Search Results (547)

Background/Objectives: Rabbit farming in Romania is increasingly important for providing high-quality meat, yet productivity is frequently threatened by enteric diseases, particularly in young animals. Among bacterial etiologies, Clostridioides difficile (C. difficile) has emerged as a significant gastrointestinal pathogen, with findings suggestive of systemic dissemination and public health implications. This study aimed to investigate a fatal case of C. difficile infection in a farmed rabbit and to characterize the pathogen’s microbiological, toxigenic, and antimicrobial profile. Methods: An 11-month-old male German Giant Spotted rabbit presenting acute diarrhea, anorexia, and rapid deterioration after unsupervised administration of enrofloxacin and sulfaquinoxaline was submitted postmortem. Necropsy was performed, and samples from cecum, colon, liver, spleen, mesenteric lymph nodes, lungs, and femoral bone marrow were collected. Microbiological analysis included selective culture on CCFA medium, ELISA for toxin A and B detection, MALDI-TOF MS identification, PCR confirmation, and antimicrobial susceptibility testing with the VITEK 2 system. Histopathological examination was conducted on intestinal and parenchymal tissues. Results: Necropsy revealed severe congestion and necrosis of the cecal and colonic mucosa, hepatomegaly, splenic congestion, and petechial hemorrhages. C. difficile was isolated from intestinal sites, confirmed as toxigenic by ELISA and PCR. Histopathology showed necrotizing colitis with epithelial desquamation, fibrin deposition, and heterophilic infiltration. The strain exhibited resistance to clindamycin, ampicillin, and tetracycline, with susceptibility to vancomycin, linezolid, and tigecycline. Conclusions: This case demonstrates that C. difficile can cause severe disease in rabbits, particularly following antimicrobial-induced dysbiosis. The findings underscore the importance of prudent antibiotic use, monitoring of toxigenic strains in rabbit populations, and implementation of preventive strategies to mitigate health risks in both animals and potentially humans. Full article

Fecal microbiota transplantation (FMT) has emerged as a microbiota-directed therapeutic strategy with established efficacy in recurrent Clostridioides difficile infection (rCDI) and expanding investigational applications in pediatric medicine. Given the central role of the gut microbiota in immune maturation, metabolic homeostasis, and colonization resistance—particularly during early life—restoring microbial diversity represents a biologically plausible intervention for disorders characterized by dysbiosis. This narrative review critically examines current evidence regarding the indications, efficacy, safety, and practical considerations of FMT in pediatric populations. A structured literature search was conducted across PubMed/MEDLINE, Scopus, Web of Science, and the Cochrane Library from inception through December 2025. Eligible studies included randomized controlled trials, observational studies, systematic reviews, meta-analyses, and guideline statements addressing pediatric FMT. RCDI remains the primary and best-supported indication, with reported success rates exceeding 80% after a single FMT and approaching 90% with repeat procedures. Evidence for other indications—including inflammatory bowel disease (IBD), malignancy-associated CDI, transplant recipients, multidrug-resistant organism (MDRO) decolonization, neurodevelopmental disorders, allergic colitis, and functional gastrointestinal disorders—remains limited and heterogeneous. While short-term remission rates in pediatric ulcerative colitis appear promising, data derive largely from small, non-standardized studies, and long-term efficacy and safety remain insufficiently defined. FMT usage in immunocompromised children, particularly oncology and transplant populations, is controversial due to limited pediatric-specific evidence and theoretical risks. Substantial variability in donor screening, preparation methods, dosing, and administration routes further limits standardization. Currently, FMT should be considered established therapy for pediatric rCDI, whereas other applications require well-designed, multicenter trials with long-term follow-up to clarify safety and clinical benefit. Full article

