Search Results (497)

Early bacterial infections (EBI) remain a major cause of morbidity and mortality after liver transplantation (LT). This study aimed to characterize their incidence, microbiological spectrum, risk factors, and clinical impact in an Eastern European cohort. We retrospectively analyzed 64 adult LT recipients from a tertiary center, focusing on perioperative parameters, infection profiles, and postoperative outcomes. EBI, defined as infections occurring within 30 days after transplantation and diagnosed according to CDC/NHSN criteria, occurred in 48.4% of patients. Gram-negative bacilli predominated (73.7%), mainly Pseudomonas aeruginosa (34.2%) and Klebsiella pneumoniae (15.8%), while Clostridioides difficile (CDI) accounted for 18.4% of confirmed cases diagnosed by stool toxin assay. Infected patients had greater intraoperative blood loss (median 6500 mL vs. 5000 mL, p = 0.036) and required more transfusions. The higher infection rate in our cohort may also be related to longer surgical duration. All deaths within the first postoperative year occurred among infected recipients, yet overall 30-day (7.8%) and 1-year (14.1%) mortality rates remained within the range reported internationally, suggesting that timely diagnosis and adequate management limited the impact of infections on survival. These findings emphasize the importance of infection prevention, optimized transfusion and bleeding control, and tailored antibiotic prophylaxis based on local microbiological patterns after LT. Full article

Background/Objectives: Guidelines recommend combination therapy with oral vancomycin and intravenous (IV) metronidazole for fulminant Clostridioides difficile infection (CDI). Although patients with severe CDI are often managed with combination therapy, evidence supporting this practice remains limited. This study was performed to compare the clinical outcomes of vancomycin monotherapy versus combination therapy in patients with severe CDI. Methods: We conducted a multicenter, retrospective, observational cohort study including adult patients with severe CDI who received oral vancomycin between January 2017 and May 2021. Patients were classified as receiving combination therapy if IV metronidazole was administered for at least 72 h within 48 h of initiating oral vancomycin; otherwise, they were classified as receiving vancomycin monotherapy. The primary outcome was a composite of inpatient all-cause death or colectomy within 60 days after CDI diagnosis. The secondary outcomes were the clinical cure rate, CDI recurrence rate, time to discharge after CDI diagnosis, and duration of ICU admission. Results: In total, 215 patients were included, with 100 (46.5%) receiving combination therapy. There were no significant differences in in-hospital mortality or colectomy between the monotherapy and combination therapy groups (25.2% vs. 26.0%, p = 1.00). Recurrence rates (19.1% vs. 16.8%, p = 0.81), total length of stay (31.0 vs. 23.0 days, p = 0.16), and ICU stay duration (35.0 vs. 32.0 days, p = 0.89) were also similar. However, the clinical cure rate was significantly higher in the monotherapy group than in the combination therapy group (79.1% vs. 65.0%, p = 0.03). Conclusions: Combination therapy with oral vancomycin and IV metronidazole was not associated with improved clinical outcomes in patients with severe CDI. Prospective randomized studies are needed to clarify optimal management strategies for severe CDI. Full article

Background/Objectives: Clostridioides difficile is an anaerobic Gram-positive bacterium and a leading cause of healthcare-associated diarrhea. In this study, C. difficile strains isolated from human patients with diarrhea and companion dogs in South Korea were compared to reveal the potential transmission between different hosts. Methods: A total of 304 C. difficile strains were isolated, including 217 human isolates and 87 dog isolates. The strains were characterized for antimicrobial susceptibility and genotypic features, including antimicrobial resistant genes and toxin genes. In addition, comparative genomic analyses were performed to investigate their genetic relatedness. Results: Although antimicrobial susceptibility test revealed no significant difference in overall resistance, human isolates had higher resistance to moxifloxacin and cefotetan, while dog isolates showed slightly higher resistance to clindamycin and ampicillin. Resistance to vancomycin (3.7%), rifampin (8.3%), and chloramphenicol (0.9%) was observed only in human isolates. Toxin genes (tcdA and tcdB) were found in 57.1% of human isolates and 43.7% of dog isolates, while binary toxin genes (cdtA and cdtB) were detected only in isolates from humans. Multilocus sequence typing (MLST) analysis identified 34 sequence types (STs) in human isolates and 16 in dog isolates. Among them, 15 STs were detected in the isolates from both origins; notably, ST203 and ST42 were the predominant taxa that were equally derived from humans and dogs. Although tcdA and tcdB have not been previously reported in ST203, they were detected in 7 out of 34 ST203 isolates. The whole genomes of 36 representative isolates belonging to ST42 and ST203 were classified according to the STs of the source origin. Conclusions: These results indicate that similar C. difficile strain populations are present in both humans and companion dogs, which is compatible with interspecies dissemination or circulation of shared strain populations, and may also reflect host adaptation. Full article

