Search Results (415)

Background and Objectives: The interplay of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection and Clostridioides difficile infection (CDI) poses a critical clinical challenge. The resultant inflammatory milieu and its impact on outcomes remain incompletely understood, especially among vulnerable subgroups such as elderly patients, those with diabetes, and individuals with cancer. This study aimed to characterize inflammatory markers and composite inflammatory severity scores—such as Acute Physiology and Chronic Health Evaluation II (APACHE II), Confusion, Urea, Respiratory rate, Blood pressure, and age ≥ 65 years (CURB-65), National Early Warning Score (NEWS), and the Systemic Immune-Inflammation Index (SII)—in hospitalized Coronavirus Disease 2019 (COVID-19) patients with and without CDI, and to evaluate their prognostic implications across key clinical subgroups. Methods: We conducted a retrospective, single-center study of 240 hospitalized adults with Reverse Transcription Polymerase Chain Reaction (RT-PCR)-confirmed COVID-19 between February 2021 and March 2023. Of these, 98 had concurrent CDI. We collected baseline demographics, comorbidities, and laboratory parameters including C-reactive protein (CRP), Interleukin-6 (IL-6), ferritin, neutrophil and lymphocyte counts, albumin, platelet counts, and calculated indices (C-reactive protein to Albumin Ratio (CAR), Neutrophil-to-Lymphocyte Ratio (NLR), Prognostic Nutritional Index (PNI), SII). Patients were stratified by CDI status and analyzed for inflammatory marker distributions, severity scores (APACHE II, CURB-65, NEWS), and outcomes (Intensive Care Unit (ICU) admission, mechanical ventilation, mortality). Subgroup analyses included diabetes, elderly (≥65 years), and cancer patients. Statistical comparisons employed t-tests, chi-square tests, and logistic regression models. Results: Patients with CDI demonstrated significantly higher CRP, IL-6, SII, and CAR, coupled with lower albumin and PNI (p < 0.05). They also had elevated APACHE II, CURB-65, and NEWS scores. CDI-positive patients experienced increased ICU admission (38.8% vs. 20.5%), mechanical ventilation (24.5% vs. 12.9%), and mortality (22.4% vs. 10.6%, all p < 0.05). Subgroup analyses revealed more pronounced inflammatory derangements and worse outcomes in elderly, diabetic, and cancer patients with CDI. Conclusions: Concurrent CDI intensifies systemic inflammation and adverse clinical trajectories in hospitalized COVID-19 patients. Elevations in inflammatory markers and severity scores predict worse outcomes, especially in high-risk subgroups. Early recognition and targeted interventions, including infection control and supportive measures, may attenuate disease severity and improve patient survival. Full article

Background/Objectives: The prolonged use of antibiotics is closely related to increased infections caused by Clostridioides difficile (Cdiff). Plant-origin compounds have been expanding in recent years as the best opportunity to identify new synergic therapies to combat antibiotic-associated diseases. Mexico has incredible plant biodiversity; natural compounds with antibacterial properties are an alternative treatment. The main objective of this study was to analyze the effect of medicinal plants with an antibacterial action against toxigenic clinical Cdiff strains that have a synergic effect on the antibiotics commonly used to combat this disease. Methods: The plants were selected for plants that were previously used in research, and their extracts were tested against Cdiff strains. The antibacterial activity, synergy, and antagonism between the extracts and their synergic effect with antibiotics were evaluated. Results: Our results demonstrated that some extracts have effective antimicrobial activity and synergic effects with vancomycin and metronidazole. Conclusions: This study suggests that plant extracts and plant compounds derived from these extracts could be used as synergic-antibiotic therapy to combat Cdiff infections. Full article

