Search Results (4,120)

Background/Objectives: Posttraumatic infections are common in emergency hand surgery. Amputation is the worst outcome and can occur at admission or during the course of antibiotic treatment and iterative surgical debridement. We wondered if the prolongation of antibiotic treatment beyond the usual indication, and more surgical debridement besides its immediate benefit, could reveal additional preventive effect against amputation during or immediately after therapy. Methods: We investigate 166 risk association (variables) of community-acquired (traumatic) hand infection with overall treatment failure using a specifically designed retrospective single-center cohort between 1 November 2018 and 31 October 2020. Results: Among 600 patients (362 males; 71 (11.8%) with diabetes mellitus), 58 (9.7%) required initially unplanned amputation during the therapeutic ourse. Multivariate Cox regression analysis identified only inherent risks associated with “amputation”: male sex (hazard ratio [HR] 3.12, 95% confidence interval [CI] 1.28–7.69, p = 0.01), age (HR 1.03, 95% CI 1.01–1.04, p = 0.03), diabetes (HR 2.40, 95% CI 1.15–5.01, p = 0.02), whereas no interventional variables such as early flapping or antibiotic-related parameters (early empirical antibiotic use, total duration of antibiotics including its initial parenteral use, and choice of agent) altered outcomes. Conclusions: In severe (traumatic) hand infections among 600 patients, the outcomes were determined by the extent of trauma and underlying comorbidities. The outcomes do not seem to be effectively reduced by more surgery or initial antibiotic treatment. Full article

Wle vanillin is widely used as a flavoring agent in food products, its potential as a non-antibiotic feed additive for broilers remains unexplored. This study primarily investigated the effects of dietary supplementation of vanillin on antioxidant activity, anti-inflammatory response, immune function, and gut microbiota composition in broilers. One-day-old male broilers were randomly assigned to five groups: a basal diet group, a positive control group (basal diet + 100 mg/kg chlortetracycline (CTC)), and three vanillin-supplemented groups (0.1%, 0.2%, or 0.4%) for 42 days. Results showed that vanillin improved antioxidant capacity, with elevated serum superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activity and reduced malondialdehyde (MDA) levels. Broilers receiving vanillin supplementation showed lower levels of pro-inflammatory cytokines (interleukin-6 (IL-6), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α)) and higher interleukin-10 (IL-10) expression compared with controls. Additionally, serum immunoglobulin A (IgA) and immunoglobulin M (IgM) levels were also greater in the vanillin group. It also enhanced intestinal health by increasing the duodenal villus height-to-crypt depth ratio, improving intestinal morphology, raising the Firmicutes-to-Bacteroidetes ratio, and promoting Lactobacillus proliferation compared with CTC. Notably, growth performance data were exploratory in nature; vanillin was associated with numerical improvements in average daily gain (ADG) and feed conversion (F/G) ratio. These preliminary findings suggest that vanillin requires further investigation as a potential feed additive. Full article

Background/Objectives: Antimicrobial resistance is a critical threat to global public health. Eugenol is a bioactive compound with broad-spectrum antimicrobial activity that has attracted increasing interest as a naturally derived antimicrobial agent with potential complementary applications to conventional antibiotics, but its clinical application is severely limited by its high volatility, low water solubility and thermo-oxidative instability. The main objective of this study was to develop eugenol-loaded microparticles using a ternary biopolymer matrix, to characterise their main physicochemical properties, and to evaluate their in vitro antimicrobial efficacy against clinically relevant bacterial reference strains. Methods: The microparticles were formulated from an emulsion of maltodextrin, gum arabic and soy lecithin, and encapsulated using a spray-drying technique. Product recovery, particle morphology assessed by scanning electron microscopy (SEM), particle size distribution determined by laser diffraction, and encapsulation efficiency quantified by GC-FID were analysed. Subsequently, antimicrobial activity was evaluated by comparing the microparticles with free eugenol using agar well diffusion and broth microdilution assays to determine the minimum inhibitory concentration (MIC) against eight bacterial strains. Results: The spray-drying process achieved a product recovery of 61.88% and an encapsulation efficiency of 52.45%. The resulting microparticles exhibited a smooth, spherical morphology with diameters of less than 20 µm. In microbiological assays, microencapsulation significantly reduced MIC values by 4- to 16-fold compared with free eugenol for susceptible strains. The formulation exhibited potent activity against most of the Gram-positive and Gram-negative pathogens tested, except for Pseudomonas aeruginosa, which remained resistant to both formulations. Conclusions: The encapsulation of eugenol in this optimised biopolymer matrix substantially improved its antimicrobial efficacy against the tested bacterial strains. These findings highlight the potential of spray-dried eugenol microparticles as a promising antimicrobial formulation and provide a basis for their further development for topical applications. Further studies are warranted to evaluate their pharmaceutical performance and antimicrobial mechanisms. Full article

