Search Results (2,487)

Background: Driveline infection (DLI) is the most common device-specific infection in patients supported with ventricular assist devices (VADs) and remains a major cause of morbidity during long-term mechanical circulatory support. This study aimed to evaluate the incidence, risk factors, microbiological characteristics, and antimicrobial resistance patterns of DLIs in patients undergoing durable left ventricular assist device (LVAD) implantation. Methods: This retrospective cohort study included 772 consecutive patients who underwent durable LVAD implantation at a single tertiary center between January 2012 and December 2024. Patients were categorized according to the development of DLI: the DLI group (n = 158) and the non-DLI group (n = 614). Demographic, clinical, laboratory, perioperative, and postoperative variables were analyzed. Multivariate logistic regression analysis was performed to identify independent predictors of DLI. Microbiological isolates and antimicrobial resistance patterns were also evaluated. Results: Driveline infection developed in 20.5% of patients during follow-up. Patients with DLI had a significantly higher body mass index (26.4 vs. 24.8 kg/m², p = 0.002) and a higher prevalence of diabetes mellitus (28.2% vs. 12.1%, p < 0.001). In multivariate analysis, diabetes mellitus (OR 3.29, p = 0.013) and longer LVAD support duration (p = 0.003) were independently associated with DLI. Device type showed differences in crude infection rates but was not an independent predictor. The most frequently isolated pathogens were Staphylococcus aureus (36%) and Pseudomonas aeruginosa (19%). The most common antimicrobial resistance patterns included fluoroquinolone resistance (23%), methicillin-resistant Staphylococcus aureus (10%), and resistance to piperacillin/tazobactam and carbapenems. Conclusions: In this large single-center cohort, diabetes mellitus and prolonged device support duration were the main independent predictors of driveline infection. Staphylococcus aureus and Pseudomonas aeruginosa were the predominant pathogens, with notable antimicrobial resistance patterns. These findings highlight the importance of metabolic optimization, meticulous driveline exit-site care, and structured long-term surveillance strategies for reducing infection risk in LVAD recipients. Full article

Background: Shikonins are natural naphthoquinones that exhibit a range of biological activities. They are typically extracted using nonpolar solvents; however, green extraction approaches remain underexplored. Methods: Phytochemical profiling of E. vulgare root extracts was performed using HPLC-ESI-QTOF-MS/MS and quantitative analysis using HPLC-PDA. Shikonin extraction was performed using VNADESs based on thymol, camphor, menthol and benzyl alcohol. The feasibility of removing the VNADES from the extracts via freeze-drying was assessed. The cytotoxic, antioxidant, anti-inflammatory and antimicrobial activities of the hexane extract and the selected VNADES-based extract (TBa 2:8) were compared. Results: Eight shikonin derivatives were identified in the extracts. VNADES extracts contained comparable amounts of shikonin to hexane extracts; however, freeze-drying resulted in significant shikonin content loss. TBa 2:8 extract exhibited noticeably lower cytotoxicity than the hexane extract while its antioxidant potential depended on the assay applied. In contrast to the hexane extract, TBa 2:8 demonstrated the ability to reduce intracellular ROS and NO levels. However, the hexane extract exhibited stronger antimicrobial activity. Conclusions: VNADES systems enable efficient extraction of shikonin derivatives with performance comparable to hexane. Although the resulting extracts exhibit multidirectional biological activity, it remains challenging to remove the VNADESs effectively without losing the shikonins. Full article

The rapid emergence of multi-drug resistant (MDR) bacteria has become a major health concern, driving the need to identify new antimicrobial resources. Recently, endophytes, inhabiting in internal tissues of medicinal plants, have drew important interest from the scientific community, as reservoirs of bioactive metabolites. Numerous studies highlight the symbiotic relationship between plants and their endophytes, in which these microorganisms produce antimicrobial compounds, helping the host plant’s defense against pathogens. Plantago major (commonly known as plantain) is widely recognized for its therapeutic properties, especially for its antimicrobial properties. In this study, endophytic fungi were isolated from Plantago major, morphologically characterized and identified using ITS sequencing. Their antibacterial activity was assessed using the agar diffusion assay. In total, 21 endophytic fungal isolates were obtained from different plant tissues, including leaves, stems, roots, and flowers. Antibacterial assays against methicillin-resistant Staphylococcus aureus (MRSA) were investigated on PDA, SDA, and CDA media. Amongst the isolates, nine strains (MD-H1, MD-L1, MD-L2, MD-L3, MD-L4, MD-L5, MD-R1, MD-T1, MD-T2, and MD-T10) showed medium to strong antibacterial effects, with inhibition zones exceeding 15 mm. The result suggests that endophytic fungi associated with Plantago is a valuable source of anti-MRSA compounds. Further work will focus on identifying the secondary metabolites responsible for this activity and elucidating their chemical structures, providing a basis for the development of new potent antibiotic agents. Full article

