Search Results (508)

Background/Objectives: Surveillance of local antibiotic resistance plays a critical role in guiding empirical antibiotic therapies in emergency departments (EDs). This study aimed to collect and analyze a five-year period of prevalence and AMR rates among “ESKAPE” pathogens in a tertiary-care ED setting. Methods: This retrospective observational study included a complete census of microbiological specimens collected from patients presenting to the emergency department between 1 January 2019 and 31 December 2023. Data was retrieved from the MedBakter laboratory information system. Non relevant isolated and duplications were excluded. Only the first isolates per patient per phenotype were included in the final dataset. Results: The final dataset contained 6510 isolates. The most frequent isolates were E. coli (2717, 41.7%), K. pneumoniae (715, 11.0%), and P. mirabilis (696, 10.7%) followed by E. faecalis (662, 10.2%). Prevalence of multi-drug resistance (MDR) was 23.26% among “ESKAPE” pathogens, with highest prevalence in M. morganii (79.6%), P. stuartii (78.5%) and S. marcescens (77.1%). Difficult-to-treat resistance (DTR) was found in 32 isolates, while extensive drug resistance (XDR) was found in 5 isolates. The prevalence of other high-priority MDR bacteria was 12.4% for MRSA and 4.7% for VRE, while among Gram-negative bacteria the prevalence of carbapenem-resistant Enterobacterales was 0.52%. The prevalence of cephalosporin-resistant Enterobacterales varied greatly between 0 and 33%. Conclusions: Despite these important AMR trends, the cumulative antibiogram, according to the World Health Organization (WHO)-issued Access, Watch and Reserve (AWaRe) classification, revealed room for empirical antibiotic choices that spare Watch and Reserve agents. The results will aid the revision of the local antibiotic guidelines. Full article

Acute pancreatitis is a common and heterogeneous inflammatory disorder whose clinical course ranges from a self-limited illness to persistent organ failure, infected pancreatic necrosis, and prolonged critical illness. Contemporary management has moved away from protocolised aggressive fluid loading, prolonged fasting, prophylactic antibiotics, and early open necrosectomy. Instead, current care emphasises repeated physiological assessment, moderate goal-directed resuscitation, early enteral or oral nutrition, organ-specific support, antimicrobial stewardship, and delayed minimally invasive intervention within a multidisciplinary step-up strategy. This narrative review examines acute pancreatitis from an intensive care perspective. Particular attention is given to early risk stratification, intensive care unit triage, haemodynamic and respiratory support, acute kidney injury, intra-abdominal hypertension, nutrition, biliary source control, diagnosis and treatment of infected necrosis, and the timing and selection of endoscopic, radiological, and surgical interventions. The implications of obesity, pregnancy, advanced age, and multimorbidity are also discussed. Recent randomised trials have clarified several clinically important questions: aggressive hydration increases fluid overload without improving outcomes; routine urgent endoscopic retrograde cholangiopancreatography is not beneficial in predicted severe biliary pancreatitis without cholangitis; postponed drainage may avoid invasive intervention in a substantial proportion of patients with infected necrosis; and endoscopic or minimally invasive approaches reduce treatment burden compared with primary open surgery. Persistent organ failure remains the principal determinant of mortality, while infected necrosis further increases risk and complexity. Future progress will depend on dynamic prediction models, biomarker-guided antimicrobial decisions, personalised haemodynamic strategies, phenotype-directed immunomodulation, and regionalised multidisciplinary care. Full article

