Search Results (28,216)

Background and clinical significance:Pasteurella spp. are Gram-negative coccobacilli, aerobic facultatively anaerobic, belonging to the Pasteurellaceae family. In humans, they are known to cause zoonotic diseases, which usually develop after dog or cat bites, licks or scratches. Case presentation: We present the case of a 61-year-old patient, with cardiovascular comorbidities, who presented to the Orthopedics Department, 38 days after knee replacement surgery, with recurrence of pain on walking, an antalgic gait with auxiliary support, and local signs of inflammation at the level of the left knee joint. The patient admitted to owning a dog who accidentally licked the post-surgical wound. The symptoms were suggestive of a post-surgical wound infection with extension to the periprosthetic area. A purulent discharge was collected from the wound during surgical debridement and sent to the microbiological laboratory for diagnosis, where Pasteurella canis was identified using MALDI-TOF MS. Antibiotic susceptibility testing (AST) was performed according to the EUCAST guidelines and empiric antibiotic treatment was started with Cefuroxime. During his future admissions to the Orthopedics and Infectious Diseases departments, two more samples were collected, in which Pasteurella canis was isolated, along with Klebsiella oxytoca (second sample), and Klebsiella oxytoca and Pseudomonas aeruginosa (third sample). Patient evolution was favorable due to the debridement of the wound and combined antibiotic treatment, with Ceftazidime and Gentamicin. Conclusions: Infections with Pasteurella canis are rare but slowly increasing due to more and more humans owning pets. The present case underlines the importance of interdisciplinary collaborations when rare pathogens are identified. Full article

Drug-resistant Klebsiella pneumoniae is a serious clinical problem, and bacteriophages are being investigated again as antibacterial agents. This study describes the phenotypic characterization and a preliminary in vivo evaluation of vB_Kpn_NIIPB-V0006, a bacteriophage isolated locally on a drug-resistant clinical K. pneumoniae strain. The genome of the phage was not sequenced. It has therefore not been screened for lysogeny-associated, toxin, virulence or antimicrobial resistance genes, and the results below describe what the phage does, not whether it is suitable for therapy. We assessed plaque morphology, specific lytic activity, titer, host range on a limited non-target panel, particle morphology, adsorption, one-step growth, chloroform exposure, the frequency of phage-resistant host variants, endotoxin reduction, short-term safety in mice and antibacterial effect in guinea pigs. The phage lysed the target strain, with an Appelman activity of 10⁻⁸ and a titer of 1.7 × 10¹¹ PFU/mL. Processing with 1-octanol lowered endotoxin content from 1200 to 12 EU/mL and preserved 80% of infective activity. Mice given the preparation intraperitoneally showed no mortality and no visible acute toxicity over 14 days. In guinea pigs with systemic K. pneumoniae infection, survival was the primary outcome: 0.5 mL three times daily gave 6/6 survivors against 1/6 in untreated controls (p = 0.015). Splenic bacterial burden, a secondary outcome, was also lower in that group (2.64 against 4.41 log₁₀ CFU/g). Two features of the design bias this second comparison in favor of treatment, since survivors and non-survivors were sampled at different times, and phage being carried over into the plating step is likely to have lowered colony counts. The 1.77 log₁₀ difference should therefore be read as an upper bound. The phage merits further study, but whole-genome sequencing, confirmation of the host species, host-range testing against diverse clinical isolates and a controlled comparison with antibiotic treatment are all needed before any therapeutic claim can be made. Full article

As a broad-spectrum antimicrobial agent, quinolones are widely used in animal husbandry. When applied to animals, 60–90% of antibiotics will be excreted in the form of the original drug or metabolites by animal excretion, contaminated soil, surface water, and ground water, affecting the normal life activities of plants, animals and microorganisms, and ultimately affecting human health through the food chain. Since some quinolone antibiotics are synthetic antibacterial agents and are used in large quantities, this paper discusses the technical routes, formulation processes, and results of three typical quinolone antibiotics. According to the existing technical guidelines in China, the optimal fitting model was used to derive the short-term water-quality criteria (SWQC) of norfloxacin as 0.019 mg/L and the long-term water-quality criteria (LWQC) as 0.0008 mg/L; the SWQC of enrofloxacin as 8.685 mg/L and the LWQC as 0.0625 mg/L; and the SWQC of ciprofloxacin as 0.5 mg/L and the LWQC as 0.106 mg/L. Full article

