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Identification and Characterization of Patient Populations at High Risk for Clostridioides difficile Infection (CDI): A Narrative Review.

Clostridioides difficile infection (CDI) is a major cause of infections worldwide and can lead to life-threatening complications and a severe impact on patients' quality of life (QoL). CDI can affect anyone, but it is generally accepted that those at greatest risk include people receiving antibiotics, of older age, and with a compromised immune system. However, beyond these broad categories, specific populations at high risk for CDI are not clearly defined. We performed a literature search to identify and characterize patients at high risk for CDI. We found that those at high risk for CDI incl…

Clonal relatedness and emerging linezolid resistance in Clostridioides difficile ribotypes 001 and 176 in the Czech Republic.

BACKGROUND AND AIMS: Clostridioides difficile ribotypes (RTs) 001 and 176 dominate the epidemiology of C. difficile infection (CDI) in the Czech Republic. We applied whole-genome sequencing (WGS) and broad-range antimicrobial susceptibility testing (AST) to provide detailed characterization of these lineages. METHODS: Between October and December 2019, 22 hospitals participated. CDI isolates were characterized by PCR ribotyping, toxin gene detection and AST to metronidazole, vancomycin and moxifloxacin. WGS and broad-range AST were performed on selected RT001 and RT176 isolates. RESULTS: The…

Mechanisms by which proline reductase of Clostridioides difficile promotes efficient metabolism and disease progression in vivo.

UNLABELLED: Clostridioides difficile is a toxin-producing pathogen that opportunistically infects those with a depleted gut microbiome, often triggered by antibiotic use. C. difficile preferentially utilizes Stickland amino acids, including proline, to promote energy generation and growth for colonization. We evaluated host outcomes from infection with wild-type and ΔprdB mouse-infective C. difficile ATCC 43255 strains to investigate how proline metabolism modulates C. difficile's pathogenesis and interactions with commensals in an enriched gut nutrient environment. While gnotobiotic mice infe…

The ongoing challenge of Clostridioides difficile infection in Austria: economic evaluation of two recommended treatment pathways.

OBJECTIVES: Clostridioides difficile (CD) is a major nosocomial pathogen causing severe and potentially life-threatening infections, particularly following disruption of gut microbiota. Transmission occurs via resilient spores through the fecal-oral route. While most infections originate in hospitals or long-term care facilities, 20-30% are community-acquired. In Austria, national surveillance data report 769 severe CDI cases in 2024, indicating a substantial disease burden. This analysis compares two treatment scenarios: (1) the pathway recommended by the Austrian Society of Gastroenterology …

The antiarrhythmic drugs dronedarone and amiodarone exhibit potent in vitro and in vivo activity against Clostridioides difficile.

Clostridioides difficile (C. difficile) is the most prevalent cause of healthcare-associated diarrhea. The limited number of FDA-approved antibiotics for C. difficile infection (CDI), along with increasing rates of treatment failure and recurrence, highlight the critical need for new therapeutic options. Here, we report the anti-C. difficile activity of the antiarrhythmic drugs, dronedarone (DRO) and amiodarone (AMD). Both drugs demonstrated strong efficacy against a panel of 25 clinical isolates of C. difficile, with MIC50 values of 4 µg/mL for DRO and 8 µg/mL for AMD. In a time-kill assay, D…

Comprehensive genomic analysis and antibiotic resistance profiles of Clostridioides difficile from cats and dogs in Türkiye.

This study aimed to isolate Clostridioides difficile (C. difficile) from healthy and diarrhoeic cats and dogs, perform comprehensive genomic characterization of the isolates obtained, and investigate their antibiotic susceptibility profiles and antigenic features. For this purpose, a total of 200 rectal swabs from 100 cats and 100 dogs (50 healthy and 50 diarrhoeic in each group) were used. Isolation was performed using culture methods, and isolates were identified through species-specific PCR. Multi-Locus Sequence Typing (MLST) was used for genotyping. Antibacterial susceptibilities of isolat…

Reverse Takotsubo Cardiomyopathy in a Woman With Clostridioides difficile Colitis and a Sepsis-Like Syndrome: A Case Study.

