Search Results (2,431)

Background: Given the increasing problem of antibiotic resistance in A. baumannii, this study examines in vitro how combinations of colistin, meropenem, and sulbactam influence the expression of genes associated with multiresistance in this pathogen. Methods: Three multidrug-resistant strains, isolated from clinical infections in Panama (2022–2023), were identified using Vitek 2 compact. Susceptibility by broth microdilution, qualitative synergy, time-kill curves, and gene expression analysis by quantitative PCR were performed. Results: Synergistic effects were observed for the colistin–meropenem combination in all three strains, while the sulbactam–colistin combination exhibit synergy only in one of the A. baumannii isolates. Time-kill assays revealed bactericidal effects for the colistin–meropenem and sulbactam–colistin combinations. qPCR analyses indicated that colistin, meropenem, and sulbactam modified the expression of the genes under study. Colistin–meropenem and meropenem–sulbactam combinations decreased the expression of blaADC and blaOXA-51, while sulbactam–colistin did not have a significant effect. carO expression levels were not reduced with any antibiotic combination, while adeB expression was reduced with all the combinations tested. omp33–36 expression varied depending on the antibiotic and strain. Conclusions: Therefore, this study offers a new perspective on how rational combinations of clinically used antibiotics have the potential to modulate gene expression and contribute to the control of MDR strains, indicating that high-dose combination therapy with sulbactam and colistin could offer improved efficacy in treating multidrug resistant Acinetobacter baumannii infections. Full article

Pneumococcal meningoencephalitis is a severe infection associated with high morbidity and mortality. Although typically community-acquired, postoperative cases following elective ENT surgery are exceedingly rare. Antimicrobial resistance (AMR) among Streptococcus pneumoniae further complicates management, and missed opportunities for vaccination represent preventable risks. We report a case of a 41-year-old man with multiple comorbidities who developed fulminant S. pneumoniae meningitis 48 h after septoturbinoplasty. The clinical course was atypical, with altered consciousness but no classical meningeal signs, necessitating urgent intubation and intensive care admission. Cerebrospinal fluid cultures identified an MDR pneumococcal strain resistant to penicillin and macrolides but susceptible to vancomycin and meropenem. Empirical therapy with vancomycin and meropenem, combined with adjunctive corticosteroids and multidisciplinary ICU care, led to complete neurological recovery. This case highlights a rare but life-threatening postoperative complication and underscores two critical lessons. First, the growing challenge of multidrug-resistant pneumococcus requires timely recognition, aggressive empiric therapy, and access to effective agents. Second, the absence of pneumococcal vaccination in this high-risk surgical patient illustrates a preventable gap in care. Integrating vaccination screening into preoperative evaluations may reduce the risk of catastrophic postoperative CNS infections. Full article

Citrobacter braakii is an emerging opportunistic pathogen of escalating clinical significance in animal hosts, though its pathogenic mechanisms remain poorly characterized. This study isolated a C. braakii strain (SCGY-1L) from diseased Siniperca chuatsi and confirmed its identity through integrated morphological, physiological, and molecular analyses. Comprehensive genomic sequencing revealed a 5.75 Mb genome comprising one circular chromosome and two plasmids. A Circos plot was constructed to visualize the genomic architecture of strain SCGY-1L, revealing 5482 protein-coding genes, 25 tRNA genes, and 86 rRNA genes. Additionally, 738 virulence-associated genes and 366 antibiotic resistance determinants were annotated, elucidating multidrug-resistant phenotypes including insensitivity to erythromycin and penicillin. Pathogenicity assessment established an LD₅₀ of 1.28 × 10⁶ CFU/mL in infected hosts, with histopathological analysis showing significant hemorrhage and necrosis in target organs (liver, spleen, kidney). Host transcriptome profiling generated 41.21 Gb of high-quality clean data, identifying 2201 differentially expressed genes post-infection (1568 up-regulated; 633 down-regulated). These were significantly enriched in phagocytosis, cytokine-mediated signaling, and inflammatory regulation pathways. These molecular insights establish C. braakii’s mechanistic framework for pathogenesis and host adaptation, providing critical targets for diagnostics and therapeutics against emerging Citrobacter infections. Full article