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a highly prevalent liver-centred manifestation of systemic metabolic dysfunction. The gut–liver axis provides a biologically credible therapeutic rationale because intestinal dysbiosis, impaired barrier integrity, microbial metabolites, bile acid signalling, short-chain fatty acids, and trimethylamine N-oxide may influence hepatic steatosis, inflammation, and fibrogenesis. This narrative review critically evaluates dietary patterns, prebiotics, probiotics, synbiotics, postbiotics, and fecal microbiota transplantation (FMT) as microbiome-directed strategies in MASLD. The comparative framework prioritises disease-specific human evidence, clinically meaningful endpoints, trial duration and sample size, reproducibility, safety, and feasibility. Dietary optimisation remains the most clinically grounded intervention, whereas probiotics and synbiotics show modest and heterogeneous signals on biochemical or metabolic surrogate endpoints. Prebiotics are mechanistically coherent but supported by limited liver-centred trials. Postbiotics and microbiome-mediated bioactives remain early-stage and require stricter definitional boundaries. FMT is investigational and should not be extrapolated from its established role in recurrent Clostridioides difficile infection. Most available evidence across all intervention categories relies principally on surrogate endpoints—including aminotransferases, insulin resistance indices, lipid parameters, and microbiome compositional shifts—rather than on validated liver-centred outcomes such as histological improvement or quantitative liver fat assessment; this constrains the strength of conclusions that can currently be drawn. Across all categories, microbiome modulation does not by itself establish liver disease modification, and no microbiome-targeted nutritional intervention has yet demonstrated histological benefit in MASLD. Future trials in this field should prioritise validated hepatic endpoints, phenotype-stratified patient enrolment, adequate follow-up duration, and direct comparisons between intervention categories to determine which microbiome-directed strategies, if any, deliver measurable and reproducible hepatic benefit beyond surrogate markers. Full article

Background/Objectives: Clostridioides difficile infection (CDI) is the leading cause of colitis and hospital-acquired diarrhea. Patients with Chronic Obstructive Pulmonary Disease (COPD) frequently have infectious exacerbations requiring treatment with antibiotics, which may be predisposing them to CDI. This study examines the prevalence and in-hospital outcomes of CDI in patients with COPD. Methods: Data for hospitalized patients with CDI was extracted from the National Inpatient Sample database for the years 2016 through 2020. Baseline risk factors were identified using the International Classification of Diseases codes. Patients were stratified into two groups: with COPD and without COPD. The primary outcome was in-hospital mortality. The secondary outcomes were septic shock, hypovolemic shock, AKI, cardiac arrest, need for intensive care unit (ICU) level of care and length of stay. Statistical analyses were conducted using SPSS. Results: 290,172 patients were included in this study. Patients with COPD had more comorbidities overall and higher in-hospital mortality rates compared to patients without COPD (7.7% vs. 5.9%, p < 0.001). On multivariate logistic regression analysis, patients with CDI and COPD had higher risk of in-hospital mortality (OR = 1.346, p < 0.001), septic shock (OR = 1.289, p < 0.001), hypovolemic shock (OR = 1.184, p < 0.001), cardiac arrest (OR = 1.362, p < 0.001) and required more ICU level of care. Conclusions: Patients with COPD experience frequent exacerbations, often requiring hospitalizations and broad-spectrum antibiotics, steroids, proton pump inhibitors and antacids. These factors contribute to the higher prevalence of CDI in this patient population. Patients with CDI and COPD are also more likely to require ICU level of care, shedding the light on the significant burden of CDI, long hospital stays and substantial hospital charges. Recognizing mortality outcomes is essential to guide patient-specific therapies and highlights the need for closer monitoring and targeted management of CDI in patients with COPD. Full article

Background: The gut microbiota constitutes a metabolically active “second genome” that profoundly modulates drug pharmacokinetics, pharmacodynamics, and adverse reaction profiles. Beyond antibiotics, widely prescribed non-antibiotic pharmacotherapies exert clinically relevant pharmacomicrobiomic effects with implications for therapeutic optimisation and pharmacovigilance. Methods: This narrative review, conducted following PRISMA 2020 reporting principles (without PROSPERO pre-registration), searched PubMed/MEDLINE, Scopus, Web of Science, and Cochrane Library (January 2015–December 2024) for evidence on proton pump inhibitors (PPIs), metformin, NSAIDs, statins, SGLT2 inhibitors, and oral iron. Evidence tables included clinical human studies with molecular microbiota characterisation (16S rRNA or shotgun metagenomics), ≥20 participants, and a control arm; preclinical data informed mechanistic synthesis. Results: Of 68 eligible studies, 20 met criteria for the evidence tables. PPIs significantly remodelled gut microbiota composition with enrichment of oral-origin taxa (“oralisation of the gut”), associating with Clostridioides difficile infection and SIBO. Metformin enriched Akkermansia muciniphila and butyrate producers, contributing causally to glycaemic efficacy. NSAIDs compromised barrier integrity, with synergistic dysbiosis under PPI co-prescription. Statins correlated with reduced prevalence of the dysbiotic Bact2 enterotype. SGLT2 inhibitor data remained discordant. Oral iron consistently enriched Enterobacteriaceae at the expense of beneficial commensals. Full article