Antibiotics and antibiotic resistance genes (ARGs) are widespread in aquatic ecosystems affected by climate variability, urbanization, and intensifying aquaculture. Yet parent-antibiotic concentrations and resistance-related genetic endpoints do not always vary in parallel across seasons, sites, or environmental compartments. This discrepancy matters for aquatic animals as ecological receptors, potential vectors, and targets for antimicrobial resistance monitoring and management. To examine whether transport, retention, and biological processes may contribute to these mismatches, we conducted a structured narrative review. We screened studies retrieved from Web of Science Core Collection, Scopus, and PubMed for paired measurements in aquatic systems. Of 98 field studies, 25 provided sufficient paired data for matched chemical–genetic assessment. Among these, 16 provided Moderate evidence and 9 provided Suggestive evidence for coupled, mismatched, or compartment-dependent responses. No study met the stricter criteria for field-supported legacy persistence. Seasonal reversals, spatial divergence, and differences among water, particles, and sediments suggest that water-column antibiotic concentrations alone are incomplete proxies for ARG abundance. Such measurements alone cannot assess ARG mobility or host context. Potential contributors include sediment and biofilm retention, extracellular DNA, hydrodynamic redistribution, horizontal gene transfer, transformation products, and co-selective stressors, although their relative roles remain unresolved. These findings support monitoring that combines chemical and genetic endpoints with information on sources, hydrology, compartments, and hosts to inform aquatic-animal risk assessment and management. Full article

Antimicrobial resistance demands new strategies capable of restoring the effectiveness of conventional antibiotics. In this study, the antibacterial activity and adjuvant potential of five Meldrum’s acid derivatives (MAD1–MAD5) against multidrug-resistant strains of Staphylococcus aureus 10 and Escherichia coli 06 were evaluated. Minimum inhibitory concentrations (MICs) were determined by broth microdilution, and the combined effects with ampicillin, gentamicin, and norfloxacin were analyzed at subinhibitory concentrations. Membrane permeability was assessed by SYTOX Green fluorescence, and bacterial energy metabolism was assessed by quantifying intracellular ATP using bioluminescence. The derivatives did not show direct antibacterial activity (MIC ≥ 1024 µg/mL), but they significantly reduced the MICs of the antibiotics, especially gentamicin and norfloxacin. Increased membrane permeability and reduced ATP levels were most evident in E. coli, particularly for MAD3, MAD4, and MAD5, while S. aureus showed a limited response. In silico ADMET predictions indicated pharmacokinetic profiles consistent with bioactive compounds. Taken together, the results demonstrate that Meldrum’s acid derivatives act as species-dependent modulators of antimicrobial resistance, highlighting their potential as antibacterial adjuvants. Full article

