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Objective: To determine whether residing in a hospital bed that previously held an occupant with Clostridioides difficile increases the risk of hospital-onset C. difficile infection (HO-CDI)., Methods: In this retrospective cohort study, we used a real-time location system to track the movement of hospital beds in 2 academic hospitals from April 2018 to August 2019. We abstracted patient demographics, clinical characteristics, and C. difficile polymerase chain reaction (PCR) results from the medical record. We defined patients as being exposed to a potentially "contaminated" bed or room if, within the preceding 7 days from their HO-CDI diagnosis, they resided in a bed or room respectively, that held an occupant with C. difficile in the previous 90 days. We used multivariable logistic regression to determine whether residing in a contaminated bed was associated with HO-CDI after controlling for time at risk and requiring intensive care. We assessed mediation and interaction from a contaminated hospital room., Results: Of 25,032 hospital encounters with 18,860 unique patients, we identified 237 cases of HO-CDI. Exposure to a contaminated bed was associated with HO-CDI in unadjusted analyses (odds ratio [OR], 1.8; 95% confidence interval [CI], 1.4-2.31) and adjusted analyses (OR, 1.5; 95% CI, 1.2-2.0). Most of this effect was due to both mediation from and interaction with a contaminated hospital room., Conclusions: Residing in a hospital bed or room that previously had a patient with C. difficile increases the risk of HO-CDI. Increased attention to cleaning and disinfecting the healthcare environment may reduce hospital transmission of C. difficile .

Clostridioides difficile is a leading cause of healthcare-associated infections. The main objective was to assess the current landscape of CDI infection prevention and control (IPC) practices. An anonymous survey of IPC practices for CDI was conducted between July 25 and October 31, 2022. Precautions for symptomatic patients were applicable for 75.9% and were discontinued 48 h minimum after the resolution of diarrhea for 40.7% of respondents. Daily cleaning of CDI patients' rooms was reported by 23 (42.6%). There was unexpected heterogeneity in IPC practices regarding the hospital management of CDI., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Nonmanual room disinfection systems may reduce the transmission of infections. A variety of systems have emerged; however, a paucity of evidence exists to make an evidence-informed decision for the implementation of a specific system. Alberta Health Services assessed one of these systems., Methods: A quasi-experimental prepost design assessed an aerosolized hydrogen peroxide disinfection system on 6 units at 3 acute care facilities in Alberta. To assess clinical effectiveness an interrupted time-series analysis with Poisson distribution compared changes in hospital-acquired Clostridioides difficile infection (HA-CDI) and hospital-acquired Methicillin-resistant Staphylococcus aureus (HA-MRSA) between preintervention, intervention, and postintervention periods. To assess operational feasibility cleaning turnaround time, time to operate, and utilization were considered. A participatory research framework was used to understand the benefits and challenges of operationalization., Results: Incidence rate ratio (IRR) of HA-CDI decreased by 25.7% on FMC-A and 6.9% on RAH-B. Following withdrawal, the IRR of HA-CDI continued to decrease. IRR of HA-MRSA decreased by 25.0% on RAH-B. Following withdrawal, the IRR of HA-MRSA continued to decrease. None of the results were statistically significant. The average time to operate was 3.2 hours. Utilization was between 1.7% and 25.6%. Most staff reported benefits and challenges., Discussion: None of the changes observed in HA-CDI and HA-MRSA after the introduction of the aerosolized hydrogen peroxide system were statistically significant. While most respondents reported multiple benefits and challenges in using the system, the core challenge was delays in inpatient admissions due to the time operate the system., Conclusion: Successful implementation of a nonmanual room disinfection system as an addition to standard cleaning and disinfection requires significant investment and must consider a variety of factors., (Copyright © 2023 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.)

Clostridioides difficile represents a major burden to public health. As a well-known nosocomial pathogen whose occurrence is highly associated with antibiotic treatment, most examined C. difficile strains originated from clinical specimen and were isolated under selective conditions employing antibiotics. This suggests a significant bias among analyzed C. difficile strains, which impedes a holistic view on this pathogen. In order to support extensive isolation of C. difficile strains from environmental samples, we designed a detection PCR that targets the hpdBCA -operon and thereby identifies low abundances of C. difficile in environmental samples. This operon encodes the 4-hydroxyphenylacetate decarboxylase, which catalyzes the production of the antimicrobial compound para -cresol. Amplicon-based analyses of diverse environmental samples demonstrated that the designed PCR is highly specific for C. difficile and successfully detected C. difficile despite its absence in general 16S rRNA gene-based detection strategies. Further analyses revealed the potential of the hpdBCA detection PCR sequence for initial phylogenetic classification, which allows assessment of C. difficile diversity in environmental samples via amplicon sequencing. Our findings furthermore showed that C. difficile strains isolated under antibiotic treatment from environmental samples were originally dominated by other strains according to PCR amplicon results. This provided evidence for selective cultivation of under-represented but antibiotic-resistant isolates. Thereby, we revealed a substantial bias in C. difficile isolation and research.IMPORTANCE Clostridioides difficile is a main cause of diarrheic infections after antibiotic treatment with serious morbidity and mortality worldwide. Research on this pathogen and its virulence has focused on bacterial isolation from clinical specimens under antibiotic treatment, which implies a substantial bias in isolated strains. Comprehensive studies, however, require an unbiased strain collection, which is accomplished by isolation of C. difficile from diverse environmental samples and avoidance of antibiotic-based enrichment strategies. Thus, isolation can significantly benefit from our C. difficile -specific detection PCR, which rapidly verifies C. difficile presence in environmental samples and further allows estimation of the C. difficile diversity by using next-generation sequencing., Competing Interests: The authors declare no conflict of interest.

The gut microbiome engenders colonization resistance against the diarrheal pathogen Clostridioides difficile, but the molecular basis of this colonization resistance is incompletely understood. A prominent class of gut microbiome-produced metabolites important for colonization resistance against C. difficile is short-chain fatty acids (SCFAs). In particular, one SCFA (butyrate) decreases the fitness of C. difficile in vitro and is correlated with C. difficile -inhospitable gut environments, both in mice and in humans. Here, we demonstrate that butyrate-dependent growth inhibition in C. difficile occurs under conditions where C. difficile also produces butyrate as a metabolic end product. Furthermore, we show that exogenous butyrate is internalized into C. difficile cells and is incorporated into intracellular CoA pools where it is metabolized in a reverse (energetically unfavorable) direction to crotonyl-CoA and ( S )-3-hydroxybutyryl-CoA and/or 4-hydroxybutyryl-CoA. This internalization of butyrate and reverse metabolic flow of a butyrogenic pathway(s) in C. difficile coincides with alterations in toxin release and sporulation. Together, this work highlights butyrate as a marker of a C. difficile -inhospitable environment to which C. difficile responds by releasing its diarrheagenic toxins and producing environmentally resistant spores necessary for transmission between hosts. These findings provide foundational data for understanding the molecular and genetic basis of how C. difficile growth is inhibited by butyrate and how butyrate alters C. difficile virulence in the face of a highly competitive and dynamic gut environment.IMPORTANCEThe gut microbiome engenders colonization resistance against the diarrheal pathogen Clostridioides difficile, but the molecular basis of this colonization resistance is incompletely understood, which hinders the development of novel therapeutic interventions for C. difficile infection (CDI). We investigated how C. difficile responds to butyrate, an end-product of gut microbiome community metabolism which inhibits C. difficile growth. We show that exogenously produced butyrate is internalized into C. difficile , which inhibits C. difficile growth by interfering with its own butyrate production. This growth inhibition coincides with increased toxin release from C. difficile cells and the production of environmentally resistant spores necessary for transmission between hosts. Future work to disentangle the molecular mechanisms underlying these growth and virulence phenotypes will likely lead to new strategies to restrict C. difficile growth in the gut and minimize its pathogenesis during CDI., Competing Interests: The authors declare no conflict of interest.

