Search Results (985)

Background/Objectives: Staphylococcus aureus is one of the leading causes of bacterial infection-related mortality worldwide, with outcomes complicated by antimicrobial resistance; asymptomatic colonization (~30% of the population) increases the risk of subsequent infection, often with the colonizing strain. Comprehensive data from LMICs are lacking, and the COVID-19 pandemic has significantly influenced the incidence and epidemiology of S. aureus infections, highlighting a critical data gap in Slovakia. Methods: We conducted data analysis using the KNIME Analytics Platform (Zurich, Switzerland), an open-source, visual workflow environment that facilitates integration, preprocessing, and advanced analysis. This study analyzed 5 years of data from routine laboratory diagnostics extracted from the laboratory information system (LIS). Results: Our data reveals that the incidence of multidrug-resistant S. aureus, including MRSA, increased during 2020–2022—particularly in surgical departments, where MDR MRSA infection reached up to 12.5 per 1000 discharges—and remained elevated into the post-pandemic period (2023–2025). In contrast, MSSA incidence was consistently higher overall, with colonization rates reaching up to 71 per 1000 discharges in non-surgical departments, and was predominantly driven by colonization rather than infection. Conclusions: This study provides essential insights into the use of big data analytics platforms. Identified gaps, such as information about the difference between colonization vs. infection, and their implementation in the future, together with whole-genome sequencing, set a foundation for epidemiological research purposes in Slovakia. Full article

Background: ESKAPE constitutes a group of six nosocomial bacteria that can evade available antimicrobials due to their great potential to develop multi-drug resistance and biofilm-forming abilities. These pathogens often cause hospital-acquired infections and pose a serious threat to public health. The search for efficient innovative therapeutic strategies to fight ESKAPE bacteria have been intensively investigated topics. One promising approach to fight resistant pathogens and their biofilms is combination therapy, which allows the effectiveness against microorganisms to be increased while reducing the applied concentrations and risks of potential unwanted side effects. Objectives: The object of the study was to determine if there is an interaction of short lipopeptides ((C₁₀)₂-KKKK-NH₂, C₁₆-KK-NH₂) together with erythromycin and tetracycline against pathogens of the ESKAPE group (Acinetobacter baumannii, Enterobacter aerogenes, Enterococcus faecium Klebsiella pneumoniae, Pseudomonas aeruginosa, and Staphylococcus aureus). Methods: The checkerboard assay was used to examine the activity of compounds applied in combinations against ESKAPE strains in planktonic cells and toward biofilms formed by Staphylococcus aures and Pseudomonas aeruginosa. Results: The lipopeptides demonstrated a great potential of their application as additives to conventional antimicrobials against Gram-negative bacteria, including microorganisms within biofilms. 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

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

Staphylococcus aureus is a high-priority pathogen causing skin and soft tissue infections (SSTIs). The frequent resistance to anti-staphylococcal agents exhibited by this underscores the need for accurate diagnostics to guide effective therapy. Therefore, this study aimed to compare phenotypic and genotypic resistance in S. aureus isolates from nasal carriers and SSTIs and to elucidate gene-silencing mechanisms. In total, 355 S. aureus isolates (256 isolated from carriers and 79 from SSTIs) were studied for their phenotypic and genotypic resistance to β-lactams, macrolides, tetracyclines, aminoglycosides, and mupirocin. The silenced mupA gene (low prevalence: 0.6%; 2/335), linked to mupirocin resistance, was sequenced, and expression was assessed via reverse transcription qualitative PCR (RT-qPCR) in all mupA-positive isolates. SSTI isolates showed significantly higher resistance to erythromycin, gentamicin, and mupirocin, along with a higher prevalence of multidrug-resistant strains and ermC and tetM genes. Sequencing revealed multiple mutations in silent mupA, including a critical frameshift (c.372 delA) in a poly(A) tract that brings about premature truncation. RT-qPCR indicated upregulation of silent mupA variants and high variability in functional strains, suggesting that frameshift alone prevents resistance. These findings highlight silent resistance genes as key targets for advancing S. aureus surveillance and for combating emerging threats. 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: Developing novel strategies to combat respiratory infections caused by multidrug-resistant “priority pathogens” like the ESKAPEE Pseudomonas aeruginosa and Staphylococcus aureus is an urgent priority. Methods: We investigated two shortened variants of the proline-rich antimicrobial peptide (PrAMP) B7-005, B7-006 (15-mer) and B7-007 (13-mer). Evaluation included MIC assays against laboratory and clinical multidrug-resistant isolates, mechanistic studies of membrane permeabilization, cytotoxicity testing on BEAS-2B bronchial epithelial cells, and proteolytic stability assays in human elastase and sputum. Results: Despite their reduced size, lower positive charge, and decreased proline content, both variants retained full antimicrobial activity against clinical pathogens with consistent MIC values ≤ 25 µM. These variants exhibit membrane permeabilization in P. aeruginosa but may also relay on a hybrid mode of action involving also intracellular targets. Notably, B7-006 and B7-007 displayed low cytotoxicity compared to the lytic peptide BMAP-18. While B7-007 showed greater susceptibility to proteolytic degradation than its parent B7-005, it preserved partial integrity during the initial hours of exposure. Conclusions: Overall, these findings demonstrate that the B7 scaffold tolerates substantial truncation while preserving potency and selectivity, identifying a minimal 13-amino-acid active core. This work provides critical insights into structure–activity relationships and supports the development of compact, mechanistically versatile antimicrobial peptides to address the growing threat of multidrug-resistant respiratory pathogens. Full article

