Search Results (2,322)

Multidrug-resistant (MDR) pathogens present a significant threat to hematopoietic stem cell transplant (HSCT) recipients; despite their critical implications, regional data on their infection patterns remain scarce. This study aimed to characterize the incidence, pathogen and antimicrobial resistance distribution of clinically confirmed bacterial infections among HSCT recipients. A retrospective analysis was conducted at King Hussein Cancer Center, Jordan (2018–2022). MDR pathogens were defined per CDC criteria. During the study period, 1157 HSCT procedures were performed. A total of 327 patients developed clinically documented bacterial infections, yielding an overall cumulative incidence of 28.3%, with a higher burden in the pediatric cohort (34.7%), including exclusive identification of Klebsiella oxytoca in pediatrics (2.3%). Gram-negative bacteria dominated, with Escherichia coli (50.5%) and Klebsiella pneumoniae (22.0%) being most common. Extended-spectrum beta-lactamase (ESBL) production was the dominant resistance mechanism (71.3%), followed by carbapenem-resistant Enterobacteriaceae (CRE; 14.1%), methicillin-resistant Staphylococcus aureus (MRSA; 8.6%), and carbapenem-resistant Pseudomonas aeruginosa (CRPA; 7.0%). The urogenital (39.1%) and bloodstream (31.2%) were the most infected sites. Significant site-specific associations were noted for ESBL production, MDR-Acinetobacter baumannii (p < 0.001) and MRSA (p = 0.007). Temporal analysis revealed a convergent MDR peak in 2021. Our findings offer critical insights into MDR pathogen incidence in HSCT recipients in the Middle East, informing improved infection management and intensified antimicrobial stewardship in this high-risk population. Full article

The increasing prevalence of multidrug-resistant Staphylococcus aureus (MRSA) has necessitated the development of alternative therapeutic strategies targeting bacterial virulence factors. This study employed an integrated in silico approach to identifying potential inhibitors of the iron-regulated surface determinant B Near-iron Transporter domain, a key protein involved in heme acquisition and pathogenicity. Virtual screening and molecular docking identified certain similarity-selected small molecules possessing strong binding affinities, with (4-(1-oxoisoindolin-2-yl)benzoic acid (TOP1) and (4-(2-oxochromen-3-yl)benzoic acid (TOP2) exhibiting the most favorable binding energies at −12.0 and −11.8 kcal/mol, respectively. Molecular dynamics simulations over 200 ns confirmed stable protein–ligand interactions that yielded reduced structural fluctuations in ligand-bound complexes when compared with the apo form. Molecular mechanics/Poisson-Boltzmann surface area (MM/PBSA) analysis revealed that van der Waals interactions were the primary contributors to binding, with TOP1 showing a more favorable overall binding energy. Drug-likeness and pharmacokinetic predictions indicated compliance with Lipinski’s rule of five and moderate bioavailability, although limited intestinal absorption was observed. Toxicity predictions indicated that both compounds are non-mutagenic but may exhibit hepatotoxicity. Notably, TOP1 exhibited potential nephrotoxicity, cardiotoxicity, and carcinogenicity, whereas TOP2 demonstrated a more favorable safety profile. These findings highlight a trade-off between binding affinity and safety, suggesting that TOP2 emerged as a computationally prioritized candidate for future experimental validation. Because the present findings represent computational predictions only, further orthogonal computational analyses and experimental studies are required to confirm the proposed binding modes, biological activity, and therapeutic potential of the identified compounds. Full article