Background/Objectives: Infective endocarditis (IE) carries substantial mortality, particularly in middle-income settings where patient profiles and microbial ecology differ from those of cohorts used to derive international prognostic scores. Syndrome-specific, locally grounded decision aids for empirical therapy are also scarce. We aimed to identify predictors of in-hospital mortality, externally evaluate the RiskE and ICE scores, and construct a Bayesian weighted-incidence syndromic combination antibiogram (WISCA) for IE. Methods: We conducted a retrospective cohort study of consecutive adults with definite or possible IE admitted between January 2019 and January 2026. Candidate predictors were screened in two phases, and a clinically specified model was estimated with maximum-likelihood and Firth penalization, with 1000-replicate bootstrap optimism correction. Calibration was assessed with bootstrap calibration plots and the Hosmer–Lemeshow test. Discrimination was compared against RiskE and ICE using DeLong’s test and reclassification metrics. For empirical coverage, we built a WISCA using identified pathogens, reporting both non-Bayesian bootstrap estimates and Bayesian hierarchical partial-pooling estimates with species- and antibiotic-level random intercepts; analyses were also stratified by IE type. Results: In-hospital mortality was 22.9% in a young cohort (median 37 years) characterized by high hemodialysis prevalence (47.4%), substantial right-sided IE (46.4%), and Staphylococcus aureus predominance (32%) with no methicillin-resistant isolates. Vasopressor-requiring shock (Firth OR 9.23, 95% CI 2.40–40.61) and acute heart failure (OR 10.01, 95% CI 2.78–41.07) were the strongest predictors; the final model achieved an AUC of 0.922 (optimism-corrected 0.908), significantly outperforming RiskE (0.598) and ICE (0.632). The Bayesian WISCA identified multiple carbapenem-sparing and anti-MRSA–sparing regimens with adequate coverage (≥80%), particularly for community-acquired IE, supporting stewardship-oriented empirical selection. Coverage was consistently lower in healthcare-associated IE. Conclusions: A parsimonious three-variable model provided strong, locally valid mortality prediction in this hemodialysis-predominant, MRSA-free cohort, substantially outperforming European-derived scores. External validation in independent cohorts is required before clinical adoption. The Bayesian WISCA demonstrated that adequate empirical coverage is achievable without routine broad-spectrum agents, offering institution-specific guidance for stewardship-compatible regimen selection; multicenter validation is warranted. Full article

Neonatal infections remain a leading cause of morbidity and mortality worldwide, particularly among preterm and low-birth-weight infants and in low- and middle-income countries. This burden has intensified with the global increase in multidrug-resistant (MDR) bacteria, especially in neonatal intensive care units, where prolonged hospitalization, invasive interventions, and exposure to broad-spectrum antibiotics promote colonization, transmission, and invasive infection. In this narrative review, we explore the epidemiology and microbiological characteristics of MDR bacterial infections in newborns, alongside their associated risk factors, diagnostic challenges, treatment outcomes, and prevention strategies. Across different settings, Gram-negative pathogens, particularly Klebsiella pneumoniae, Escherichia coli, and Acinetobacter baumannii, account for a substantial proportion of severe neonatal infections, whereas methicillin-resistant Staphylococcus aureus remains important in selected units. The risk of MDR infection is driven by a complex interplay of factors, ranging from maternal and perinatal exposures to the inherent immunological vulnerability of newborns, hospital-based transmission, antibiotic selection pressure, and structural deficiencies in healthcare infrastructure. Diagnosis remains challenging because clinical presentations are nonspecific and culture-based methods are constrained by low blood volumes, prior antimicrobial exposure, and delayed turnaround times. Treatment is increasingly complicated due to resistance to standard empirical regimens, substantial regional variation in susceptibility profiles, and limited neonatal pharmacokinetic and safety data for reserve agents. Current evidence mainly supports surveillance-informed empirical therapy, susceptibility-guided treatment adjustment, antimicrobial stewardship, and strict infection prevention measures. Future progress will require neonatal-specific clinical trials, harmonized surveillance systems, stronger molecular epidemiology, and more equitable access to microbiological diagnostics and effective treatment. Full article

