] [Indexed: 12/12/2022]
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González-Abad MJ, Alonso Sanz M. Recovery from episodes of Clostridium difficile infection following the implementation of a consensus document. ANALES DE PEDIATRÍA (ENGLISH EDITION) 2018. [DOI: 10.1016/j.anpede.2017.05.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/17/2022] Open
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Reigadas E, Alcalá L, Gómez J, Marín M, Martin A, Onori R, Muñoz P, Bouza E. Breakthrough Clostridium difficile Infection in Cirrhotic Patients Receiving Rifaximin. Clin Infect Dis 2018; 66:1086-1091. [PMID: 29069372 DOI: 10.1093/cid/cix918] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2017] [Accepted: 10/17/2017] [Indexed: 01/05/2025] Open
Abstract
BACKGROUND Patients with cirrhosis are at high risk of Clostridium difficile infection (CDI). Rifaximin is commonly used in cirrhotic patients as prophylaxis for hepatic encephalopathy (HE). Several studies have demonstrated the efficacy of rifaximin in the treatment of CDI; however, resistance to rifaximin has also been reported. Few studies have assessed the risk of developing CDI in cirrhotic patients receiving rifaximin. Our objective was to assess the incidence and characteristics of CDI in patients with cirrhosis, especially in those who received rifaximin. METHODS We assessed the incidence and clinical characteristics of CDI in cirrhotic patients over a 6-year period in our hospital. Medical charts were retrospectively reviewed. Ribotyping and antimicrobial susceptibility testing of all strains against rifaximin were performed. RESULTS A total of 388 cirrhotic patients were included, of whom 127 patients had at least 1 episode of diarrhea in which a sample was sent to the laboratory. CDI was detected in 46 patients. Fourteen patients (30.4%) were receiving rifaximin as prophylaxis for HE. The main ribotypes detected were 001 (30.4%), followed by 014 (19.6%). Resistance to rifaximin was 34.1% overall, and 84.6% in patients who had received rifaximin. Multivariate analysis showed that rifamycin therapy and ribotype 001 were significant risk factors for having a rifaximin-resistant C. difficile strain. CONCLUSIONS A high percentage of CDI cases were detected in cirrhotic patients receiving rifaximin, mostly owing to selection of rifaximin-resistant C. difficile strains. Clinicians should be aware of the risk of CDI in cirrhotic patients, even in those receiving rifaximin.
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Affiliation(s)
- Elena Reigadas
- Department of Clinical Microbiology and Infectious Diseases, Hospital General Universitario Gregorio Marañón
- Medicine Department, School of Medicine, Universidad Complutense de Madrid
- Instituto de Investigación Sanitaria Gregorio Marañón
| | - Luis Alcalá
- Department of Clinical Microbiology and Infectious Diseases, Hospital General Universitario Gregorio Marañón
- Instituto de Investigación Sanitaria Gregorio Marañón
- CIBER de Enfermedades Respiratorias (CIBERES CB06/06/0058), Spain
| | - Javier Gómez
- Department of Clinical Microbiology and Infectious Diseases, Hospital General Universitario Gregorio Marañón
| | - Mercedes Marín
- Department of Clinical Microbiology and Infectious Diseases, Hospital General Universitario Gregorio Marañón
- Medicine Department, School of Medicine, Universidad Complutense de Madrid
- Instituto de Investigación Sanitaria Gregorio Marañón
- CIBER de Enfermedades Respiratorias (CIBERES CB06/06/0058), Spain
| | - Adoración Martin
- Department of Clinical Microbiology and Infectious Diseases, Hospital General Universitario Gregorio Marañón
- Instituto de Investigación Sanitaria Gregorio Marañón
| | - Raffaella Onori
- Department of Clinical Microbiology and Infectious Diseases, Hospital General Universitario Gregorio Marañón
| | - Patricia Muñoz
- Department of Clinical Microbiology and Infectious Diseases, Hospital General Universitario Gregorio Marañón