Antimicrobial resistance is increasing, necessitating the development of novel and efficacious therapies. Plants contain phytochemicals, some of which may possess antibacterial properties. This research employed broth dilution experiments to investigate the antibacterial efficacy of fifteen phytochemicals identified in medicinal plant extracts. The sum of fractional inhibitory concentration of phytochemicals in conjunction with reference antibiotics were also analysed. The inhibitory effects of phytochemicals against β-lactamase were evaluated to explore their potential mechanisms of action. The phytochemicals were evaluated for toxicity on human dermal fibroblast cells. Gallic acid and luteolin significantly inhibited Staphylococcus aureus and the methicillin-resistant S. aureus (MRSA) strain, with minimum inhibitory concentration (MICs) of 62.5 µg/mL. Gallic acid also demonstrated restricted efficacy against Gram-negative species, with MICs ranging from 312.5 to 1250 µg/mL. Gram-negative bacteria exhibited no response to luteolin. Ellagic acid, catechin, naringenin, and quercetin exhibited moderate antibacterial efficacy against the tested pathogens (625–2500 µg/mL MIC). Corilagin exhibited significant antibacterial activity against S. aureus and MRSA, with a MIC of 7.81 µg/mL. Corilagin also exhibited notable efficacy against Bacillus. cereus, Shigella flexneri, and Klebsiella pneumoniae, with MICs ranging from 62.5 to 250 µg/mL. Fractional inhibitory concentration studies revealed a synergistic effect between amoxicillin and corilagin against B. cereus. Additionally, catechin, luteolin, and quercetin synergised penicillin G against S. aureus. Quercetin potentiated the activity of β-lactams (amoxicillin, penicillin G, and oxacillin) against MRSA. Notably, these antibiotics were ineffective against MRSA alone. Isobologram analysis revealed potentiation between penicillin G and quercetin against MRSA at all tested ratios. The β-lactamase inhibitory activity of the phytochemicals was evaluated using a commercial screening kit, and the percentage of relative inhibition was determined. Quercetin and luteolin both inhibited β-lactamase, achieving relative inhibition rates of 77–100% across two-time intervals. All phytochemicals were nontoxic against human dermal fibroblasts. Indeed, quercetin enhanced cell survival by 200%. Full article

Staphylococcus aureus (Staph) infections are a pressing health concern in the White Mountain Apache (WMA) Tribal community, where invasive Staph infection rates far exceed those in the general U.S. population. This study explored community perspectives to guide culturally tailored education and prevention strategies. We conducted 42 in-depth interviews and focus group discussions with healthcare providers, traditional practitioners, and community members. Thematic analysis showed that participants had familiarity with the term “MRSA” (methicillin-resistant Staph), although many did not recognize it as a form of Staph, per se. Barriers to timely care-seeking included lack of transportation, stigma, and misconceptions about infection causes. With regard to biomedical approaches to prevention, participants preferred products like antiseptic nasal sprays and antimicrobial skin cleansers due to ease of use. Community members emphasized the need for simple, bilingual educational materials grounded in Apache culture and delivered by trusted figures. The findings underscore the importance of culturally grounded education and prevention approaches. Implementation and scaling of these strategies may enhance health literacy, reduce infection rates, and promote holistic wellness in Indigenous communities. Full article

Antimicrobial resistance (AMR) has emerged as one of the foremost global threats to public health, with the veterinary sector, responsible for nearly three-quarters of global antimicrobial consumption, representing an underappreciated epicenter of this crisis. Despite the extensive literature on bacteriocins as antibiotic alternatives, most reviews focus on human medicine or food preservation, leaving a conspicuous gap in evidence specific to veterinary medicine. The present review addresses this gap by examining the molecular basis of bacteriocin activity (lipid II, bacterial RNA polymerase, cytoplasmic membrane), strategies for clinical deployment (topical therapy, antibiotic combinations, disruption of biofilm tolerance), and preclinical evidence relevant to bovine mastitis, canine pyoderma and otitis externa, and infections caused by multidrug-resistant pathogens (MRSA (Methicillin-Resistant Staphylococcus aureus), MRSP (Methicillin-Resistant Staphylococcus pseudintermedius), colistin-resistant P. aeruginosa, XDR (extensively drug-resistant) Acinetobacter baumannii). Translational barriers—pharmacokinetic, regulatory, and evidentiary—are critically appraised, alongside emerging directions including precision nanocarriers, biofilm-targeted therapies, and the animal microbiota as a reservoir of novel molecules. Bacteriocins represent a promising yet underexploited antibacterial class in response to the escalating AMR crisis in the animal sector. Full article