Background: Prevention of hospital-onset Clostridioides difficile infection (HO-CDI) is a priority for hospitals. In addition to standard infection control measures, some probiotics show promise in reducing HO-CDI incidence. However, prior research has produced mixed results. Methods: Retrospective, observational cohort study of HO-CDI incidence among inpatients treated with or without BioK+ probiotic prophylaxis. BioK+, a probiotic with three Lactobacilli strains, was administered to patients on antibiotics with high risk for HO-CDI. BioK+ was continued for 5 days after antibiotics were discontinued, or the patient was discharged. The primary outcome was HO-CDI incidence. Results: Out of 494 eligible patients on high-risk antibiotics, 343 patients received BioK+ probiotics. No cases of HO-CDI were identified in patients who received BioK+, compared to three cases among patients not on BioK+ (p = 0.028). In the baseline period (1 April 2021–31 March 2022) the HO-CDI incidence density was 5.62 per 10,000 bed-days. In the BioK+ probiotic period (1 April 2022–31 March 2023), the incidence density was 2.22 cases per 10,000 patient days (p = 0.03). Conclusions: When bundled with standard infection control practices, the use of BioK+ probiotics was associated with a statistically significant decreased incidence of HO-CDI among patients prescribed high-risk antibiotics. Full article

Background/Objectives: Goat and sheep farming is an important agro-economic resource in Benin. However, their milk is both underutilized and insufficiently characterized, which limits the development of innovative dairy products and raises concerns about its safety. Against this backdrop, our pioneering study set out to investigate, for the first time in Benin and using an advanced metagenomic approach, the microbial diversity present in goat and sheep raw milk. The aim was to lay the groundwork for safer and more efficient dairy valorization. Methods: To achieve this, metagenomic DNA was extracted from 20 pooled milk samples representing both animal species, followed by shotgun sequencing. Results: Analyses revealed seven dominant phyla: Bacillota (17.44–27.23%), Pseudomonadota (12.39–15.55%), Campylobacterota (3.65–5.29%), Actinomycetota (1.47–6.03%), Spirochaetota (1.14–2.02%), Apicomplexa (0.28–0.50%), and Bacteroidota (0.17–0.22%) in the raw milk of both species. However, their proportions differ. Bacillota, which was the most dominant in both types of milk, was significantly more abundant in goat (27.23 ± 5.33) than in sheep milk (17.44 ± 8.44). In sheep milk, Enterobacteriaceae (11.36 ± 5.79) were the most predominant family, followed by Streptococcaceae (5.57 ± 2.29) and Staphylococcaceae (4.51 ± 3.63). Goat milk, on the other hand, presents a different hierarchy. Streptococcaceae (6.65 ± 2.19) and Staphylococcaceae (6.43 ± 2.33) were the most abundant families, surpassing Enterobacteriaceae (5.33 ± 1.66). The genus Escherichia was the most abundant in sheep milk (6.18 ± 5.33). The genera Staphylococcus (4.50 ± 3.63) and Streptococcus (5.05 ± 1.98) were also present. In contrast, in goat milk, the genera Streptococcus (6.54 ± 2.35) and Staphylococcus (6.42 ± 2.32) were the most dominant, while the average abundance of Escherichia was much lower (1.98 ± 1.28). In terms of species, Sheep milk was dominated by Escherichia coli (6.14 ± 5.28) and Staphylococcus aureus (5.17 ± 2.28) while Klebsiella pneumoniae (2.82 ± 1.72), Streptococcus pneumoniae (1.92 ± 1.36), and Campylobacter coli (1.52 ± 1.27) were also found. In addition to a relatively high abundance of Staphylococcus aureus (6.40 ± 2.45), goat milk was characterized by the presence of Corynebacterium praerotentium (5.32 ± 2.28) and Clostridium perfringens (3.39 ± 2.09). Additional pathogens identified included Clostridioides difficile (1.17–2.00%), Clostridium botulinum (0.27–0.43%), Listeria monocytogenes, Mycobacterium tuberculosis, Helicobacter pylori (0.36–0.62%), Salmonella enterica (0.22–0.26%). As for fungi, Ascomycota were predominant, with the presence of Aspergillus fumigatus, Saccharomyces cerevisiae, Trichophyton mentagrophytes, and Candida auris. Moreover, lactic acid bacteria with technological interest such as Oenococcus oeni (0.60–0.97%), Levilactobacillus namurensis (0.25–0.44%), Lactobacillus agrestimuris, and Lacticaseibacillus rhamnosus were also detected. Conclusions: These findings provide essential insights into the technological potential and health risks associated with these milks, which are key to developing safer and more efficient local dairy value chains. Full article

