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Outbreak epidemiology, virulence and quality of life in Clostridioides difficile infection
Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Department of Infectious Diseases, Region Jönköping County, Jönköping, Sweden.ORCID iD: 0000-0002-5540-8930
2025 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Clostridioides difficile is a toxigenic, anaerobic spore-forming bacterium. C. difficile infection (CDI) is the leading cause of healthcare-associated diarrhea and pseudomembranous colitis, particularly in elderly, hospitalized patients that have received antibiotic treatment.

The aims of this thesis were to investigate the molecular epidemiology, transmission and virulence of CDI in Region Jönköping County, including a local outbreak of C. difficile ribotype (RT) 046. Additionally, the thesis aimed to assess the impact of fecal microbiota transplantation (FMT) on the health related quality of life (HRQoL) in patients with recurrent CDI (rCDI).

In paper I we collected and ribotyped C. difficile isolates from patients in the county during one year. Two different RTs, RT 001 and RT 012, were associated with nosocomial transmission. In paper II we analyzed a large local outbreak dominated by RT 046 using ribotyping and whole genome sequencing to explore epidemiological links. Furthermore the virulence of RT 046 was assessed, and interventions implemented to stop the outbreak were evaluated. RT 046 was widely spread throughout Högland Hospital, and was associated with a higher mortality compared to other strains. In paper III, toxin production and sporulation capacity in epidemic RT 046 were compared to other less prominent RTs. RT 046 produced higher levels of toxin and exhibited a higher degree of antibiotic resistance compared to the other strains from the outbreak. Finally, in paper IV we evaluated the HRQoL in patients with rCDI before and after treatment with FMT. We found that patients with rCDI had low HRQoL which increased significantly after treatment with FMT.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2025. , p. 86
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1942
National Category
Infectious Medicine
Identifiers
URN: urn:nbn:se:liu:diva-212780DOI: 10.3384/9789180758246ISBN: 9789180758239 (print)ISBN: 9789180758246 (electronic)OAI: oai:DiVA.org:liu-212780DiVA, id: diva2:1949274
Public defence
2025-05-09, Aulan, Länssjukhuset Ryhov, Jönköping, 09:00 (English)
Opponent
Supervisors
Available from: 2025-04-02 Created: 2025-04-02 Last updated: 2025-04-02Bibliographically approved
List of papers
1. Ribotyping of lostridium difficile strains associated with nosocomial transmission and relapses in a Swedish County
Open this publication in new window or tab >>Ribotyping of lostridium difficile strains associated with nosocomial transmission and relapses in a Swedish County
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2013 (English)In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 121, no 2, p. 153-157Article in journal (Refereed) Published
Abstract [en]

Clostridium difficile is an emerging threat in hospital environments. To analyse possible transmission and to distinguish between relapse and reinfection a collection of C. difficile isolates, sampled from 162 consecutive episodes of C. difficile infection, were PCR ribotyped. Two ribotypes (001 and 012) were prone to cause nosocomial acquisition. Moreover, ribotype 001 had a tendency to cause relapses as almost one in two patients with this ribotype had one or more relapses. By using PCR ribotyping strains inclined to cause relapses and strains associated with hospital transmission might be detected. This enables optimized hygiene measures and may improve the choice of treatment regimen.

Place, publisher, year, edition, pages
John Wiley & Sons, 2013
Keywords
Clostridium difficile, molecular epidemiology, ribotyping, transmission, CDI, hygiene measures
National Category
Infectious Medicine
Identifiers
urn:nbn:se:liu:diva-212778 (URN)10.1111/j.1600-0463.2012.02950.x (DOI)000313830700009 ()23030627 (PubMedID)2-s2.0-84872665873 (Scopus ID)
Note

Funding: Financial support was received from Futurum The Academy of Healthcare, County Council of Jönköping, Sweden.