Antimicrobial resistance is emerging in clinical strains of Clostridioides difficile . Ibezapolstat (IBZ) is a DNA polymerase IIIC inhibitor that has completed phase II clinical trials. IBZ has potent in vitro activity against wild-type, susceptible strains but its effect on C. difficile strains with reduced susceptibility to metronidazole (MTZ), vancomycin (VAN), or fidaxomicin (FDX) has not been tested. The primary objective of this study was to test the antibacterial properties of IBZ against multidrug-resistant C. difficile strains. The in vitro activity, bactericidal, and time-kill activity of IBZ versus comparators were evaluated against 100 clinical strains of which 59 had reduced susceptibility to other C. difficile antibiotics. Morphologic changes against a multidrug resistance strain were visualized by light and scanning electron microscopy. The overall IBZ MIC 50/90 values (µg/mL) for evaluated C. difficile strains were 4/8, compared with 2/4 for VAN, 0.5/1 for FDX, and 0.25/4 for MTZ. IBZ MIC 50/90 values did not differ based on non-susceptibility to antibiotic class or number of classes to which strains were non-susceptible. IBZ bactericidal activity was similar to the minimum inhibitory concentration (MIC) and maintained in wild-type and non-susceptible strains. Time-kill assays against two laboratory wild-type and two clinical non-susceptible strains demonstrated sustained IBZ activity despite reduced killing by comparator antibiotics for IBZ and VAN non-susceptible strains. Microscopy visualized increased cell lengthening and cellular damage in multidrug-resistant strains exposed to IBZ sub-MIC concentrations. This study demonstrated the potent antibacterial activity of IBZ against a large collection of C. difficile strains including multidrug-resistant strains. This study highlights the therapeutic potential of IBZ against multidrug-resistant strains of C. difficile ., Competing Interests: K.W.G.: research support paid to his institution from Acurx Pharmaceuticals, Paratek Pharmaceuticals, and Merck Inc., and consulting support from Ferring, Inc. A.J.G.L. received research grants paid to her institution from Seres Therapeutics and is a consultant for Ferring Pharmaceuticals. All other authors declare no conflict of interest.

C. difficile or Clostridioides difficile infection (CDI) is currently one of the major causes of epidemics worldwide. Toxin B from Clostridioides difficile toxin B (TcdB) infection is the main target protein inhibiting CDI recurrence. Clinical research suggested that bezlotoxumab's (Bez) efficiency is significantly reduced in neutralizing the B2 strain compared to the B1 strain. The monoclonal antibody (mAb) functions by binding to the epitope 1 and 2 regions in the combined repetitive oligopeptide (CROP) domain. Some binding residues are distinctively different between B1 and B2 strains. In this work, we aimed to elucidate and compare insights into the interaction of toxins B1 and B2 in complex with Bez by using all-atom molecular dynamics (MD) simulations and binding free energy calculations. The predicted Δ G binding values suggested that the antibody (Ab) could bind to toxin B1 significantly better than B2, supported by higher salt bridge and hydrogen bonding (H-bonding) interactions, as well as the number of contact residues between the two focused proteins. The toxin B1 residues important for binding with Bez were E1878, T1901, E1902, F1905, N1941, V1946, N2031, T2032, E2033, V2076, V2077, and E2092. The lower susceptibility of Bez towards toxin B2 was primarily due to a change of residue E2033 from glutamate to alanine (A2033) and the loss of E1878 and E1902 contributions, as determined by the intermolecular interaction changes from the dynamic residue interaction network (dRIN) analysis. The obtained data strengthen our understanding of Bez/toxin B binding.

With the aim of discovering small molecule inhibitors of the sporulation process in Clostridioides difficile , we prepared a series of C-7 α-(4-substituted-1 H -1,2,3-triazol-1-yl)acetamide analogues of cefotetan, a known inhibitor of the C. difficile sporulation-specific protein target Cd SpoVD. These analogues were evaluated using both in vitro binding assays with Cd SpoVD and antisporulation assays against C. difficile . Further design concepts were aided utilizing the predicted docking scores (DS) using both AlphaFold (AF) models, and a crystal structure of the Cd SpoVD protein (PDB 7RCZ). Despite being 1 order of magnitude more potent as a sporulation inhibitor than cefotetan, in vivo studies on compound 6a in a murine-model of C. difficile infection demonstrated comparable spore shedding capabilities as cefotetan. Importantly, compound 6a had no concerning broad spectrum antibacterial activities, toxicity, or hemolytic activity and thus has potential for further drug development.

Importance: Clostridioides difficile is one of the leading causes of hospital-acquired infections worldwide and presents challenges in treatment due to recurrent gastrointestinal disease after treatment with antimicrobials. The mechanisms by which C. difficile colonizes the gut represent a key gap in knowledge, including its association with host cells and mucosa. Our results show the importance of flagellin for specific adhesion to mucosal hydrogels and can help to explain prior observations of adhesive defects in flagellin and pilin mutants., Competing Interests: The authors declare no conflict of interest.

The gut microbiome has coevolved with humans to aid in physiologic functions and prevent disease. An increasing prevalence of gut dysbiosis in modern society exists and has strong linkages to multiple disease processes common in the developed world. Mechanisms for microbiome-human interactions that impact host homeostasis include bacterial metabolite/toxin production, biofilm formation with mucous layer infiltration, and host immune system modulation. Most of this crosstalk occurs at the epithelial layer of the gut, and as such the role of these interactions in the induction of colorectal cancer-a highly prevalent disease globally and one undergoing significant epidemiologic shifts-is under increasing scrutiny. Although multiple individual gut bacteria have been hypothesized as possible driver organisms in the oncogenic process, no bacterium has been definitively identified as a causal agent of colorectal cancer, suggesting that host lifestyle factors, microbiome community interactions, and the mucosal and/or systemic immune response may play a critical role in the process. Recent evidence has emerged implicating the ubiquitous human pathogen Clostridioides difficile as a possible promoter of colorectal cancer through chronic toxin-mediated cellular changes. Although much remains to be defined regarding the natural history of infections caused by this pathogen and its potential for oncogenesis, it provides a strong model for the role of both individual bacteria and of the gut microbial community as a whole in the development of colorectal cancer., Competing Interests: Potential conflicts of interest. C. S. reports royalties from UpToDate to CLS for writing and reviews of content, US Utility Application number 16/976,721, Bacterial Biofilms and Cancer, and received salary support to the institution for their role as Editor in Chief of the Journal of Infectious Diseases. S. M. A. reports no potential conflicts. Both authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Clostridioides difficile is the most common cause of nosocomial antibiotic-associated diarrhea, and is responsible for a spectrum of diseases characterized by high levels of recurrence, morbidity, and mortality. Treatment is complex, since antibiotics constitute both the main treatment and the major risk factor for infection. Worryingly, resistance to multiple antibiotics is becoming increasingly widespread, leading to the classification of this pathogen as an urgent threat to global health. As a consummate opportunist, C. difficile is well equipped for promoting disease, owing to its arsenal of virulence factors: transmission of this anaerobe is highly efficient due to the formation of robust endospores, and an array of adhesins promote gut colonization. C. difficile produces multiple toxins acting upon gut epithelia, resulting in manifestations typical of diarrheal disease, and severe inflammation in a subset of patients. This review focuses on such virulence factors, as well as the importance of antimicrobial resistance and genome plasticity in enabling pathogenesis and persistence of this important pathogen.