- Medicine Department, School of Medicine, Universidad Complutense de Madrid
- Instituto de Investigación Sanitaria Gregorio Marañón
- CIBER de Enfermedades Respiratorias (CIBERES CB06/06/0058), Spain
| | - Emilio Bouza
- Department of Clinical Microbiology and Infectious Diseases, Hospital General Universitario Gregorio Marañón
- Medicine Department, School of Medicine, Universidad Complutense de Madrid
- Instituto de Investigación Sanitaria Gregorio Marañón
- CIBER de Enfermedades Respiratorias (CIBERES CB06/06/0058), Spain
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Namiki H, Kobayashi T. Long-term, low-dose of clarithromycin as a cause of community-acquired Clostridium difficile infection in a 5-year-old boy. Oxf Med Case Reports 2018; 2018:omx106. [PMID: 29593875 PMCID: PMC5861397 DOI: 10.1093/omcr/omx106] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2017] [Revised: 11/09/2017] [Accepted: 12/07/2017] [Indexed: 12/14/2022] Open
Abstract
Clostridium difficile is one of the most common causes of antibiotic-associated diarrhoea. Despite C. difficile infection (CDI) has increased in all ages worldwide, episodes of CDI are often misdiagnosed due to the lack of clinical suspicion. Macrolides are also associated with CDI. Additionally, exposure to macrolides in the 12 weeks preceding infection is reported to be a significant risk factor of CDI in a child. We report here a 5-year-old Japanese boy who presented with acute onset of watery diarrhoea. He was diagnosed with community-acquired CDI induced by long-term (20 weeks), low-dose, oral clarithromycin for otitis media with effusion, and he recovered by conservative treatment. Physicians should be more cautious of community-acquired CDI in children who take long-term, low-dose macrolides, not to misdiagnose as diarrhoea by its side effect, and avoid unnecessary use of systemic antibiotics.
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Affiliation(s)
- Hirofumi Namiki
- Yonaguni Municipal Clinic Japan Association for Development of Community Medicine, Yonaguni-cho, Yaeyama-gun, Okinawa 9071801, Japan
| | - Tadashi Kobayashi
- Department of General Medicine, University School of Medicine & Hospital, Hirosaki-shi, Aomori-ken 0368563, Japan
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Wiuff C, Banks AL, Fitzpatrick F, Cottom L. The Need for European Surveillance of CDI. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2018; 1050:13-25. [PMID: 29383661 DOI: 10.1007/978-3-319-72799-8_2] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Since the turn of the millennium, the epidemiology of Clostridium difficile infection (CDI) has continued to challenge. Over the last decade there has been a growing awareness that improvements to surveillance are needed. The increasing rate of CDI and emergence of ribotype 027 precipitated the implementation of mandatory national surveillance of CDI in the UK. 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 surveillance.However a lack of consensus on case definitions, clinical guidelines and optimal laboratory diagnostics across Europe has lead 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 surveillance programme and optimised diagnostic strategies are required not only to detect and control CDI in Europe, but for a better understanding of the epidemiology, 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, has lead to the development of an over-arching long-term CDI surveillance strategy for 2014-2020. Fulfilment of the ECDC priorities and targets will no doubt be challenging and will require significant investment however the hope is that both a national and Europe-wide picture of CDI will finally be realised.
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Affiliation(s)
- Camilla Wiuff
- Strategic Lead Microbiology, NHS National Services Scotland, Health Protection Scotland, HAI & IC Section, Glasgow, UK.