Distinguishing tuberculous spondylodiscitis (TS) from pyogenic spondylodiscitis (PS) on imaging remains clinically important because the two entities differ in antimicrobial strategy, surgical timing, and the urgency of microbiological workup, yet no single imaging sign is pathognomonic for either diagnosis. When tissue confirmation is delayed, imaging becomes the primary tool that shifts pre-test probability and guides biopsy strategy—a role that is particularly critical in culture-negative disease, in antibiotic-exposed patients, and in settings with limited access to rapid mycobacterial diagnostics. This narrative review maps the imaging evidence most useful for routine TS-versus-PS differentiation, synthesizes recent prediction models and quantitative tools, and evaluates the adjunctive role of ¹⁸F-FDG PET/CT in biopsy-oriented decision-making. PubMed/MEDLINE was searched from inception to 31 March 2026 using pre-specified search terms across three concept blocks. This was a narrative review without formal pooling of quantitative estimates or prospective protocol registration. A secondary Scopus search identified no additional eligible records. Priority was given to comparative TS-versus-PS imaging cohorts, meta-analyses of MRI and CT features, prediction-model studies, and the recent radiomics and PET/CT literature; radiomics and deep-learning studies are appraised as a distinct evidence tier given their retrospective single-center derivation and predominantly internal-only validation. In total, 14 comparative TS-versus-PS imaging cohorts, three meta-analyses, and 14 prediction-model, quantitative-scoring, radiomics, or deep-learning studies formed the core evidence base. MRI yields the greatest differentiating information and is the recommended first-line modality. Features favoring TS include thoracic predominance, multilevel or non-contiguous involvement, relative early disc preservation, subligamentous spread, intraosseous abscesses, thin-walled paravertebral collections, and severe vertebral collapse with kyphotic deformity. Features favoring PS include lumbar predominance, early disc-endplate destruction, homogeneous inflammatory enhancement, facet-joint arthritis, and epidural phlegmon. CT adds osseous detail—including sequestra, subligamentous bone erosion, and paravertebral calcification—and remains the primary guidance modality for biopsy. Recent prediction models combining imaging and laboratory variables have shown high discriminative performance in derivation cohorts; however, most remain internally validated and locally calibrated. Pending external validation, none should be considered ready for unmodified clinical adoption, and they should therefore be used as probability modifiers rather than stand-alone diagnostic rules. ¹⁸F-FDG PET/CT is complementary rather than primary and is most useful when MRI is contraindicated or equivocal, in hardware-associated infection, and for whole-body staging in suspected disseminated tuberculosis. Non-infectious mimics and alternative infectious diagnoses should be considered when the imaging pattern is internally inconsistent or when standard cultures remain negative. Imaging findings should refine etiological probability and guide biopsy strategy, but should not replace tissue confirmation when tissue is feasible. Non-imaging evidence complementing this review is addressed in the companion manuscript, Part I. Full article

Mucosal microbiota contribute broadly to host defense and immune homeostasis, while the lung and gut microbiota form a particularly important bidirectional ecological and immunological network that shapes pulmonary host defense, inflammatory injury, and tissue repair. In pneumonia, loss of colonization resistance and altered microbial metabolite production may weaken innate and adaptive immunity; respiratory infection, antibiotics, and critical-care exposures can, in turn, remodel both microbial communities. In acute lung injury (ALI) and acute respiratory distress syndrome (ARDS), intestinal barrier failure, circulating microbial products, immune cell trafficking and, in selected settings, lymphatic or hematogenous dissemination of gut-derived organisms may aggravate alveolar–capillary injury. Alveolar macrophages integrate these signals through pattern-recognition, metabolic, and epigenetic pathways, linking microbial ecology to pathogen clearance and inflammatory resolution. The evidence, however, remains uneven. Mechanistic causality rests largely on animal studies, most human data are associative, and trials of microbiota-directed interventions are heterogeneous and strain-specific. This Review examines bacterial and viral pneumonia, sepsis-associated ALI and ventilator-associated injury; separates mechanistic, observational, and interventional evidence; and evaluates probiotics, live biotherapeutic products, microbial metabolites, and dietary approaches. Translation will depend on longitudinal sampling, source-resolved microbial tracking, metabolite-informed patient stratification, and adequately powered trials with clinically relevant endpoints. Full article