Background: Amikacin remains a key agent in the treatment of severe and complicated infections due to its bactericidal activity and low risk of Clostridioides difficile infection. It retains activity against most aerobic Gram-negative bacteria, including multidrug-resistant Enterobacterales and Pseudomonas. However, its use is limited by nephrotoxicity and ototoxicity. Methods: This narrative review evaluates clinical indications, pharmacokinetic and pharmacodynamic properties, dosing strategies, therapeutic drug monitoring (TDM), and safety profile of amikacin in adult patients based on 56 selected publications. A total of 24 articles were identified through database searches (PubMed and Embase), complemented by 32 additional sources to provide clinical and pharmacological context. Results: Available evidence demonstrates considerable uncertainty regarding the comparative effectiveness of different monitoring strategies. Lower trough concentrations are generally associated with reduced nephrotoxicity; however, an optimal safety threshold has not been clearly established. Guideline-recommended targets vary substantially and are supported by low-quality evidence. Amikacin pharmacokinetics, tissue penetration and toxicity are influenced by patient-specific factors, including critical illness, renal function variability, and concomitant nephrotoxic therapy, particularly vancomycin. Ototoxicity remains an additional clinically relevant concern. Conclusions: Current evidence suggests that uniform dosing and monitoring paradigms are insufficient. Patient-tailored strategies integrating TDM and mitigation of modifiable risk factors are required. Prospective studies comparing monitoring regimens are needed to optimize the safe clinical use of amikacin and inform future guideline development. Full article

The gut microbiome, often termed the human “second genome”, profoundly influences host physiology through metabolic interactions, immune modulation, and gut–brain axis signaling. Dysbiosis is implicated in the pathogenesis of obesity, inflammatory bowel disease (IBD), malignancies, and neuropsychiatric disorders. However, traditional gut microbiota interventions, such as probiotic supplementation and fecal microbiota transplantation (FMT), still exhibit significant limitations in precision therapeutics. Probiotic intervention fails to achieve precise regulation at the strain or genetic level, and although FMT demonstrates definitive efficacy against recurrent Clostridioides difficile infection (rCDI), its therapeutic outcomes and safety profiles show marked interindividual variability in ulcerative colitis (UC), metabolic syndrome, and other diseases, with insufficient treatment specificity to meet the practical demands of clinical precision intervention. Recent advancements in genome editing technologies, particularly Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)–CRISPR-associated (Cas) proteins systems and base editors, have enabled targeted functional manipulation of specific gut commensals and optimization of community architectures. These engineered strategies, combined with sophisticated delivery systems, demonstrate substantial potential in disease treatment, diagnostic monitoring, and immune modulation. This review systematically examines core editing methodologies, innovative delivery platforms, and targeted design strategies, elucidating their applications in metabolic disorders, IBD, cancer immunotherapy, and neuropsychiatric conditions. We critically analyze current technical bottlenecks and biosafety concerns while prospecting future directions, including in situ editing, artificial intelligence (AI)-driven design, and personalized engineering. Collectively, these insights aim to facilitate the clinical translation of gut microbiome engineering from bench to bedside. Full article