| | - A-Lan Banks
- Strategic Lead Microbiology, NHS National Services Scotland, Health Protection Scotland, HAI & IC Section, Glasgow, UK
| | - Fidelma Fitzpatrick
- Department of Clinical Microbiology, The Royal College of Surgeons in Ireland, Dublin, Ireland
- Department of Clinical Microbiology, Beaumont Hospital, Dublin, Ireland
| | - Laura Cottom
- Department of Microbiology, Glasgow Royal Infirmary, Glasgow, UK
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38
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Couturier J, Davies K, Gateau C, Barbut F. Ribotypes and New Virulent Strains Across Europe. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2018; 1050:45-58. [PMID: 29383663 DOI: 10.1007/978-3-319-72799-8_4] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Clostridium difficile is a major bacterial cause of post-antibiotic diarrhoea. The epidemiology of C. difficile infections (CDI) has dramatically changed since the early 2000s, with an increasing incidence and severity across Europe. This trend is partly due to the emergence and rapid worldwide spread of the hypervirulent and epidemic PCR ribotype 027. Profiles of patients with CDI have also evolved, with description of community-acquired (CA) infections in patients with no traditional risk factors for CDI. However, recent epidemiological studies indicated that some European countries have successfully controlled the dissemination of the 027 clone whereas other countries recently reported the emergence of other virulent or unusual strains. The aims of this review are to summarize the current European CDI epidemiology and to describe the new virulent C. difficile strains circulating in Europe, as well as other potential emerging strains described elsewhere. Standardized typing methods and surveillance programmes are mandatory for a better understanding and monitoring of CDI in Europe.
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Affiliation(s)
- Jeanne Couturier
- National Reference Laboratory for C. difficile, Hôpital Saint-Antoine, Paris, France. .,Université Paris Descartes, Faculté de Pharmacie, Paris, France.
| | - Kerrie Davies
- Healthcare Associated Infections Research Group, Leeds Teaching Hospitals NHS Trust and University of Leeds, Leeds, UK
| | - Cécile Gateau
- National Reference Laboratory for C. difficile, Hôpital Saint-Antoine, Paris, France
| | - Frédéric Barbut
- National Reference Laboratory for C. difficile, Hôpital Saint-Antoine, Paris, France.,Université Paris Descartes, Faculté de Pharmacie, Paris, France
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39
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Diagnostic Guidance for C. difficile Infections. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2018; 1050:27-44. [PMID: 29383662 DOI: 10.1007/978-3-319-72799-8_3] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Diagnosis of Clostridium difficile infection (CDI) can be challenging. First of all, there has been debate on which of the two reference assays, cell cytotoxicity neutralization assay (CCNA) or toxigenic culture (TC) should be considered the gold standard for CDI detection. Although the CCNA suffers most from suboptimal storage conditions and subsequent toxin degradation, TC is reported to falsely increase CDI detection rates as it cannot differentiate CDI patients from patients asymptomatically colonised by toxigenic C. difficile. Several rapid assays are available for CDI detection and fall into three broad categories: (1) enzyme immunoassays for glutamate dehydrogenase, (2) enzyme immunoassays for toxins A/B and (3) nucleic acid amplification tests detecting toxin genes. All three categories have their own limitations, being suboptimal specificity and/or sensitivity or the inability to discern colonised patients from CDI patients. In light of these limitations, multi-step algorithmic testing has now been advocated by international guidelines in order to optimize diagnostic accuracy. Despite these recommendations, testing methods between hospitals vary widely, which impacts CDI incidence rates. CDI incidence rates are also influenced by sample selection criteria, as several studies have shown that if not all unformed stool samples are tested for CDI, many cases may be missed due to an absence of clinical suspicion. Since methods for diagnosing CDI remain imperfect, there has been a growing interest in alternative testing strategies like faecal biomarkers, immune modulating interleukins, cytokines and imaging methods. At the moment, these alternative methods might play an adjunctive role, but they are not suitable to replace conventional CDI testing strategies.
