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.

Clostridioides difficile infections (CDIs) in Sweden are mostly hospital-associated (HA) with limited knowledge regarding community-associated (CA) infections. Here, we investigated the molecular epidemiology of clinical isolates of CA-CDI and HA-CDI in a Swedish county. Data and isolates (n = 156) of CDI patients (n = 122) from Jonkoping county, October 2017-March 2018, were collected and classified as CA (without previous hospital care or onset <= 2 days after admission or >12 weeks after discharge from hospital) or HA (onset >3 days after hospital admission or within 4 weeks after discharge). Molecular characterization of isolates included PCR ribotyping (n = 156 isolates) and whole genome sequencing with single nucleotide polymorphisms (SNP) analysis (n = 53 isolates). We classified 47 patients (39%) as CA-CDI and 75 (61%) as HA-CDI. Between CA-CDI and HA-CDI patients, we observed no statistically significant differences regarding gender, age, 30-day mortality or recurrence. Ribotype 005 (RR 3.1; 95% CI: 1.79-5.24) and 020 (RR 2.5; 95% CI: 1.31-4.63) were significantly associated with CA-CDI. SNP analysis identified seven clusters (0-2 SNP difference) involving 17/53 isolates of both CA-CDI and HA-CDI. Molecular epidemiology differed between CA-CDI and HA-CDI and WGS analysis suggests transmission of CDI within and between hospitals and communities.

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.