To date, the problem of mastitis in cattle remains relevant for both the industrial sector and scientific research. Despite numerous active investigations, the causes of this disease have not been fully established. It is postulated that several factors may be involved, such as bacterial pathogens, animal husbandry practices, and weather and climatic conditions. In this study, we selected cows from farms in Yakutia to investigate microbial isolates present in the milk of cows affected by mastitis and treated with antibiotics. Five identified Staphylococcus aureus isolates were investigated using whole-genome sequencing (Illumina sequencing and nanopore sequencing), followed by analysis of virulence factors in the genomes and cultural properties of the isolates. The profile of S. aureus virulence genes (exotoxins, cytotoxins, superantigen-like proteins, adhesins) was identified via WGS. Hemolysin gene (hla) was detected in all isolates. An investigation of the cultural properties of the isolates, specifically through hemolysis of rabbit erythrocytes and Western blot analysis of the culture liquid of S. aureus, revealed different expression levels of alpha-hemolysin among the strains. One isolate (17-21) exhibited the highest secretion level of about 320 ± 37 ng, both in the hemolysis test and immunoblotting assay. An investigation of the isolates’ antibiotic resistance showed that all isolates exhibited multidrug resistance, as confirmed by the presence of antibiotic resistance genes in these isolates. One isolate (7-7) exhibited the broadest range of phenotypic resistance and was resistant to all tested antibiotics (except clindamycin). Phylogenetic analysis suggested that the evolution of these isolates occurred independently in their respective ecological niches, although their transfer from cattle to humans, and vice versa, is possible. Isolates 7-7, 18-22, 33-40, and 35-42 are most typical to Yakutian cattle, while isolate 17-21 might have been introduced from a different region. To the best of our knowledge, this is the first in-depth study into a range of S. aureus isolates associated with mastitis infection in Yakutian cattle. Full article

Antimicrobial resistance is an emerging challenge in veterinary medicine, particularly in dogs, where bacterial skin infections are highly prevalent. Honey and its bioactive extracts have emerged as potential natural alternatives to conventional antimicrobials. This study evaluated the antimicrobial activity of methanolic extracts from four honey types collected in Central Chile against multidrug-resistant (MDR) bacterial isolates from canine patients, including Enterococcus faecium, Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Pasteurella multocida, and Enterobacter cloacae. Antimicrobial potency was assessed by minimum inhibitory concentration (MIC), and phenolics, flavonoids, and antioxidant capacity were quantified. All extracts inhibited bacterial growth, with E. coli, E. faecium and S. aureus being the most susceptible (MIC 3.13% w/v), while Gram-negative bacteria such a P. aeruginosa, P. multocida, and E. cloacae required higher concentrations (MIC 12.5% w/v). Secondary metabolite analysis revealed seasonal and apiary-related variations, with apiary 2 honey showing significantly higher phenolic (195.58 ± 4.28 mg GAE/100 g) and flavonoid (65.46 ± 4.35 mg QE/100 g) contents in summer. In contrast, antioxidant capacity (FRAP) did not differ significantly. These findings indicate that honey’s antimicrobial properties are closely related to its bioactive composition and influenced by season and floral origin, reinforcing its potential as a sustainable alternative to antibiotics in veterinary medicine under the One Health approach. Full article