Background/Objectives: Methicillin-resistant Staphylococcus aureus (MRSA) is a multidrug-resistant pathogen that poses a major public health concern. It predominantly infects immunocompromised individuals and is frequently associated with severe pulmonary complications, including acute lung injury. Diosmetin, a natural flavonoid, known for its anti-inflammatory, antioxidant, and anti-infective properties. Nevertheless, its therapeutic mechanism in the treatment of acute pneumonia induced by MRSA remains unclear. Methods: In this study, we employed network pharmacology and molecular docking to elucidate the mechanisms underlying the therapeutic effect of diosmetin against MRSA-induced pneumonia. An MRSA pneumonia model was established in Balb/c mice. The impacts of diosmetin on murine pneumonia were evaluated by detecting biochemical indicators via HE staining, ELISA, RT-qPCR, and WB. In vitro experiments utilized RAW264.7 macrophages to establish an MRSA infection model for further validation of the therapeutic mechanisms of diosmetin. Results: In vivo results demonstrated that diosmetin alleviated MRSA-induced lung injury and reduced mortality by inhibiting the release of pro-inflammatory cytokines. Furthermore, compared with model mice, diosmetin-treated mice showed reduced phosphorylation levels of NLRP3, pro-caspase-1, ASC, and NF-κB p65, along with an increased level of IκBα in lung tissue. In vitro experiments indicated that diosmetin effectively reduced the levels of pro-inflammatory cytokines in MRSA-infected RAW264.7 macrophages and exerted anti-inflammatory effects by modulating the expression of NLRP3, pro-caspase-1, ASC, IκBα, and NF-κB p65. Conclusions: Our results demonstrate that diosmetin alleviates MRSA-induced pneumonia in mice, and this protective effect is achieved through dual inhibition of the NF-κB/NLRP3 inflammasome axis. Full article

Background/Objectives: Staphylococcus aureus, particularly methicillin-resistant strains, is a leading cause of severe pneumonia. Understanding local molecular epidemiology, including virulence gene profiles and antimicrobial resistance (AMR) mechanisms, is crucial for effective infection control. This pilot study aimed to characterize S. aureus isolates from pneumonia patients in Karaganda, Kazakhstan. Methods: We collected 48 respiratory samples from patients with pneumonia across three medical institutions. Bacterial identification was performed using MALDI-TOF MS. Antimicrobial susceptibility testing (AST) was carried out using European Committee on Antimicrobial Susceptibility Testing (EUCAST) guidelines. Whole-genome sequencing of S. aureus isolates was conducted on an Ion Torrent S5 platform. Genomic analysis included multilocus sequence typing (MLST), identification of virulence and AMR genes, and phylogenetic reconstruction. Results: S. aureus was identified in 14.6% (n = 7) of pneumonia cases included in this study. All isolates (100%, n = 7) were phenotypically resistant to benzylpenicillin. The mecA gene was detected in 57.1% of isolates (n = 4), while phenotypic resistance to methicillin was observed in 28.6% (n = 2) of the isolates. Resistance to azithromycin (57.1%, n = 4) and levofloxacin (42.9%, n = 3) was observed among the isolates. Two isolates (28.6%) were multidrug-resistant (MDR). Genomic analysis revealed the prevalence of the ST22 clone (57.1%, n = 4) in the studied cohort. Other sequence types were ST97, ST8, and ST45 (14.3% each). Phylogenetic analysis showed clustering consistent with MLST profiles. All isolates carried a conserved core virulence arsenal, including hemolysin (hla, hlg), biofilm-forming genes (icaADBC), immune evasion genes (sak, scn), and iron acquisition genes (isd). The Panton–Valentine leukocidin (PVL) genes were detected in three isolates. AMR gene analysis revealed the ubiquitous presence of mepA and tetracycline efflux pump genes, along with regulatory genes (arlRS, mepR, mgrA). The blaZ and ermA genes were not detected despite high phenotypic resistance to penicillin and macrolides. Conclusions: This study reports the identification of the virulent and resistant ST22 S. aureus clone in pneumonia cases in Karaganda, Kazakhstan. The discordance between phenotypic and genotypic AMR profiles underscores the necessity for integrated diagnostic approaches. Full article