Background: Clostridioides difficile is classified within the first 18 threats for antimicrobial resistance and is the leading cause of hospital-acquired enteric infection. Community-associated cases have notably increased in recent decades, highlighting that accurate and up-to-date statistics characterizing the epidemiology of C. difficile infection (CDI) are critical. Methods: We conducted a retrospective (2019–2023) case-control study evaluating the prevalence of CDI in 249 stool samples from hospitalized patients in the sanitary region III of Buenos Aires, Argentina. The presence of C. difficile was detected by combining EIA, PCR, and toxigenic culture via a diagnostic algorithm. Clinical and demographic data from patients were analyzed to identify CDI-associated risk factors. We also conducted a systematic review and a meta-analysis contrasting our results with 38 studies selected from different countries. Results: One in five patients presented C. difficile as the etiological agent of diarrhea. Eighty percent of the CDI+ cases carried toxigenic strains, with a third of cases associated with community environments. Age ≥ 69 years, previous use of antibiotics, previous hospitalization, and previous episodes of CDI emerged as predisposing factors for CDI in our study cohort. In an exploratory evaluation of clinical data, CDI+ patients showed higher leukocytes and platelets counts, a decreased basophil count, and increased urea concentration. At the global level, the meta-analysis reinforced advanced age, previous consumption of antibiotics, previous consumption of proton pump inhibitors, previous hospitalization, and previous CDI as risk factors for CDI. Conclusions: These results emphasize the importance of continued epidemiological surveillance of CDI. Our findings confirm previously described risk factors, both in our cohort and at the global level. Exploratory alterations in laboratory parameters were observed, although their clinical relevance and specificity require further investigation. Full article

Background and Objectives: Healthcare-associated infections (HAIs) remain a major cause of morbidity and mortality among hospitalized patients. During the COVID-19 pandemic, SARS-CoV-2 infection emerged as a major contributor to HAIs, alongside Clostridioides difficile infection (CDI) and other bacterial infections. This study aimed to evaluate the clinical characteristics and outcomes of HAIs in surgical departments and to identify factors associated with in-hospital mortality. Materials and Methods: We conducted a retrospective observational study including 170 patients with documented HAIs admitted between July 2018 and June 2022 in surgical departments of a county emergency hospital. Patients were categorized into SARS-CoV-2 infection (n = 85), CDI (n = 73), and other bacterial infections (n = 12), the latter being included for descriptive purposes only due to limited sample size. Clinical variables, comorbidities, prior antibiotic exposure, length of hospital stay, and in-hospital mortality were analyzed. Survival analysis and logistic regression were performed to identify predictors of mortality. Results: SARS-CoV-2 infection represented the largest subgroup, followed by CDI. Overall, in-hospital mortality was 15.9%, with comparable rates between SARS-CoV-2 infection (17.6%) and CDI (16.4%), while no deaths were observed in the small subgroup of other bacterial infections. CDI patients had a significantly higher burden of comorbidities (p = 0.004). Kaplan–Meier analysis did not show a statistically significant difference in survival between SARS-CoV-2 and CDI groups (log-rank p = 0.28). In univariate analysis, acute respiratory failure (OR ≈ 13.5, p < 0.001), chronic kidney disease (OR ≈ 4.4, p = 0.018), and number of comorbidities (p = 0.019) were associated with mortality, but none remained significant in multivariable analysis. Conclusions: In-hospital mortality was similar between SARS-CoV-2 infection and CDI, highlighting the persistent clinical impact of CDI in hospitalized patients. Comorbidity burden and acute complications, particularly respiratory failure, were key determinants of mortality. These findings highlight the persistent clinical impact of CDI and the role of comorbidity burden and acute complications, particularly respiratory failure, in shaping in-hospital mortality. The absence of independent predictors in multivariable analysis should be interpreted cautiously given the limited sample size. Full article

Far-UVC 222 nm is a promising adjunctive disinfection technology for occupied healthcare environments, though antimicrobial efficacy varies significantly across pathogen types due to fundamental differences in microbial biology. This review synthesizes evidence on microbiological determinants of far-UVC resistance, examining cell envelope structure, biofilm formation, DNA repair capacity, and antioxidant defenses. A clear resistance hierarchy emerges. Enveloped viruses lacking enzymatic repair systems are highly vulnerable, requiring fluences below 3 mJ/cm². Gram-negative bacteria are readily inactivated through membrane disruption and reactive oxygen species accumulation. Gram-positive bacteria demonstrate higher resistance via thick peptidoglycan barriers, DNA repair mechanisms, and redundant antioxidant systems. Biofilm-embedded cells show 10–1000-fold increased tolerance due to protective extracellular matrices, stress-response gene upregulation, and microenvironmental heterogeneity. Clostridioides difficile spores exhibit extreme resistance through multilaminar protective coats and metabolic dormancy, requiring impractical doses exceeding 1000 mJ/cm². Field studies in real-world polymicrobial biofilm communities demonstrate substantially lower efficacy than laboratory predictions, typically achieving only 55–81% bioburden reductions. Understanding these pathogen-specific resistance mechanisms is essential for the rational deployment of far-UVC as an adjunctive infection prevention intervention in healthcare settings. Full article