Background/Objectives: Wastewater treatment plants (WWTPs) are recognized point sources of pharmaceutical residues and antimicrobial-resistant bacteria. This challenge is explicitly addressed in the 2024 recast of the Urban Wastewater Treatment Directive (UWWTD), which introduces risk-based obligations for micropollutant removal. Methods: Here, five antibiotics (azithromycin, clarithromycin, erythromycin, ciprofloxacin and sulfamethoxazole) were retrospectively (2017–2018) assessed in influent and effluent of four WWTPs and in their receiving waters (riverine and marine outfalls), including the Vistula Estuary. Measured incoming load (MIL) was compared with predicted incoming load (PIL), a cost-efficient proxy derived from outpatient consumption data. Results: The screening-level PIL–MIL consistency check showed closer agreement in catchments without major hospital inputs. In WWTPs, ciprofloxacin showed consistently high apparent aqueous-phase removal in both campaigns (>95%), sulfamethoxazole showed moderate removal (64–85%), while macrolides exhibited highly variable and sometimes apparent negative removal, yielding effluent concentrations up to 3989 ng L⁻¹ (azithromycin) and 2866 ng L⁻¹ (clarithromycin). Receiving waters generally contained < 10 ng L⁻¹ of the investigated antibiotics, but a low-dilution-capacity river showed a clear WWTP influence. Presumptive cefotaxime-resistant Escherichia coli, used as proxies for emerging ESBL/AmpC-associated resistance, reached ~5% and 20% of CFU downstream of WWTP discharges. Environmental (ERA) and AMR-related (AMR-RA) risk quotients (RQs) were mostly <0.1. However, RQs for azithromycin approached or exceeded unity in Gdańsk and Puck Bay. Coastal recipients are more vulnerable despite high dilution, since marine predicted no-effect concentrations (PNECs) for antimicrobials are lower than those for freshwater. Conclusions: The study supports the value of retrospective baseline data and site-specific screening frameworks for risk-based prioritization under the recast UWWTD. Full article

In the broiler production industry, antibiotics such as florfenicol are widely used. Although these antibiotics exert therapeutic effects against bacterial diseases, they can induce a series of physiological alterations in broilers under certain exposure scenarios. This study aimed to investigate the effects of chicory aqueous extract (CAE) on broiler growth performance, immune function, and intestinal health, and to compare the impacts of CAE and florfenicol exposure on the physiological status of broilers. A total of 200 one-day-old broilers were randomly divided into five groups (5 replicates per group): the blank control group (NC) drank tap water freely, the florfenicol group (FFC) was given 0.15 g/L of florfenicol solution in the drinking water, the CAE groups were given 1.25 g/L (LCAE), 2.5 g/L (MCAE), and 5 g/L (HCAE) of CAE in the drinking water, respectively. The experimental period was 42 days. The results showed that the addition of CAE to drinking water could significantly improve the growth performance of broilers, specifically manifested as increased body weight and a significantly decreased feed-to-gain ratio (F/G) (p < 0.05). Regarding immune function, CAE enhanced immune capacity by increasing immune organ indices, serum antibody titers, and serum levels of immunoglobulin A (IgA) and immunoglobulin G (IgG) (p < 0.05). In terms of intestinal function, CAE significantly increased villus height (VH) and villus-crypt ratio (V/C), elevated activities of digestive enzymes including chymotrypsin, α-amylase, and lipase, and raised both secretory immunoglobulin A (sIgA) content and Occludin mRNA relative expression levels (p < 0.05), thereby improving intestinal digestion and absorption. Additionally, CAE enhanced serum superoxide dismutase (SOD) activity and reduced malondialdehyde (MDA) content (p < 0.05), effectively enhancing the antioxidant capacity of broilers. Notably, compared with the NC group and all CAE-treated groups, broilers in the FFC group exhibited significantly reduced growth performance, suppressed immune function, and evident damage to intestinal tissue structure and physiological functions. Comprehensive analysis indicates that CAE can effectively promote broiler growth and development, enhance immune status and intestinal digestive-absorptive function, and enrich gut bacteria such as Lactobacillus and Bifidobacterium, thus optimizing intestinal microbiota composition. Among the gradient doses tested in this study, the 2.5 g/L dose of CAE demonstrated the best overall effect, suggesting that CAE may exert beneficial physiological effects under the present experimental conditions, and further investigations are needed to assess its practical application potential. Full article