Background and Objectives: Co-infection with Clostridioides difficile (C. difficile) in COVID-19 patients has emerged as a clinical challenge associated with increased morbidity and mortality. While both infections elicit systemic inflammation, the interplay between inflammatory markers, disease severity, and outcomes in patients with COVID-19 and concurrent C. difficile infection remains poorly characterized. This study aimed to evaluate the inflammatory status and clinical outcomes of patients hospitalized with COVID-19, with and without C. difficile co-infection, and to identify the inflammatory markers most predictive of severe disease. Methods: We conducted a retrospective cohort study of 200 hospitalized adults with confirmed COVID-19, of whom 92 had laboratory-confirmed C. difficile infection. Baseline demographic data, comorbidities, inflammatory markers (C-reactive protein [CRP], interleukin-6 [IL-6], ferritin, neutrophil-to-lymphocyte ratio [NLR], platelet count, albumin, and derived indices such as the CRP-to-Albumin Ratio [CAR] and Prognostic Nutritional Index [PNI]) were recorded. Clinical outcomes included ICU admission, need for mechanical ventilation, length of stay, and in-hospital mortality. Results: Patients with COVID-19 and C. difficile co-infection had significantly elevated inflammatory markers (CRP, IL-6, NLR) and higher CAR, alongside lower PNI, compared to those with COVID-19 alone (p < 0.001). Inflammatory indices correlated strongly with disease severity: elevated CAR and low PNI were associated with higher odds of ICU admission and mortality (p < 0.001). Multivariate analysis identified co-infection status, increased IL-6, and elevated CAR as independent predictors of severe outcomes. Conclusions: C. difficile co-infection in COVID-19 patients is associated with an intensified inflammatory response and worse clinical outcomes. Among the evaluated markers, CAR and PNI emerged as robust predictors of severe disease. Timely recognition of C. difficile co-infection and use of targeted anti-inflammatory and supportive therapies may improve patient management. Future studies should expand on these findings to optimize care and guide therapeutic strategies. Full article

Clostridioides difficile is an urgent public health threat that affects approximately half a million patients annually in the United States. Despite concerted efforts aimed at the prevention of Clostridioides difficile infection (CDI), it remains a leading cause of healthcare-associated infections. CDI is associated with significant clinical, social, and economic burdens. Therefore, it is imperative to provide optimal and timely therapy for CDI. We conducted a systematic literature review and offer treatment recommendations based on available evidence for the treatment and prevention of CDI. Full article

Background/Objectives: Clostridioides difficile is a Gram-positive, spore-forming enteric pathogen that causes intestinal disorders, including inflammation and diarrhea, primarily through toxin production. Standard treatment options for C. difficile infection (CDI) involve a limited selection of antibiotics that are not fully effective, leading to high recurrence rates. Vaccination presents a promising strategy for preventing both CDI and its recurrence. Cell wall protein 2 (Cwp2), a highly immunogenic and abundant surface-exposed C. difficile cell wall protein, plays an important role in the bacterium’s adherence in vitro. In this study, we aimed to analyze the homology and immunogenicity of Cwp2 and its protection efficacy as a vaccine candidate against CDI in mice. Methods: we conducted in silico analyses to assess the homology and immunogenicity of Cwp2, and we evaluated its potential as a vaccine candidate against CDI using a mouse model of immunization and infection. Results: Our in silico analyses predicted the immunogenic region (functional domain) of Cwp2 and revealed its high homology among various toxinotypes and ribotypes (R.T.s) or sequence types (S.T.s). Immunizations of mice with the Cwp2 functional domain (Cwp2_A) induced potent IgG/A antibody responses against Cwp2_A, protected mice from CDI, and reduced C. difficile spore and toxin levels in feces post-infection. Additionally, anti-Cwp2_A sera inhibited the binding of C. difficile vegetative cells to HCT8 cells. Conclusions: Our report demonstrates for the first time the potential of Cwp2_A as an effective vaccine candidate against CDI in mice. Full article

A diverse and well-functioning gut microbiota normally serves as a protective shield against the invasion of harmful bacteria or the proliferation of opportunistic pathogens. Clostridioides difficile infection (CDI) is predominantly associated with the overuse of antibiotics, resulting in a significant alteration in the gut’s microbial balance. Unfortunately, the lack of global standardization does not allow for the identification of a set of biomarkers associated with the onset and progression of this disease. In this study, we examined the composition of the gut microbiota in patients at the time of the initial detection of CDI compared to a control group of CDI-negative individuals, with a focus on identifying potential CDI biomarkers for diagnosis. While no significant differences in the alpha and beta diversity between CDI-negative and CDI-positive individuals were found, we found that certain genera (such as Clostridium XIVa and Clostridium XVIII) showed different abundance patterns in the two groups, indicating potential differences in gut microbiota balance. In conclusion, am enrichment in Clostridium XI and a decrease in Faecalibacterium emerged in the CDI-positive patients and following antibiotic treatment, indicating that changes in the Clostridium/Faecalibacterium ratio may be a promising biomarker that warrants further investigation for CDI diagnosis. Full article

