Evaluation of a Geographic Screening Protocol for Chronic Parasitic Infections Before Kidney Transplant: An Institutional Experience in Minnesota.

Pretransplant recommendations advise risk-based screening for strongyloidiasis, schistosomiasis, and Chagas disease. We evaluated the implementation of a chronic parasite screening protocol at a health system in a nonendemic region serving a large foreign-born population. Candidates listed for kidney transplant at Hennepin Healthcare (Minneapolis, MN) between 2010 and 2020 were included. Country of birth and serologic screening for strongyloidiasis, schistosomiasis, and Chagas disease were retrospectively obtained from electronic medical records. Parasite screening frequency and seropositivity was assessed before and after implementation of a geographic risk factor-based screening protocol in 2014. Cost-efficiency of presumptive treatment was modeled. Of 907 kidney transplant candidates, 312 (34%) were born in the United States and 232 (26%) outside the United States, with the remainder missing country of birth information. The 447 (49%) candidates evaluated after implementation of the screening protocol had fewer unidentified countries of birth (53%-27%, P < 0.001) and were more frequently screened for strongyloidiasis, schistosomiasis, and Chagas disease (14%-44%, 8%-22%, and 1-14%, respectively, all Ps < 0.001). The number of identified seropositive candidates increased after protocol implementation from two to 14 for strongyloidiasis and from one to 11 for schistosomiasis, with none seropositive for Chagas disease. The cost-efficiency model favored presumptive ivermectin when strongyloidiasis prevalence reaches 30% of those screened. Implementing a geographic risk screening protocol before kidney transplant increases attention to infectious disease risk associated with country of birth and identification of chronic parasitic infections. In populations with higher strongyloidiasis prevalence or lower ivermectin costs, presumptive treatment may be cost-efficient.

Global Health Education during the COVID-19 Pandemic: Challenges, Adaptations, and Lessons Learned.

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.

Prevalence and Molecular Characteristics of Clostridium difficile in Retail Meats, Food-Producing and Companion Animals, and Humans in Minnesota.

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.

Environmental Contamination in Households of Patients with Recurrent Clostridium difficile Infection.

Recurrent Clostridium difficile infection (R-CDI) is common and difficult to treat, potentially necessitating fecal microbiota transplantation (FMT). Although C. difficilespores 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 ofC. 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 pulsed-field 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.

Changes in Colonic Bile Acid Composition following Fecal Microbiota Transplantation Are Sufficient to Control Clostridium difficile Germination and Growth.

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.

Ursodeoxycholic Acid Inhibits Clostridium difficile Spore Germination and Vegetative Growth, and Prevents the Recurrence of Ileal Pouchitis Associated With the Infection.

GOALS: To test whether ursodeoxycholic acid (UDCA) is inhibitory to Clostridium difficile and can be used in the treatment of C. difficile-associated ileal pouchitis. BACKGROUND: The 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 nonantibiotic therapeutics for this indication. The need for such a treatment alternative is especially significant in patients with refractory C. difficile-associated pouchitis, where the efficacy of FMT may be limited. STUDY: We measured the ability of UDCA to suppress the germination and the 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 to be inhibitory to the germination and the vegetative growth of all C. difficile strains tested. Fecal concentrations of UDCA from the patient with RCDI pouchitis exceeded levels necessary to inhibit the germination and the growth of C. difficile in vitro. The patient has remained infection free for over 10 months after the initiation of UDCA. CONCLUSIONS: UDCA can be considered as a therapeutic option in patients with C. difficile-associated pouchitis. Further studies need to be conducted to define the optimal dose and duration of such a 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.

Unnecessary antimicrobial use in patients with current or recent Clostridium difficile infection.

OBJECTIVE: To determine the fraction of unnecessary antimicrobial use among patients with current and/or recent Clostridium difficile infection (CDI). DESIGN: Retrospective review from January 2004 through December 2006. SETTING: Minneapolis Veterans Affairs Medical Center (MVAMC). PARTICIPANTS: Patients with new-onset CDI diagnosed at the MVAMC without another CDI diagnosis in the prior 30 days. METHODS: Pharmacy and medical records were reviewed to identify incident CDI cases, non-CDI antimicrobial use during and up to 30 days after completion of CDI treatment, and patient characteristics. Two infectious disease physicians independently assessed non-CDI antimicrobial use, which was classified as unnecessary if not fully indicated. Factors associated with only unnecessary use were identified through univariable and multivariable analysis. RESULTS: Of 246 patients with new-onset CDI, 141 (57%) received non-CDI antimicrobials during and/or after their CDI treatment, totaling 2,147 antimicrobial days and 445 antimicrobial courses. The two reviewers agreed regarding the necessity of antimicrobials in more than 99% of antimicrobial courses (85% initially, 14% after discussion). Seventy-seven percent of patients received at least 1 unnecessary antimicrobial dose, 26% of patients received only unnecessary antimicrobials, and 45% of total non-CDI antimicrobial days included unnecessary antimicrobials. The leading indications for unnecessary antimicrobial use were putative urinary tract infection and pneumonia. Drug classes frequently used unnecessarily were fluoroquinolones and ß-lactams. CONCLUSIONS: 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.

Evaluation of hospital room assignment and acquisition of Clostridium difficile infection.

BACKGROUND AND OBJECTIVE: Clostridium difficile spores persist in hospital environments for an extended period. We evaluated whether admission to a room previously occupied by a patient with C. difficile infection (CDI) increased the risk of acquiring CDI. DESIGN: Retrospective cohort study. SETTING: Medical intensive care unit (ICU) at a tertiary care hospital. METHODS: Patients admitted from January 1, 2005, through June 30, 2006, were evaluated for a diagnosis of CDI 48 hours after ICU admission and within 30 days after ICU discharge. Medical, ICU, and pharmacy records were reviewed for other CDI risk factors. Admitted patients who did develop CDI were compared with admitted patients who did not. RESULTS: Among 1,844 patients admitted to the ICU, 134 CDI cases were identified. After exclusions, 1,770 admitted patients remained for analysis. Of the patients who acquired CDI after admission to the ICU, 4.6% had a prior occupant without CDI, whereas 11.0% had a prior occupant with CDI (P = .002). The effect of room on CDI acquisition remained a significant risk factor (P = .008) when Kaplan-Meier curves were used. The prior occupant's CDI status remained significant (p = .01; hazard ratio, 2.35) when controlling for the current patient's age, Acute Physiology and Chronic Health Evaluation III score, exposure to proton pump inhibitors, and antibiotic use. CONCLUSIONS: 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.