Methicillin-resistant Staphylococcus aureus (MRSA) is a major antimicrobial-resistant pathogen affecting both human and animal health. Although historically associated with healthcare settings, MRSA is now established in livestock production and throughout the production chain. Its detection in animals, food products, and processing environments reflects the complex ecology of antimicrobial resistance (AMR) in modern food systems. This narrative review synthesizes current evidence on the molecular basis of methicillin resistance and multidrug resistance determinants, as well as the epidemiology of MRSA in food-associated settings. Particular emphasis is placed on its occurrence in animal-derived foods and key reservoirs within farms, slaughterhouses, and processing environments. Livestock-associated populations are dominated by clonal complex CC398. In contrast, CC9 is prevalent in pig production systems in Asia, while CC5-related lineages occur at the human and animal interface. MRSA has been detected in retail meat and animal-derived foods at low but measurable prevalence, indicating contamination during slaughter and processing. Virulence determinants include staphylococcal enterotoxins linked to food poisoning and Panton–Valentine leukocidin associated with severe infections. Biofilm formation and adhesins further support persistence and colonization. Epidemiological and molecular evidence indicates that livestock, processing environments, and food-contact surfaces act as interconnected reservoirs sustaining MRSA circulation. Human exposure occurs primarily through occupational contact and environmental pathways, whereas foodborne transmission appears less common. Effective control requires integrated surveillance, responsible antimicrobial use in livestock production, and strict hygiene practices throughout the production chain within a One Health framework. Full article

Antimicrobial resistance (AMR) is an increasing concern in veterinary medicine and may compromise empirical treatment of feline urinary tract infections (UTIs). This retrospective observational study evaluated antimicrobial resistance patterns and their association with multidrug resistance (MDR) in bacterial isolates obtained from urine cultures of cats presented to a feline referral practice in Lisbon, Portugal, between January 2023 and December 2025. A total of 174 cats with positive urine cultures were included, yielding 178 bacterial isolates. Escherichia coli was the most frequent pathogen (57.30%), followed by Enterococcus spp. (16.98%) and Staphylococcus spp. (14.61%). Antimicrobial resistance was detected in 107/178 isolates (60.11%), and 76/178 (42.70%) were classified as multidrug-resistant. Extended-spectrum beta-lactamase-producing Escherichia coli and methicillin-resistant Staphylococcus strains were also identified. Resistance to penicillins and fluoroquinolones was significantly associated with MDR (p < 0.001). These findings highlight the high burden of antimicrobial resistance in feline urinary isolates in this clinical setting and support routine urine culture and susceptibility testing to guide therapeutic decision-making, particularly in recurrent, complicated, or high-risk cases. Full article

Methicillin-resistant Staphylococcus aureus (MRSA) is a major clinical problem due to its resistance, virulence, and biofilm formation, which diminish antibiotic efficacy. This review explores natural products and antimicrobial nanoparticles (NPs) as alternative and combined strategies for controlling MRSA. Natural compounds, such as plant metabolites, essential oils, antimicrobial peptides, and fungal products, act by disrupting membranes, interfering with cellular processes, and limiting biofilm formation. Antimicrobial NPs, especially metal and metal oxide materials, act through membrane damage, oxidative stress, and metal ion release, enabling activity against resistant bacteria and improving biofilm penetration. Combining natural products with NPs increases stability, delivery, and local activity, enhances antibacterial effects, and reduces effective doses. Green synthesis enables direct integration of bioactive compounds, while nano-delivery platforms optimize solubility and controlled release. Nanotechnology-based applications such as wound dressings, nanocarriers, and multifunctional platforms support localized and sustained treatment and promote tissue repair. Despite these advances, clinical use is still constrained by safety concerns, variability in NP properties, and the lack of standardized evaluation and regulatory frameworks. Overall, combining natural products with antimicrobial NPs offers a practical strategy to augment MRSA treatment, but further progress depends on consistent design, robust safety evaluation, and clinical translation. Full article