Background/Objective: Tedizolid (TZD), an oxazolidinone, causes fewer adverse events than linezolid (LZD). However, studies on the long-term efficacy and safety of TZD, particularly in patients with hematological malignancies (HMs), remain limited. This study aimed to evaluate the safety of long-term TZD use in Japanese patients, including those with HM. Methods: We retrospectively reviewed the medical records of patients aged 15 years and older who received TZD treatment at St. Luke’s International Hospital between 2018 and 2023. Patient demographics, treatment duration, adverse events, and clinical outcomes were analyzed. Results: Data from 35 patients and 40 treatment episodes were analyzed, including 13 episodes in patients with HM, of whom 65.0% were male, with a median age of 69.0 years (IQR: 24.5 years). The median treatment duration was 13.5 days (IQR: 46.8), with a maximum of 203 days. TZD was switched from other anti-MRSA agents in 82.5% of cases, including 42.5% from LZD. One patient discontinued TZD due to liver dysfunction, attributed to concomitant medication use. Clinical cure rates were significantly higher in the non-HM group compared to the HM group (88.9% vs. 38.5%). The 90-day mortality rate differed notably between the HM and non-HM groups (69.2% and 3.7%). Despite 100% microbiological eradication, infection-related mortality rates were 3.7% in the non-HM and 38.5% in the HM group. No reported cases of optic neuritis, Clostridioides difficile colitis, or major bleeding; Conclusions: TZD appears to be safe for long-term use, regardless of HM status, with no major complications observed in this cohort. Full article

Clostridioides difficile is a common etiological factor of hospital infections, which, in extreme cases, can lead to the death of patients. Most strains belonging to this bacterium species synthesize very dangerous toxins: toxin A (TcdA) and B (TcdB) and binary toxin (CDT). The aim of this study was to assess the suitability of agarose gel electrophoresis separation of multiplex PCR amplicons to investigate the toxinogenic potential of C. difficile strains. Additionally, the frequency of C. difficile toxin genes and the genotypes of toxin-producing strains were determined. Ninety-nine C. difficile strains were used in the detection of the presence of genes encoding all of these toxins using the multiplex PCR method. In 85 (85.9%) strains, the presence of tcdA genes encoding enterotoxin A was detected. In turn, in 66 (66.7%) isolates, the gene encoding toxin B (tcdB) was present. The lowest number of strains tested was positive for genes encoding a binary toxin. Only 31 (31.3%) strains possessed the cdtB gene and 22 (22.2%) contained both genes for the binary toxin subunits (the cdtB and cdtA genes). A relatively large number of the strains tested had genes encoding toxins, whose presence may result in a severe course of disease. Therefore, the accurate diagnosis of patients, including the detection of all known C. difficile toxin genes, is very important. The multiplex PCR method allows for the quick and accurate determination of whether the tested strains of this bacterium contain toxin genes. Agarose gel electrophoresis is a useful tool for visualizing amplification products, allowing one to confirm the presence of specific C. difficile toxin genes as well as investigate their dissemination for epidemiological purposes. Full article

Recently, fecal microbiota transplantation (FMT) has been introduced as an effective treatment option for Clostridioides difficile infection (CDI). However, the risk factors associated with FMT treatment failure have not been well demonstrated. Therefore, we aimed to investigate the risk factors of treatment failure or recurrence after FMT for CDI. This retrospective study included 124 patients with CDI who underwent FMT at Inha University Hospital between November 2017 and August 2021 and were followed up for 8 weeks after FMT for symptoms of CDI. FMT failure was defined as diarrhea recurrence or a positive stool test. We assessed the risk factors for treatment failure, including comorbidities, antibiotic use pre- and post-FMT, and the number of CDI episodes before FMT. Ninety-three patients (75%) experienced symptom improvement <7 days after FMT, while treatment failure occurred in 40 patients (32.3%). Multivariate analysis revealed that males had a lower symptom improvement rate <7 days after FMT (p = 0.049). Patients using antibiotics after FMT showed a higher rate of recurrence or treatment failure in <8 weeks (p = 0.032). Patients requiring antibiotics after FMT should be considered at higher risk of treatment failure. Careful antibiotic stewardship, particularly minimizing non-essential antibiotic use before and after FMT, may significantly enhance treatment outcomes. Further large-scale prospective studies are warranted to confirm these findings and develop targeted antibiotic management protocols for improving the efficacy of FMT in CDI treatment. Full article