Infections caused by antibiotic resistant bacteria pose a serious threat to global health, leading to higher medical costs, longer hospital stays, and increased morbidity and mortality. An increasing number of bacteria have been implicated in untreatable infections due to multiple resistance mechanisms. In 2017, the World Health Organization published a list of the most important antibiotic resistant bacteria worldwide, for which there is an urgent need to develop new therapeutic options. In recent years, fortunately, new antibiotics have been approved for the treatment of infections caused by multidrug-resistant bacteria. The purpose of this review is to present the most impactful new antibiotics that are currently available for the treatment of these infections. The discovery of new therapeutic strategies will help to limit the spread of multidrug-resistant bacteria, but careful prescribing, appropriate use and monitoring of resistant strains will be crucial to ensure that they remain effective in the future. Full article

The present work reports the bioguided isolation of constituents from the ethanol extract of Holarrhena floribunda stem bark, their identification by UHPLC-ESI-QTOF-MS/MS identification, and the in silico prediction of the pharmacokinetic and toxicity parameters. The crude extract, along with its n-hexane and alkaloid-rich fractions, displayed moderate to good antiplasmodial activity in vitro against chloroquine-sensitive (3D7) and multidrug-resistant (Dd2) strains of Plasmodium falciparum, with IC₅₀ values ranging from 6.54 to 43.54 µg/mL. Seventeen steroidal alkaloids (1–17) were identified in the most active fraction using UHPLC-ESI-QTOF-MS/MS, based on their fragmentation patterns and analysis with the Structural Similarity Network Annotation Platform for Mass Spectrometry (SNAP-MS). Furthermore, bioguided isolation of the ethanol extract yielded twenty-one compounds (3, 5, 10, 14–16, 18–31), whose structures were elucidated by spectroscopic methods. Among them, compounds 5, 14, and 27 showed the highest potency against the two strains of P. falciparum, with IC₅₀ values between 25.97 and 55.78 µM. In addition, the in silico prediction of pharmacokinetic parameters and drug-likeness using the SwissADME web tool indicated that most of the evaluated compounds (1, 3–5, and 14–16) complied with Lipinski’s rule of five. Full article

Infectious diseases present a significant global health challenge, further exacerbated by the rising prevalence of antimicrobial resistance and the limited availability of effective antiviral and antimicrobial agents. The Erythrina genus has garnered scientific interest due to its diverse array of bioactive phytoconstituents, with potential therapeutic relevance. This review aims to synthesize and critically assess the existing literature on the antiviral, antibacterial, antifungal, and antiplasmodial properties of Erythrina species. A comprehensive literature search was conducted using PubMed, Scopus, and Google Scholar databases. Relevant studies were identified through keyword searches combining pathogen-specific terms with “Erythrina”. The extracted data were categorized based on the pathogen type and its associated bioactive compounds. Several Erythrina species exhibited substantial antiviral activity against prominent viral pathogens, such as HIV and SARS-CoV-2. Notably, strong antibacterial efficacy was observed against Staphylococcus aureus, including multidrug-resistant strains. Antifungal activity was most pronounced against Candida albicans, while potent antiplasmodial effects were reported against both drug-sensitive and drug-resistant strains of Plasmodium falciparum. These pharmacological effects were predominantly attributed to prenylated flavonoids, isoflavones, pterocarpans, and erythrina-type alkaloids. Further mechanistic studies and in vivo evaluations are essential to fully assess their clinical efficacy and support the development of plant-derived antimicrobial agents. Full article

Background/Objectives: Modern healthcare faces a growing burden of antimicrobial resistance, prominently driven by ESKAPE pathogens. These organisms—Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp.—are the leading causes of healthcare-associated infections, associated with limited therapeutic options and increased morbidity. Continuous surveillance is crucial for informing empirical therapy and guiding stewardship. Methods: We perform a single-center, seven-year retrospective study (2018–2024) at a 1000-bed tertiary hospital in Warsaw, Poland. Bloodstream isolates of ESKAPE pathogens were identified according to the EUCAST guidelines. Data were analyzed by pathogen, ward, and year of isolation. Results: From 2483 positive blood cultures, 3724 ESKAPE pathogens were recovered. S. aureus and K. pneumoniae predominated, particularly in the Intensive Care Unit and Hematology ward. Resistance analysis revealed persistently high vancomycin resistance in E. faecium, variable but notable methicillin resistance in S. aureus, and frequent ESBL production in K. pneumoniae with an alarming rise in carbapenemase-producing strains, including dual NDM + OXA-48 co-producers. A. baumannii exhibited near-universal multidrug resistance. P. aeruginosa demonstrated lower resistance rates with preserved colistin susceptibility, while Enterobacter spp. remained fully carbapenem-susceptible. Linezolid retained activity against E. faecium, while colistin remained effective against A. baumannii and P. aeruginosa. Modern β-lactam/β-lactamase inhibitor combinations were active against K. pneumoniae. Conclusions: Our findings underscore the critical role of ESKAPE pathogens in bloodstream infections and highlight divergent resistance patterns across species. The emergence of carbapenemase-producing K. pneumoniae and the persistence of multidrug-resistant A. baumannii are of particular concern. Sustained surveillance, robust antimicrobial stewardship, and tailored infection control strategies remained essential to curb the evolving resistance threat in tertiary care settings. Full article