Super oxidized water is a disinfectant generated by electrolysis whose effectiveness depends mainly on oxidation–reduction potential and pH. In this study, a 2² factorial Design of Experiments was applied to evaluate the influence of applied potential (8.2–12.2 V) and NaCl concentration (0.05–0.25 wt.%) on the redox properties of SOW, aiming to produce solutions with targeted disinfection profiles. The obtained models showed excellent predictive capacity (R² > 0.99), identifying NaCl concentration as the most influential factor affecting both oxidation–reduction potential and pH. The system enabled the controlled generation of SOW with ORP values ranging from approximately 950 to 1100 mV and pH between ~3.8 and 5.0, with experimental errors below 1.5%. Stability tests demonstrated that oxidation–reduction potential and pH remained within ±25 mV and ±0.15 units, respectively, over 24 weeks of storage. Microbiological evaluation revealed effective antimicrobial activity against Escherichia coli, Staphylococcus aureus, methicillin-resistant Staphylococcus aureus, and Candida albicans, with inhibition halos of up to ~5 mm depending on ORP and microorganism. The results demonstrate that Design of Experiments enables precise adjustment of SOW redox properties, allowing optimization of antimicrobial performance for specific applications. This positions super oxidized water as a flexible, stable, and scalable disinfection technology for industrial and clinical use. Full article

Background: Eravaycline is a novel fully synthetic fluorocycline that is currently approved for complicated intra-abdominal infections. However, it is sometimes also used off-label in tertiary care centers for other infection sites as an antibiotic of last resort due to its broad spectrum of activity and efficacy against Enterobacterales, including multidrug-resistant pathogens like extended spectrum β-lactamase (ESBL) producers or carbapenem-resistant Enterobacterales, as well as all Gram-positive organisms including methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin- and linezolid-resistant Enterococcus faecium (VRE). Methods: We retrospectively included a total of 78 patients from Austria and Udine who received eravacycline between April 2023 and August 2024 to evaluate the real-world efficacy of eravacycline in various infection sites and pathogens using descriptive statistics. Results: Eravacycline was most commonly used in intra-abdominal infections (44.9%), followed by pneumonia (12.8%) and infections of unknown origin (7.7%). Escherichia coli, including ESBL producers, was the most common pathogen (24.4%), followed by Enterococcus spp. (12.8%) and Klebsiella pneumoniae (12.8%). Clinical cure was achieved in 65% of patients, whereas microbiological cure was documented in 46%; source control was attained in 48.7%, and 16.7% died within 30 days. A total of 48% of patients required intensive care. Conclusions: Eravacycline represents a possible therapeutic option for a wide range of pathogens, but its use must be evaluated in the context of infection site and severity. Full article

Background/Objectives: The Korean Global Antimicrobial Resistance Surveillance System monitors bloodstream Staphylococcus aureus infections by combining antimicrobial susceptibility testing (AST) with conventional polymerase chain reaction (PCR). Considering the clinical significance of methicillin-resistant S. aureus (MRSA), we performed an in-depth analysis of isolates showing genotypic–phenotypic discrepancies. Methods: Isolates were collected from designated collection centers in the Republic of Korea between 2017 and 2024. The 30 μg cefoxitin disk diffusion method was used to define the phenotypes. PCR targeting mecA and the staphylococcal cassette chromosome mec (SCCmec) was used to identify genotypes through gel electrophoresis. Long-read whole-genome sequencing (WGS) was performed using the Revio system (Pacific Biosciences) for isolates exhibiting discrepancies between phenotypes and genotypes. Results: In total, 5808 isolates were screened, and seven cases of genotypic–phenotypic discrepancies were identified, including one infant and six elderly patients with chromosomal SCCmec type IV. Although WGS confirmed intact PCR primer-binding sites, structural alterations were observed: three isolates had normal-length mecA and mecR1, two had partial deletions in mecA, and two featured either mecA or mecR1 split into two proteins. Notably, although the six isolates with intact mecR1 genes matched the nucleotide length of SCCmec type IV, their sequences exhibited high homology with SCCmec type II. Conclusions: Despite the presence of mecA, the non-standard configuration of regulatory genes within the SCCmec elements suppressed actual resistance expression. Because conventional PCR focusing on partial gene segments could overlook such phenotypic traits, the meticulous observation and implementation of WGS are crucial for the accurate characterization of genotypic–phenotypic discrepancies. Full article