Macadamia (Macadamia spp.) is an economically important nut crop whose severe recalcitrance to genetic transformation substantially hinders progress in functional genomics and molecular breeding. To overcome this critical technical bottleneck, this study established a highly efficient and broadly applicable in planta hairy root genetic transformation system with integrated visual screening. This system utilizes an Agrobacterium rhizogenes-mediated transformation method, employing multiple visual reporter gene systems (DsRed2, eGFP, RUBY, and AtPAP2) to achieve antibiotic-independent and non-destructive screening of transgenic roots. Notably, the system innovatively incorporates the air layering (marcotting) technique to extend in planta genetic transformation to branches of mature trees in the field. By circumventing the stringent sterile conditions required for conventional in vitro tissue culture, this approach achieves a largely genotype-independent transformation across open-pollinated seedlings with diverse genetic backgrounds (A4, GR1, HAES900, and O.C.). The transgenic hairy root induction frequencies ranged from 39.25% to 47.38%, although the GR1 genotype exhibited a notable developmental stage-dependent decline in transformation efficiency. Furthermore, transgenic hairy roots were successfully induced on mature tree branches, with a maximum induction rate of 28.2%. Gene expression analyses confirmed the stable, high-level expression of the target transgenes in all the transgenic hairy root lines. This in planta transformation system provides a reliable in vivo experimental platform for the rapid functional validation of candidate genes and the investigation of root biology in Macadamia. Moreover, it establishes a novel strategy for plant regeneration via root-to-shoot organogenesis, offering a promising avenue for the genetic improvement of recalcitrant woody plants. Full article

Nanomedicine-based liposomal delivery systems are gaining increasing attention as advanced therapeutic platforms for managing ocular infections associated with antimicrobial resistance (AMR) and biofilm formation. The primary objective of this review is to critically evaluate the potential of liposomal drug delivery systems for improving the treatment of antimicrobial-resistant and biofilm-associated ocular infections by integrating current knowledge on antimicrobial resistance mechanisms, biofilm-targeted therapeutic strategies, and advances in liposomal formulations, while also identifying the major limitations, translational challenges, and knowledge gaps in this rapidly evolving field. Traditional ocular antimicrobial treatments are frequently limited by poor drug penetration, short precorneal residence time, low bioavailability, systemic side effects, and inadequate activity against resistant microorganisms and biofilm-embedded pathogens. This review provides a comprehensive overview of different liposomal systems, including conventional, cationic, polyethylene glycol (PEG)-modified, deformable, and stimulus-responsive liposomes, and discusses their advantages in ophthalmic drug delivery, such as enhanced corneal permeation, prolonged drug retention, controlled release, improved biocompatibility, and reduced ocular toxicity. The review further examines the mechanisms through which liposomes help overcome AMR, including improved epithelial transport, membrane disruption, intracellular drug delivery, efflux pump evasion, and enhanced antimicrobial efficacy. In addition, liposomal approaches targeting ocular biofilms are explored, focusing on improved biofilm penetration and the delivery of anti-biofilm agents such as antibiotics, enzymes, quorum-sensing inhibitors, and antimicrobial peptides. Current evidence from in vitro and in vivo ocular infection models is summarized together with disease-specific applications in keratitis, endophthalmitis, and contact lens-related infections. The article also compares liposomes with other ocular nanocarriers and addresses important considerations related to safety, stability, sterilization, large-scale production, and regulatory translation. In addition to highlighting recent advances, this review critically discusses the current limitations of liposomal formulations, the major barriers to clinical translation, and the key knowledge gaps that should be addressed to facilitate the future development and successful clinical application of these systems. Finally, emerging directions including ligand-targeted and stimulus-responsive liposomes, AI-driven formulation development, personalized nanotherapy, and gene therapy combinations are discussed as promising future strategies for combating resistant ocular infections. Full article

The chronic overuse of antibiotics has accelerated the emergence of antibiotic-resistant bacteria, creating a global public health crisis as conventional therapies fail against multidrug-resistant pathogens spreading through water and food chains. Cadmium sulfide (CdS) has been established as an important visible-light-driven photocatalyst for antibacterial applications. This brief review systematically examines the structure–property relationships governing CdS-based antibacterial materials, including crystallographic polymorphs (cubic sphalerite and hexagonal wurtzite), morphological diversity from quantum dots to hierarchical architectures, and synthesis methodologies that critically influence particle size, crystallinity, and surface chemistry. The mechanisms of antibacterial action are elucidated, encompassing photocatalytic reactive oxygen species (ROS) generation, controlled Cd²⁺ ion release, and membrane disruption. A detailed tabulated analysis is presented across three material classes: pristine CdS, binary composites, and ternary Z-scheme heterostructures. Density functional theory (DFT) calculations and molecular docking simulations provide atomic-level insights into charge transfer dynamics and enzyme inhibition mechanisms. Finally, critical challenges, photocorrosion, toxicity, biocompatibility concerns, and scalability limitations are addressed. This review bridges fundamental materials science with antimicrobial applications to guide rational design of next-generation CdS-based antibacterial materials. Full article