In this report, we present a case of reverse Takotsubo cardiomyopathy (rTTC) in an elderly female, 74 years old, with Clostridioides difficile colitis and sepsis-like features complicated by hypotension and arrhythmias. The diagnosis was eventually established through echocardiography and cardiac catheterization. Supportive therapy favored recovery after diagnosis. This case of rTTC highlights a serious, although rare, cardiac condition that emphasizes the importance of workup and recognition to support optimal management and recovery and underscores the need to keep stress-induced cardiomyopa…

In vitro susceptibility of clinical Clostridioides difficile isolates in Israel to metronidazole, vancomycin, fidaxomicin, ridinilazole and ibezapolstat.

BACKGROUND: Antibiotics are currently the primary treatment of Clostridioides difficile (C. difficile) infection. Yet, due to rapid development of resistance and high recurrences rates, there is an unmet need for new antimicrobials for C. difficile infections. This study assessed the in vitro susceptibility of clinical isolates from Israel to two recently developed antibiotics, ridinilazole (RDZ) and ibezapolstat (IBZ), and to standard-of-care antibiotics. METHODS: C. difficile isolates (n = 313) recovered from patients at both community and hospital medical centers across Israel, were typed …

Nasogastric Delivery of Fecal Microbiota Transplantation for the Treatment of Fulminant Clostridioides difficile Infection: A Case Report.

INTRODUCTION: Clostridioides difficile infection (CDI) is a significant cause of antibiotic-associated diarrhea with high morbidity and mortality, particularly in cases of fulminant disease. Fecal microbiota transplantation (FMT) has demonstrated efficacy in treating severe and refractory CDI, typically administered via colonoscopy. However, in cases complicated by toxic megacolon, alternative methods of FMT delivery may be necessary. CASE REPORT: This case report describes a 46-year-old female with cirrhosis and fulminant CDI complicated by toxic megacolon. Due to the patient's hemodynamic i…

Proinflammatory pathways contribute to the pathogenesis of Clostridioides difficile infection in a murine model using Spatial transcriptomics.

Clostridioides difficile (C. difficile) is a common cause of antibiotic-induced diarrhea and causes the highest number of nosocomial infections. Only two antibiotics are currently recommended for treating C. difficile infection (CDI), which may contribute to unsatisfactory treatment outcomes and an increased likelihood of recurrence. In this study, we aim to evaluate the difference in gene expression between symptomatic and asymptomatic mice after infection with C. difficile using spatial transcriptomics analysis. We also aim to evaluate the spatial aspect of altered genes between different la…

Периодическая инфекция Clostridioide у пациента с хроническим колитом: успешная реакция на трансплантацию Фекальной микробиоты.

Одной из серьезных проблем, связанных с лечением, особенно у пациентов, страдающих основными желудочно-кишечными заболеваниями, по-прежнему является периодическая диффицирующая инфекция Clostridioide. Мы представляем случай 72-летней женщины с множественным склерозом и саркоидозом, которая пережила четыре отдельных эпизода RCDI, несмотря на лечение ванкомицином, фидаксомицином и внутривенным метронизолом. Колоноскопия выявила воспаление афтонозными язвами, а гистология подтвердила хронический колит без дисплазии или цитомегаловирусной инфекции. После структурированного ванкомицинового тапера п

Совпадение в аннотации оригинала
Recurrent Clostridioides difficile infection (rCDI) remains a significant treatment challenge, particularly in patients with underlying gastrointestinal conditions. We present the case of a 72-year-old woman with multiple sclerosis and sarcoidosis, who experienced four separate episodes of rCDI despite treatment with vancomycin, fidaxomicin, and intravenous …

The global burden and trend of Clostridioides difficile and its association with world antibiotic consumption, 1990-2019.

BACKGROUND: To estimate the global trends and disease burden of Clostridioides difficile infection (CDI) and its correlation with worldwide antibiotic consumption. METHODS: Clostridioides difficile infection and antibiotic consumption data were retrieved from the Global Burden of Disease 2019, ResistanceMap-AntibiocUse, Food and Drug Administration (FDA) Adverse Event Reporting System, and Global Antimicrobial Resistance and Use Surveillance System. Jointpoint regression and age-period-cohort model were developed to show the global trends and burden of CDI. Correlation tests were calculated t…

Genetic determinants of resistance to antimicrobial therapeutics are rare in publicly available Clostridioides difficile genome sequences.