Introduction: Clostridium perfringens is a gram-positive, anaerobic sporulating bacillus which can infect several hosts, thereby being considered the causative agent of many gut illnesses. Some studies have suggested that C. perfringens's virulence factors may negatively affect gut microbiota homeostasis by decreasing beneficial bacteria; however, studies have failed to evaluate the simultaneous presence of other pathogenic bacteria, such as C. difficile (another sporulating bacillus known to play a role in gut microbiota imbalance). Conscious of the lack of compelling data, this work has ascertained how such microorganisms' coexistence can be associated with a variation in gut microbiota composition, compared to that of C. perfringens colonisation., Methods: PCR was thus used for identifying C. perfringens and C. difficile in 98 samples. Amplicon-based sequencing of 16S- and 18S-rRNA genes' V4 hypervariable region from such samples was used for determining the microbiota's taxonomical composition and diversity., Results: Small differences were observed in bacterial communities' taxonomic composition and diversity; such imbalance was mainly associated with groups having hospital-acquired diarrhoea., Conclusion: The alterations reported herein may have been influenced by C. difficile and diarrhoea acquisition site, despite C. perfringens' ability to cause alterations in microbiota due to its virulence factors. Our findings highlight the need for a holistic view of gut microbiota., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Older age is a well-known risk factor for recurrent and severe Clostridioides difficile infection (CDI). Fecal microbiota transplantation (FMT) is widely recognized as an effective and safe therapeutic option for the treatment of recurrent CDI (rCDI). However, the efficacy and safety of FMT for rCDI in very old patients are uncertain. This study evaluated the efficacy and safety of FMT in a group of very old subjects with rCDI, and the reliability of overall comorbidity and frailty assessment for identifying patients at higher risk of worse clinical outcomes., Methods: This is a retrospective single-center study including patients ≥85 years undergoing FMT for rCDI between 2014 and 2022. Primary outcomes included efficacy of FMT, defined as cure of CDI at 8 week-follow-up, and safety evaluation. At baseline, comorbidity was measured with the Charlson Comorbidity Index (CCI). Frailty was measured with the Clinical Frailty Scale (CFS)., Results: Overall, 43 patients with a median age of 88 years underwent FMT by colonoscopy in the study period. The rate of first FMT success was 77%. Five of the 10 patients who failed the first FMT infusion were cured after repeat FMT, with an overall efficacy of 88%. In patients with successful treatment, the CFS was significantly lower compared to those who failed the FMT or underwent repeat FMT (p < 0.01 for both). Mild adverse events occurred in 11 patients (25%). One death, not related to FMT or rCDI, occurred within 7 days from the first procedure., Conclusions: FMT is effective and safe in very old patients. Frailty and high comorbidity do not limit use of FMT in these patients. Frailty assessment has potential to better identify patients at higher risk of worse outcomes or for repeat treatment with FMT., (© 2023 The American Geriatrics Society.)

Objective: To determine risk factors for Clostridioides difficile colonization and C. difficile infection (CDI) among patients admitted to the intensive care unit (ICU)., Design: Retrospective observational cohort study., Setting: Tertiary-care facility., Patients: All adult patients admitted to an ICU from July 1, 2015, to November 6, 2019, who were tested for C. difficile colonization. Patients with CDI were excluded., Methods: Information was collected on patient demographics, comorbidities, laboratory results, and prescriptions. We defined C. difficile colonization as a positive nucleic acid amplification test for C. difficile up to 48 hours before or 24 hours after intensive care unit (ICU) admission without evidence of active infection. We defined active infection as the receipt of an antibiotic whose only indication is the treatment of CDI. The primary outcome measure was the development of CDI up to 30 days after ICU admission. Logistic regression was used to model associations between clinical variables and the development of CDI., Results: The overall C. difficile colonization rate was 4% and the overall CDI rate was 2%. Risk factors for the development of CDI included C. difficile colonization (aOR, 13.3; 95% CI, 8.3-21.3; P < .0001), increased ICU length of stay (aOR, 1.04; 95% CI, 1.03-1.05; P < .0001), and a history of inflammatory bowel disease (aOR, 3.8; 95% CI, 1.3-11.1; P = .02). Receipt of any antibiotic during the ICU stay was associated with a borderline increased odds of CDI (aOR, 1.9; 95% CI, 1.0-3.4; P = .05)., Conclusion: C. difficile colonization is associated with the development of CDI among ICU patients.

BACKGROUND Clostridioides difficile (C. difficile) is a bacterium that is well known for causing serious diarrheal infections and can even lead to colon cancer if left untreated. Disruption of the normal healthy bacteria in the colon can lead to development of C. difficile colitis. Risk factors for C. difficile infections (CDI) include recent antibiotic exposure, hospital or nursing home stays, inflammatory bowel disease (IBD), or impaired immunity. There is an increasing incidence of community-associated CDI (CA-CDI) in individuals without the common risk factors, which has implicated natural reservoirs, zoonoses, originating from animals such as domestic cats and dogs, livestock, shellfish, and wild animals. CASE REPORT A previously healthy 31-year-old woman with recurrent CA-CDI suspected to be acquired from a household cat represents a novel presentation. The patient had an initial case of severe diarrhea following recent antibiotic exposure, was briefly monitored in hospital, and was diagnosed with CDI. She was trialed on oral vancomycin, which resulted in temporary resolution of her symptoms. Her symptoms recurred, however, and did not improve despite treatment with multiple therapeutic options over a period of months. Ultimately, the patient was not able to achieve long-term resolution of her symptoms until her newly adopted pet cat was treated by a veterinarian. CONCLUSIONS In conclusion, this case report explores the epidemiologic risk factors of zoonotic CA-CDI and the importance of early identification, evaluation, and prevention of disease. This case demonstrates the significance of thorough history taking, contact (pet) tracing, and proper treatment of recurrent CA-CDI.

The discovery of compound 57 , a new, totally synthetic 1,2,4-oxadiazole antibacterial agent, is described. This oxadiazole displays highly selective, bactericidal killing of Clostridioides (Clostridium) difficile , the bacterium that causes C. difficile infection (CDI) in both hospital and community settings. The narrow spectrum of activity exhibited by 57 should avoid any disruption of commensal anaerobic bacteria in the gut microbiome, minimizing chances for recurrent CDI.

We have previously reported on the susceptibility and epidemiology of Clostridioides difficile isolates from six geographically dispersed medical centers in the United States. This current survey was conducted with isolates collected in 2020-2021 from six geographically dispersed medical centers in the United States, with specific attention to susceptibility to ridinilazole as well as nine comparators. C. difficile isolates or stools from patients with C. difficile antibiotic-associated diarrhea were collected and referred to a central laboratory. After species confirmation of 300 isolates at the central laboratory, antibiotic susceptibilities were determined by the agar dilution method [M11-A9, Clinical and Laboratory Standards Institute (CLSI)] against the 10 agents. Ribotyping was performed by PCR capillary gel electrophoresis on all isolates. Ridinilazole had a minimum inhibitory concentration (MIC) 90 of 0.25 mcg/mL, and no isolate had an MIC greater than 0.5 mcg/mL. In comparison, fidaxomicin had an MIC 90 of 0.5 mcg/mL. The vancomycin MIC 90 was 2 mcg/mL with a 0.7% resistance rate [both CLSI and European Committee on Antimicrobial Susceptibility Testing (EUCAST) criteria]. The metronidazole MIC 90 was 1 mcg/mL, with none resistant by CLSI criteria, and a 0.3% resistance rate by EUCAST criteria. Among the 50 different ribotypes isolated in the survey, the most common ribotype was 014-020 (14.0%) followed by 106 (10.3%), 027 (10%), 002 (8%), and 078-126 (4.3%). Ridinilazole maintained activity against all ribotypes and all strains resistant to any other agent tested. Ridinilazole showed excellent in vitro activity against C. difficile isolates collected between 2020 and 2021 in the United States, independent of ribotype., Competing Interests: D.S. had research contracts with Tufts Medical Center from Prolacta, Summit Therapeutics, Seres Health, and Merck. Consultant to Prolacta and Merck. E.D. is an employee of Summit (Oxford) Ltd. at the time of manuscript submission, and owns stock options in Summit Therapeutics (parent company). K.G. had research funding paid to the University of Houston from Summit Therapeutics, Seres Health, Paratek, and Acuryx Pharmaceuticals. K.C. has research funds paid to her institution from Meridian, BioRad, Qiagen, and Great Basin as well as a consultant fee from B.D. Diagnostics. She serves on the Scientific Advisory Boards of Co-Diagnostics, Inc., Cytovale, Inc., and Pattern Diagnostics, Inc. E.G. is a consultant for Accurx Pharmaceuticals, L.L.C., Merck, Summit Pharmaceuticals P.L.C., Shionogi, Kindred Hospital system, BioK+, and speakers bureaus for Merck and Shionogi. S.J. is a consultant for Accurx, BioK+, Ferring Pharmaceuticals, and Summit Therapeutics. D.G. is a consultant for Destiny Pharma, Plc., and holds a patent for treatment of CDI with a non-toxigenic C. difficile licensed to Destiny Pharma. C.T. has received research funding through grants to Tufts Medical Center from Actelion, Merck, and Summit Therapeutics, Plc. She has served as a consultant to Summit Plc and Delnove. S.W., Q.W., A.S., D.B., L.G., L.M., and C.L. have no conflicts to disclose.

