Systematic review of the orally administered microbiome therapeutic, fecal microbiota spores, live-brpk, to prevent recurrence of Clostridioides difficile infection in adults.

Background: Clostridioides difficile infection (CDI) has been linked to over 200,000 cases of illness in hospitalized patients and over 20,000 deaths annually. Up to 25% of patients with an initial CDI episode will experience recurrent CDI (rCDI), which most commonly occurs in the first 8 weeks following antibiotic therapy. In patients with first or multiple rCDI, infection, the microbiome is similarly disrupted, which highlights the challenges of using antibiotics alone while underscoring the need for microbiome restoration regardless of the number of recurrences. In this systematic review, we describe the role of the gastrointestinal microbiome in CDI, and systematically review fecal microbiota spores, live-brpk (VOWST™; VOS for Vowst Oral Spores) for prevention of recurrence in rCDI. Methods: The PubMed database was searched using "recurrent Clostridioides difficile infection" AND (SER-109 OR VOS) and limited to clinical trials. The search yielded 7 results: 3 articles describing 3 clinical trials (two Phase 3 trials (ECOSPOR III and ECOSPOR IV) and one Phase 2 trial (ECOSPOR)), 1 describing follow-up of ECOSPOR III, 1 describing a post hoc analysis of comorbidities in ECOSPOR III, and 2 describing health-related quality of life in ECOSPOR III. Results: Compared with placebo, VOS following standard-of-care antibiotics for CDI significantly reduced risk of recurrence at 8 weeks (relative risk, 0.32 (95% CI: 0.18-0.58); p < 0.001; number needed to treat: 4) with a tolerable safety profile; rCDI rates remained low through 24 weeks. The disrupted microbiome, secondary to/exacerbated by antibiotic treatment, was rapidly (i.e., Week 1) restored with VOS. Compared with placebo, VOS demonstrated greater improvements in health-related quality of life. Conclusions: Clinical care of patients with rCDI now includes Food and Drug Administration-approved therapeutics to address microbiome restoration. Clinical trial evidence supports use of VOS following antibiotics and importance of microbiome restoration in rCDI.

Early treatment for Clostridioides difficile infection: retrospective cohort study.

INTRODUCTION: Clostridioides difficile (CDI) is a common cause of infectious diarrhea. The current recommendation is to initiate empirical antibiotic treatment for suspected CDI who have an anticipated delay of confirmatory results or fulminant colitis. This is based on limited clinical trials. The study aims to examine the impact of early treatment on mortality and clinical outcomes. METHODS: This retrospective cohort study included adult patients with CDI. Early treatment was defined as the initiation of an anti-Clostridioides medication within the first 24 h following stool sampling. Outcomes were 30 and 90 day mortality, length of hospital stay (LOS), recurrence, and colectomy rate. To address potential bias, propensity score matching followed by logistic regression was performed, P value less than 5% was considered statistically significant. RESULTS: Study cohort consisted of 796 patients; clinical characteristics were balanced following matching. There was no difference, in favor of early treatment, between the groups regarding 30 day mortality and 90 day mortality with HR of 0.91 (95% CI 0.56-1.47) and 0.7 (95% CI 0.45-1.08), respectively. No statistically significant difference in recurrence rate, ICU admission or colectomy rate was observed. The LOS was shorter in the early-treatment group with 6 days vs. 8 days. CONCLUSION: Early treatment for CDI had shortened hospital stay. However, it did not affect clinical outcomes in adult patients.

Comparative genomics of zoonotic pathogen Clostridioides difficile of animal origin to understand its diversity.