Avian coccidiosis is an intestinal disease caused by Eimeria spp. infection. A deeper understanding of the interaction between host gut microbiota and the Eimeria parasite is crucial for developing alternative therapies to control avian coccidiosis. Here, we used full-length sequencing of 16S ribosomal RNA amplicons to compare changes in the gut microbiota of chickens infected with Eimeria tenella, Eimeria maxima, and Eimeria necatrix, aiming to identify both species-specific and common alterations in gut microbiota at 4 and 10 days post-infection. The result revealed that infection with all three Eimeria species led to a decrease in the abundance of the microbial genera Limosilactobacillus, Streptococcus, Alistipes, Lactobacillus and Phocaeicola, while the abundance of Bacteroides, Escherichia and Ligilactobacillus increased. Escherichia and Enterococcus were most abundant in the jejunum of the E. necatrix-infected group and in the cecum of the E. tenella-infected group, whereas Megamonas abundance was highest in the E. maxima-infected group. LEfSe analysis showed that infection with all three Eimeria species significantly reduced the abundance of 13 bacterial species, including Acetilactobacillus jinshanensis, Bacteroides ndongoniae, Barnesiella viscericola, Christensenella minuta, Enterocloster clostridioformis, Gemella haemolysans_A, Granulicatella adiacens, Lawsonibacter sp000177015, Limosilactobacillus reuteri, Limosilactobacillus reuteri_D, Limosilactobacillus vaginalis_A, Limosilactobacillus caviae, Limosilactobacillus vaginalis. Infection with E. tenella significantly increased the abundance of five bacterial species, including Bacteroides fragilis, Enterococcus cecorum, Helicobacter pylori, Methylovirgula ligni, and Phocaeicola sp900066445. Infection with E. maxima significantly increased the abundance of seven bacterial species, including Clostridioides difficile, Faecalibacterium prausnitzii, Mediterraneibacter torques, Muribaculum intestinale, Mediterraneibacter massiliensis, Phascolarctobacterium faecium, and Phocaeicola plebeius. Infection with E. necatrix significantly increased the abundance of seven bacterial species, including Alistipes sp900290115, Anaerotignum faecicola, Bacteroides fragilis_A, Escherichia coli, Harryflintia acetispora, Pseudoclostridium thermosuccinogenes, and Tidjanibacter inops_A. The results showed that Eimeria infection causes significant species- and time-dependent changes in the gut microbiota of chickens. These findings enhance our understanding of coccidiosis pathogenesis and offer potential targets for developing probiotics. Full article