Clostridioides difficile infection (CDI) is one of the main causes of morbidity associated with antibiotic use, producing both healthcare-associated infections and community infections. This study aims to describe the epidemiological characteristics, the clinical outcomes, previous antibiotic exposure, and other risk factors of hospitalized patients with CDI in a tertiary infectious disease hospital in Bucharest, Romania. We performed a descriptive analysis based on four-year surveillance data, collected in a tertiary infectious disease hospital in Bucharest, Romania. The annual incidence of CDIs varied from 65.1 cases per 10,000 discharges in 2020 to 211.7 cases per 10,000 discharges in 2023, with a continuously ascending trend. Most of the cases were hospital-acquired cases. There was a high share of antibiotic consumption three months before admission (61.3%). Third-generation cephalosporins, β-lactams with inhibitor combination, and carbapenems were the most used antibiotics, with shares of 46.0%, 25.2%, and 18.6%, respectively. Hospitalization in the previous 12 months and contact with a confirmed CDI case were other frequent factors in the study group, the occurrences of which were recorded as 66.2% and 2.4%, respectively. The surveillance data identified that the annual trend in CDIs is very variable, suggesting the need for continuous and multiannual analysis. Full article

Objectives: This systematic review evaluates the effectiveness of fecal microbiota transplantation (FMT) in treating Clostridioides difficile infection (CDI) in mouse models using a metabolomics-based approach. Methods: A comprehensive search was conducted in three databases (PubMed, Scopus, Google Scholar) from 10 April 2024 to 17 June 2024. Out of the 460 research studies reviewed and subjected to exclusion criteria, only 5 studies met all the inclusion criteria and were analyzed. Results: These studies consistently showed that FMT effectively restored gut microbiota and altered metabolic profiles, particularly increasing short-chain fatty acids (SCFAs) and secondary bile acids, which inhibited C. difficile growth. FMT proved superior to antibiotic and probiotic treatments in re-establishing a healthy gut microbiome, as evidenced by significant changes in the amino acid and carbohydrate levels. Despite its promise, variability in the outcomes—due to factors such as immune status, treatment protocols, and donor microbiome differences—underscores the need for standardization. Rather than pursuing immediate standardization, the documentation of factors such as donor and recipient microbiome profiles, preparation methods, and administration details could help identify optimal configurations for specific contexts and patient needs. In all the studies, FMT was successful in restoring the metabolic profile in mice. Conclusions: These findings align with the clinical data from CDI patients, suggesting that FMT holds potential as a therapeutic strategy for gut health restoration and CDI management. Further studies could pave the way for adoption in clinical practice. Full article

We investigated the intra-hospital distribution of C. difficile strains by whole-genome sequencing (WGS) of isolates collected in 2022 at the University Hospital Centre (UHC) Zagreb. In total, 103 patients with first-episode CDI in 2022 at UHC Zagreb were included, based on the screening stool antigen test for GDH (RidaQuick CD GDH; R-Biopharm AG, Germany), confirmed by Eazyplex C. difficile assays (Eazyplex CD assay; AmplexDiagnostics GmbH, Germany) specific for A, B, and binary toxins. Demographic and clinical data were retrospectively analyzed from electronic medical records. All samples were subjected to WGS analysis. Genetic clusters were formed from isolates with no more than six allelic differences according to core genome MLST. We identified six clusters containing 2–59 isolates with 15 singletons and 30 instances of possible intra-hospital transmission, mostly in the COVID-19 ward. WGS analysis proved useful in identifying clusters of isolates connecting various patient wards with possible transmission routes in the hospital setting. It could be used to support local and national surveillance of CDI infections and their transmission pathways. Full article