Helicobacter pylori is one of the most common bacterial pathogens in humans and the primary etiological agent of chronic gastritis, peptic ulcer disease, and gastric cancer. Its ability to establish persistent gastric colonization relies on multiple virulence factors, including adhesins, urease, cytotoxins, motility, outer membrane vesicles, and biofilm formation, which collectively promote bacterial survival, chronic inflammation, and treatment failure. The increasing prevalence of antibiotic-resistant H. pylori strains has intensified the search for therapeutic strategies targeting both bacterial viability and virulence. Berberine (BBR), a natural isoquinoline alkaloid, has emerged as a promising candidate because of its antibacterial, anti-inflammatory, and antioxidant properties. Increasing evidence derived from native berberine, its derivatives, and berberine-based formulations indicates multifaceted anti-H. pylori activity, including direct antibacterial effects, inhibition of virulence determinants, and modulation of host inflammatory responses. This review summarizes current knowledge on the epidemiology and pathogenic mechanisms of H. pylori and provides a comprehensive overview of the available evidence regarding the anti-H. pylori pharmacological profile of BBR-based compounds. Particular attention is given to their effects on bacterial adhesion, motility, urease activity, efflux pump function, biofilm formation, and host inflammatory signaling pathways. The review also discusses findings from preclinical and clinical studies supporting BBR-based strategies as adjuncts to conventional eradication therapies. In addition, recent advances in nanotechnology-based drug delivery systems designed to overcome the poor oral bioavailability of BBR and improve its therapeutic efficacy against H. pylori are highlighted. Full article

Antimicrobial resistance is a major global health challenge that has created an urgent need for new antibacterial agents capable of overcoming emerging resistance mechanisms. Among nitrogen-containing heterocycles, pyrrolidine has been widely investigated in medicinal chemistry due to its structural versatility, favourable physicochemical properties, and ability to enhance interactions with biological targets. This review provides a comprehensive and critical overview of pyrrolidine-based compounds investigated for antibacterial applications. Relevant studies describing clinically approved antibiotics, natural products, synthetic derivatives, hybrid molecules, and antibacterial adjuvants containing a pyrrolidine scaffold were collected, classified, and critically evaluated, with particular emphasis on structural features, antibacterial activity, and structure–activity relationships. The reviewed evidence demonstrates that the pyrrolidine moiety is present in several antibacterial drug classes, including carbapenems, cephalosporins, fluoroquinolones, lincosamides, streptogramins, and tetracyclines, where it contributes to improved target affinity, antibacterial potency, and pharmacokinetic behaviour. Numerous recently reported pyrrolidine derivatives have shown promising activity against clinically relevant, multidrug-resistant bacterial pathogens. The pyrrolidine scaffold is valuable for the design of next-generation antibacterial agents and resistance-modifying compounds, though further in vivo studies and pharmacological evaluation are required to support their clinical development. Full article

In this study, alginate hydrogels (A) cross-linked with a mixture of calcium and europium ions (Ca+Eu)A were developed for the first time as potential carriers for the targeted delivery and sustained release of drugs to specific regions of the gastrointestinal tract. Comparative studies were conducted to investigate the effect of the cross-linking agent (Ca²⁺, Eu³⁺, or their mixture) on the physicochemical properties of alginate hydrogels and the release kinetics of metronidazole in media simulating different gastrointestinal environments. Rheological analysis demonstrated that (Ca+Eu)A hydrogels form mechanically robust, highly cross-linked networks. The hydrogels exhibited negligible swelling in an acidic medium (swelling ratio, SR ≈ 1–1.5 g/g); however, in PBS, calcium alginate (CaA) hydrogels swelled 7–8 times more (SR ≈ 42.5 g/g) than hydrogels cross-linked with Eu³⁺ ions or a Ca²⁺/Eu³⁺ mixture (SR = 5–8 g/g). Metronidazole was released 1.5–2 times faster from calcium-cross-linked hydrogels than from hydrogels cross-linked with Eu³⁺ ions or the mixed Ca²⁺/Eu³⁺ system, whereas (Ca+Eu)A hydrogels exhibited a more sustained and uniform release profile. These results demonstrate that the drug release kinetics can be tuned by adjusting the Ca²⁺/Eu³⁺ ratio during alginate cross-linking. Consequently, such hydrogels represent a promising platform for the targeted delivery and controlled release of therapeutic agents, particularly antibiotics, to specific regions of the gastrointestinal tract. Full article