OBJECTIVES: To determine the frequencies and clonal distributions of putative genetic determinants of resistance to antimicrobials applied for treatment of Clostridioides difficile infection (CDI), as documented in the genomic record. METHODS: We scanned 26 557 C. difficile genome sequences publicly available from the EnteroBase platform for plasmids, point mutations and gene truncations previously reported to reduce susceptibility to vancomycin, fidaxomicin or metronidazole, respectively. We measured the antimicrobial susceptibility of 143 selected C. difficile isolates. RESULTS: The freque…

Analysis of factors affecting the length of hospitalization of patients with Clostridioides difficile infection: a cross-sectional study.

BACKGROUND: Clostridioides difficile infection (CDI) is an infectious disease caused by the gram-positive, anaerobic bacterium C. difficile. The vulnerable populations for CDI include the elderly, immunocompromised individuals, and hospitalized patients, especially those undergoing antimicrobial therapy, which is a significant risk factor for this infection. Due to its complications and increased resistance to treatment, CDI often leads to longer hospital stays. This study aimed to determine the average length of hospital stay (LOS) of Polish patients with CDI and to identify factors affecting…

VE303, a Defined Bacterial Consortium, for Prevention of Recurrent Clostridioides difficile Infection: A Randomized Clinical Trial.

IMPORTANCE: The effect of rationally defined nonpathogenic, nontoxigenic, commensal strains of Clostridia on prevention of Clostridioides difficile infection (CDI) is unknown. OBJECTIVE: To determine the efficacy of VE303, a defined bacterial consortium of 8 strains of commensal Clostridia, in adults at high risk for CDI recurrence. The primary objective was to determine the recommended VE303 dosing for a phase 3 trial. DESIGN, SETTING, AND PARTICIPANTS: Phase 2, randomized, double-blind, placebo-controlled, dose-ranging study conducted from February 2019 to September 2021 at 27 sites in the…

Clostridioides difficile and Enterococci's Interplay in the Human Gut: Bacterial Alliance or Competition? A Systematic Literature Review.

Clostridioides difficile and Enterococcus spp. are two common bacterial pathogens populating the human microbiota. We possess scant data on how Clostridioides difficile interacts with Enterococcus spp. in the gut microbiota in subjects colonized with Clostridioides difficile or during a Clostridioides difficile infection. We carried out a systematic review of studies on Enterococcus spp. and Clostridioides difficile's interaction in the gut microbiota and on the effect of Enterococcus spp. gut colonization on CDI development. Studies on Enterococcus spp. and Clostridioides difficile's interact…

Clinical prediction rule for identifying older patients with toxigenic clostridioides difficile at the time of hospital admission.

BACKGROUND: This study aimed to develop and validate a clinical prediction rule to screen older patients at risk of being toxigenic Clostridioides difficile carriers at the time of hospital admission. METHODS: This retrospective case-control study was performed at a university-affiliated hospital. Active surveillance using a real-time polymerase chain reaction (PCR) assay for the toxin genes of C. difficile was conducted among older patients (≥ 65 years) upon admission to the Division of Infectious Diseases of our institution. This rule was drawn from a derivative cohort between October 2019 …

Cytotoxic synergism of Clostridioides difficile toxin B with proinflammatory cytokines in subjects with inflammatory bowel diseases.

Clostridioides difficile (C. difficile) is progressively colonizing humans and animals living with humans. During this process, hypervirulent strains and mutated toxin A and B of C. difficile (TcdA and TcdB) are originating and developing. While in healthy subjects colonization by C. difficile becomes a risk after the use of antibiotics that alter the microbiome, other categories of people are more susceptible to infection and at risk of relapse, such as those with inflammatory bowel disease (IBD). Recent in vitro studies suggest that this increased susceptibility could be due to the strong cy…

High rate of Clostridioides difficile colonization in patients admitted to intensive care: A prospective cohort study.

Here, we evaluated the frequency of C. difficile colonization and its impact on clinical outcomes in patients admitted to intensive care units in Brazil. From ninety-two patients screened 16 (17.3%) were colonized by C. difficile. Colonized patients had higher Simplified Acute Physiology Score III (SAPS III), however there was no association between C. difficile colonization with diarrhea or mortality. The C. difficile strains sequenced belonged to clade 1 and presented high vancomycin-resistant rates.