Escherichia coli is a significant cause of Neonatal Calf Diarrhoea (NCD). Its extensive antigenic diversity, coupled with the ability to acquire antimicrobial resistance determinants, hampers treatment effectiveness and compromises the control measures. This study investigated the link between the presence of multidrug-resistant (MDR) E. coli and virulence factors (VFs) in NCD from central France (Departments of Cantal, Haute-Loire, Loire, and Puy-de-Dôme), between 2016 and 2022. E. coli was identified at TERANA Laboratories, France, using API 20E (BioMérieux^®) and MALDI-TOF Mass Spectrometry. Virulence factors, namely adhesins, were assessed with the slide agglutination method, and antimicrobial susceptibility testing was conducted across various antimicrobial classes. Out of 2367 E. coli strains isolated from cases of NCD, a high percentage were resistant to aminopenicillins (88.8%), aminoglycosides (89.1%), tetracyclines (79.7%), quinolones (48.4%), and sulphonamides (42.4%). More than half (58.6%) carried VFs, and 84.9% exhibited MDR profile, of which 61.34% (1233/2010) also harboured VFs. The adhesin CS31A-producing E. coli was the most prevalent, followed by the fimbrial adhesins F5 and F17 (60.8%, 20.0%, and 8.3%, respectively), all of which were associated with a high prevalence of MDR strains (79.1–93.9%). The highest occurrence of MDR profiles was observed in E. coli strains carrying CS31A and in those lacking VFs, both groups showing co-resistance to aminopenicillins, aminoglycosides, and tetracyclines or sulphonamides. The calf production sector may act as a reservoir for MDR E. coli strains, regardless of the presence of VFs, posing a major threat to public health and safety. Full article

Pseudomonas aeruginosa is an opportunistic pathogen of public health concern. This study aimed to investigate the prevalence of P. aeruginosa, some virulence factors, and antimicrobial resistance patterns and highlight the potential pathways of horizontal bla_SHV-resistant gene transfer from diverse sources. A total of 220 samples were collected from fish (n = 90), water (n = 30), poultry (n = 50), and humans (n = 50). All samples were isolated, confirmed by the Vitek 2 system, and tested against antimicrobial agents. Some virulence and resistance genes were examined by PCR and sequenced for the bla_SHV-resistant gene from four selected isolates from each source. SPSS v26, with chi-squared tests and Pearson correlations (p < 0.05), was implemented for statistical investigation. P. aeruginosa was isolated at 33.3%, 20%, 14%, and 24% from fish, water, poultry, and humans, respectively. Using the diffusion disk method, extensively drug-resistant (XDR) and multidrug-resistant (MDR) strains were detected. All strains harbored the oprL and toxA genes, while the lasB gene was present in 40% of fish samples but not present in human samples. All strains lacked the exoS gene. The tetA, sul1, bla_SHV, and bla_TEM resistance genes were detected at different percentages. The bla_SHV genes from fish and water isolates were closely related to each other and showed similarity to those of the human isolates. The poultry isolates formed a separate phylogenetic lineage. The emergence of XDR and MDR P. aeruginosa highlights a possible public health threat. Based on the gene similarity between fish and water isolates, our results suggest that these isolates have a common origin. The similarity between the human isolates and environmental isolates (fish and water) raises concerns about possible transmission to humans. Full article