Clostridioides difficile, a zoonotic pathogen causing enteric diseases in different animals and humans. A comprehensive study on the presence of toxin genes and antimicrobial resistance genes based on genome data of C. difficile in animals is scanty. In the present study, a total of 15 C. difficile isolates were recovered from dogs and isolates with toxin genes (D1, CD15 and CD26) along with two other non-toxigenic strains (CD28, CD32) were used for whole genome sequencing and comparative genomics. Sequence type-based clustering was noted in the whole genome phylogeny with 4 known multi-locus sequence typing (MLST) clades namely I, II, IV, and V and a cryptic clade. ST11 and ST54 were reported for the 2nd time worldwide in dogs. Out of 109 genomes used in the study, 29 genomes were predicted with all four toxin genes (toxA, toxB, cdtA, cdtB) while 22 did not have any of the toxin genes. ST11 of MLST clade V had the maximum number of 46 genomes predicted with at least one toxin gene. Among the genomes sequenced in this study, CD26 had a maximum of 5 AMR genes (aac(6')-aph(2″), ant(6)-Ia, catP, erm(B)_18, and tet(M)_11) and CD15 was predicted with 2 AMR genes (aac(6')-aph(2″), erm(B)_18). Tetracycline resistance genes were predicted most in the ST11 genome. Of the 22 non-toxigenic strains, 9 genomes (ST48 = 5, ST3 = 2, ST109 = 1, ST15 = 1) were predicted with a minimum of one AMR gene. Pangenome analysis indicated that the Bpan value is 0.12 showing that C. difficile has an open pangenome structure. This indicates that the organism can evolve by the addition of new genes. This study reports the circulation of clinically important ST11 and multidrug-resistant non-toxigenic strains among animals. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-024-04102-7.

Recurrent Clostridioides difficile infections in solid organ transplant recipients: the international CALIPSO study.

OBJECTIVE: To evaluate the risk of recurrent Clostridioides difficile infection (CDI) in solid-organ transplant (SOT) recipients. METHODS: Retrospective multicenter study including SOT recipients with a first CDI episode in the year after transplantation (Jan 2017-June 2020). The primary outcome measure was recurrence, defined as a new CDI≤56 days from the first episode. A competing risk analysis was performed using the sub-distribution hazard model multivariable analysis. RESULTS: 191 SOT recipients were included: 101 (52.9%) were kidney, 66 (34.6%) liver, 11 (5.8%) lung, 8 (4.2%) simultaneous pancreas-kidney, 4 (2.1%) heart and 1 (0.5%) pancreas alone recipients. Treatment for the first CDI were: vancomycin (n=114,59.7%), vancomycin+metronidazole (n=39,20.4%), metronidazole (n=26,13.6%), fidaxomicin (n=9,4.7%), 3 patients did not receive any therapy. After the first CDI, 17/191 (8.9%) patients died within 56-day mortality without having a recurrence, while 23/191 (12%) patients had a recurrence. Among patients with recurrent CDI, 56-day mortality rate was 30.4% (7/23 patients). On multivariable analysis, severe CDI (sHR4.01, 95% CI 1.77-9.08, p<.001) and metronidazole monotherapy (sHR 3.65, 95% CI 1.64-8.14, p=.001) were factors independently associated with recurrence. CONCLUSIONS: Metronidazole monotherapy is associated with increased risk of recurrent CDI in SOT recipients. Therapeutic strategies aimed to reduce the risk of recurrence should be implemented in this setting.

The sympathetic nervous system drives hyperinflammatory responses to Clostridioides difficile infection.

Clostridioides difficile infection (CDI) is a leading cause of hospital-acquired infections in the United States, known for triggering severe disease by hyperactivation of the host response. In this study, we determine the impact of the sympathetic nervous system (SNS) on CDI disease severity. Mouse models of CDI are administered inhibitors of SNS activity prior to CDI. Chemical sympathectomy or pharmacological inhibition of norepinephrine synthesis greatly reduces mortality and disease severity in the CDI model. Pharmacological blockade or genetic ablation of the alpha 2 adrenergic receptor ameliorates intestinal inflammation, disease severity, and mortality rate. These results underscore the role of the SNS and the alpha 2 adrenergic receptor in CDI pathogenesis and suggest that targeting neural systems could be a promising approach to therapy in severe disease.

Metagenomic, metabolomic, and lipidomic shifts associated with fecal microbiota transplantation for recurrent Clostridioides difficile infection.