The COVID-19 pandemic shifted pediatric infection epidemiology from bacterial toward viral predominance as public health measures relaxed. To determine how hospital antibiotic prescribing adapted, antimicrobial consumption was characterized and linked to underlying pathogen type. Antibiotic use was retrospectively analyzed among 567 children admitted with a positive microbiological finding to the pediatric ward of a tertiary hospital in Split, Croatia, during the first quarters of 2021–2024. Consumption was quantified using Days of Therapy (DOT), Length of Therapy (LOT), and Days of Antibiotic Spectrum Coverage (DASC) per 1000 patient-days (PD). Antibiotics were grouped by the WHO Access/Watch/Reserve (AWaRe) classification and linked to discharge diagnosis and pathogen type. The proportion of children receiving antibiotics rose from 60.5% (26/43) in 2021 to 71.4% (130/182) in 2024, with the cohort shifting toward younger infants and virally driven diagnoses. DOT, DASC, and DOT/LOT peaked in 2022 (DOT 2164/1000 PD, DOT/LOT 2.2) before settling near 1400/1000 PD, with mean per-day spectrum (DASC/DOT) declining modestly (7.7 to 6.8). Watch-group antibiotics dominated throughout (~80%), with Access contribution of ~20% and Reserve antibiotic use negligible. Ceftriaxone usage rose fivefold (150 to 755 DOT/1000 PD) to become the leading agent. Ceftriaxone and azithromycin were administered more often to children with viral than bacterial infections (respiratory syncytial virus being most common), whereas vancomycin and meropenem were tied to bacterial isolates. These findings identify a high-yield stewardship target and underscore the value of multi-metric, pathogen-aware surveillance. Full article

Although most upper respiratory tract infections (URTIs) have a viral etiology, antibiotics are widely prescribed, thus contributing substantially to antimicrobial resistance. This study investigated the potential beneficial effects of a novel strain, Limosilactobacillus reuteri LMG P-27481, against major URT pathobionts (Staphylococcus aureus, Streptococcus pyogenes, Streptococcus pneumoniae, Moraxella catarrhalis, and Haemophilus influenzae) with the aim of reducing or delaying antibiotic use. Antibacterial and immunomodulatory activities were evaluated using L. reuteri alone or combined with resveratrol, a natural compound with antiviral and anti-inflammatory properties. Both agents inhibited pathogen growth, while their combination showed additive antibacterial activity, particularly against Gram-negative bacteria. Antioxidant assays demonstrated significant antioxidant capacity for both agents, with enhanced effects in combination in NBT and ABTS assays but antagonistic in ORAC. Immune mediators (IL-6, IL-8, IL-1β, TNF-α, IL-25, IL-33, CCL17, CCL22) were assessed in epidermal, epithelial, and macrophage cell lines, together with epidermal integrity markers (Filaggrin, Loricrin, Involucrin) in a 3D reconstructed human skin model (EpiDermFT^TM). L. reuteri, resveratrol, and their combination exerted cell-specific effects in the different models, modulating cytokine expression and production, and barrier integrity. Our findings support the potential efficacy of oral L. reuteri LMG P-27481 plus resveratrol in URTIs. Full article

The intricate interplay between the gut microbiome and the enteric nervous system remains a paramount focus in understanding the multifactorial pathogenesis of disorders of gut–brain interaction (DGBI), most notably irritable bowel syndrome (IBS). While the clinical entity of post-infectious IBS is well-established, the independent, long-term pathophysiological impact of iatrogenic antibiotic exposure is garnering critical attention within neurogastroenterology. This narrative review provides a comprehensive synthesis of current epidemiological and mechanistic evidence positioning antibiotic-induced microbial depletion as a potential predisposing factor for incident IBS. By evaluating recent literature, we highlight epidemiological trends demonstrating a consistent, dose-dependent relationship between cumulative antibiotic courses, particularly broad-spectrum agents, and an elevated risk of developing IBS, independent of prior acute enteric infections. Furthermore, we explore the mechanistic underpinnings of this association, focusing on how systemic antibiotics induce persistent, detrimental alterations in commensal diversity. This resulting dysbiosis initiates a proposed cascade of downstream consequences, including compromised epithelial barrier integrity, persistent low-grade mucosal inflammation, and altered bile acid metabolism. These localized disruptions serve as established triggers for visceral hypersensitivity and dysregulated gastrointestinal motility communicated via the gut–brain axis. Ultimately, this review underscores that antibiotic exposure may act as a significant, modifiable risk factor for IBS pathogenesis. Recognizing this substantial iatrogenic risk reinforces an urgent clinical imperative for stringent antimicrobial stewardship and emphasizes the necessity for future research directed toward prophylactic, microbiome-sparing strategies to mitigate the escalating global burden of DGBIs. Full article