Carbapenem-resistant Acinetobacter baumannii (CRAB) is classified by the World Health Organization among the critical-priority pathogens, reflecting high mortality, near-ubiquitous nosocomial spread, and a depleted therapeutic pipeline. No antibiotic chemical class with a genuinely novel target and activity against A. baumannii reached patients for more than fifty years, and current options—sulbactam–durlobactam, cefiderocol, polymyxins, high-dose ampicillin–sulbactam and tetracyclines—are constrained by toxicity, inconsistent efficacy, or emerging resistance. Against this background, zosurabalpin (RG6006), the first member of the tethered macrocyclic peptide (MCP) class, represents a potentially important conceptual advance. Identified through whole-cell phenotypic screening of nearly 45,000 macrocyclic peptides and optimized into a zwitterionic clinical candidate, zosurabalpin inhibits the LptB₂FGC complex, the inner-membrane ATP-binding-cassette transporter that initiates lipopolysaccharide (LPS) export. By trapping LPS within the transporter, the drug causes lethal accumulation of the molecule at the inner membrane. This mechanism is structurally distinct from that of every clinically used antibiotic and, in preclinical studies, is not affected by the major currently recognized CRAB resistance mechanisms. Zosurabalpin shows potent, narrow-spectrum activity essentially restricted to the Acinetobacter baumannii–calcoaceticus complex, retaining activity in vitro against isolates resistant to cefiderocol and last-line agents; its clinical efficacy in patients, however, remains to be established. Here we review the discovery, structural mechanism, microbiological spectrum, and clinical development of zosurabalpin, and we situate it within a broader revival of pathogen-specific (narrow-spectrum) antibiotic development, discussing the diagnostic, stewardship, and economic implications of this paradigm. Full article

Preterm birth is associated with a higher risk of neurodevelopmental adverse outcomes later in life. This increased risk is partly due to interrupted brain development during critical early periods. Early nutrition is a key factor that can influence both brain growth and the development of the gut microbiota, which plays an important role in overall health. Evidence shows that human milk, including fortified human milk, supports the growth of beneficial gut bacteria such as Bifidobacterium and Lactobacillus. These bacteria help protect the immature intestine, reduce inflammation, and support normal development. In contrast, formula feeding, frequent use of antibiotics, and perinatal stress, common conditions for preterm infants in neonatal intensive care units, can disturb the normal development of the gut microbiota. These factors may lead to dysbiosis, a state in which harmful bacteria become more dominant. Early changes in gut microbiota may affect brain development through the gut–brain axis. This communication system connects the gut and the brain through immune responses, metabolic products, and hormonal pathways. Disruption of this system during early life may have long-term effects on cognitive, motor, and behavioral development. Both clinical and experimental studies suggest that improving early nutrition may support better neurodevelopmental outcomes. Nutritional strategies such as optimizing protein and energy intake and using probiotics or prebiotics may help promote a healthier gut microbiota and support brain development. In conclusion, early nutrition in preterm infants plays a crucial role during a sensitive period of brain development. By supporting healthy gut microbiota formation, early nutritional interventions may help improve long-term neurodevelopmental outcomes in this vulnerable population. The aim of this narrative review is to explore the relationship between early nutrition, gut microbiota development, and later neurodevelopment in preterm neonates. Full article

Sustainable rabbit production requires effective nutritional strategies to enhance productivity, health status, and immune competence. Following the restriction of antibiotic growth promoters, organic acids (OAs) have gotten increasing attention as promising functional feed additives due to their multiple biological roles. This review aims to offer a comprehensive overview of the functional roles of OAs in rabbit nutrition, with a focus on their effects on gut morphology, nutrient digestibility, intestinal microbiota, antioxidative status, immunity, and growth performance in growing rabbits. The OAs may modulate gut microbiota balance through inhibition of pathogenic bacteria and promotion of beneficial microbial populations, thereby contributing to the establishment of a balanced intestinal ecosystem. This effect is particularly important during the post-weaning period, a critical stage characterized by increased susceptibility to enteric disorders and associated economic losses. The OAs may also enhance digestive enzyme activities, leading to improving nutrient digestibility, feed efficiency, and reducing feed wastage. In addition, OAs have been shown to improve intestinal histomorphology through coordinated effects on epithelial proliferation, mucosal renewal, and tight junction integrity. Furthermore, OAs have been shown to modulate antioxidative status and immune responses, which are essential for maintaining intestinal health and overall production sustainability. Collectively, OAs represent a promising and viable nutritional strategy to enhance the sustainability and efficiency of rabbit production systems through their beneficial effects on gut health, nutrient utilization, immune competence, and antioxidative status. Full article

