A prior room occupant with CDI is a significant risk factor for CDI acquisition, independent of established CDI risk factors. These findings have implications for room placement and hospital design.
Fecal microbiota transplantation (FMT) is a highly effective therapy for recurrent Clostridium difficile infection (R-CDI), but its mechanisms remain poorly understood. Emerging evidence suggests that gut bile acids have significant influence on the physiology of C. difficile, and therefore on patient susceptibility to recurrent infection. We analyzed spore germination of 10 clinical C. difficile isolates exposed to combinations of bile acids present in patient feces before and after FMT. Bile acids at concentrations found in patients’ feces prior to FMT induced germination of C. difficile, although with variable potency across different strains. However, bile acids at concentrations found in patients after FMT did not induce germination and inhibited vegetative growth of all C. difficile strains. Sequencing of the newly identified germinant receptor in C. difficile, CspC, revealed a possible correspondence of variation in germination responses across isolates with mutations in this receptor. This may be related to interstrain variability in spore germination and vegetative growth in response to bile acids seen in this and other studies. These results support the idea that intra-colonic bile acids play a key mechanistic role in the success of FMT, and suggests that novel therapeutic alternatives for treatment of R-CDI may be developed by targeted manipulation of bile acid composition in the colon.
Goals
Test whether ursodeoxycholic acid is inhibitory to Clostridium difficile and can be used in the treatment of C. difficile associated ileal pouchitis.
Background
Restoration of secondary bile metabolism may be the key mechanism for fecal microbiota transplantation (FMT) in treating recurrent C. difficile infections (RCDI). Therefore, it is possible that exogenous administration of inhibitory bile acids may be used directly as non-antibiotic therapeutics for this indication. The need for such a treatment alternative is especially great in patients with refractory C. difficile associated pouchitis, where the efficacy of FMT may be limited.
Study
We measured the ability of ursodeoxycholic acid (UDCA) to suppress germination and vegetative growth of 11 clinical isolate strains of C. difficile from patients treated with FMT for RCDI. In addition, we used oral UDCA to treat a patient with RCDI pouchitis that proved refractory to multiple antibiotic treatments and FMT.
Results
UDCA was found inhibitory to germination and vegetative growth of all C. difficile strains tested. Fecal concentrations of UDCA from the patient with RCDI pouchitis exceeded levels necessary to inhibit germination and growth of C. difficile in vitro. The patient has remained infection-free for over ten months following initiation of UDCA.
Conclusions
UDCA can be considered as a therapeutic option in patients with C. difficile associated pouchitis. Further studies need to be done to define the optimal dose and duration of such treatment. In addition, bile acid derivatives inhibitory to C. difficile that are able to achieve high intracolonic concentrations may be developed as therapeutics for RCDI colitis.
Twenty-six percent of patients with recent CDI received only unnecessary (and therefore potentially avoidable) antimicrobials. Heightened awareness and caution are needed when antimicrobial therapy is contemplated for patients with recent CDI.
Recurrent Clostridium difficile infection (R-CDI) is common and difficult to treat, potentially necessitating fecal microbiota transplantation (FMT). Although C. difficile spores persist in the hospital environment and cause infection, little is known about their potential presence or importance in the household environment. Households of R-CDI subjects in the peri-FMT period and of geographically matched and age-matched controls were analyzed for the presence of C. difficile. Household environmental surfaces and fecal samples from humans and pets in the household were examined. Households of post-FMT subjects were also examined (environmental surfaces only). Participants were surveyed regarding their personal history and household cleaning habits. Species identity and molecular characteristics of presumptive C. difficile isolates from environmental and fecal samples were determined by using the Pro kit (Remel, USA), Gram staining, PCR, toxinotyping, tcdC gene sequencing, and pulsedfield gel electrophoresis (PFGE). Environmental cultures detected C. difficile on >1 surface in 8/8 (100%) peri-FMT households, versus 3/8 (38%) post-FMT households and 3/8 (38%) control households (P ؍ 0.025). The most common C. difficile-positive sites were the vacuum (11/27; 41%), toilet (8/30; 27%), and bathroom sink (5/29; 17%). C. difficile was detected in 3/36 (8%) fecal samples (two R-CDI subjects and one household member). Nine (90%) of 10 households with multiple C. difficile-positive samples had a single genotype present each. In conclusion, C. difficile was found in the household environment of R-CDI patients, but whether it was found as a cause or consequence of R-CDI is unknown. If household contamination leads to R-CDI, effective decontamination may be protective.
Global health education programs should strive continually to improve the quality of education, increase access, create communities that foster excellence in global health practices, and ensure sustainability. The COVID-19 pandemic forced the University of Minnesota’s extensive global health education programs, which includes a decade of hybrid online and in-person programing, to move completely online. We share our experience, a working framework for evaluating global health educational programming, and lessons learned. Over the decades we have moved from a predominantly passive, lecture-based, in-person course to a hybrid online (passive) course with an intensive hands-on 2-week requirement. The pandemic forced us to explore new active online learning models. We retained our on-demand, online passive didactics, which used experts’ time efficiently and was widely accessible and well received. In addition, we developed a highly effective synchronous online component that we felt replaced some of the hands-on activities effectively and led us to develop new and innovative “hands-on” experiences. This new, fully online model combining quality asynchronous and synchronous learning provided many unanticipated advantages, such as increasing access while decreasing our carbon footprint dramatically. By sharing our experience, lessons learned, and resources, we hope to inspire other programs likewise to innovate to improve quality, access, community, and sustainability in global health, especially if these innovations can help decrease negative aspects of global health education such as its environmental impact.
Community-associated Clostridium difficile infection (CA-CDI) now accounts for approximately 50% of CDI cases in central Minnesota; animals and meat products are potential sources. From November 2011 to July 2013, we cultured retail meat products and fecal samples from food-producing and companion animals in central Minnesota for C. difficile by using standard methods. The resulting 51 C. difficile isolates, plus 30 archived local veterinary C. difficile isolates and 208 human CA-CDI case isolates from central Minnesota (from 2012) from the Minnesota Department of Health, were characterized molecularly, and source groups were compared using discriminant analysis. C. difficile was recovered from 0 (0%) of 342 retail meat samples and 51 (9%) of 559 animal fecal samples. Overall, the 81 animal source isolates and 208 human source isolates were highly diverse genetically. Molecular traits segregated extensively in relation to animal versus human origin. Discriminant analysis classified 95% of isolates correctly by source group; only five (2.5%) human source isolates were classified as animal source. These data do not support meat products or food-producing and companion animals as important sources of CA-CDI in the central Minnesota study region.
Introduction: Severe bacterial infection is an unusual initial presentation of systemic lupus erythematosus (SLE). Case presentation: We describe two cases of severe encapsulated bacterial infection in women with previously undiagnosed SLE. Conclusion: Hypocomplementaemia associated with SLE is an important infection risk and should be considered in the evaluation of patients who present with unusual and severe infection with encapsulated bacteria.
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