Antibiotic contamination of water, particularly by tetracycline (TC), requires effective and sustainable treatment strategies. In this study, CoFe₂O₄ nanoparticles were synthesized using lime juice as a natural stabilizing agent and combined with ZnO to obtain a ZnO/CoFe₂O₄ nanocomposite for visible-light-driven TC degradation. Complementary characterization confirmed the coexistence of ZnO and CoFe₂O₄ without detectable secondary phases, with predominantly spherical and irregular particles. The composite exhibited ferromagnetic behavior, suggesting potential magnetic recovery, and showed broader visible-light absorption and a reduced band gap of 3.05 eV compared with 3.23 eV for ZnO. Although its specific surface area and pore volume were lower than those of CoFe₂O₄, the nanocomposite displayed the highest photocatalytic performance. Under the optimized conditions of pH 6, 20 mg L⁻¹ TC, and 1 g L⁻¹ catalyst, 96.8% degradation was achieved after 120 min, with a pseudo-first-order rate constant of 0.029 min⁻¹. The degradation efficiency remained 88.3% after five cycles. Scavenger experiments identified photogenerated holes (h⁺) and hydroxyl radicals (·OH) as the dominant reactive species. The improved photocatalytic activity may be associated with interfacial interactions between ZnO and CoFe₂O₄, suggesting that the green-synthesized nanocomposite has potential as a visible-light photocatalyst for TC degradation under the investigated conditions. Full article

Background: Candida albicans constitutes part of the normal human gastrointestinal (GI) microbiome(GM). Alterations inthe GM induced by antibiotics may disrupt colonization resistance and promote fungal overgrowth. This review summarizes the effects of antibiotics on GI C. albicans colonization in experimental animal models and humans. Methods: A narrative review was conducted using data from the PubMed/MEDLINE and Scopus databases. Studies evaluating changes in GI C. albicans populations following antibiotic administration in mice or humans were included. Results: Twenty-six articles met the inclusion criteria, comprising 16 murine and 10 human studies. Across all studies, antibiotics were consistently associated with increased GI C. albicans colonization. The greatest increases were observed with broad-spectrum agents with activity against anaerobic bacteria. Elevated fungal concentrations frequently persisted after treatment discontinuation. Human studies largely reproduced findings from murine models. Despite substantial increases in GI colonization, dissemination beyond the GI tract was uncommon. Conclusions: Available evidence demonstrates that antibiotic-induced disruption of the GM promotes GI overgrowth of C. albicans. Hence, C. albicans concentration can serve as an indicator of antibiotics’ impact on the GM. While increased colonization alone rarely results in invasive disease, antibiotic-associated yeast expansion may represent an important step in the pathogenesis of disseminated candidiasis. Full article

Background: Ignatzschineria species are rare emerging human pathogens that are typically associated with myiasis. Methods: We report the first case of Ignatzschineria indica bacteraemia in Greece in a male patient presenting with maggot-infested wounds of the thorax, shoulders, and arms. The isolate was identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), and antimicrobial susceptibility testing was performed according to EUCAST guidance. A review of the published literature on I. indica bacteraemia was also conducted. Results: The patient was diagnosed with bacteraemia caused by a multisusceptible I. indica isolate and was successfully treated with antibiotic therapy, resulting in complete recovery. This represents the first reported case of I. indica infection in Greece. Review of the literature showed that most published I. indica isolates were susceptible to a broad range of antimicrobial agents, and all reported patients survived, although some required limb amputation because of severe underlying soft tissue disease. Conclusions: Ignatzschineria indica infection should be considered in patients with neglected, maggot-infested wounds. Increased awareness of this emerging pathogen, together with the use of modern microbiological identification methods, may improve recognition of these uncommon infections. Socio-economic inequalities and the changing distribution of insect vectors due to climate change may contribute to the occurrence of such infections. Full article