The genus Lavandula represents one of the most valuable aromatic and medicinal plants, holding significant economic importance in the pharmaceutical, food, perfumery, and cosmetics industries. Among them, L. multifida is a traditionally used medicinal plant in the Mediterranean region. This work provides a comprehensive review of L. multifida, focusing on its traditional uses, phytochemistry, and pharmacological properties. Unlike conventional lavenders, its essential oil is dominated by phenolic monoterpenes, principally carvacrol, alongside significant concentrations of β-bisabolene, 1,8-cineole, and camphor. This distinct phytochemical profile is further complemented by a rich range of non-volatile constituents, including flavonoids, phenolic acids, and triterpenoids. Pharmacological investigations have validated its broad-spectrum antimicrobial activity, demonstrating efficacy against multidrug-resistant bacterial strains and fungal pathogens through mechanisms such as membrane disruption, metabolic interference, and quorum sensing inhibition. Furthermore, the species exhibits significant antioxidant and anti-inflammatory properties, mediated primarily through radical scavenging, cyclooxygenase inhibition, and cytokine modulation. Owing to its distinct chemistry, specific traditional uses for respiratory and digestive ailments, limited endemic habitat, and underexplored status, L. multifida presents a promising candidate for future research with high potential for novel drug discovery, particularly in antiparasitic and respiratory therapies. This review concludes by identifying key research priorities for L. multifida, including a detailed analysis of its non-volatile compounds, mechanistic elucidation, toxicological assessments, and standardization of extracts. Addressing these gaps is essential to validate its traditional applications and advance its development into evidence-based phytomedicines, adjuvant therapies, and natural agrochemicals. Full article

Keratinous wastes, generated from various industries such as poultry processing, slaughterhouses, and salons, accumulate in the environment due to their slow degradation caused by high disulfide cysteine bonds. Traditional methods of managing these wastes, including incineration, composting, open-air burning, and landfilling, have several disadvantages, such as environmental pollution, release of toxic compounds, and breeding of pathogenic and multidrug-resistant microorganisms. Microbial keratinases, produced by bacteria, fungi, and actinomycetes, offer an eco-friendly alternative for valorizing keratinous waste into valuable peptides and amino acids. The biodegradation of keratinous biomass involves four sequential steps: adhesion, colonization, production of keratinolytic enzymes, and breakdown of the keratin substrate. Optimization of culture conditions, such as pH, temperature, substrate concentration, and metal ions, can enhance keratinase production for industrial applications. Keratinases have multifaceted applications in various sectors, including cosmetics, organic fertilizers, leather treatment, animal feed, detergents, and pharmaceuticals. This review highlights the need to explore keratinolytic strains further and improve keratinase yields to develop sustainable solutions for keratinous waste management and generate value-added products, promoting a circular economy. The techno-economic considerations and current limitations in industrial-scale keratinase production are also discussed, emphasizing the importance of future research in this field. Full article

Background: The rapid emergence of antibiotic resistance in Acinetobacter baumannii has led the World Health Organization (WHO) to designate it as a “high priority” pathogen. The emergence of multidrug-resistant (MDR) and pandrug-resistant (PDR) strains poses considerable treatment challenges. As antimicrobial resistance (AMR) escalates toward a post-antibiotic era, innovative therapeutic solutions are urgently needed. Objectives: To clone, over-express, and characterize a novel endolysin, LysTAC1, from Acinetobacter phage TAC1 for its antibacterial efficacy against multidrug-resistant bacteria. Methods: A 24 kDa endolysin featuring a glycoside hydrolase Family 19 chitinase domain was tested against carbapenem-resistant Acinetobacter baumannii clinical isolates and various Escherichia coli strains following outer membrane permeabilization with Ethylenediaminetetraacetic acid (EDTA). Stability assays and molecular docking studies were performed. Results: LysTAC1 demonstrated potent lytic activity against Gram-negative bacteria but showed no activity against Gram-positive bacteria (Staphylococcus aureus ATCC 29213 and Enterococcus gallinarum HCD 28-1). LysTAC1 maintained activity across pH 6–9 and temperatures 4–65 °C, with differential sensitivity to metal ions where K⁺ showed no inhibitory effect at any concentration (0.1–100 mM), and Fe²⁺ was non-inhibitory at lower concentrations (0.1–1 mM), while Mg²⁺ and Ca²⁺ demonstrated concentration-dependent inhibition across the tested range (0.1–100 mM). Molecular docking revealed LysTAC1 interactions with chitinase substrates 4-nitrophenyl N-acetyl-β-D-glucosaminide and 4-nitrophenyl N, N-Diacetyl-β-D-chitobioside, with binding energies of −5.82 and −6.85 kcal/mol, respectively. Conclusions: LysTAC1 shows significant potential as a targeted therapeutic agent against A. baumannii with robust stability under physiological conditions. Full article