Fecal microbiota transplantation (FMT) is a therapeutic strategy designed to modify and enrich the recipient’s gut microbiota by administering processed donor stool, with the goal of treating dysbiosis and related conditions. In 2013, the United States Food and Drug Administration (FDA) approved FMT for recurrent Clostridioides difficile infection (rCDI). Since then, its use has been proposed and investigated in several other disorders characterized by gut microbiota imbalance and altered host–microbiota interactions, including inflammatory bowel disease (IBD), immune checkpoint inhibitor-induced colitis (ICI-iC), and gastrointestinal graft-versus-host disease (GI-GVHD). This review aims to highlight the commonalities among these conditions, the pathophysiological mechanisms that support the rationale for FMT, and emerging evidence from clinical studies. Although available studies are heterogeneous, FMT is a rapidly evolving field of research with promising potential to treat IBD and improve outcomes following oncological immunotherapy and allogenic stem cell transplantation. With further validation, FMT could become an important approach in managing immune-mediated gastrointestinal diseases. Full article

Background: Clostridioides difficile infections (CDIs) are caused by a Gram-positive, spore-forming bacillus and are defined by more than three episodes of watery diarrhoea per day. CDI is a major cause of morbidity and mortality in older adults, particularly over 65 years. Recurrent CDI leads to higher mortality and prolonged, debilitating illness. Case Presentations: This article presents two patients, aged over 80 years old, who developed recurrent CDI causing complicated and prolonged treatment courses. Patient 1 required an extended course of antibiotics for treatment of discitis and a congruent psoas abscess. Patient 2 developed CDI after multiple short courses of antibiotics for urinary tract infections (UTIs) in the context of multiple comorbidities. Both patients experienced three distinct episodes of CDI and were treated in collaboration with microbiology specialists. Following the third episode, both were successfully treated with oral capsule faecal microbiome transplants (FMTs). Their cases highlight the challenge of balancing systemic antibiotic use against CDI risk. Discussions: These cases underscore known risk factors for recurrent CDI, including advanced age and prolonged antibiotic exposure. Recurrence rates in patients over 65 can reach 58%. The British Society of Gastroenterology and Healthcare Infection Society support the use of FMTs in recurrent cases. Environmental decontamination, including terminal cleaning with sporicidal agents, is critical in reducing reinfection in hospital settings. Conclusions: Recurrent CDI in elderly patients reflects a complex interplay between infection control and managing comorbidities. New guidelines suggest that FMTs can significantly reduce morbidity and mortality. These cases emphasise the need for individualised, multidisciplinary care, adherence to guidelines, and further research to improve safe, effective CDI management in older adults. Full article

LD-Transpeptidases (LDTs) are a widely conserved class of peptidoglycan (PG) crosslinking enzymes in bacteria. They are sometimes overlooked as they often act secondary to penicillin binding proteins (PBPs) under standard conditions. However, LDTs are essential in key pathogens such as Clostridioides difficile and are responsible for β-lactam resistance in Mycobacterium tuberculosis and Enterococcus faecium due their low affinity for penicillins and cephalosporins, allowing them to form LD-crosslinks when DD-crosslinking PBPs are inactivated. This role makes LDTs a promising target when developing new treatments for these pathogens. LDTs can perform different enzymatic reactions. Most commonly they reinforce the PG with 3,3-LD-crosslinks or, in a few cases, 1,3-LD-crosslinks, during stationary phase or stress responses. Some LDTs also incorporate endogenous and exogenous non-canonical D-amino acids into the PG. In many Gram-negative bacteria, specialised LDTs tether lipoproteins or outer membrane proteins (OMPs) to the PG to maintain cell envelope integrity; in some cases this regulates virulence factors. Specialised LDTs have also been implied to have roles in polar growth, toxin secretion, and symbiotic colonisation. Recent discoveries include novel subgroups of the major YkuD family and the identification of the VanW family; this has opened new research directions surrounding LDTs. We aim to understand LDTs and their roles to expand our knowledge of PG synthesis and modification and how these enzymes can be targeted for antibiotic treatment. Full article