Antibiotic-induced microbiota disruption and its persistence create conditions for dysbiosis and colonization by opportunistic pathogens, such as those causing Clostridioides difficile ( C. difficile ) infection (CDI), which is the most severe hospital-acquired intestinal infection. Given the wide differences in microbiota across hosts and in their recovery after antibiotic treatments, there is a need for assays to assess the influence of dysbiosis and its recovery dynamics on the susceptibility of the host to CDI. Germination of C. difficile spores is a key virulence trait for the onset of CDI, which is influenced by the level of primary vs secondary bile acids in the intestinal milieu that is regulated by the microbiota composition. Herein, the germination of C. difficile spores in fecal supernatant from mice that are subject to varying degrees of antibiotic treatment is utilized as an ex vivo assay to predict intestinal dysbiosis in the host based on their susceptibility to CDI, as determined by in vivo CDI metrics in the same mouse model. Quantification of spore germination down to lower detection limits than the colony-forming assay is achieved by using impedance cytometry to count single vegetative bacteria that are identified based on their characteristic electrical physiology for distinction vs aggregated spores and cell debris in the media. As a result, germination can be quantified at earlier time points and with fewer spores for correlation to CDI outcomes. This sets the groundwork for a point-of-care tool to gauge the susceptibility of human microbiota to CDI after antibiotic treatments.

Background: Two-step testing for Clostridioides difficile infection (CDI) aims to improve diagnostic specificity but may also influence reported epidemiology and patterns of treatment. Some providers fear that 2-step testing may result in adverse outcomes if C. difficile is underdiagnosed., Methods: Our primary objective was to assess the impact of 2-step testing on reported incidence of hospital-onset CDI (HO-CDI). As secondary objectives, we assessed the impact of 2-step testing on C. difficile-specific antibiotic use and colectomy rates as proxies for harm from underdiagnosis or delayed treatment. This longitudinal cohort study included 2 657 324 patient-days across 8 regional hospitals from July 2017 through March 2022. Impact of 2-step testing was assessed by time series analysis with generalized estimating equation regression models., Results: Two-step testing was associated with a level decrease in HO-CDI incidence (incidence rate ratio, 0.53 [95% confidence interval {CI}, .48-.60]; P < .001), a similar level decrease in utilization rates for oral vancomycin and fidaxomicin (utilization rate ratio, 0.63 [95% CI, .58-.70]; P < .001), and no significant level (rate ratio, 1.16 [95% CI, .93-1.43]; P = .18) or trend (rate ratio, 0.85 [95% CI, .52-1.39]; P = .51) change in emergent colectomy rates., Conclusions: Two-step testing is associated with decreased reported incidence of HO-CDI, likely by improving diagnostic specificity. The parallel decrease in C. difficile-specific antibiotic use offers indirect reassurance against underdiagnosis of C. difficile infections still requiring treatment by clinician assessment. Similarly, the absence of any significant change in colectomy rates offers indirect reassurance against any rise in fulminant C. difficile requiring surgical management., Competing Interests: Potential conflicts of interest. N. A. T. reports grant funding from the CDC, NIH/ARLG, and Rockefeller Foundation; research contract funding from PDI, Purio, and Basilea; and consulting fees for Techspert. D. J. A. reports grant funding from the CDC and Agency for Healthcare Research and Quality; contracts from CDC; interests as owner of Infection Control Education for Major Sports, LLC; and royalties from UpToDate. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

A newly developed Clostridioides difficile-selective growth broth, which can be cultured under aerobic conditions, was found to have a sensitivity/specificity (98%/89%) comparable to conventional anaerobic culture methods. This might be a powerful tool for diagnosing Clostridioides difficile infection in resource-limited regions and health care settings in the future., Competing Interests: Declaration of Competing Interest This study was conducted with commercial of financial relationships that could be construed as potential conflict of interest. Clostridioides difficile-selective growth broth used in this study was provided free of charge by Kanto Chemical Co (Tokyo, Japan)., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Clostridioides difficile (C. difficile) is a common hospital-acquired infection which can lead to major implications for patients and our health care system. In this study, we examine a policy change at a single-site Veterans Affairs Healthcare system that allowed bedside nurses to order C. difficile testing in addition to physicians on the time to obtain test results and initiate treatment., Methods: The time to receive results and initiate treatment were analyzed before and after the policy change, and between physicians and nurses using descriptive statistics and paired student t-tests. Variables associated with lower ordering times were also analyzed using logistic regression while adjusting for patient admission location and length of inpatient hospital stay., Results: The difference in time to obtain the result both before and after the policy change and between ordering provider type were both statistically significant (P < .05). In unadjusted models, nurses were associated with faster test results compared to physicians (OR (95% CI) 1.72 (1.45-2.05)., Conclusions: Allowing bedside nurses more autonomy to order the stool sample significantly decreased the amount of time to receive the results, potentially decreasing the risk of additional infections among patients and decreasing the economic burden on the hospital., (Published by Elsevier Inc.)

Despite enhanced infection prevention efforts, Clostridioides difficile remains the leading cause of healthcare-associated infections in the United States. Current prevention strategies are limited by their failure to account for patients who carry C. difficile asymptomatically, who may act as hidden reservoirs transmitting infections to other patients. To improve the understanding of asymptomatic carriers' contribution to C. difficile spread, we conducted admission and daily longitudinal culture-based screening for C. difficile in a US-based intensive care unit over nine months and performed whole-genome sequencing on all recovered isolates. Despite a high burden of carriage, with 9.3% of admissions having toxigenic C. difficile detected in at least one sample, only 1% of patients culturing negative on admission to the unit acquired C. difficile via cross-transmission. While patients who carried toxigenic C. difficile on admission posed minimal risk to others, they themselves had a 24-times greater risk for developing a healthcare-onset C. difficile infection than noncarriers. Together, these findings suggest that current infection prevention practices can be effective in preventing nosocomial cross-transmission of C. difficile, and that decreasing C. difficile infections in hospitals further will require interventions targeting the transition from asymptomatic carriage to infection., (© 2023. The Author(s).)