Background/Objectives: Hand hygiene is a cornerstone of infection prevention, yet the extent to which multimodal institutional hand hygiene interventions translate into measurable reductions in healthcare-associated infections (HAIs) remains uncertain. This systematic review aimed to evaluate the association between hospital-wide or multi-ward multimodal hand hygiene interventions and clinical HAI outcomes in acute care hospitals. Methods: A structured literature search was conducted in PubMed, Scopus, Embase, and Google Scholar using a combination of Medical Subject Headings (MeSH) and free-text terms related to hand hygiene, healthcare-associated infections, hospital settings, and intervention strategies. Eligible studies were quasi-experimental designs, including before–after, controlled before–after, and interrupted time-series studies, evaluating multimodal hand hygiene interventions implemented at hospital-wide or multi-ward level and reporting clinical HAI outcomes. Two reviewers independently assessed risk of bias using the ROBINS-I tool, and certainty of evidence across major outcome categories was summarized using GRADE. Results: twelve studies met the inclusion criteria. Overall, multimodal hand hygiene interventions were generally associated with favorable directional trends in clinical outcomes. Reductions were most consistent for broader institutional HAI measures and some device-associated infections, particularly central line-associated bloodstream infections. In contrast, organism-specific outcomes, including methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus, and Clostridioides difficile, were more heterogeneous across studies and settings. All included studies were judged to be at serious or critical overall risk of bias, primarily because of confounding, lack of contemporaneous controls, co-interventions, and phased implementation. Conclusions: Multimodal hand hygiene programs in acute care hospitals may be associated with improvement in selected clinically relevant HAI outcomes, particularly at the institutional level. However, the overall certainty of evidence remains low to very low, and the strength of inference is limited by the non-randomized nature of the available studies and the difficulty of isolating the independent effect of hand hygiene within complex infection-prevention strategies. Full article

Background/Objectives: Antimicrobial agents play an important role in the pathogenesis and treatment of Clostridioides (C.) difficile infections. C. difficile isolates have shown different genotypic and phenotypic resistance patterns and could serve as antimicrobial resistance reservoirs. Methods: To gain insight into accordance and potential disagreements between genotypic and phenotypic antimicrobial resistances in C. difficile, we compared the genotypic and phenotypic resistance patterns of 108 bovine C. difficile isolates collected in Germany between 2010 and 2012. These isolates represent a collection of different ribotypes (RT) and originated from different husbandries in Germany. Whole genome sequencing of all isolates was performed with Illumina^® Miseq™, and sequences were screened for antimicrobial resistance determinants. For phenotypic antimicrobial susceptibility testing, the agar dilution procedure according to the CLSI document M11 was used. Minimal inhibitory concentration values were determined for penicillin, meropenem, tetracycline, moxifloxacin, vancomycin, metronidazole, erythromycin and clindamycin. Results: Various phenotypic and genotypic antimicrobial resistances were found in the isolates examined that belonged to different ribotype/sequence type (ST) lineages, even if these originated from the same source and geographical region (bovine isolates from Germany). Agreement between phenotypic and genotypic resistance was seen for most antimicrobial agents tested. A total of 92% (83/90) of the investigated ST11 isolates showed phenotypic resistance or were classified as non-wild type to at least one of the antimicrobials tetracycline, moxifloxacin, erythromycin and clindamycin. Conclusions: The results of this comparison contribute to a better understanding of antimicrobial resistance in C. difficile by relating phenotypic susceptibility patterns to genomic resistance determinants. Full article