Recurrent C. difficile infection (rCDI) is an urgent public health threat, for which the last resort and lifesaving treatment is a fecal microbiota transplant (FMT). However, the exact mechanisms that mediate a successful FMT are not well-understood. Here, we use longitudinal stool samples collected from patients undergoing FMT to evaluate intra-individual changes in the microbiome, metabolome, and lipidome after successful FMTs relative to their baselines pre-FMT. We show changes in the abundance of many lipids, specifically a decrease in acylcarnitines post-FMT, and a shift from conjugated bile acids pre-FMT to deconjugated secondary bile acids post-FMT. These changes correlate with a decrease in Enterobacteriaceae, which encode carnitine metabolism genes, and an increase in Lachnospiraceae, which encode bile acid altering genes such as bile salt hydrolases (BSHs) and the bile acid-inducible (bai) operon, post-FMT. We also show changes in gut microbe-encoded amino acid biosynthesis genes, of which Enterobacteriaceae was the primary contributor to amino acids C. difficile is auxotrophic for. Liquid chromatography, ion mobility spectrometry, and mass spectrometry (LC-IMS-MS) revealed a shift from microbial conjugation of primary bile acids pre-FMT to secondary bile acids post-FMT. Here, we define the structural and functional changes associated with a successful FMT and generate hypotheses that require further experimental validation. This information is meant to help guide the development of new microbiota-focused therapeutics to treat rCDI.IMPORTANCERecurrent C. difficile infection is an urgent public health threat, for which the last resort and lifesaving treatment is a fecal microbiota transplant. However, the exact mechanisms that mediate a successful FMT are not well-understood. Here, we show changes in the abundance of many lipids, specifically acylcarnitines and bile acids, in response to FMT. These changes correlate with Enterobacteriaceae pre-FMT, which encodes carnitine metabolism genes, and Lachnospiraceae post-FMT, which encodes bile salt hydrolases and baiA genes. There was also a shift from microbial conjugation of primary bile acids pre-FMT to secondary bile acids post-FMT. Here, we define the structural and functional changes associated with a successful FMT, which we hope will help aid in the development of new microbiota-focused therapeutics to treat rCDI.

Characterization of the Clostridioides difficile 630Δerm putative Pro-Pro endopeptidase CD1597.

Clostridioides difficile is the leading cause of antibiotic-associated infections worldwide. Within the host, C. difficile can transition from a sessile to a motile state by secreting PPEP-1, which releases the cells from the intestinal epithelium by cleaving adhesion proteins. PPEP-1 belongs to the group of Pro-Pro endopeptidases (PPEPs), which are characterized by their unique ability to cleave proline-proline bonds. Interestingly, another putative member of this group, CD1597, is present in C. difficile. Although it possesses a domain similar to other PPEPs, CD1597 displays several distinct features that suggest a markedly different role for this protein. We investigated the proteolytic activity of CD1597 by testing various potential substrates. In addition, we investigated the effect of the absence of CD1597 by generating an insertional mutant of the cd1597 gene. Using the cd1597 mutant, we sought to identify phenotypic changes through a series of in vitro experiments and quantitative proteomic analyses. Furthermore, we aimed to study the localization of this protein using a fluorogenic fusion protein. Despite its similarities to PPEP-1, CD1597 did not show proteolytic activity. In addition, the absence of CD1597 caused an increase in various sporulation proteins during the stationary phase, yet we did not observe any alterations in the sporulation frequency of the cd1597 mutant. Furthermore, a promoter activity assay indicated a very low expression level of cd1597 in vegetative cells, which was independent of the culture medium and growth stage. The low expression was corroborated by our comprehensive proteomic analysis of the whole cell cultures, which failed to identify CD1597. However, an analysis of purified C. difficile spores identified CD1597 as part of the spore proteome. Hence, we predict that the protein is involved in sporulation, although we were unable to define a precise role for CD1597 in C. difficile.