Lactic Acid Bacteria (LAB)-derived antimicrobial compounds are recognized as a promising source of novel antimicrobial agents, particularly for the treatment of Methicillin-Resistant Staphylococcus aureus (MRSA), where the mode of action and associated cellular effects remain largely unexplored. This study aims to evaluate antibacterial activity of Limosilactobacillus fermentum YTPP05 isolated from pickled radish against MRSA. Upon the initial antibacterial evaluations, it was found that strain YTPP05 inhibited the growth of MRSA isolates. Multiplex PCR identified multiple resistance genes in our MRSA strains, including mecA, blaZ, and aacA genes, aligning with antibacterial susceptibility profiles determined by the disc diffusion assay. An agar overlay assay showed that YTPP05 possessed antibacterial potential, with the largest inhibition zone diameters of 40.83 ± 8.43 mm, while the inhibition zones of the Cell Free Supernatant (CFS) of YTPP05 by an agar well diffusion were 27.16 ± 2.93 mm against the MRSA isolates. The minimum inhibitory concentration and minimum bactericidal concentration of YTPP05-derived CFS were 125 mg/mL. Scanning Electron Microscopy (SEM) demonstrated YTPP05 extracts caused cell membrane disruption, bubble-like protrusion, and cell lysis. Collectively, this study highlights the anti-MRSA potential of YTPP05 as an alternative antimicrobial agent for combating MRSA infections. Full article

Background/Objectives: The emergence of methicillin-resistant Staphylococcus aureus (MRSA) necessitates innovative strategies to overcome conventional resistance mechanisms. This study investigated the potential of the natural flavonolignan silibinin (SIL) as an antivirulence agent against S. aureus, with a particular emphasis on its putative multi-target antibacterial activity and its capacity to potentiate the effects of ciprofloxacin (CIP). Methods: The antibacterial and antivirulence properties of SIL were assessed using both in vitro and in silico approaches. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were determined, and its synergistic interaction with CIP was evaluated using checkerboard assays. Inhibition of biofilm formation, as well as disruption of established biofilms, was assessed using an MTT-based viability assay. Staphyloxanthin (STX) inhibition was examined through pigment extraction and spectrophotometric quantification of pathway intermediates. Molecular docking studies were conducted to predict the binding affinities of the compounds to key bacterial targets, while safety was evaluated through haemolytic and cytotoxicity assays. Results: SIL exhibited weak to moderate direct antibacterial activity (MICs of 256–512 µg/mL), which is characteristic of many natural product scaffolds. Notably, SIL potentiated the activity of CIP, reducing its MIC by up to fourfold against selected resistant strains of S. aureus. SIL significantly inhibited biofilm formation and disrupted established mature biofilms in a strain-dependent manner. In vitro metabolic profiling and in silico analyses provided mechanistic insights into the effects of SIL on STX biosynthesis. Precursor accumulation data suggest inhibition at the diapophytoene desaturase (CrtN) catalytic step, representing a potential mechanism not previously reported for flavonolignans. Molecular docking studies further predicted favourable binding affinities for CrtM and other key targets. Importantly, SIL exhibited no haemolytic activity and low cytotoxicity in macrophages at synergistic concentrations. Conclusions: This study provides evidence that SIL functions as a dual-action agent, potentiating ciprofloxacin efficacy while reducing STX production and inhibiting biofilm formation, thereby impairing key virulence mechanisms of S. aureus. These findings, together with its favourable safety profile, provide a strong rationale for the development of silibinin-based topical adjuvants to combat drug-resistant Staphylococcus infections in humans. Full article