The increasing prevalence of antimicrobial resistance (AMR) has promoted the development of advanced biomaterials capable of overcoming the limitations of conventional antibiotics. In this context, metal nanoparticle hybrid hydrogels (MNHHs) have emerged as multifunctional platforms that integrate the high water-retention capacity and biocompatibility of hydrogels with the antimicrobial properties of metallic nanoparticles (MNPs). This review critically analyzes recent advances in the design, physicochemical properties, antimicrobial mechanisms, and biomedical applications of these systems. Current evidence demonstrates that MNHHs can achieve antimicrobial efficiencies above 98–99%, with minimum inhibitory concentrations as low as 0.78 µg mL⁻¹ and inhibition zones of up to 25 mm against clinically relevant pathogens. Furthermore, the incorporation of MNPs significantly improves the mechanical properties of hydrogels and enables controlled and sustained metal ion release for periods of up to 14 days. Despite these promising results, important challenges remain regarding cytotoxicity, release control, the lack of experimental standardization, and the limited understanding of long-term biological effects. Overall, MNHHs represent a promising strategy for infection control, regenerative medicine, and controlled drug delivery; however, their clinical translation still requires the development of reproducible, safe, scalable, and highly biocompatible systems. Full article

Water solubility is a key physicochemical property during drug development, yet about 90% of new drug candidates exhibit low solubility. Numerous approaches have been proposed to enhance drug solubility, including physical modification and the use of solubilizing agents, formulation modifications, and nanotechnology techniques. Increasing both the solubility and dissolution rate of the drug substance is an important element of drug formulation technology, aimed at improving therapeutic efficacy and bringing economic benefits—both in the production process and by reducing the cost of therapy for the patient. Moreover, enhancing solubility helps reduce dosing, which is key to combating antibiotic overuse and resistance. This article reviews the newest methods and effects for increasing solubility and the dissolution rate of antibacterial substances in biopharmaceutics classification system (BCS) class IV, characterized by low water solubility and limited intestinal permeability. Particular attention was paid to summarizing the newest strategies to guide future formulation development and critically evaluate the literature. Full article

The sorption behavior of antibiotics in wastewater treatment systems plays a critical role in determining their environmental fate and removal efficiency. In this study, the sorption of 15 antibiotics representing multiple classes was investigated using two sewage sludge samples with different physicochemical characteristics. Batch equilibrium experiments were conducted to evaluate time-dependent sorption behavior and to determine solid–water distribution coefficients (K_d). The results showed that sorption occurred rapidly, with most compounds approaching a stable concentration within 24 h. The K_d values varied widely depending on the compound, ranging from 74 to 737 L/kg. For 13 of the 15 investigated antibiotics, higher K_d values were observed in sludge B than in sludge A, with the largest difference observed for tiamulin (402 ± 53 and 737 ± 76 L/kg for sludge A and sludge B, respectively). Sludge B generally exhibited higher sorption capacity for most compounds than sludge A, despite having a lower specific surface area, indicating that sorption was governed primarily by chemical composition and pore structure rather than surface area alone. Elemental and morphological analyses suggested that differences in metal-associated components and pore structure may contribute to the higher sorption capacity observed in sludge B. However, the specific sorption mechanisms could not be directly confirmed by the present analyses. Comparison with previous studies confirmed that the measured K_d values fall within reported ranges but are generally higher for sulfonamides, suggesting enhanced sorption capacity of the investigated sludge matrices. Application of an equilibrium-based model demonstrated that sorption alone can account for approximately 20–70% of antibiotic removal under typical activated sludge conditions, depending on compound affinity. These findings highlight the importance of sludge-specific properties in controlling antibiotic partitioning and demonstrate that incorporating such characteristics into predictive models can improve the accuracy of environmental fate assessments in wastewater treatment systems. Full article