Patients with CF (pwCF) have high antibiotic use and an altered intestinal microbiome, known risk factors for infection with Clostridioides difficile. However, in adults with CF, C. difficile infection (CDI) is uncommon and asymptomatic colonization with C. difficile occurs frequently, for reasons that remain unclear. We investigated the rate, risk factors, and sequelae of asymptomatic C. difficile colonization in children with CF (cwCF). We identified that 32% of cwCF were colonized with C. difficile without acute gastrointestinal symptoms. Higher BMI and exposure to specific antibiotic classes (cephalosporins, fluoroquinolones, and vancomycin) were significantly associated with C. difficile colonization. No children developed symptomatic CDI in 90-days following enrollment., Competing Interests: Conflicts of Interest All authors declare that they have no conflicts of interest relevant to this work., (Copyright © 2022. Published by Elsevier B.V.)

Many colorectal diseases depend on complex interactions between several pathophysiological factors, including the intestinal microbiota. In recent years, the widespread use of antibiotics has been recognized as a main cause of intestinal dysbiosis and a favouring factor for Clostridioides difficile infection. The latter, in addition, causes infectious diarrhoea, pseudomembranous colitis, and toxic megacolon by means of its toxins (A and, especially, B), is characterized by frequent relapses; thus, its persistence in a host may be long-lasting. Based on recent experimental evidence, here we analyse the possibility that, similarly to other bacteria, Clostridioides difficile may be considered a potential carcinogen for colorectal cancer., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Fidaxomicin is a first-line treatment for Clostridioides difficile infections (CDIs). Fidaxomicin resistance has rarely been reported in this urgent antimicrobial resistance threat as defined by the CDC., Objectives: To report a case of fidaxomicin-resistant C. difficile isolation in a patient treated by fidaxomicin, characterize the genetic determinant for resistance and the consequences on pathophysiological traits, and review the literature., Patient and Methods: A 38-year-old male patient with several risk factors for CDI experienced three episodes of hospital-acquired CDI and received fidaxomicin for the first episode. The successive isolates were subjected to phenotypic characterization (antimicrobial susceptibility, growth, sporulation ability and toxin production) and WGS analysis to evaluate clonality and modifications associated with resistance., Results: Resistance to fidaxomicin arose in isolates from the recurrences of CDI (MIC: 16 mg/L). WGS analysis showed a close genetic link between strains suggestive of relapses in this patient. A T3428G mutation in the rpoB gene might be associated with fidaxomicin resistance. The resistance was associated with defects in growth, sporulation and production of toxins. A review of the literature found only three previous fidaxomicin-resistant C. difficile clinical strains., Conclusions: Although rarely reported, resistance to fidaxomicin may quickly emerge in vivo after a single course of treatment. This observation supports the need for prospective surveillance of the susceptibility of C. difficile to treatment antibiotics. However, the clinical relevance of fidaxomicin resistance still needs to be elucidated, particularly due to its apparent rareness and associated fitness cost., (© The Author(s) 2023. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: Clostridioides difficile infection is an urgent public health threat, and the incidence has been increasing over the last decades. Knowledge of the prevalence of C. difficile in acutely admitted patients and risk factors for colonization with C. difficile assists emergency departments (EDs) in prioritizing preventive initiatives. This national study aimed to describe prevalence and risk factors for C. difficile carriers acutely admitted to EDs, focusing on the impact of earlier antibiotic prescription., Methods: We conducted a nationwide analytic cross-sectional study with prospective data collection combined with a nested case-control study with retrospective data collection. All adults visiting one of eight Danish EDs were interviewed and examined for C. difficile. Using a national register, we collected the antibiotic history within the 2 years prior to enrolment. The primary outcome was the prevalence of C. difficile colonization, and secondary outcomes were related to risk factors and prior antibiotic prescription. Multivariate analyses examined the association between earlier antibiotic prescription and C. difficile colonization., Results: Of 5019 participants, 89 were colonized with C. difficile (prevalence of 1.8%). A significant and exposure-dependent association was found for penicillins [DDD/person-year(PY) > 20; OR 4.93 (95% CI 2.22-10.97)] and fluoroquinolones [DDD/PY > 20; OR 8.81 (95% CI 2.54-30.55)], but not macrolides. Timing of the prescription did not affect the association., Conclusions: One out of 55 patients visiting a Danish ED were colonized with C. difficile. Risk factors for colonization included high age, comorbidity and prior prescription of fluoroquinolones and penicillins., (© The Author(s) 2023. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Ordering Clostridioides difficile diagnostics without appropriate clinical indications can result in inappropriate antibiotic prescribing and misdiagnosis of hospital onset C. difficile infection. Manual processes such as provider review of order appropriateness may detract from other infection control or antibiotic stewardship activities., Methods: We developed an evidence-based clinical algorithm that defined appropriateness criteria for testing for C. difficile infection. We then implemented an electronic medical record-based order-entry tool that utilized discrete branches within the clinical algorithm including history of prior C. difficile test results, laxative or stool-softener administration, and documentation of unformed bowel movements. Testing guidance was then dynamically displayed with supporting patient data. We compared the rate of completed C. difficile tests after implementation of this intervention at 5 hospitals to a historic baseline in which a best-practice advisory was used., Results: Using mixed-effects Poisson regression, we found that the intervention was associated with a reduction in the incidence rate of both C. difficile ordering (incidence rate ratio [IRR], 0.74; 95% confidence interval [CI], 0.63-0.88; P = .001) and C. difficile -positive tests (IRR, 0.83; 95% CI, 0.76-0.91; P < .001). On segmented regression analysis, we identified a sustained reduction in orders over time among academic hospitals and a new reduction in orders over time among community hospitals., Conclusions: An evidence-based dynamic order panel, integrated within the electronic medical record, was associated with a reduction in both C. difficile ordering and positive tests in comparison to a best practice advisory, although the impact varied between academic and community facilities.

Background: Limited information is available on the natural history of Clostridioides difficile colonization and infection in patients with new acquisition of C. difficile in healthcare settings., Methods: In 3 hospitals and affiliated long-term care facilities, we collected serial perirectal cultures from patients with no diarrhea on enrollment to identify new acquisition of toxigenic C. difficile carriage and determined the duration and burden of carriage. Asymptomatic carriage was defined as transient if only 1 culture was positive, with negative cultures before and after, or persistent if 2 or more cultures were positive. Clearance of carriage was defined as 2 consecutive negative perirectal cultures., Results: Of 1432 patients with negative initial cultures and at least 1 follow-up culture, 39 (2.7%) developed C. difficile infection (CDI) without prior detection of carriage and 142 (9.9%) acquired asymptomatic carriage, with 19 (13.4%) subsequently diagnosed with CDI. Of 82 patients analyzed for persistence of carriage, 50 (61.0%) had transient carriage and 32 (39.0%) had persistent carriage, with an estimated median of 77 days to clearance of colonization (range, 14-133 days). Most persistent carriers had a relatively high burden of carriage and maintained the same ribotype over time, whereas most transient carriers had a low burden of carriage detected only using broth enrichment cultures., Conclusions: In 3 healthcare facilities, 9.9% of patients acquired asymptomatic carriage of toxigenic C. difficile, and 13.4% were subsequently diagnosed with CDI. Most carriers had transient rather than persistent carriage and most patients developing CDI did not have prior detection of carriage., Competing Interests: Potential conflicts of interest. C. J. D. has received research funding from Clorox, Ecolab, and Pfizer. All other authors report no potential conflicts. The authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest., (Published by Oxford University Press on behalf of Infectious Diseases Society of America 2023.)