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Choice of treatment in Clostridium difficile-associated diarrhoea: Clinical practice guidelines or risk classifications. Enferm Infecc Microbiol Clin 2017; 35:613-616. [PMID: 29179981 DOI: 10.1016/j.eimc.2017.11.004] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2017] [Accepted: 11/07/2017] [Indexed: 12/17/2022]
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41
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Chen YB, Gu SL, Shen P, Lv T, Fang YH, Tang LL, Li LJ. Molecular epidemiology and antimicrobial susceptibility of Clostridium difficile isolated from hospitals during a 4-year period in China. J Med Microbiol 2017; 67:52-59. [PMID: 29160203 DOI: 10.1099/jmm.0.000646] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023] Open
Abstract
OBJECTIVE The aim of this study was to perform molecular characterization for and determine the antimicrobial susceptibility profiles of Clostridium difficile collected from hospitals during a 4-year period (2009-2013) in China. METHODS Strains of toxigenic C. difficile were isolated from patients with diarrhoea, and this was followed by typing using multilocus sequence typing (MLST) and testing for susceptibility to 10 antimicrobials by using the E-test. The mechanisms of resistance to moxifloxacin, erythromycin, clindamycin and tetracycline were investigated by PCR. RESULTS A total of 405 non-duplicate toxigenic C. difficile isolates were identified, while 31 sequence types (STs) were identified. A predominant type, ST-54, accounted for 20.2 % of the STs, followed by ST-35 (16.3 %) and ST-37 (13.6 %). We found that 6.2 % of the isolates were binary toxin genes-positive, and 83.7 % of these belonged to ST-5. All of the isolates demonstrated 100 % susceptibility to first-line Clostridium difficile infection (CDI) therapies (i.e. metronidazole and vancomycin), while the resistance rates varied for the other antibiotics tested. Two hundred and ninety three (72.3 %) isolates were susceptible to moxifloxacin. All 112 moxifloxacin-resistant isolates had mutations resulting in an amino acid substitution in gryA and/or gyrB. The ermB gene was detected in 86.7 % (241/278) of the erythromycin- and clindamycin-resistant isolates, while the tetM gene was present in 97.1 % (85/87) of the tetracycline-resistant isolates. CONCLUSION MLST typing revealed a wide variety of STs causing CDI, while ST-54 was the most common ST. All of the isolates were susceptible to metronidazole and vancomycin, while the resistance rates varied for the other antibiotics tested. There were no changes in the trends for the STs and antibiotic susceptibility profiles over 4 years.
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Affiliation(s)
- Yun-Bo Chen
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, PR China.,Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, PR China
| | - Si-Lan Gu
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, PR China.,Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, PR China
| | - Ping Shen
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, PR China.,Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, PR China
| | - Tao Lv
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, PR China.,Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, PR China
| | - Yun-Hui Fang
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, PR China.,Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, PR China
| | - Ling-Ling Tang
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, PR China.,Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, PR China.,Hospital Infection-Control Department, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, PR China
| | - Lan-Juan Li
- Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, PR China.,State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, PR China
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Prechter F, Katzer K, Bauer M, Stallmach A. Sleeping with the enemy: Clostridium difficile infection in the intensive care unit. CRITICAL CARE : THE OFFICIAL JOURNAL OF THE CRITICAL CARE FORUM 2017; 21:260. [PMID: 29058580 PMCID: PMC5651627 DOI: 10.1186/s13054-017-1819-6] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/26/2017] [Revised: 08/15/2017] [Accepted: 08/17/2017] [Indexed: 02/06/2023]
Abstract
Over the last years, there was an increase in the number and severity of Clostridium difficile infections (CDI) in all medical settings, including the intensive care unit (ICU). The current prevalence of CDI among ICU patients is estimated at 0.4–4% and has severe impact on morbidity and mortality. An estimated 10–20% of patients are colonized with C. difficile without showing signs of infection and spores can be found throughout ICUs. It is not yet possible to predict whether and when colonization will become infection. Figuratively speaking, our patients are sleeping with the enemy and we do not know when this enemy awakens. Most patients developing CDI in the ICU show a mild to moderate disease course. Nevertheless, difficult-to-treat severe and complicated cases also occur. Treatment failure is particularly frequent in ICU patients due to comorbidities and the necessity of continued antibiotic treatment. This review will give an overview of current diagnostic, therapeutic, and prophylactic challenges and options with a special focus on the ICU patient. First, we focus on diagnosis and prognosis of disease severity. This includes inconsistencies in the definition of disease severity as well as diagnostic problems. Proceeding from there, we discuss that while at first glance the choice of first-line treatment for CDI in the ICU is a simple matter guided by international guidelines, there are a number of specific problems and inconsistencies. We cover treatment in severe CDI, the problem of early recognition of treatment failure, and possible concepts of intensifying treatment. In conclusion, we mention methods for CDI prevention in the ICU.