Background: Ceftobiprole is an advanced-generation cephalosporin approved in Europe in 2013 for various indications, and in the United States (US) in 2024 for community-acquired bacterial pneumonia (CABP), acute bacterial skin and skin structure infections, and Staphylococcus aureus bacteremia, including right-sided endocarditis. Methods: The in vitro activity of ceftobiprole and comparators was evaluated against 2793 Streptococcus pneumoniae causing lower respiratory tract infections in 32 US sites (2016–2020), including against subsets from various geographic regions, resistance phenotypes and prevalent serotypes. Results: Ceftobiprole inhibited 99.5% of all S. pneumoniae at the MIC of ≤0.5 mg/L (MIC_50/90, 0.015/0.25 mg/L). Susceptibilities of 98.2% to 100% were observed for ceftobiprole against isolates originating from each surveyed year or each US Census Division. Ceftobiprole retained activity against isolates resistant to macrolides (98.8%), tetracycline (98.2%), oral penicillin (95.4%), against multidrug-resistant isolates (97.0%), and various serotypes (93.8–100%). Ceftriaxone (97.4%) and amoxicillin–clavulanate (95.1%) also showed elevated susceptibilities overall, but inconsistent results and lower than those observed for ceftobiprole were noted against isolates with elevated penicillin MIC or specific serotypes (i.e., 19A). Conclusions: These in vitro results, coupled with documented clinical efficacy, indicate that ceftobiprole is a valuable option to treat CABP caused by S. pneumoniae in the US. Full article

The increasing prevalence of multidrug-resistant (MDR) pathogens, particularly avian pathogenic Escherichia coli (APEC) and methicillin-resistant Staphylococcus aureus (MRSA), poses a severe threat to the breeding industry and human health. To develop novel antibiotic alternatives, we adopted a “converting virulence into therapy” strategy by leveraging the type VI secretion system (T6SS) of the APEC strain ACN17-20. Guided by the structural analysis of T6SS Protein 00145, we rationally designed a series of amphipathic α-helical polypeptides. Among them, polypeptide A7 emerged as a lead candidate, exhibiting potent broad-spectrum antibacterial activity with negligible cytotoxicity against mammalian cells. Mechanistic studies revealed that A7 exerts a rapid bactericidal effect through a dual mode of action: physical disruption of bacterial membrane integrity leading to cytoplasmic leakage, and induction of lethal oxidative stress via reactive oxygen species (ROS) accumulation. Furthermore, A7 demonstrated excellent efficacy in eradicating pre-formed bacterial biofilms, addressing the challenge of persistent infections in breeding environments. In a mouse sepsis model induced by APEC and MRSA, A7 treatment significantly improved survival rates (60–80%), reduced bacterial loads in vital organs, and attenuated the systemic cytokine storm (TNF-α and IL-1β), thereby alleviating immune-mediated tissue damage. In conclusion, this study identifies polypeptide A7 as a safe therapeutic agent with a dual mechanism of action, providing a promising strategy to combat MDR infections and reduce antibiotic dependence. Full article

Background/Objectives: Methicillin-resistant Staphylococcus aureus (MRSA) causes hospital- and community-acquired infections. MRSA is a highly diverse strain that includes several epidemic clones, including CC45. A previous study conducted among MRSA isolates in Kuwait identified CC45 in two isolates in the early 2000s. This study provides an update on the prevalence and molecular characteristics of CC45 among MRSA isolates in Kuwait hospitals, during 2016–2022. Methods: A total of 13,276 MRSA isolates were collected during 2016–2022 and typed using antibiogram, DNA microarray, Staphylococcal protein A (spa) typing, pulsed-field gel electrophoresis (PFGE), and multi-locus sequence typing (MLST). Results: CC45 was detected in 87 (0.65%) of the 13,276 MRSA isolates. The isolates were resistant to fusidic acid (n = 71), erythromycin (n = 16), and inducible clindamycin resistance (n = 15). Twenty-one isolates were resistant to multiple antibiotics. Spa typing identified 19 types, with t362 (n = 35) and t132 (n = 27) as the dominant types. DNA microarray identified seven genotypes with CC45-MRSA-[IV + fus] (n = 36) and CC45-MRSA-[VI + fus] (n = 30) as the dominant types. MLST identified six sequence types (STs): ST7119, ST508, ST45, ST46, ST9548, and ST10699. PFGE clustered the isolates into two major types, A and B, with type A being the major type (n = 83), mostly consisting of CC45-MRSA-[IV + fus] isolates. The CC45-MRSA-[IV + fus] and CC45-MRSA-[VI + fus] genotypes were detected throughout the study period (2016–2022), whereas the other genotypes were detected less frequently. Conclusions: The CC45-MRSA circulating in Kuwait hospitals comprises genetically diverse isolates that may have originated from different sources. The emergence of multidrug resistance among the isolates poses challenges for therapy and infection prevention. Full article