Background/Objectives: Antimicrobial stewardship programmes (ASPs) are essential for improving antimicrobial use and limiting the emergence of antimicrobial resistance. Although national ASP key performance indicators (KPIs) have been implemented across Saudi Ministry of Health (MOH) hospitals, large-scale evaluations of programme performance remain limited. This study evaluated national ASP performance across MOH hospitals from 2021 to 2024 using formal KPIs and complementary stewardship measures. Methods: This retrospective multicentre surveillance analysis included 124,452 antimicrobial prescription reviews from 96 Saudi MOH hospitals actively reporting stewardship activities. Hospitals were classified according to ASP capacity as category A, B, or C. The evaluated KPIs included protocol adherence, restricted-antibiotic dispensing compliance, active intervention rate, annual trends in optimization interventions, and physician acceptance of ASP recommendations. Secondary assessments included appropriateness of therapy management, therapeutic drug monitoring (TDM) for vancomycin and aminoglycosides, and hospital-level antimicrobial use expressed as defined daily doses per 100 available bed-days. Multivariable logistic regression was used to identify factors associated with guideline non-adherence and physician non-acceptance. Results: Overall protocol adherence was 87.1%, exceeding the national target of 80%, while the active intervention rate was 64.6%, exceeding the 60% benchmark. Restricted-antibiotic dispensing compliance reached 87.6% but remained below the 100% target. Physician acceptance of ASP recommendations was high at 93.0%, although it did not achieve the national target of 98%. The optimization-intervention KPI was not met because de-escalation, antibiotic discontinuation, and intravenous-to-oral conversion did not demonstrate a sustained annual increase. Appropriate ongoing therapy management was documented in 68.3% of cases with available data, whereas TDM was requested in 44.5% of eligible vancomycin or aminoglycoside cases. Antimicrobial use varied across years and hospital categories, with higher monitored broad-spectrum and reserve-agent use in higher-capacity hospitals. Lower ASP capacity, non-critical care settings, and combination therapy were consistently associated with less favourable stewardship outcomes. Conclusions: Saudi MOH hospitals actively reporting stewardship activities demonstrated favourable performance in protocol adherence, intervention activity, and physician acceptance. However, persistent gaps in restricted-antibiotic dispensing, optimization interventions, TDM, and inter-hospital variation indicate the need for continued strengthening of ASP infrastructure, monitoring, and feedback systems. Future research should link stewardship indicators with clinical outcomes, antimicrobial resistance trends, and patient safety. Full article

This study examines the potential of physically activated PET fibers (PA-PET) as an adsorbent for adsorption of two antibiotics (rifampicin (RIF) and rifaximin (RIX)) from aqueous solution. To evaluate the performance of PA-PET, the effects of the initial antibiotic concentration and the contact time were experimentally investigated at pH 2.0 and an adsorbent dosage of 0.4 g/L. While no notable differences were observed regarding the contact time, equilibrium being reached after 180 min, similar to raw PET fibers, a significant increase in adsorption capacity was recorded across the entire range of initial antibiotic concentrations. The highest increases in adsorption capacity were obtained at RIF concentrations of 68 mg/L, where the adsorption capacity increased by more than 107%, and at RIX concentrations of 4.28 mg/L, where the increase reached approximately 84%, compared with the raw PET fibers. To further highlight the performance of PA-PET in the adsorption of RIF and RIX, the isotherm and kinetic data were modeled. Desorption of RIF and RIX from PA-PET was carried out using a medical-grade polyelectrolyte solution (SL) as the desorbing agent. Although the desorption efficiency is relatively modest (below 33% for RIF and 26% for RIX, after 360 min), the molecular structure of RIF and RIX does not change after desorption, and antibiotics can be reintroduced into the technological circuit. These results demonstrate that PA-PET is as a promising, low-cost, and efficient adsorbent for antibiotic removal, offering a practical solution for pollution reduction and more sustainable waste management. Full article

The increased occurrence of tetracycline resistance (conferred by the tet(X3)/tet(X4) resistance genes) poses a major challenge to the clinical treatment of infections using tetracyclines, including tigecycline, which is the “last-resort” therapeutic agent. Thus, there is an urgent need to develop inhibitors targeting Tet(X3)/Tet(X4) to address the crisis of tetracycline resistance. This study revealed that quercetin is an inhibitor of Tet(X3)/Tet(X4), which, when combined with different tetracyclines, can exert synergistic growth-inhibitory effects against Tet(X3)/Tet(X4)-positive bacteria (fractional inhibitory concentration < 0.5). Quercetin + tigecycline significantly decreased the biofilm-forming ability of bacteria. Mechanistic investigations revealed that quercetin inhibits the catalytic activity of Tet(X4) against tetracycline antibiotics by binding to the catalytic active site. In the Galleria mellonella larval infection model of Tet(X4)-positive E. coli J53p47EC or Tet(X4)-negative E. coli J53, tigecycline + quercetin enhanced the survival rate, decreased melanization, and suppressed bacterial load. Thus, the findings of this study will enable the development of novel Tet(X3)/Tet(X4)-targeted therapeutic strategies for clinical infections caused by drug-resistant Enterobacteriaceae and Acinetobacter baumannii, especially Tet(X3)/Tet(X4)-positive pathogens. Full article