Fluoroquinolones are effective synthetic broad-spectrum antibiotics, but their use can be associated with persistent adverse effects, sometimes described as fluoroquinolone-induced disability. The molecular mechanisms underlying these effects remain incompletely understood, although accumulating evidence implicates mitochondrial dysfunction, oxidative stress, and DNA damage. We hypothesized that the convergence of these stress responses may promote cellular senescence and thereby contribute to persistent fluoroquinolone-associated adverse effects. We examined three clinically used fluoroquinolones—ciprofloxacin, moxifloxacin, and levofloxacin—in primary human fibroblasts in vitro. Exposure for 7 days revealed that 200 µM ciprofloxacin, but not 200 µM moxifloxacin or 500 µM levofloxacin, induced a senescence-like phenotype characterized by increased senescence-associated β-galactosidase (SA-β-Gal) activity and an elevated senescence index (SI), which integrates increased cell size and autofluorescence measured by imaging flow cytometry. At 7 days, ciprofloxacin did not induce a broad canonical senescence-associated secretory phenotype (SASP) at either the transcriptional or secretory level, consistent with a non-canonical senescence-like state; only a modest increase in IL-1β secretion emerged after 14 days. The ciprofloxacin-induced phenotype was not accompanied by a robust increase in the canonical p53, p16, or p21 protein markers, but was associated with reduced retinoblastoma protein (RB) phosphorylation at Ser795. However, ciprofloxacin removal from the culture medium after 1 or 2 weeks of incubation resulted in the recovery of the resazurin signal to approximately control values by the end of the 3-week experimental period. Ciprofloxacin also increased oxidative stress, as assessed using dihydroethidium and dichlorodihydrofluorescein diacetate. Both the antioxidant Trolox and the mitochondria-targeted antioxidant SkQ3 attenuated the ciprofloxacin-induced increase in SA-β-Gal activity and SI. These findings identify oxidative stress as a putative mediator of ciprofloxacin-induced senescence-like remodeling in human fibroblasts and support further investigation of drug-induced cellular senescence as a potential contributor to persistent fluoroquinolone-associated adverse effects. Full article

Bacterial population heterogeneity serves as the intrinsic basis for persister formation. Single-cell RNA sequencing is a powerful tool for investigating such heterogeneity. In this study, we analyzed single-cell transcriptomic data, previously generated via RiboD-PETRI-seq, from exponential-phase Escherichia coli MG1655 populations. We identified subpopulations with heterogeneous expression of gadA and gadB. Dual-fluorescent reporter strains were subsequently utilized to verify the heterogeneous protein abundance of GadA and GadB across the bacterial community. The expression levels of these two proteins were positively correlated within individual cells. We further observed that the naturally occurring GadA/GadB-low subpopulation exhibited a higher persister ratio than the GadA/GadB-high subpopulation under acid stress, and a similar phenotype was recapitulated in the ΔgadAB mutant. Integrated transcriptomic and metabolomic analyses collectively demonstrated that the gadAB double mutant exhibits a dormant-like state upon acid exposure. This study confirms heterogeneous gadA and gadB expression within bacterial populations. The GadA/GadB-low subpopulation exhibits enhanced antibiotic tolerance under acid stress. This work offers theoretical insights into the acid and antibiotic tolerance mechanisms of enteric pathogens in the acidic gastrointestinal niche. Full article

Essential oils (EOs) of Lamiaceae family have been reported to possess antimicrobial properties. However, commercial preparations of EOs are often of variable quality and inconsistent efficacy due to adulteration and chemotypic variation. This study comprehensively profiled six retail Lamiaceae EOs (Origanum vulgare, O. vulgare subsp. hirtum, Thymus vulgaris, Lavandula angustifolia, Salvia officinalis, and Melissa officinalis) available in Türkiye using GC-MS, complemented by principal component analysis (PCA) and hierarchical cluster analysis (HCA) to discern chemotypic relationships. Antimicrobial and anti-biofilm activities were evaluated against standard bacterial and fungal strains via disc diffusion, broth microdilution, and crystal violet assays. GC-MS and chemometric analyses resolved three distinct chemotypes: phenol-rich (carvacrol/thymol, 49.7–78.2%), ester/alcohol-rich (linalool/linalyl acetate, ~74%), and ketonic/aldehydic-rich (thujone/camphor or citral, 38–54%). Phenol-dominant EOs exhibited potent broad-spectrum activity, with MIC values as low as 0.19% v/v against Enterococcus faecalis and 0.78% v/v against Candida albicans, often surpassing reference antibiotics against Gram-positive and fungal pathogens. In contrast, non-phenolic EOs showed selective or reduced bioactivity, and Pseudomonas aeruginosa remained highly resistant across all samples. These findings confirm that retail Lamiaceae EOs retain authentic phytochemical profiles that emphasize their robust, constituent-dependent antimicrobial efficacy, supporting their therapeutic reliability for consumers when quality is assured. Full article