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Affiliation(s)
- Florian Prechter
- Department of Internal Medicine IV, Jena University Hospital, Am Klinikum 1, 07743, Jena, Germany.
| | - Katrin Katzer
- Department of Internal Medicine IV, Jena University Hospital, Am Klinikum 1, 07743, Jena, Germany
| | - Michael Bauer
- Department of Anesthesiology and Intensive Care Medicine, Jena University Hospital, Am Klinikum 1, 07743, Jena, Germany.,Center for Sepsis Control & Care, Jena University Hospital, Am Klinikum 1, 07743, Jena, Germany
| | - Andreas Stallmach
- Department of Internal Medicine IV, Jena University Hospital, Am Klinikum 1, 07743, Jena, Germany.,Center for Sepsis Control & Care, Jena University Hospital, Am Klinikum 1, 07743, Jena, Germany
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43
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Point-prevalence survey of healthcare facility-onset healthcare-associated Clostridium difficile infection in Greek hospitals outside the intensive care unit: The C. DEFINE study. PLoS One 2017; 12:e0182799. [PMID: 28813492 PMCID: PMC5559069 DOI: 10.1371/journal.pone.0182799] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2016] [Accepted: 07/25/2017] [Indexed: 12/17/2022] Open
Abstract
BACKGROUND The correlation of Clostridium difficile infection (CDI) with in-hospital morbidity is important in hospital settings where broad-spectrum antimicrobial agents are routinely used, such as in Greece. The C. DEFINE study aimed to assess point-prevalence of CDI in Greece during two study periods in 2013. METHODS There were two study periods consisting of a single day in March and another in October 2013. Stool samples from all patients hospitalized outside the ICU aged ≥18 years old with diarrhea on each day in 21 and 25 hospitals, respectively, were tested for CDI. Samples were tested for the presence of glutamate dehydrogenase antigen (GDH) and toxins A/B of C. difficile; samples positive for GDH and negative for toxins were further tested by culture and PCR for the presence of toxin genes. An analysis was performed to identify potential risk factors for CDI among patients with diarrhea. RESULTS 5,536 and 6,523 patients were screened during the first and second study periods, respectively. The respective point-prevalence of CDI in all patients was 5.6 and 3.9 per 10,000 patient bed-days whereas the proportion of CDI among patients with diarrhea was 17% and 14.3%. Logistic regression analysis revealed that solid tumor malignancy [odds ratio (OR) 2.69, 95% confidence interval (CI): 1.18-6.15, p = 0.019] and antimicrobial administration (OR 3.61, 95% CI: 1.03-12.76, p = 0.045) were independent risk factors for CDI development. Charlson's Comorbidity Index (CCI) >6 was also found as a risk factor of marginal statistical significance (OR 2.24, 95% CI: 0.98-5.10). Median time to CDI from hospital admission was shorter with the presence of solid tumor malignancy (3 vs 5 days; p = 0.002) and of CCI >6 (4 vs 6 days, p = 0.009). CONCLUSIONS The point-prevalence of CDI in Greek hospitals was consistent among cases of diarrhea over a 6-month period. Major risk factors were antimicrobial use, solid tumor malignancy and a CCI score >6.