Background: Robust antimicrobial consumption monitoring and correlation with antibiotic resistance trends is critical to informing evidence-based antimicrobial stewardship and is recommended by the World Health Organization Global Action Plan on the containment of antimicrobial resistance. We estimated national and hospital-level antibacterial consumption patterns in Kenya. Materials and methods: National consumption data (January 2023–December 2024) was derived from aggregated import and donation permits at the Pharmacy and Poisons Board and standardized using the WHO ATC/DDD Index 2025. Consumption data for 2020 and 2021 that had been previously submitted by Kenya to WHO GLASS was retrieved and incorporated to allow a description of trends. Hospital-level data was collected from ten facilities across the country for the period from January 2024 to April 2025. Quality of use was evaluated using the WHO Access, Watch, and Reserve (AWaRe) categorisation with high-consumption antibiotics identified using the Drug Utilization 75% metric. Results: There was a gradual increase in national antibiotic consumption from 14.3 DID in 2020 to 22.2 DID in 2024. Oral formulations accounted for more than three quarters of antibiotics consumed. Access category antibiotic consumption ranged from 50.4% to 56.9% nationally and was 61.2% at hospital level. The national consumption of Watch antibiotics increased from 38.9% in 2020 to 46.1% in 2023 and declined to 40.7% in 2024. Amoxicillin and amoxicillin/clavulanic acid were the most commonly consumed antibiotics nationally in 2020 (40%), 2021 (27%) and 2024 (33%). Azithromycin was the most commonly consumed antibiotic in 2023 (27%), rising from 10% in 2020. Among parenteral antibiotics, benzylpenicillin was the most commonly consumed in 2020 and 2021, while ceftriaxone was the most commonly consumed agent in 2023 (24%) and 2024 (41%). At hospital level, ceftriaxone accounted for 56.5% of parenteral antibiotic use in county referral hospitals. Conclusions: Kenya’s antibacterial consumption is increasing. Use of Access antibiotics remains below the WHO target of 60%. The increasing use of Watch antibiotics, and in particular ceftriaxone and azithromycin, needs to be addressed to support Kenya’s efforts against antimicrobial resistance. Full article

Background/Objectives: Listeria monocytogenes is a critical foodborne pathogen, with poultry products serving as a potential reservoir. Its ability to form biofilms may aid in its persistence on processing equipment and food-contact surfaces, while antibiotic resistance complicates efforts to control and treat infections. This study aimed to characterize, in parallel, the biofilm-forming capacity and antibiotic susceptibility of a large collection of poultry-derived L. monocytogenes isolates (n = 93) to better understand their potential for persistence and to clarify how the biofilm phenotype may relate to the bacterial antibiotic response and to inform risk assessment and targeted control strategies along poultry processing and supply chains. Methods: Biofilms were evaluated on polystyrene microtiter plates at 12 and 30 °C in a nutrient-rich laboratory medium. Susceptibility to eight clinically and food-relevant antibiotics was tested using disk diffusion and interpreted according to European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoints when available. Results: At 30 °C for 48 h, 69.9% of isolates were classified as weak biofilm formers and 30.1% as non-biofilm formers, whereas at 12 °C for 120 h, 55.9% were weak, 16.1% moderate, and 28.0% non-biofilm formers, with no strong biofilm producers identified under either condition. Overall, the isolates remained largely susceptible to ampicillin, penicillin G, vancomycin, tetracycline, and chloramphenicol, with 87.3% of inhibition zones across all drugs falling within the 20–29 mm and 30–39 mm categories, while small subpopulations showed reduced susceptibility or resistance to trimethoprim–sulphamethoxazole (TMP-SMX) and, particularly, erythromycin and streptomycin. No consistent correlation was found between biofilm-forming ability and antibiotic susceptibility, indicating that these phenotypic traits are largely independent in this collection. Conclusions: These findings reveal that poultry-derived L. monocytogenes isolates can form weak to moderate biofilms under the tested monoculture conditions while generally maintaining susceptibility to first-line antibiotics. However, the development of macrolide- and aminoglycoside-resistant subpopulations, along with the potential for increased colonization within complex multispecies biofilms in real processing environments, emphasizes the importance of ongoing integrated surveillance across animal food systems. Full article