There is growing interest in the role of the gut microbiome in immune development and homeostasis during childhood. Increasing evidence suggests that early alterations in microbial composition might influence susceptibility to both respiratory and rheumatic diseases through interconnected pathways. While the gut–lung and gut–joint axes have been investigated separately, their integration into a biologically specific and testable model remains largely unexplored. In this narrative review, the literature was searched in PubMed/MEDLINE and Scopus for evidence syntheses published from 2020 to 2026; 37 eligible evidence syntheses were included, comprising 26 addressing the gut–lung/respiratory domain and 11 addressing the gut–joint/rheumatic domain. We examine current knowledge of microbiome-mediated interactions linking the gut, lungs, and joints in childhood. We discuss the development of the paediatric microbiome and the influence of early-life factors, including mode of delivery, breastfeeding, infections, antibiotic exposure, and environmental determinants, on immune programming. We then summarise evidence supporting the gut–lung axis in paediatric respiratory diseases and the gut–joint axis in juvenile idiopathic arthritis (JIA), highlighting recurrent but non-specific findings such as dysbiosis, impaired epithelial barrier integrity, altered microbial metabolite production, and immune dysregulation. Recent paediatric epidemiological evidence also showed that JIA was more prevalent among children with asthma than among those without asthma (0.81% vs. 0.23%), with asthma associated with approximately twofold higher odds of JIA after propensity-score weighting (OR 2.10, 95% CI 1.56–2.81), although this association does not establish microbiome-mediated causality. We finally critically examine whether more specific mechanisms, including gut-primed immune-cell trafficking, antigen-specific amplification, and metabolite–receptor convergence, could provide testable links between pulmonary and articular inflammation. On this basis, we propose the gut–lung–joint axis as a conceptual, hypothesis-generating model. Future research integrating microbiome profiling, immune-cell clonality, immunophenotyping, and metabolomics will be required to test its predictions and clarify its clinical relevance. Full article

Idiosyncratic drug-induced severe neutropenia and agranulocytosis are rare but potentially life-threatening adverse drug reactions. They cause profound neutrophil depletion after exposure to non-cytotoxic medications. Advances in supportive care have substantially reduced mortality. Long-term management nevertheless remains challenging. Clinicians must decide whether a structurally or pharmacologically related drug can be prescribed safely (cross-reactivity). They must also decide whether the culprit drug can ever be reintroduced (rechallenge). Current evidence supports an immune-mediated pathogenesis. It involves reactive drug metabolites, hapten formation, human leukocyte antigen (HLA)-restricted antigen presentation, and T-cell activation. The strength of evidence for cross-reactivity varies considerably across drug classes. Clinically meaningful cross-reactivity is well established for antithyroid thionamides. Evidence for beta-lactam antibiotics and thienopyridine antiplatelet agents remains limited, resting largely on case reports and pharmacovigilance data. For most other medications, evidence is insufficient to support generalized class-wide avoidance. Evidence supporting drug rechallenge is similarly heterogeneous. The most robust data concern clozapine. Carefully selected patients with previous neutropenia—but generally not agranulocytosis—may successfully undergo rechallenge under intensive hematologic monitoring, often with granulocyte colony-stimulating factor (G-CSF) support. Outside this setting, deliberate rechallenge is rarely justified. It should be reserved for exceptional clinical circumstances when no effective therapeutic alternative exists. This review summarizes current mechanistic insights. It evaluates the available evidence for cross-reactivity and rechallenge across major drug classes, discusses the emerging role of pharmacogenomics, and proposes a practical framework to guide individualized clinical decision-making. Permanent discontinuation of the culprit drug remains the standard approach. Advances in immunology, pharmacogenomics, and international pharmacovigilance registries are progressively enabling more personalized risk assessment. Full article