Available from: 2025-04-02 Created: 2025-04-02 Last updated: 2025-04-02Bibliographically approved
2. Characterization of a Clostridioides difficile outbreak caused by PCR ribotype 046, associated with increased mortality
Open this publication in new window or tab >>Characterization of a Clostridioides difficile outbreak caused by PCR ribotype 046, associated with increased mortality
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2022 (English)In: Emerging Microbes & Infections, E-ISSN 2222-1751, Vol. 11, no 1, p. 850-859Article in journal (Refereed) Published
Abstract [en]

This study describes a large nosocomial outbreak of Clostridioides difficile infections (CDI) dominated by ribotype (RT) 046 in a Swedish hospital. The present study aimed to examine the pathogenicity of this RT, explore epidemiological links by whole genome sequencing (WGS), and evaluate different interventions implemented to stop the outbreak. Clinical isolates (n = 366) collected during and after the outbreak were ribotyped and 246 isolates were subjected to WGS. Medical records of patients infected with the seven most common RTs were evaluated. RT046 was spread effectively throughout the hospital and was the most common among the 44 different RTs found (114/366 isolates). Infection with RT046 was associated with higher mortality compared to other strains (20.2% to 7.8%), although there were no differences in concomitant disease, age or antibiotic treatment. To control the outbreak, several measures were successfully implemented.

Place, publisher, year, edition, pages
Taylor & Francis Ltd, 2022
Keywords
Clostridioides difficile; CDI; mortality; outbreak; epidemiology; ribotyping; whole-genome sequencing
National Category
Infectious Medicine
Identifiers
urn:nbn:se:liu:diva-184057 (URN)10.1080/22221751.2022.2049981 (DOI)000771404100001 ()35240942 (PubMedID)
Note

Funding: Academy for Health and Care, Region Jonkoping County, Sweden

Available from: 2022-04-04 Created: 2022-04-04 Last updated: 2025-04-02
3. Improved health-related quality of life in patients with recurrent Clostridioides difficile infection after treatment with faecal microbiota transplantation
Open this publication in new window or tab >>Improved health-related quality of life in patients with recurrent Clostridioides difficile infection after treatment with faecal microbiota transplantation
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2025 (English)In: Infectious Diseases, ISSN 2374-4235, E-ISSN 2374-4243, Vol. 57, no 3, p. 239-246Article in journal (Refereed) Published
Abstract [en]

BackgroundClostridioides difficile is a major burden for both healthcare systems and the patients. Faecal microbiota transplantation (FMT) is becoming more common as a treatment since it reduces the risk of recurrent Clostridioides difficile infection (rCDI).ObjectivesTo evaluate how treatment with FMT is affecting the health-related quality of life (HRQoL) in patients with rCDI.MethodsA prospective observational cohort study was conducted where patients who were offered FMT as a treatment for rCDI were asked to fill in a questionnaire based on the Short Health Scale (SHS) and EuroQol 5-Dimensions 5-Levels (EQ-5D-5L) about their HRQoL before and after treatment.ResultsPatients with rCDI had poor HRQoL, which improved following FMT.ConclusionsSince FMT cures, reduces the risk of new recurrences of CDI and improves the HRQoL of the patients, it should be offered as a treatment for patients with rCDI. Also, SHS is a useful and reliable instrument for measuring HRQoL in patients with rCDI.

Place, publisher, year, edition, pages
TAYLOR & FRANCIS LTD, 2025
Keywords
; faecal microbiota transplantation; Short Health Scale
National Category
Surgery
Identifiers
urn:nbn:se:liu:diva-209330 (URN)10.1080/23744235.2024.2415694 (DOI)001343047000001 ()39460926 (PubMedID)2-s2.0-85208134144 (Scopus ID)
Note

Funding Agencies|Academy for Health and Care, Region Jonkoping County, Medical Research Council of Southeast Sweden; Region Ostergotland, Sweden

Available from: 2024-11-12 Created: 2024-11-12 Last updated: 2025-04-30

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