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Orden C, Neila C, Blanco JL, Álvarez-Pérez S, Harmanus C, Kuijper EJ, García ME. Recreational sandboxes for children and dogs can be a source of epidemic ribotypes of Clostridium difficile. Zoonoses Public Health 2017; 65:88-95. [PMID: 28686001 DOI: 10.1111/zph.12374] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2017] [Indexed: 12/13/2022]
Abstract
Different studies have suggested that the sand of public playgrounds could have a role in the transmission of infections, particularly in children. Furthermore, free access of pets and other animals to the playgrounds might increase such a risk. We studied the presence of Clostridium difficile in 20 pairs of sandboxes for children and dogs located in different playgrounds within the Madrid region (Spain). Clostridium difficile isolation was performed by enrichment and selective culture procedures. The genetic (ribotype and amplified fragment length polymorphism [AFLP]) diversity and antibiotic susceptibility of isolates was also studied. Overall, 52.5% (21/40) of samples were positive for the presence of C. difficile. Eight of the 20 available isolates belonged to the toxigenic ribotypes 014 (n = 5) and 106 (n = 2), both regarded as epidemic, and CD047 (n = 1). The other 12 isolates were non-toxigenic, and belonged to ribotypes 009 (n = 5), 039 (n = 4), and 067, 151 and CD048 (one isolate each). Nevertheless, all isolates (even those of a same ribotype) were classified into different AFLP genotypes indicating non-relatedness. In conclusion, our results revealed the presence of epidemic ribotypes of C. difficile in children's and dog's sandboxes located nearby, which constitutes a major health risk.
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Affiliation(s)
- Cristina Orden
- Department of Animal Health, Faculty of Veterinary, Universidad Complutense de Madrid, Madrid, Spain
| | - Carlos Neila
- Department of Animal Health, Faculty of Veterinary, Universidad Complutense de Madrid, Madrid, Spain
| | - José L Blanco
- Department of Animal Health, Faculty of Veterinary, Universidad Complutense de Madrid, Madrid, Spain
| | - Sergio Álvarez-Pérez
- Department of Animal Health, Faculty of Veterinary, Universidad Complutense de Madrid, Madrid, Spain
| | - Celine Harmanus
- Department of Medical Microbiology, Center of Infectious Diseases, Leiden University Medical Center, Leiden, Netherlands
| | - Ed J Kuijper
- Department of Medical Microbiology, Center of Infectious Diseases, Leiden University Medical Center, Leiden, Netherlands
| | - Marta E García
- Department of Animal Health, Faculty of Veterinary, Universidad Complutense de Madrid, Madrid, Spain
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Prevalence and characteristics of Clostridium perfringens and Clostridium difficile in dogs and cats attended in diverse veterinary clinics from the Madrid region. Anaerobe 2017; 48:47-55. [PMID: 28687280 DOI: 10.1016/j.anaerobe.2017.06.023] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2017] [Revised: 06/21/2017] [Accepted: 06/30/2017] [Indexed: 12/15/2022]
Abstract
Despite extensive research on the epidemiology of pathogenic clostridia in dogs and cats, most published studies focus on a selected animal population and/or a single veterinary medical centre. We assessed the burden of Clostridium perfringens and C. difficile shedding by small animals in 17 veterinary clinics located within the Madrid region (Spain) and differing in size, number and features of animals attended and other relevant characteristics. In addition, we studied the genetic diversity and antibiotic susceptibility of recovered isolates. Selective culture of all fecal specimens collected during a single week from dogs (n = 105) and cats (n = 37) attended in participating clinics yielded C. perfringens/C. difficile from 31%, 4.8% of the dogs, and 20%, 0% of the cats analyzed, respectively, and three dogs yielded both species. Furthermore, 17 animals (15 dogs and two cats) that yielded a positive culture for either species were recruited for a follow-up survey and C. perfringens was again obtained from nine dogs. Considerable differences in prevalence were observed among participating clinics for both clostridial species. C. perfringens isolates (n = 109) belonged to toxinotypes A (97.2%) and E (three isolates from one dog), whereas C. difficile isolates (n = 18) belonged to the toxigenic ribotypes 106 (33.3%) and 154 (16.7%), a 009-like ribotype (33.3%) and an unknown non-toxigenic ribotype (16.7%). Amplified fragment length polymorphism-based fingerprinting classified C. perfringens and C. difficile isolates into 105 and 15 genotypes, respectively, and tested isolates displayed in vitro resistance to benzylpenicillin (2.8%, 88.8%), clindamycin (0%, 16.7%), erythromycin (0.9%, 16.7%), imipenem (1.8%, 100%), levofloxacin (0.9%, 100%), linezolid (5.5%, 0%), metronidazole (4.6%, 0%) and/or tetracycline (7.3%, 0%). All animals from which multiple isolates were retrieved yielded ≥2 different genotypes and/or antimicrobial susceptibility profiles. Future studies should focus on the seasonal and geographical variations of prevalence and diversity patterns of clostridial species in small animals.