Background: Clostridioides difficile (C. difficile) is a hospital-acquired infection. Overtesting for C. difficile leads to false positive results due to a high rate of asymptomatic colonization, resulting in unnecessary and harmful treatment for patients., Methods: This was a quality improvement initiative to decrease the rate of inappropriate C. difficile testing across 11 hospitals in an urban, safety-net setting. Three best practice advisories were created, alerting providers of recent laxative administration within 48 hours, a recent positive test within 14 days, and a recent negative test within 7 days. The outcome measures were the number of C. difficile tests per 1,000 patient days, as well as the rate of hospital onset C. difficile infection was compared pre- and post-intervention. The process measures included the rate of removal of the C. difficile test from the best practice advisory, as well as the subsequent 24-hour re-order rate., Results: The number of C. difficile tests decreased by 27.3% from 1.1 per 1,000 patient days preintervention (May 25, 2020-May 24, 2021) to 0.8 per 1,000 patient days postintervention, (May 25, 2021-March 25, 2022), P < .001. When stratified by hospital, changes in testing ranged from an increase of 12.5% to a decrease of 60%. Analysis among provider type showed higher behavior change among attendings than compared to trainees or advanced practice providers. There was a 12.1%, nonsignificant decrease in C. difficile rates from preintervention, 0.33 per 1,000 patient days compared to postintervention, 0.29 per 1,000 patient days, P=.32., Conclusions: Using only an electronic health record intervention, we successfully decreased C. difficile orders after 72 hours of admission in a large, safety-net system. Variation existed among hospitals and by provider type., (Copyright © 2022. Published by Elsevier Inc.)

Background: When surgery is indicated for fulminant Clostridioides difficile infection (CDI), total abdominal colectomy (TAC) is the most common approach. Diverting loop ileostomy (DLI) with antegrade colonic lavage has been introduced as a colon-sparing surgical approach. Prior analyses of National Inpatient Sample (NIS) data suggested equivalent postoperative outcomes between groups but did not evaluate healthcare resource utilization. As such, we aimed to analyze a more recent NIS cohort to compare these two approaches in terms of both postoperative outcomes and healthcare resource utilization., Methods: A retrospective analysis of the NIS from 2016 to 2019 was conducted. The primary outcome was postoperative in-hospital morbidity. Secondary outcomes included postoperative in-hospital mortality, system-specific postoperative complications, total admission cost, and length of stay (LOS). Univariable and multivariable regressions were utilized to compare the two operative approaches., Results: In total, 886 patients underwent TAC and 409 patients underwent DLI with antegrade colonic lavage. Adjusted analyses demonstrated no difference between groups in postoperative in-hospital morbidity (aOR 0.96, 95%CI 0.64-1.44, p = 0.851) or in-hospital mortality (aOR 1.15, 95%CI 0.81-1.64, p = 0.436). Patients undergoing TAC experienced significantly decreased total admission cost (MD $79,715.34, 95%CI 133,841-25,588, p = 0.004) and shorter postoperative LOS (MD 4.06 days, 95%CI 6.96-1.15, p = 0.006)., Conclusions: There are minimal differences between TAC and DLI with antegrade colonic lavage for fulminant CDI in terms of postoperative morbidity and mortality. Healthcare resource utilization, however, is significantly improved when patients undergo TAC as evidenced by clinically important decreases in total admission cost and postoperative LOS., (© 2023. The Society for Surgery of the Alimentary Tract.)

•The outcomes of CDI were evaluated in 65 patients with CDI in a Brazilian tertiary hospital. •Lack of clinical improvement after treatment and the severity score (ATLAS) increased the risk of death. •The use of multiple antimicrobial agents was associated with longer hospital stays. •Patients with high Charlson comorbidity index (>7) were more likely to recur. Background - Clostridioides difficile infection (CDI) is a potentially severe disease that can present with refractoriness, recurrence, and evolution to death. In Brazil, the epidemiology of CDI seems to differ from that of the United States and most European countries, with only one ribotype (RT) 027-related case and a high prevalence of RT106. Objective - The aim of this study was to evaluate the outcomes of CDI and its possible association with ribotypes at a university hospital in Brazil. Methods - A total of 65 patients with CDI were included and stool samples were submitted to A/B toxin detection and toxigenic culture, and toxigenic isolates (n=44) were also PCR ribotyped. Results - Patients' median age was 59 (20-87) years and there were 16 (24.6%) deaths. The median Charlson comorbidity index (CCI) was 4 (0-15) and 16.9% of the patients had CCI ≥8. The ATLAS score and non-improvement of diarrhea were related to higher mortality. A longer length of hospitalization was related to the enteral nutrition and use of multiple antibiotics. The period between CDI diagnosis and hospital discharge was longer in those who received new antibiotics after diagnosis, multiple antibiotics, and required intensive care treatment. Recurrence was associated with CCI >7. Twenty ribotypes were identified and RT106 was the most frequently detected strain (43.2%). No relationship was observed between the ribotypes and outcomes. CDI was present in patients with more comorbidities. Conclusion - Risk factors for higher mortality, longer hospital stay and recurrence were identified. A diversity of ribotypes was observed and C. difficile strains were not related to the outcomes.

Introduction: Clostridioides difficile infection (CDI) is a major cause for antibiotic-associated diarrhea. Specific factors put the pediatrics at risk. International guidelines lists specific recommendations for the diagnosis and treatment of pediatric CDI. The practice of diagnosing and treating pediatric CDI in Saudi Arabia is slightly different from the recommendations of the guidelines., Areas Covered: This review summarizes pediatric CDI in Saudi Arabia in terms of epidemiology, current diagnostics, and how the practice compares to recommendations of the guidelines, and available treatment options., Expert Opinion: Although pediatric CDI epidemiology in Saudi Arabia doesn't impose a burden on the healthcare system, it should be noted that not all hospitals follow CDI diagnostic recommendations of international guidelines, which may result in cases underreporting. However, due to the presumed low CDI prevalence, the traditional regimen of oral metronidazole for non-severe CDI remains effective, whereas vancomycin is used for severe cases. While fidaxomicin is approved for pediatrics, its high acquisition cost and low CDI rates make it challenging for hospitals to use it. Overall, pediatrics at risk of CDI recurrence should be evaluated, such as reviewing current antibiotics for potential discontinuation. Future studies evaluating the epidemiology and treatment for CDI in Saudi children are needed.

Clostridioides difficile bacteria can cause excessive diarrhoea in patients, leading to further complications, such as severe dehydration and sepsis. Although C.difficile bacteria tend to reside harmlessly in many people's bowels, prolonged antibiotic use can alter the bacterial balance of the bowel resulting in a C.difficile infection. Guidance from the National Institute for Health and Care Excellence recommends treating a C.difficile infection with further antibiotic therapy; however, it also states that in cases of recurrent infection, a faecal microbiota transplant (FMT) should be considered. This article focuses on the treatment modality of FMT and is aimed at increasing awareness of the treatment. As well as discussing how the nurse can approach the topic with a patient considering FMT, the article also considers the nurse's role throughout the process.

Infectious enteritis is common in patients with inflammatory bowel disease (IBD). This case presented a young woman who underwent remission maintenance therapy for ulcerative colitis (UC). She was suspected of having concomitant Clostridioides difficile and Edwardsiella tarda infections. The patient's symptoms did not improve after initial antibiotic therapy; thus, the treatment strategy was modified to include an intravenous corticosteroid to treat the UC flare-up. Her symptoms significantly improved after corticosteroid administration. This is the first report of a case in which concomitant C. difficile and E. tarda infections occurred with UC flare-up.