We previously reported that two bile acid (BA) analogs, CamSA and CA-Quin, demonstrate potent anti-germination activity against Clostridioides difficile (C. difficile) spores, protecting rodents from C. difficile infections. Here, we further evaluated the impact of these analogs on the hepatic transcriptome and BA homeostasis in vivo by focusing BA profiles on the liver, feces, and chyme as well as the hepatic transcriptome after a 7-day treatment. The two compounds demonstrated similar impact on BA profiles among the three samples, with significantly increased BA excretion in feces. This change is aligned with significantly altered expression of genes involved in BA homeostasis in both liver and gut tissues. Also, both compounds increased levels of deconjugated BAs in the feces, possibly suggesting increased activity of gut microbiota. Fecal levels of anti-C. difficile germination chenodeoxycholic acid and pro-germination taurocholic acid are significantly increased and decreased by the treatments, respectively. The hepatic transcriptome showed limited difference in gene expression between the three groups, suggesting a minimal adverse impact of the two compounds on liver function. Overall, our study suggests that in vivo CamSA and CA-Quin treatment demonstrated safe and significantly altered BA homeostasis that inhibits C. difficle germination. Full article

Introduction: Patients with inflammatory bowel disease (IBD) have an increased risk of Clostridioides difficile infection (CDI). While antibiotic exposure has been considered the most prominent risk factor for CDI, proton pump inhibitor (PPI) use is another potential risk factor. Methods: From January 2017 to April 2021, we examined the University of Missouri’s IBD patients’ medical records. Laboratory-confirmed CDI diagnosis was the main outcome of interest. The usage of PPIs was the exposure of interest. The odds ratio between CDI risk in PPI users and non-users was estimated using logistic regression models. We investigated CDI risk with PPI use duration using stratified analysis. Results: Overall prevalence of CDI was 9%. 358 patients (42%) reported using PPI, with an average duration of ~30 months, with a range of 0.1 to 255. PPI use was associated with a higher risk of CDI in both the unadjusted (OR = 1.58 [0.98–2.53]; p = 0.06) and adjusted models (9.23 [2.11–40.34]; p = 0.003). Only those who used PPIs for less than 30 months had a greater risk of CDI in the stratified analysis (OR = 2.10 [1.16–3.38], p = 0.014). Long-term use (≥30 months) did not increase the incidence of CDI (OR = 0.74 [0.29, 1.83]; p = 0.510). Discussion: This is the single largest study of the US general IBD population to evaluate the association between PPI use and risk of developing CDI. PPI therapy was linked to a significant elevation in CDI risk, restricted to PPI use for up to 30 months. Histamine-2 receptor antagonists (H2RAs) did not increase the risk of CDI. Full article

Background/Objectives: The rising global prevalence of inflammatory bowel disease (IBD), encompassing Crohn’s disease and ulcerative colitis, has resulted in an increase in the number of affected patients requiring dental care. The heightened risk of Clostridioides difficile infection (CDI) in IBD patients, particularly when exposed to commonly used dental antibiotics, is attributable to their altered gut microbiota and frequent immunosuppressive therapy. The objective of this review is to evaluate current antibiotic strategies for dental management in IBD and to identify safe and effective alternatives that minimise CDI risk. Methods: A narrative review was conducted in accordance with the SANRA guidelines. A comprehensive analysis of literature sourced from PubMed, Embase, Scopus, and Google Scholar was conducted. Results: The available evidence suggests that first- and second-line dental antibiotics—amoxicillin, ampicillin, and clindamycin—carry the highest risk of CDI. In contrast, metronidazole, which exhibits a comparable antimicrobial spectrum, has been shown to possess significantly reduced CDI potential and minimal disruption of gut microbiota. The utilisation of emerging local delivery systems, such as platelet-rich fibrin (PRF), has the potential to further reduce systemic antibiotic exposure. The adjunctive use of probiotics, prebiotics and synbiotics has been demonstrated to have the capacity to maintain microbial balance during therapy. Conclusions: Tailored, microbiome-conscious antibiotic strategies are essential in dental management of IBD patients. Further clinical research is needed to develop evidence-based guidelines and validate promising adjunctive approaches. Full article