The rapid emergence and global dissemination of colistin resistance pose a critical threat to public health by limiting therapeutic options against Gram-negative infections. In this study, we report that bakuchiol (BAK), a natural antioxidant meroterpenoid, significantly restores colistin (COL) efficacy against a range of clinically relevant Gram-negative pathogens, including colistin-resistant strains. The combination of BAK and COL reduced the minimum inhibitory concentrations (MICs) of colistin by 8- to 32-fold, indicating strong synergistic antibacterial activity. Mechanistic studies revealed that BAK disrupts bacterial iron homeostasis via chelation-mediated intracellular iron depletion and concurrently compromises membrane integrity through interaction with phospholipids. This dual action induces collapse of the proton motive force and severe metabolic dysfunction. Importantly, the BAK–COL combination exhibited no detectable toxicity and demonstrated potent in vivo efficacy in a Galleria mellonella infection model. Furthermore, formulation with polyvinylpyrrolidone (PVP) markedly improved the solubility and sustained the synergistic effects of BAK over a broad concentration range. Our findings highlight the potential of bakuchiol as a novel antioxidant adjuvant and provide a promising combinatory strategy for overcoming multidrug-resistant bacterial infections. Full article

Colibacillosis, caused by avian pathogenic Escherichia coli (APEC), represents a major threat to poultry production, leading to significant mortality and economic losses. This study aimed to characterize an APEC strain, HPVN24, isolated from diarrheic chickens at a farm in Hai Phong, Vietnam. The strain was investigated through phenotypic assays, antibiotic susceptibility profiling, and whole-genome sequencing using the Illumina platform. HPVN24 exhibited β-hemolytic activity and resistance to trimethoprim, ampicillin, and ciprofloxacin. Whole-genome analysis identified the strain as serotype O78:H9 and sequence type ST23, with a genome size of 5.05 Mb and a GC content of 50.57%. Genome annotation revealed a wide repertoire of genes involved in metabolism, secretion systems, virulence, and biofilm formation. Virulence-associated genes included those related to adhesion, iron acquisition, hemolysin production, and stress response. Analysis predicted multidrug resistance to 18 antibiotic classes, with particularly strong resistance to fluoroquinolones. Phylogenetic comparison demonstrated that HPVN24 clustered closely with O78:H9 strains isolated from poultry in other regions, suggesting potential transmission across populations. These findings indicate that HPVN24 is a multidrug-resistant and highly virulent APEC strain linked to colibacillosis outbreaks in Vietnam and highlight the need for ongoing surveillance, judicious antibiotic usage, and alternative strategies to ensure poultry health and food safety. Full article

Background/Objectives: Escherichia coli is one of the leading causes of surgical site infections (SSIs) and poses a growing public health concern due to its increasing antimicrobial resistance. High rates of extended-spectrum beta-lactamase (ESBL) production among E. coli strains complicate treatment outcomes and emphasize the need for effective surveillance and control strategies. Methods: A total of 691 E. coli isolates from general surgery clinics (2020–2025) were identified using MALDI-TOF MS. Antibiotic susceptibility data and patient variables were cleaned, encoded, and used to predict resistance using the Random Forest, CatBoost, and Naive Bayes algorithms. SMOTE addressed class imbalance, and model performance was assessed through various validation methods. Results: Among the three machine learning models tested, Random Forest (RF) showed the best performance in predicting antibiotic resistance of E. coli, achieving median accuracy, precision, recall, and F1-scores of 0.90 and AUC values up to 0.99 for key antibiotics. CatBoost performed similarly but was less stable with imbalanced data, while Naive Bayes showed lower accuracy. Feature importance analysis highlighted strong inter-antibiotic resistance links, especially among β-lactams, and some influence of demographic factors. Conclusions: This study highlights the potential of simple, high-performing models using structured clinical data to predict antimicrobial resistance, especially in resource-limited clinical settings. By incorporating machine learning into antimicrobial resistance (AMR) surveillance systems, our goal is to support the advancement of rapid diagnostics and targeted antimicrobial stewardship approaches, which are essential in addressing the growing challenge of multidrug resistance. Full article