Clostridioides difficile (C. difficile) is a global threat and has significant implications for individuals and health care systems. Little is known about host molecular mechanisms and transcriptional changes in peripheral immune cells. This is the first gene expression study in whole blood from patients with C. difficile infection. We took blood and stool samples from patients with toxigenic C. difficile infection (CDI), non-toxigenic C. difficile infection (GDH), inflammatory bowel disease (IBD), diarrhea from other causes (DC), and healthy controls (HC). We performed transcriptome-wide RNA profiling on peripheral blood to identify diarrhea common and CDI unique gene sets. Diarrhea groups upregulated innate immune responses with neutrophils at the epicenter. The common signature associated with diarrhea was non-specific and shared by various other inflammatory conditions. CDI had a unique 45 gene set reflecting the downregulation of humoral and T cell memory functions. Dysregulation of immunometabolic genes was also abundant and linked to immune cell fate during differentiation. Whole transcriptome analysis of white cells in blood from patients with toxigenic C. difficile infection showed that there is an impairment of adaptive immunity and immunometabolism. Full article

Background/Objectives: Faecal microbiota transplantation (FMT) is considered a safe and effective therapy for recurrent Clostridioides difficile infection. It is the only current clinical indication for this technique, although numerous clinical research studies and trials propose its potential usefulness for treating other pathologies. Donor selection is a very rigorous process, based on a personal lifestyle interview and the absence of known pathogens in faeces and serum, leading to only a few volunteers finally achieving the corresponding certification. However, despite the high amount of data generated from the ongoing research studies relating microbiota and health, there is not yet a consensus defining what is a “healthy” microbiota. To date, knowledge of the composition of the microbiota is not a requirement to be a faecal donor. The aim of this work was to evaluate whether the analysis of the composition of the microbiota by massive sequencing of 16S rDNA could be useful in the selection of the faecal donors. Methods: Samples from 10 certified donors from Mikrobiomik Healthcare Company were collected and sequenced using 16S rDNA in a MiSeq (Illumina) platform. Alpha (Chao1 and Shannon indices) and beta diversity (Bray–Curtis) were performed using the bioinformatic web server Microbiome Analyst. The differences in microbial composition at the genera and phyla levels among the donors were evaluated. Results: The microbial diversity metric by alpha diversity indexes showed that most donors exhibited a similar microbial diversity and richness, whereas beta diversity by 16S rDNA sequencing revealed significant inter-donor differences, with a more stable microbial composition over time in some donors. The phyla Bacillota and Bacteroidota were predominant in all donors, while the density of other phyla, such as Actinomycota and Pseudomonota, varied among individuals. Each donor exhibited a characteristic genera distribution pattern; however, it was possible to define a microbiome core consisting of the genera Agathobacter, Eubacterium, Bacteroides, Clostridia UCG-014 and Akkermansia. Conclusions: The results suggest that donor certification does not need to rely exclusively on their microbiota composition, as it is unique to each donor. While one donor showed greater microbial diversity and richness, clear criteria for microbial normality and health have yet to be established. Therefore, donor certification should focus more on clinical and lifestyle aspects. Full article

The zebrafish (Danio rerio) has emerged as a valuable model for studying host-pathogen interactions due to its unique combination of characteristics. These include extensive sequence and functional conservation with the human genome, optical transparency in larvae that allows for high-resolution visualization of host cell-microbe interactions, a fully sequenced and annotated genome, advanced forward and reverse genetic tools, and suitability for chemical screening studies. Despite anatomical differences with humans, the zebrafish model has proven instrumental in investigating immune responses and human infectious diseases. Notably, zebrafish larvae rely exclusively on innate immune responses during the early stages of development, as the adaptive immune system becomes fully functional only after 4–6 weeks post-fertilization. This window provides a unique opportunity to isolate and examine infection and inflammation mechanisms driven by the innate immune response without the confounding effects of adaptive immunity. In this review, we highlight the strengths and limitations of using zebrafish as a powerful vertebrate model to study innate immune responses in infectious diseases. We will particularly focus on host-pathogen interactions in human infections caused by various bacteria (Clostridioides difficile, Staphylococcus aureus, and Pseudomonas aeruginosa), viruses (herpes simplex virus 1, SARS-CoV-2), and fungi (Aspergillus fumigatus and Candida albicans). Full article