'Does this fecal microbiota transplant work?' Quality assurance of capsule based fecal microbiota transplant production.

BACKGROUND: Fecal Microbiota Transplant (FMT) is an effective treatment for recurring Clostridioides Difficile Infections (rCDI). FMT administered via oral capsules (caFMT) offers several practical advantages to conventional liquid FMT. We began using caFMT in 2021 imported from an external institution. Based on similar production methods, we began our own caFMT production in 2022. We aimed to evaluate the quality of our caFMT. STUDY DESIGN AND METHODS: We created a database of all FMT treatments (n = 180) provided by our institution. Quality of all FMT was evaluated by treatment success rates. We compared our caFMT to the imported caFMT. RESULTS: Our caFMT yielded similar success rates compared to that of the imported caFMT, 65% (CI 95% 58-72%) and 72% (CI 95% 66-79%) respectively. FMT administered via colonoscopy had a significantly higher success rate, 79% (CI 95% 73-85%) than own our caFMT and other routes of administration. The combined success rate of treatments increased notably for all routes of administration when repeating FMT after prior failure. DISCUSSION: The fact that our caFMT compared similarly to the imported caFMT was viewed as a success in terms of quality assurance. Our caFMT had a slightly lower success rates compared to data from other studies, but could be affected by several other factors than our FMT-production methods. A lower success rate of caFMT compared to FMT via colonoscopy is acceptable due to the practical advantages offed by caFMT. Our study serves as a practical example, proving that of the standardization of caFMT production is indeed viable.

[Clostridioides difficile infections: Update and therapeutic guidelines]. / Infections à Clostridioides difficile : mise au point et repères thérapeutiques.

Clostridioides difficile infection (CDI) represents a significant challenge due to its increasing incidence, severity, and treatment difficulty. Effective management requires a multifactorial approach that includes preventive strategies, prudent antibiotic use, and adapted therapeutic options. Ongoing research and innovation offer promising prospects for improving ICD management, making vigilance and informed practices essential among healthcare professionals. Two main complications of ICD are pseudomembranous colitis (PMC) and toxic megacolon. PMC involves severe colonic inflammation due to C. difficile toxins, leading to pseudomembrane formation. Diagnosis relies on clinical criteria, microbiological tests, and endoscopy. Toxic Megacolon is characterized by severe colonic dilation and systemic toxicity, requiring immediate medical intervention. ICD diagnosis combines clinical signs and microbiological tests. These tests include toxin tests, GDH antigen detection, PCR for toxin genes, and stool culture. Imaging techniques assess colonic inflammation and complications. Combined diagnostic criteria from the American Gastroenterological Association (AGA) and European guidelines emphasize integrating clinical and laboratory findings for accurate diagnosis. ICD treatment involves stopping the implicated antibiotics and starting specific antimicrobial therapy. Common treatments include mainly fidaxomicin and oral vancomycin. Fecal microbiota transplantation (TMF) is recommended for recurrent cases unresponsive to standard treatments. Bezlotoxumab, an antibody targeting C. difficile toxin B, is used to prevent recurrence in high-risk adults. ICD poses a major challenge due to its increasing incidence, severity, and difficulty in treatment. A multifactorial approach involving rigorous preventive strategies, prudent antibiotic management, and adapted therapeutic options is essential for controlling the infection. Ongoing research and innovations in treatment offer promising prospects for improving patient management. Healthcare professionals must remain vigilant and informed to ensure effective practices in combating this infection and utilizing available resources optimally.

A Retrospective Assessment of Guideline Adherence and Treatment Outcomes From Clostridioides difficile Infection Following the IDSA 2021 Clinical Guideline Update: Clostridioides difficile Infection.