The increasing prevalence of antibiotic-resistant microbes necessitates new antimicrobial strategies. In this study, the antibacterial activity of leaf extracts from a number of plants, Pistacia lentiscus, Laurus nobilis, Solanum lycopersicum, Ruta chalepensis, Inula viscosa, Myrtus communis, and Ficus carica, under photodynamic and sonodynamic activation was evaluated against S. aureus (methicillin-susceptible Staphylococcus aureus, MSSA), methicillin-resistant S. aureus (MRSA), and E. coli. Crude extracts of all the plants exhibited antibacterial activity against S. aureus, eradicating bacterial cells in 2–20 min. However, none of the extracts was active against E. coli. The most active extracts from P. lentiscus, L. nobilis, I. viscosa, and F. carica were tested against two clinical MRSA strains, and all inhibit cells within 5 to 40 min. These four active extracts were separated by reversed-phase chromatography, yielding fractions of varying polarity that exhibited dark activity (more hydrophilic fractions) or photodynamic properties (more hydrophobic fractions) when tested against S. aureus. Two extracts (from P. lentiscus and I. viscosa) exhibited sonodynamic activity against S. aureus, and only one (from P. lentiscus) against E. coli. Full article

A synthesis of current knowledge on the composition and dynamics of marine biofouling, and its role in altering the ecological setting of Southern Ocean benthic communities, is presented here. Current research on biofouling focuses on two main drivers of change: the introduction of invasive marine species (IMS) via hull biofouling, and plastic debris, and the dispersal of antibiotic-resistant bacteria through the development of microbial biofilms, often mediated by the persistence of artificial substrates. Despite the logistical difficulties of conducting experimental studies in such a harsh polar environment, macrofouling communities have been found to display high levels of complexity, a feature also observed within microbial communities. Macrofouling assemblages are dominated by bryozoans and spirorbid polychaetes; however, colonization by these communities is extremely slow compared to temperate regions. The emerging role of plastic-associated microbial biofilms (plastisphere) as novel ecological niches in Antarctic waters is also addressed. These microbial assemblages may act as reservoirs and potential dispersal vectors of antibiotic resistance, raising new concerns regarding ecosystem health under increasing anthropogenic pressure and climate-driven environmental changes. Full article

The options for controlling agricultural plant-pathogenic bacterial diseases with antibiotics are rather limited. Applications of naturally derived antimicrobial peptides may offer an alternative. Objectives. The cell-free conditioned media of Xenorhabdus budapestensis and X. szentirmaii bacteria inactivate Erwinia amylovora, the causative agent of fire blight in Rosaceae, both in vitro and in planta. The working hypothesis was that the active ingredient was fabclavine. To test this hypothesis, inducible fabclavine-producing strains were constructed in both Xenorhabdus species. The anti-Erwinia potential of non-induced and induced fabclavine-producing cultures was compared in vitro and in planta. Methods. Promoter exchange mutants known to exclusively produce the fabclavine antibiotic were generated and their fabclavine production was confirmed by LC-HRMS, and in vitro bioassays. Finally, apple blossoms in an incubator were subjected to antimicrobial and control treatments before experimental inoculation of the buds with Erwinia amylovora strain Ea1. Results. Cell-free medium from both induced fabclavine-producing Xenorhabdus species exerted strong antagonistic effects on Ea1 cells in vitro, whereas the non-induced ones showed substantially reduced antibacterial activity. Similarly, both induced culture media prevented fire blight symptoms in experimentally inoculated flowers in a dose-dependent manner. The non-induced X. szentirmaii mutant strain was completely inactive in planta, whereas the X. budapestensis strain exhibited some protective activity. Conclusions. The results support the hypothesis that the fermentation product of the inducible Xenorhabdus mutants producing only fabclavines can be used for protection against E. amylovora. Some aspects of the application perspectives are discussed in comparison with conventional streptomycin and kasugamycin treatments. Full article