Clostridioides difficile, the primary cause of nosocomial antibiotic-associated diarrhea, has a complex relationship with antibiotics. While the use of broad-spectrum antibiotics disrupts the gut microbiota and increases the risk of C. difficile infection (CDI), antibiotics are also the primary treatment for CDI. However, only a few antibiotics, including vancomycin, fidaxomicin, and rifaximin, are effective against CDI, and resistance to these antibiotics has emerged recently. In this study, we report the identification of two RT027 C. difficile clinical isolates (TGH35 and TGH64) obtained from symptomatic CDI-diagnosed patients in Tampa, Florida in 2016. These two strains showed an elevated minimum inhibitory concentration (MIC) of vancomycin (MIC = 4 μg/mL, compared to the EUCAST breakpoint of 2 μg/mL) and contained a vanR Cd 343A>G mutation resulting in a Thr115Ala substitution in the VanR Cd response regulator. This mutation was absent in the vancomycin-sensitive control epidemic strain RT027/R20291. TGH64 was also resistant to rifaximin (MIC ≥ 128 μg/mL) and carried the previously reported Arg505Lys and Ile548Met mutations in RpoB. Furthermore, we report on the antimicrobial resistance (AMR) and genomic characterization of additional C. difficile isolates, including RT106/TGH120, RT017/TGH33, and RT017/TGH51, obtained from the same patient sample cohort representing the highly prevalent and regionally distributed C. difficile ribotypes worldwide. Considering that the VanR Cd Thr115Ala mutation was also independently reported in seven C. difficile clinical isolates from Texas and Israel in 2019, we recommend epidemiological surveillance to better understand the impact of this mutation on vancomycin resistance. IMPORTANCE The perpetually evolving antimicrobial resistance (AMR) of C. difficile is an important contributor to its epidemiology and is a grave concern to global public health. This exacerbates the challenge of treating the infections caused by this multidrug-resistant causative organism of potentially life-threatening diarrhea. Further, the novel resistance-determining factors can be transferred between different strains and species of bacteria and cause the spread of AMR in clinical, environmental, and community settings. In this study, we have identified a mutation ( vanR Cd 343A>G) that causes a Thr115Ala substitution and is linked to an increased MIC of vancomycin in clinical isolates of C. difficile obtained from Florida in 2016. Understanding the mechanisms of AMR, especially those of newly evolving strains, is essential to effectively guide antibiotic stewardship policies to combat antibiotic resistance as well as to discover novel therapeutic targets., Competing Interests: The authors declare no conflict of interest.

Background: Management of suspected Clostridioides difficile infection (CDI) in the hospital setting typically results in patient isolation, laboratory testing, infection control, and presumptive treatment. We investigated whether implementation of rapid near-patient testing (NPT) reduced patient isolation time, hospital length of stay (LOS), antibiotic usage, and cost., Methods: A 2-period pragmatic cluster randomized crossover trial was conducted. Thirty-nine wards were randomized into 2 study arms. The primary outcome measure was effect of NPT on patient isolation time using a mixed-effects generalized linear regression model. Secondary outcomes examined were hospital LOS and antibiotic therapy based on a negative binomial regression model. Natural experiment (NE), intention-to-treat (ITT), and per-protocol (PP) analyses were conducted., Results: During the entire study period, a total of 656 patients received NPT for CDI and 1667 received standard-of-care testing. For the primary outcome, a significant decrease of patient isolation time with NPT was observed (NE, 9.4 hours [P < .01]; ITT, 2.3 hours [P < .05]; PP, 6.7 hours [P < .1]). A significant reduction in hospital LOS was observed with NPT for short stay (NE, 47.4% [P < .01]; ITT, 18.4% [P < .01]; PP, 34.2% [P < .01]). Each additional hour delay for a negative result increased metronidazole use (24 defined daily doses per 1000 patients; P < .05) and non-CDI-treating antibiotics by 70.13 mg (P < .01). NPT was found to save 25.48 US dollars per patient when including test cost to the laboratory and patient isolation in the hospital., Conclusions: This pragmatic cluster randomized crossover trial demonstrated that implementation of CDI NPT can contribute to significant reductions in isolation time, hospital LOS, antibiotic usage, and healthcare cost. Clinical Trials Registration. NCT03857464., Competing Interests: Potential conflicts of interest. All authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Aims: To investigate the prevalence, molecular type, and antimicrobial susceptibility of Clostridioides difficile in the environment in Vietnam, where little is known about C. difficile., Methods and Results: Samples of pig faeces, soils from pig farms, potatoes, and the hospital environment were cultured for C. difficile. Isolates were identified and typed by polymerase chain reaction (PCR) ribotyping. The overall prevalence of C. difficile contamination was 24.5% (68/278). Clostridioides difficile was detected mainly in soils from pig farms and hospital soils, with 70%-100% prevalence. Clostridioides difficile was isolated from 3.4% of pig faecal samples and 5% of potato surfaces. The four most prevalent ribotypes (RTs) were RTs 001, 009, 038, and QX574. All isolates were susceptible to metronidazole, fidaxomicin, vancomycin, and amoxicillin/clavulanate, while resistance to erythromycin, tetracycline, and moxifloxacin was common in toxigenic strains. Clostridioides difficile RTs 001A+B+CDT- and 038A-B-CDT- were predominantly multidrug resistant., Conclusions: Environmental sources of C. difficile are important to consider in the epidemiology of C. difficile infection in Vietnam, however, contaminated soils are likely to be the most important source of C. difficile. This poses additional challenges to controlling infections in healthcare settings., (© The Author(s) 2023. Published by Oxford University Press on behalf of Applied Microbiology International.)

Although infections caused by Clostridioides difficile have historically been attributed to hospital acquisition, growing evidence supports the role of community acquisition in C. difficile infection (CDI). Symptoms of CDI can range from mild, self-resolving diarrhoea to toxic megacolon, pseudomembranous colitis, and death. In this study, we sampled C. difficile from clinical, environmental, and canine reservoirs in Flagstaff, Arizona, USA, to understand the distribution and transmission of the pathogen in a One Health framework; Flagstaff is a medium-sized, geographically isolated city with a single hospital system, making it an ideal site to characterize genomic overlap between sequenced C. difficile isolates across reservoirs. An analysis of 562 genomes from Flagstaff isolates identified 65 sequence types (STs), with eight STs being found across all three reservoirs and another nine found across two reservoirs. A screen of toxin genes in the pathogenicity locus identified nine STs where all isolates lost the toxin genes needed for CDI manifestation ( tcdB , tcdA ), demonstrating the widespread distribution of non-toxigenic C. difficile (NTCD) isolates in all three reservoirs; 15 NTCD genomes were sequenced from symptomatic, clinical samples, including two from mixed infections that contained both tcdB+ and tcdB - isolates. A comparative single nucleotide polymorphism (SNP) analysis of clinically derived isolates identified 78 genomes falling within clusters separated by ≤2 SNPs, indicating that ~19 % of clinical isolates are associated with potential healthcare-associated transmission clusters; only symptomatic cases were sampled in this study, and we did not sample asymptomatic transmission. Using this same SNP threshold, we identified genomic overlap between canine and soil isolates, as well as putative transmission between environmental and human reservoirs. The core genome of isolates sequenced in this study plus a representative set of public C. difficile genomes ( n =136), was 2690 coding region sequences, which constitutes ~70 % of an individual C. difficile genome; this number is significantly higher than has been published in some other studies, suggesting that genome data quality is important in understanding the minimal number of genes needed by C. difficile . This study demonstrates the close genomic overlap among isolates sampled across reservoirs, which was facilitated by maximizing the genomic search space used for comprehensive identification of potential transmission events. Understanding the distribution of toxigenic and non-toxigenic C. difficile across reservoirs has implications for surveillance sampling strategies, characterizing routes of infections, and implementing mitigation measures to limit human infection.