Background: The 2021 update to the Infectious Diseases Society of America Clostridioides difficile infection (CDI) guidelines recommended fidaxomicin as the preferred treatment over vancomycin for patients with initial and recurrent CDI. Few studies have examined how treatment patterns and clinical outcomes of hospitalized CDI patients changed after the postguideline update or contemporary real-world outcomes of fidaxomicin vs vancomycin. Methods: This retrospective, observational study used the PINC AI Healthcare Database on adult patients who received CDI treatment between 1/2020 and 6/2021 (pre period) and between 10/2021 and 9/2022 (post period). We examined treatment patterns of fidaxomicin, vancomycin, and metronidazole, as well as clinical and health care resource use outcomes of patients treated exclusively with fidaxomicin vs vancomycin, using nearest-neighbor propensity matching and hierarchical regression methods. As a sensitivity analysis, we repeated the fidaxomicin vs vancomycin comparisons among patients with recurrent and nonrecurrent index infections. Results: A total of 45 049 patients with CDI from 779 US hospitals met initial inclusion criteria. Comparing the pre vs post periods, the proportion of patients treated with fidaxomicin increased from 5.9% to 13.7% (P < .001), vancomycin use decreased from 87.9% to 82.9% (P < .001), and metronidazole use decreased from 21.6% to 17.2% (P < .001). When comparing fidaxomicin vs vancomycin in the post period, fidaxomicin was associated with lower CDI recurrence (6.1% vs 10.2%; P < .001) and higher sustained clinical response (91.7% vs 87.8%; P < .001). Ninety-day postdischarge costs were not significantly different between groups. A sensitivity analyses showed similar findings. Conclusions: Since the 2021 guideline update, fidaxomicin use has increased significantly but could be further utilized given its association with better clinical outcomes and no increase in postdischarge costs.

Dogs in Rio de Janeiro as reservoirs of Clostridioides difficile ribotypes causing CDI in humans.

INTRODUCTION: In the past decade, the incidence of community-acquired Clostridioides difficile infection (CA-CDI) has increased, suggesting a role for animal species in its spread. OBJECTIVE: This study aimed to isolate and characterize C. difficile strains from domestic dogs at veterinary clinics to enhance our understanding of C. difficile epidemiology in Rio de Janeiro. MATERIAL AND METHODS: For this study 90 stool samples from dogs were collected and cultured in a selective medium (Clostridioides difficile Brucella agar - CDBA) for isolation. Species were identified by MALDI-TOF MS, with confirmation provided by PCR targeting the tpi gene. The antibiotic susceptibility test of the strains was performed using five antibiotics: vancomycin, metronidazole, moxifloxacin, rifampicin, and erythromycin. Strains resistant to metronidazole were further analyzed for the presence of the plasmid pCD-METRO using PCR. The presence of toxin genes (tcdA, tcdB, and cdtB) was investigated, alongside ribotyping and tcdC sequencing analyses. The strains were also tested for biofilm formation and motility. RESULTS: C. difficile was isolated in 15.5% (14/90) of the samples. Among the strains analyzed, 87.71% (12/14) tested positive for both toxin genes A and B and belonged to ribotypes 106 (10/14) and 014/020 (2/14). The remaining 14.3% (2/14) were non-toxigenic and were identified as RT010. Regarding the antibiotic profile, 42.85% (6/14) of the strains exhibited resistance to at least one antibiotic, including vancomycin (1/14) and metronidazole (1/14). The metronidazole-resistant strain was also positive for the plasmid pCD-METRO. All strains exhibited both biofilm formation and motility. Among the 10 toxigenic strains sequenced for the tcdC gene, two exhibited a deletion in the same region as the epidemic strain, NAP1 (RT027). CONCLUSION: Our study found that C. difficile most of the ribotypes isolated from dogs are involved in cases of CDI in humans, and the prevalence was higher in dogs with diarrhea (p = 0.034). Although we could not confirm that diarrhea in these dogs was solely due to C. difficile, their colonization may represent a common transmission route for human C. difficile infections.

Fecal microbiota transplantation through colonoscopy in the treatment of recurrent Clostridioides difficile: Experience at a university center.