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An outbreak of Clostridium difficile PCR ribotype 027 in Spain: risk factors for recurrence and a novel treatment strategy. Eur J Clin Microbiol Infect Dis 2017; 36:1777-1786. [PMID: 28501926 DOI: 10.1007/s10096-017-2991-y] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2017] [Accepted: 04/17/2017] [Indexed: 12/15/2022]
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Borren NZ, Ghadermarzi S, Hutfless S, Ananthakrishnan AN. The emergence of Clostridium difficile infection in Asia: A systematic review and meta-analysis of incidence and impact. PLoS One 2017; 12:e0176797. [PMID: 28463987 PMCID: PMC5413003 DOI: 10.1371/journal.pone.0176797] [Citation(s) in RCA: 84] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2017] [Accepted: 04/17/2017] [Indexed: 12/18/2022] Open
Abstract
Background Clostridium difficile infection (CDI) is the most common healthcare associated infection and is highly prevalent in Europe and North America. Limited data is available on the prevalence of CDI in Asia. However, secular increases in prevalence of risk factors for CDI suggest that it may be emerging as a major cause of morbidity, highlighting the urgent need for a systematic study of the prevalence of CDI in Asia. Methods We systematically searched PubMed/Medline and Embase for publications from Asia between 2000–16 examining prevalence of CDI. A random-effects meta-analysis was performed to calculate the pooled prevalence of CDI in Asia and to identify subgroups and regions at high risk. Results Our meta-analysis included 51 studies from throughout Asia including 37,663 patients at risk among whom confirmed CDI was found in 4,343 patients. The pooled proportion of confirmed CDI among all patients with diarrhea was 14.8% with a higher prevalence in East Asia (19.5%), compared with South Asia (10.5%) or the Middle East (11.1%). There were an estimated 5.3 episodes of CDI per 10,000 patient days, similar to rates reported from Europe and North America. Infections due to hypervirulent strains were rare. CDI-related mortality was 8.9%. Conclusions In a meta-analysis of 51 studies, we observed similar rates of CDI in Asia in comparison to Europe and North America. Increased awareness and improved surveillance of Clostridium difficile is essential to reduce incidence and morbidity.
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Affiliation(s)
- Nienke Z. Borren
- Division of Gastroenterology, Massachusetts General Hospital, Boston, Massachusetts, United States of America
- University of Groningen, Groningen, The Netherlands
| | - Shadi Ghadermarzi
- Division of Gastroenterology & Hepatology, Johns Hopkins University, Baltimore, Maryland, United States of America
| | - Susan Hutfless
- Division of Gastroenterology & Hepatology, Johns Hopkins University, Baltimore, Maryland, United States of America
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States of America
| | - Ashwin N. Ananthakrishnan
- Division of Gastroenterology, Massachusetts General Hospital, Boston, Massachusetts, United States of America
- Harvard Medical School, Boston, Massachusetts, United States of America
- * E-mail:
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48
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Martínez-Meléndez A, Camacho-Ortiz A, Morfin-Otero R, Maldonado-Garza HJ, Villarreal-Treviño L, Garza-González E. Current knowledge on the laboratory diagnosis of Clostridium difficile infection. World J Gastroenterol 2017; 23:1552-1567. [PMID: 28321156 PMCID: PMC5340807 DOI: 10.3748/wjg.v23.i9.1552] [Citation(s) in RCA: 43] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/15/2016] [Revised: 01/21/2017] [Accepted: 02/17/2017] [Indexed: 02/06/2023] Open
Abstract
Clostridium difficile (C. difficile) is a spore-forming, toxin-producing, gram-positive anaerobic bacterium that is the principal etiologic agent of antibiotic-associated diarrhea. Infection with C. difficile (CDI) is characterized by diarrhea in clinical syndromes that vary from self-limited to mild or severe. Since its initial recognition as the causative agent of pseudomembranous colitis, C. difficile has spread around the world. CDI is one of the most common healthcare-associated infections and a significant cause of morbidity and mortality among older adult hospitalized patients. Due to extensive antibiotic usage, the number of CDIs has increased. Diagnosis of CDI is often difficult and has a substantial impact on the management of patients with the disease, mainly with regards to antibiotic management. The diagnosis of CDI is primarily based on the clinical signs and symptoms and is only confirmed by laboratory testing. Despite the high burden of CDI and the increasing interest in the disease, episodes of CDI are often misdiagnosed. The reasons for misdiagnosis are the lack of clinical suspicion or the use of inappropriate tests. The proper diagnosis of CDI reduces transmission, prevents inadequate or unnecessary treatments, and assures best antibiotic treatment. We review the options for the laboratory diagnosis of CDI within the settings of the most accepted guidelines for CDI diagnosis, treatment, and prevention of CDI.