Purpose: Clostridioides difficile infection (CDI) has a high mortality among older patients. Identification of older patients with CDI in increased mortality risk is important to target treatment and thereby reduce mortality. The aim of this study was to investigate mortality rates and compare frailty levels at discharge, measured by the record-based Multidimensional Prognostic Index (MPI), with age and severity of CDI as mortality predictors in patients with CDI diagnosed during hospitalisation., Methods: This was a population-based cohort study from Central Denmark Region, Denmark, including all patients  ≥ 60 years with a positive CD toxin test without prior infection and diagnosed from 1 January to 31 December 2018. Frailty level, estimated from the electronic medical record, was defined as low, moderate, or severe frailty. CDI severity was graded according to international guidelines. Primary outcome was 90-day mortality., Results: We included 457 patients with median age 77 years (interquartile range 69-84) and females (49%). Overall, 90-day mortality was 28%, and this was associated with age (hazard ratio (HR): 2.71 (95% confidence interval 1.64-4.47)), CDI severity (HR 4.58 (3.04-6.88)) and frailty (HR 10.15 (4.06-25.36)). Frailty was a better predictor of 90-day mortality than both age (p < 0.001) and CDI severity (p = 0.04) with a receiver operating characteristic curve area of 77%., Conclusion: The 90-day mortality among older patients with CDI in a Danish region is 28%. Frailty measured by record-based MPI at discharge outperforms age and disease severity markers in predicting mortality in older patients with CDI., (© 2023. The Author(s).)

Objectives: Diagnosis of Clostridium difficile infection (CDI) can be challenging due to high colonization rates. Unlike PCR-only testing, two-step algorithm testing (that includes toxin and PCR) may help differentiate colonization from active infection, but it is unknown if this type of testing impacts treatment decisions. We examined the association between changing CDI diagnostic methods, the way the testing results were displayed, and the rates of CDI-specific treatment., Methods: We performed a retrospective analysis of positive C. difficile cases over 2 years, a year preceding and following our institution's transition from PCR to two-step testing. During the PCR period, results were displayed in the electronic medical record as 'positive'. In the two-step period, positive results were either displayed as 'likely colonized' or 'toxin positive'. Rates of CDI-specific therapy and adverse patient outcomes (30-day mortality and intensive care unit admission) were compared among the three groups., Results: A total of 610 patients had positive results over the study period. Of the 354 patients in the PCR group, 329 (93%) were treated with CDI-specific therapy. Of the 142 patients in the likely colonized group, 59 (42%) were treated. All 114 patients in the toxin-positive group were treated. Multivariate analysis of patients who were PCR positive or likely colonized showed that tests sent in the two-step era were less likely to be associated with treatment for CDI (odds ratio 0.05, 95% CI 0.03-0.09)., Discussion: We found a correlation between changing the type of test and the way the results were displayed and reduction in CDI-specific antibiotic use without restricting clinician diagnostic ordering., (Copyright © 2023 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Commercial probiotic strains inhibited C. difficile, and other Clostridium cultures with zones 14.2-78.9 mm. The highest inhibition was observed with commercial culture on C. difficile ATCC 700057. Organic acids were the leading cause of inhibition. Probiotic cultures may be used as a support culture or through fermented foods for treatment., Competing Interests: Declaration of competing interest There is no conflict of interest between the article's authors and other persons and/or institutions., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: The incidence of Clostridioides difficile infection (CDI) is high in ulcerative colitis and is associated with disease flares and adverse outcomes. However, the data on the dynamics of CDI in patients with acute severe ulcerative colitis (ASUC) is rather scarce. We evaluated the prevalence of CDI in patients with ASUC., Methods: This retrospective analysis of a prospectively maintained cohort admitted to the All India Institute of Medical Sciences, India, from May 2016 to December 2021, included patients with ASUC (as per Truelove and Witts criteria) who were tested for CDI. CDI testing was performed using enzyme-linked immunoassay for toxins A and B. Risk factors for developing CDI were analyzed along with short-term outcomes of ASUC. Steroid failure was defined as the need for medical rescue therapy or colectomy., Results: Total 153 patients with ASUC were included (mean age 34.92 ± 12.24 years; males 56.2%; disease duration 36 (IQR: 16-55.5) months, pancolitis 67.3%). Ninety-eight (63.4%), 72 (47%) and 10 (6.5%) patients, respectively, had received steroids, azathioprine and biologics in the past. Forty patients (26.14%) had a prior history of ASUC. Among risk factors for CDI, 14% of the patients had prior admission within 30 days, 22.2% had a recent history of antibiotics and 3.9% had long-term non-steroidal anti-inflammatory drug intake. Only one sample was positive for Clostridioides difficile toxin assay. Tissue Cytomegalovirus DNA-PCR positivity was noted in 57 patients (37.3%). Fifty-seven patients (37.3%) had steroid failure, 35 required medical rescue therapy and 30 (19.6%) required colectomy (eight after medical rescue therapy failure)., Conclusion: Despite antecedent risk factors for CDI, the overall prevalence of CDI in ASUC was low and the outcomes were determined by underlying disease severity., (© 2023. Indian Society of Gastroenterology.)

In this retrospective cohort of adult hematology-oncology and transplant patients, discontinuation of universal gloving did not result in significant changes in rates of central line-associated bloodstream infection, Clostridioides difficile infection, or vancomycin-resistant Enterococcus colonization. Active surveillance and subsequent isolation may be a viable alternative strategy to universal precautions., (Copyright © 2022 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.)

After an increase in Clostridioides difficile infections (CDI) until 2013 due to epidemic ribotypes such as 027 and 078, CDI incidence in Germany is now declining, as confirmed by recent epidemiological data. Despite this success through antimicrobial stewardship and hospital hygiene, the burden of disease remains high, especially in older patients (>65 years) with comorbidities. The main risk factor for CDI is the use of broad-spectrum antibiotics, which disrupt the gut microbiota, allowing C. difficile colonization. Coinfection with other intestinal pathogens such as enterococci can further increase the virulence of C. difficile . The updated 2021 ESCMID guidelines recommend fidaxomicin instead of vancomycin as the antibiotic of choice for the treatment of CDI because of its lower recurrence rate. Vancomycin remains a good alternative; however, metronidazole should only be used if neither antibiotic is available. In the future, ridinilazole may be available as another therapeutic option that has a narrow spectrum of activity and low intestinal absorption. For the treatment of recurrent CDI, the new guidelines also include the use of the monoclonal antibody bezlotoxumab. In addition, a new oral microbiome therapy, SER-109 (capsules containing purified Firmicutes spores), which showed promising results in a phase 3 study, may provide an easy-to-administer alternative to fecal microbiota transplantation. Hopes for a well-performing toxoid vaccine for primary and secondary prevention of CDI have unfortunately not been fulfilled in the CLOVER trial., Competing Interests: CL erhielt Vortrags- und Beratungshonorare von den Firmen MSD Sharp & Dohme und Tillots Pharma. SGS und LJ erklären keinen Interessenkonflikt., (Thieme. All rights reserved.)

In the human gut, the growth of the pathogen Clostridioides difficile is impacted by a complex web of interspecies interactions with members of human gut microbiota. We investigate the contribution of interspecies interactions on the antibiotic response of C. difficile to clinically relevant antibiotics using bottom-up assembly of human gut communities. We identify 2 classes of microbial interactions that alter C. difficile's antibiotic susceptibility: interactions resulting in increased ability of C. difficile to grow at high antibiotic concentrations (rare) and interactions resulting in C. difficile growth enhancement at low antibiotic concentrations (common). Based on genome-wide transcriptional profiling data, we demonstrate that metal sequestration due to hydrogen sulfide production by the prevalent gut species Desulfovibrio piger increases the minimum inhibitory concentration (MIC) of metronidazole for C. difficile. Competition with species that display higher sensitivity to the antibiotic than C. difficile leads to enhanced growth of C. difficile at low antibiotic concentrations due to competitive release. A dynamic computational model identifies the ecological principles driving this effect. Our results provide a deeper understanding of ecological and molecular principles shaping C. difficile's response to antibiotics, which could inform therapeutic interventions., Competing Interests: The authors have declared no competing interests exist., (Copyright: © 2023 Hromada, Venturelli. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)