INTRODUCTION: The majority of cases of Clostridioides difficile infection (CDI) respond to antibiotic treatment. Fecal microbiota transplantation (FMT) has been accepted as an effective treatment in cases of recurrent CDI. AIM: Our aim was to describe the clinical results of FMT performed for the treatment of recurrent CDI. MATERIAL AND METHODS: The study was conducted on patients with recurrent CDI treated with FMT through colonoscopy, within the time frame of January 2021 and December 2023. Demographic and clinical data were collected, including pre-FMT treatment data, the FMT success rate, and clinical progression during follow-up. Telephone surveys were carried out to evaluate satisfaction. RESULTS: Thirteen patients with a mean age of 55 years underwent FMT (including 7 patients above 65 years of age and one pregnant woman). Patients presented with a median of 3 previous episodes of CDI (range 2-4). The median time interval from first episode of CDI to FMT was 4 months (range 3-10). The effectiveness of a single FMT session was 100%. During post-FMT follow-up (median of 11 months, range 3-32), 3 patients have presented with a new CDI episode, and a successful second FMT was performed on 2 of them. No adverse events were registered, and all patients had a positive perception of FMT. CONCLUSIONS: In the present study, despite its small size, FMT through colonoscopy was shown to be a safe, effective, and lasting therapy in cases of recurrent CDI, concurring with results from larger studies.

Normalization of short-chain fatty acid concentration by bacterial count of stool samples improves discrimination between eubiotic and dysbiotic gut microbiota caused by Clostridioides difficile infection.

Short-chain fatty acids (SCFAs) represent a cornerstone of gut health, serving as critical mediators of immune modulation and overall host homeostasis. Patients with dysbiosis caused by Clostridioides difficile infection (CDI) typically exhibit lower SCFAs levels compared to healthy stool donors and, thus, the concentration of SCFAs has been proposed as a proxy marker of a healthy microbiota. However, there is no consistency in the methods used to quantify SCFAs in stool samples and usually, the results are normalized by the weight of the stool samples, which does not address differences in water and fiber content and ignores bacterial counts in the sample (the main component of stool that contributes to the composition of these metabolites in the sample). Here, we show that normalized SCFAs concentrations by the bacterial count improve discrimination between healthy and dysbiotic samples (patients with CDI), particularly when using acetate and propionate levels. After normalization, butyrate is the metabolite that best discriminates eubiotic and dysbiotic samples according to the area under the receiver operating characteristic (ROC) curve (AUC-ROC = 0.860, [95% CI: 0.786-0.934], p < .0001).

Human microbiome: Impact of newly approved treatments on C. difficile infection.

DISCLAIMER: In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. PURPOSE: The primary purposes of this review are to provide a brief overview of the microbiome, discuss the most relevant outcome data and key characteristics of each live microbiome agent, and pose questions for consideration going forward as these agents are integrated into clinical practice. SUMMARY: The management of Clostridiodes difficile infection (CDI) remains a difficult clinical conundrum, with recurrent CDI occurring in 15% to 35% of patients and causing significant morbidity and decreased quality of life. For patients with frequent CDI recurrences, fecal microbiota transplantation (FMT) has been demonstrated to have significant benefit but also significant risks, and FMT is not approved by the US Food and Drug Administration (FDA) for that indication. FDA has established a new therapeutic class for agents known as live biotherapeutic products (LBPs) that offer significant advantages over FMT, including standardized screening, testing, and manufacturing as well as known quantities of organisms contained within. Two new live microbiome products within this class were recently approved by FDA for prevention of CDI recurrences in adult patients following treatment for recurrent CDI with standard antimicrobial therapy. Both agents had demonstrated efficacy in registry trials in preventing CDI recurrence but differ significantly in a number of characteristics, such as route of administration. Cost as well as logistics are current obstacles to use of these therapies. CONCLUSION: Live microbiome therapy is a promising solution for patients with recurrent CDI. Future studies should provide further evidence within yet-to-be-evaluated populations not included in registry studies. This along with real-world evidence will inform future use and clinical guideline placement.

Diversity of Clostridioides difficile PCR ribotypes isolated from freshwater sediments depends on the isolation method.