Background: Healthcare-associated infections (HAIs) are a significant public health problem, having a decisive impact on the prognosis of patients hospitalized with COVID-19. In Romania, the absence of a uniform reporting system and the lack of epidemiological data comparable to European standards limit the real assessment of their incidence and consequences. Methods: In this context, the present study aimed to conduct an integrated analysis of the clinical, epidemiological, and microbiological factors involved in the mortality of patients with COVID-19 and HAIs in a county located in southeastern Romania. This research was based on a retrospective observational study that included 295 patients with a confirmed diagnosis of COVID-19 and at least one documented HAI between January 2020 and December 2022. Data were extracted from standardized reporting forms, and statistical analyses included tests (Fisher’s exact test, Mann–Whitney U), ROC curves, Kaplan–Meier survival analysis, and Cox proportional hazard regression. Results: The analysis revealed a mortality rate of 32.5%, significantly associated with advanced age, gastrointestinal surgery, and respiratory infections. Clostridioides difficile was the predominant pathogen (84.1%), and the threshold of ≥63.5 years demonstrated predictive value for mortality. In multivariate models, age greater than 63 years and gastrointestinal surgery were confirmed as independent predictors of death. Conclusions: The findings highlight the substantial impact of HAIs on the clinical progression of COVID-19 patients, underscoring the need for comprehensive systemic interventions, including enhanced prevention and control strategies, prudent antimicrobial therapy, and standardized epidemiological monitoring. Implementing these measures is crucial to mitigating HAIs’ effects and improving patient outcomes in similar situations. Full article

Recurrent Clostridioides difficile infection (rCDI) remains a major therapeutic challenge. Although faecal microbiota transplantation (FMT) is highly effective and thought to restore microbial composition and metabolic function, the mechanisms underlying its success are not fully understood. In particular, the contribution of non-bacterial components such as soluble metabolites remains unclear. Therefore, further investigation is needed to identify the mechanistic drivers of FMT efficacy and clarify how non-bacterial factors contribute to therapeutic outcomes. Here, we applied untargeted three-dimensional Orbitrap secondary ion mass spectrometry (3D OrbiSIMS) to profile faecal metabolic reprogramming in rCDI patients pre- and post-FMT, alongside C. difficile cultures exposed to sterile faecal filtrates. FMT induced extensive metabolic shifts, restoring glyoxylate/dicarboxylate and glycerophosphoinositol pathways and normalising disrupted bile acid and amino acid profiles. Faecal filtrate exposure caused strain-specific metabolic disruption in C. difficile, depleting proline, fumarate and succinate while enriching tryptophan. While multiple metabolite classes were profiled, the most significant functional changes were observed in lipids. Lipidomics identified >3.8-fold enrichment of phosphatidylinositol (PI) species, which localised to bacterial membranes and conferred cytoprotection against C. difficile toxins and other epithelial insults. Spatial metabolomics imaging revealed, for the first time, metabolite compartmentalisation within C. difficile, with proline and succinate broadly distributed across the cell surface and fumarate confined to distinct microdomains, highlighting functional heterogeneity in pathogen metabolism. Collectively, these findings demonstrate that soluble metabolites within faecal filtrates mediate pathogen suppression and epithelial barrier protection, establishing metabolite-driven mechanisms underlying FMT efficacy and identifying PI lipids as candidate post-biotic therapeutics for rCDI. Full article

Intra-abdominal infections (IAIs) remain among the most challenging problems in surgical clinical practice. They range from uncomplicated appendicitis to life-threatening peritonitis, demanding rapid diagnosis, timely source control, and appropriate antibiotic therapy. Antibiotics are crucial to manage patients with complicated IAIs. Antibiotics should always be prescribed appropriately, ensuring the correct spectrum, timing, duration, and dosage. Appropriate prescribing within hospitals enhances treatment success and patient safety, while also reducing the risk of opportunistic infections such as Clostridioides difficile and lowering the likelihood of selecting resistant pathogens. Over recent decades, antimicrobial resistance has escalated into a worldwide public health threat. The rapid rise in multidrug-resistant organisms, especially Gram-negative bacteria, has created a pressing global concern. The objective of this narrative review is to describe (a) when antibiotics should be used in patients with IAIs; (b) which antibiotics should be selected in patients with IAIs; (c) how they should be managed in patients with IAIs; and (d) how long they should be administered in patients with IAIs. Full article