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Orden C, Blanco JL, Álvarez-Pérez S, Garcia-Sancho M, Rodriguez-Franco F, Sainz A, Villaescusa A, Harmanus C, Kuijper E, Garcia ME. Isolation of Clostridium difficile from dogs with digestive disorders, including stable metronidazole-resistant strains. Anaerobe 2016; 43:78-81. [PMID: 27965048 DOI: 10.1016/j.anaerobe.2016.12.008] [Citation(s) in RCA: 36] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2016] [Revised: 11/29/2016] [Accepted: 12/08/2016] [Indexed: 02/08/2023]
Abstract
The prevalence of Clostridium difficile in 107 dogs with diverse digestive disorders attended in a Spanish veterinary teaching hospital was assessed. The microorganism was isolated from 13 dogs (12.1%) of different disease groups. Isolates belonged to PCR ribotypes 078, 106, 154 and 430 (all of them toxigenic) and 110 (non-toxigenic), and were resistant to several antimicrobial drugs. Notably, seven isolates obtained from different dogs displayed stable resistance to metronidazole. The results of this study provide further evidence that dogs can act as a reservoir of C. difficile strains of epidemic ribotypes with resistance to multiple antibiotics.
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Affiliation(s)
- Cristina Orden
- Departamento de Sanidad Animal, Facultad de Veterinaria, Universidad Complutense, 28040, Madrid, Spain
| | - Jose L Blanco
- Departamento de Sanidad Animal, Facultad de Veterinaria, Universidad Complutense, 28040, Madrid, Spain; Hospital Clínico Veterinario Complutense, Universidad Complutense, 28040, Madrid, Spain.
| | - Sergio Álvarez-Pérez
- Departamento de Sanidad Animal, Facultad de Veterinaria, Universidad Complutense, 28040, Madrid, Spain
| | | | | | - Angel Sainz
- Hospital Clínico Veterinario Complutense, Universidad Complutense, 28040, Madrid, Spain
| | - Alejandra Villaescusa
- Hospital Clínico Veterinario Complutense, Universidad Complutense, 28040, Madrid, Spain
| | - Celine Harmanus
- Department of Medical Microbiology, Center of Infectious Diseases, Leiden University Medical Center, Leiden, The Netherlands
| | - Ed Kuijper
- Department of Medical Microbiology, Center of Infectious Diseases, Leiden University Medical Center, Leiden, The Netherlands
| | - Marta E Garcia
- Departamento de Sanidad Animal, Facultad de Veterinaria, Universidad Complutense, 28040, Madrid, Spain; Hospital Clínico Veterinario Complutense, Universidad Complutense, 28040, Madrid, Spain
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García-Lozano T, Aznar-Oroval E, Martín-Utrilla S. Recurrencias en infecciones por Clostridium difficile en pacientes con cáncer. Med Clin (Barc) 2016; 147:417-418. [DOI: 10.1016/j.medcli.2016.04.020] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2016] [Revised: 04/18/2016] [Accepted: 04/28/2016] [Indexed: 02/04/2023]
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