Clostridioides difficile is an intestinal pathogen of humans and animals. In community-associated infections, the environment is suggested to play a significant role in overall transmission routes. Although the prevalence of C. difficile in freshwater and soil has been widely studied, little is known about its presence in sediments. In this study, we tested 15 sediment samples collected from various freshwater sources. C. difficile was isolated from all sampled sites, yielding a total of 171 strains grouped into 26 ribotypes, with 001/072 and 014/020 being the most prevalent. Genome sequencing of 37 isolates from 17 PCR ribotypes confirmed the presence of highly related strains in the geographically distant and unlinked water samples. Eight divergent PCR ribotypes from clades C-II and C-III were found in six samples. In each sample, the unbound fraction (supernatant after sediment wash) and bound fraction (sonicated sediment sample) were subjected to enrichment. Sonication was only slightly better than washing in terms of sample positivity (14 positive samples with sonication and 11 with washing). However, sonication substantially increased the diversity of the PCR ribotypes obtained (23 in sonicated samples vs nine in washed samples). In conclusion, sediments are a rich source for investigating the diversity of environmental C. difficile, including isolates from divergent lineages. Selection of the isolation method can significantly impact the diversity of captured PCR ribotypes.IMPORTANCEClostridioides difficile, a pathogenic bacterium that can cause intestinal infections in humans and animals, thrives in the gut but also disperses widely through spores found in the environment. Clinical and environmental strains often overlap with common PCR ribotypes, which are consistently isolated worldwide. Environmental studies have mostly focused on water and soil, but sediments have been very poorly studied. In this study, we investigated the presence of C. difficile in various freshwater sediments and evaluated the effectiveness of two different isolation approaches on positivity rates and strain diversity. C. difficile was found to be highly prevalent in sediments, with an isolation rate of 100%. Sonication proved to be more effective than simple washing for capturing a greater diversity of PCR ribotypes. Overall, this study underscores the widespread presence of C. difficile in freshwater sediments and emphasizes the importance of continued surveillance and monitoring to understand its ecology and transmission dynamics.

Insights into Gut Dysbiosis: Inflammatory Diseases, Obesity, and Restoration Approaches.

The gut microbiota is one of the most critical factors in human health. It involves numerous physiological processes impacting host health, mainly via immune system modulation. A balanced microbiome contributes to the gut's barrier function, preventing the invasion of pathogens and maintaining the integrity of the gut lining. Dysbiosis, or an imbalance in the gut microbiome's composition and function, disrupts essential processes and contributes to various diseases. This narrative review summarizes key findings related to the gut microbiota in modern multifactorial inflammatory conditions such as ulcerative colitis or Crohn's disease. It addresses the challenges posed by antibiotic-driven dysbiosis, particularly in the context of C. difficile infections, and the development of novel therapies like fecal microbiota transplantation and biotherapeutic drugs to combat these infections. An emphasis is given to restoration of the healthy gut microbiome through dietary interventions, probiotics, prebiotics, and novel approaches for managing gut-related diseases.

Epidemiologic characteristics and risk factors of Clostridioides difficile infection in patients with active tuberculosis in the Republic of Korea: A nationwide population-based study.

BACKGROUND: The relationship between anti-tuberculosis (TB) agents and Clostridioides difficile infection (CDI) remains unclear. This study aimed to investigate the epidemiological characteristics and risk factors for CDI in patients with TB. METHODS: This nationwide, population-based cohort study was conducted in the Republic of Korea (ROK) between January 2018 and December 2022. Data were extracted from the National Health Insurance Service (NHIS) National Health Information Database. The risk factors for CDI in patients with TB were identified through multivariate logistic regression analysis using a 1:4 greedy matching method based on age and sex. RESULTS: During the study period, CDI developed in 2,901 of the 131,950 patients with TB who were prescribed anti-TB agents. The incidence of CDI in patients with TB has increased annually in the ROK from 12.31/1000 in 2018 to 33.51/1000 in 2022. Oral metronidazole (81.94%) was the most common first-line treatment for CDI. The in-hospital mortality rate of patients with concomitant CDI and tuberculosis was 9.9% compared with 6.9% in those with TB alone (P<0.0001). Multivariate logistic regression analysis found intensive care unit admission, Charlson Comorbidity Index ≥3, antibiotics exposure, standard regimen, multidrug resistant TB, and extrapulmonary TB as significant risk factors for development of CDI in patients with TB. CONCLUSION: CDI is uncommon in patients with TB, but it results in a significantly increased mortality rate. Patients being treated for TB should be carefully monitored for the development of CDI. Further clinical research is warranted to identify effective interventions for preventing and controlling CDI during TB treatment.