Background: Due to dysbiosis, intestinal barrier dysfunction, and immunosuppressive therapy, pediatric inflammatory bowel disease (PIBD) patients are more susceptible to infections. However, data on bacterial gastrointestinal (GI) infections in this population are scarce, and no guidelines explicitly address immunosuppressive therapy management during such infections. This single-center study aims to address these knowledge gaps. Methods: A retrospective study of bacterial GI infections was conducted in PIBD patients aged 0–18 years, treated between 2011 and 2021 at the Department of Pediatrics and Adolescent Medicine, Medical University of Graz. Data to assess the study endpoints were extracted from the hospital information system. Results: A total of 139 PIBD patients were screened for bacterial GI infections. The mean follow-up time was 49 months (standard deviation ±33) and the total follow-up time amounted to approximately 473 person-years. Fourteen patients developed infections, with three experiencing them twice, resulting in 17 cases of infection. Most infections were caused by opportunistic bacteria, and 10 infections were treated with antibiotics (11 antibiotic prescriptions in total). At infection onset, 12 patients were on (combined) immunosuppressive therapy, including corticosteroids (3 patients), immunomodulators (9 patients), and/or biologics (3 patients). Six infections required escalation of immunosuppressive therapy due to increased PIBD activity. Hospitalization was required in five cases, and one Clostridioides difficile infection progressed to sepsis, necessitating intensive care unit admission. This corresponds to an incidence of three infections (95% confidence interval 1.75–4.80) and 0.2 severe infections per 100 person-years (95% confidence interval 0.01–1.11). Conclusions: The incidence of bacterial GI infections was 3 per 100 person-years (95% confidence interval: 1.75–4.80), with most cases being clinically mild. Clostridioides difficile was the most common pathogen. Immunosuppressive therapy was generally continued or intensified, when necessary, while antibiotic therapy was administered as indicated. Full article

C. difficile is a major cause of antibiotic-associated diarrhea and hospital-acquired infections, although increasing community-acquired cases suggest alternative transmission routes. Livestock, particularly pigs, have been proposed as potential reservoirs. This study aimed to investigate the presence of zoonotic ribotypes in piglets from Tenerife (Spain) and to assess their pathogenic potential by detecting toxin genes. A total of 140 samples were analyzed, including 58 fecal samples from slaughtered piglets (4–8 weeks old) and 82 rectal swabs from piglets aged 2–25 days. Samples were cultured, identified by MALDI-TOF MS, and characterized by PCR ribotyping and toxin gene detection. No isolates were obtained from fecal samples collected at slaughter, whereas 14 (17%) rectal swabs were positive. Colonization was strongly age-dependent, with the highest prevalence at 2 days of age (100%), decreasing by day 9 (10.7%), and absent after 21 days (p < 0.05). All isolates were ribotype RT033 with a tcdA⁺/tcdB⁻/cdtA⁺/cdtB⁺ profile. The exclusive detection of RT033, a clade V lineage linked to animal reservoirs and occasional human infections, suggests a potential zoonotic risk, especially for farm workers. These findings reinforce the need for integrated C. difficile surveillance under a One Health framework to monitor emerging ribotypes and their role in community-acquired infections. Full article

Treatment guidelines for Clostridioides difficile infection (CDI) have been published by infectious disease and gastroenterology professional societies; however, adherence in clinical practice remains poorly characterized, particularly for recurrent disease. We conducted a retrospective chart review of 100 patients with CDI (350 episodes: 115 initial, 235 recurrent) referred to a tertiary complicated CDI clinic between 2018 and 2023. Guideline adherence was assessed by comparing treatment with IDSA/SHEA and ACG recommendations, and referring diagnoses were compared with final specialist diagnoses. Guideline adherence was significantly higher in initial compared to recurrent episodes (70.4% vs. 41.3%, p < 0.0001). Among guideline non-adherent recurrent episodes, 51.3% used standard antibiotic regimens inappropriate for the recurrence tier. Specialist review reclassified 12.0% of episodes, with colonization increasing from 2.6% to 8.9%. Misdiagnosed colonization cases had a 6.2-fold higher treatment failure rate than confirmed CDI (39.3% vs. 6.3%, p < 0.0001). Guideline non-adherence showed a non-significant trend toward treatment failure (10.0% vs. 6.7%, p = 0.31). Guideline adherence for recurrent CDI is inadequate in pre-referral settings, and diagnostic misclassification is common. Early specialist involvement may improve both diagnostic accuracy and treatment appropriateness for patients with recurrent CDI. Full article