Preferences for a Clostridioides difficile vaccine among adults in the United States.

INTRODUCTION: Clostridioides difficile (C.diff) infection (CDI) causes significant morbidity and mortality among older adults. Vaccines to prevent CDI are in development; however, data on the target population's preferences are needed to inform vaccination recommendations in the United States (US). This study assessed US adults' willingness to receive a C.diff vaccine and examined how vaccine attributes influence their choices. METHODS: A cross-sectional online survey with a discrete choice experiment (DCE) was conducted among US adults aged ≥50 years. DCE attributes included effectiveness, duration of protection, reduction in symptom severity, out-of-pocket (OOP) costs, number of doses, and side effects. The DCE included 11 choice tasks, each with two hypothetical vaccine profiles and an opt-out (i.e., no vaccine). Attribute-level preference weights were estimated using hierarchical Bayesian modeling. Attribute relative importance (RI) was compared between select subgroups. RESULTS: Of 1216 adults in the analyses, 29.9% reported they knew either 'a little' (20.7%) or 'a lot' (9.2%) about C.diff before the study. A C.diff vaccine was chosen 58.0% of the time (vs. opt-out) across choice tasks. It was estimated that up to 75.0% would choose a vaccine when OOP was $0. Those who were immunocompromised/high-risk for CDI (vs. not) more frequently chose a C.diff vaccine. Decreases in OOP costs (RI = 56.1), improvements in vaccine effectiveness (RI = 17.7), and reduction in symptom severity (RI = 10.3) were most important to vaccine choice. The rank ordering of attributes by importance was consistent across subgroups. CONCLUSION: OOP cost, improvements in vaccine effectiveness, and reduction in CDI severity were highly influential to vaccine selection. Most adults aged ≥50 years were receptive to a C.diff vaccine, especially with little-to-no OOP cost, suggesting that mandating insurance coverage of vaccination with no copayment may increase uptake. The limited awareness about C.diff among adults presents an opportunity for healthcare providers to educate their patients about CDI prevention.

[Clostridioides difficile infection diagnosed by nucleic acid amplification test in a patient with Epstein-Barr Virus-related T-cell lymphoproliferative disorder].

Steroid usage poses a risk of Clostridioides difficile infection (CDI), but high-dose corticosteroid treatment can lead to false-negative CD toxin test results. Moreover, CDI-induced nausea can complicate administration of oral antibiotics, which are typically the primary therapy for CDI. In the present case, a 43-year-old woman diagnosed with EBV-associated T-cell post-transplant lymphoproliferative disorder developed CDI during treatment with cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP). Following five cycles of CHOP, the patient presented with nausea and diarrhea. CT scans revealed swelling in the ileocecal to transverse area of the colon. While the glutamate dehydrogenase (GDH) antigen test result was positive, the CD toxin test result was negative. However, the nucleic amplification test (NAAT) result was positive, confirming the diagnosis of CDI. Oral treatment with fidaxomicin was initially impractical due to persistent nausea. Instead, treatment began with intravenous metronidazole, and was later switched to fidaxomicin pills. Symptoms improved notably within 10 days, and the patient ultimately made a complete recovery. This case underscores the significance of exploring alternative approaches to CDI management, particularly in immunosuppressed patients.