Staphylococcus aureus is an important zoonotic pathogen. In recent years, it has been isolated from diseased aquatic animals, causing skin ulcers and septicemia, establishing itself as an emerging pathogen in aquaculture. Rampant antibiotic use has accelerated antimicrobial resistance, a trend that has gradually curtailed the potency of conventional antibiotic therapies, underscoring the urgent need for novel therapies. Here, we screened 20 amino acids and found that exogenous proline significantly enhances the bactericidal activity of amikacin against S. aureus. This synergistic effect extends to other aminoglycoside antibiotics, including neomycin sulfate and gentamicin, and is also effective against drug-resistant strains such as MRSA USA300. Furthermore, we evaluated the efficacy of this combination in eradicating persisters and biofilms. Mechanistically, exogenous proline potentiates amikacin-mediated killing by modulating two key bactericidal pathways. On one hand, it enhances antibiotic uptake by augmenting the proton motive force via the electron transport chain. On the other hand, it amplifies oxidative stress through a multi-pronged mechanism involving the suppression of ROS-scavenging enzymes, activation of the Fenton reaction, and reduction in intracellular nitric oxide (NO) levels, ultimately culminating in bacterial cell death. This study proposes a promising strategy for combating S. aureus in aquaculture and healthcare-associated infections. Full article

Background: Polymicrobial skin and soft tissue infections (SSTIs) are frequently complicated by methicillin-resistant Staphylococcus aureus (MRSA) and co-colonizing Gram-negative pathogens like Pseudomonas aeruginosa (P. aeruginosa). Mupirocin, the clinical gold standard, is limited by rising resistance and an intrinsic “mupirocin gap” against P. aeruginosa. This study evaluates a novel Nigella sativa (NS) seed oil topical formulation as an alternative. Methods: A 4-tier preclinical platform assessed the NS formulation against MRSA, methicillin-sensitive S. aureus (MSSA), Streptococcus pyogenes, and P. aeruginosa. The pipeline included: (1) in vitro agar diffusion, (2) a gauze biofilm prevention model, (3) an ex vivo porcine ear skin model challenging epidermal lipid barriers, and (4) an in vivo Galleria mellonella model evaluating trans-cuticular systemic protection. Results: The NS formulation produced extensive diffusion zones, completely inhibiting S. pyogenes and outperforming controls against MSSA and P. aeruginosa. In the gauze model, NS achieved complete eradication of MSSA and S. pyogenes, while significantly suppressing MRSA and P. aeruginosa biofilms (p < 0.001). In the ex vivo porcine model, NS yielded >1.5 to >2.5 log reductions across all pathogens at 24 h (p < 0.001). Furthermore, in the in vivo G. mellonella model, topical NS significantly reduced the systemic bioburden of MSSA, S. pyogenes, and P. aeruginosa (p < 0.001), though MRSA reduction lacked statistical significance. Conclusions: The novel NS formulation demonstrates potent broad-spectrum antimicrobial activity. By effectively bridging the “mupirocin gap” against P. aeruginosa and demonstrating significant efficacy against MRSA in in vitro and ex vivo environments, it represents a promising plant-based pre-clinical candidate that strongly warrants future evaluation in live mammalian wound healing models. Full article

Antibiotic-resistant bacteria are widely distributed and threaten public health. Photocatalytic antimicrobial technology can effectively inactivate multidrug-resistant bacteria without readily inducing resistance. We previously showed that oxygen-rich vacancy Bi₂MoO₆ (OBM) exhibits excellent activity against methicillin-resistant Staphylococcus aureus (MRSA), but the underlying molecular mechanisms remain poorly understood. Here, we employed integrated transcriptomics and metabolomics, with qRT-PCR validation, to systematically elucidate the antibacterial mechanism of OBM against MRSA. OBM treatment induced profound transcriptional and metabolic alterations: 231 differentially expressed genes and 206 differentially abundant metabolites were identified. Functional enrichment analysis revealed cooperative involvement in multiple critical pathways, including inhibition of amino acid biosynthesis and protein translation, disruption of cell wall and membrane integrity, induction of oxidative stress, collapse of energy metabolism (suppression of oxidative phosphorylation and impaired ATP synthesis), and imbalance in nucleotide metabolism (down-regulation of DNA helicase and mismatch repair genes, dysregulation of purine/pyrimidine metabolism). These findings demonstrate that OBM photocatalytically inactivates MRSA through a multi-target systemic attack at both the transcriptional and metabolic levels, providing a novel theoretical foundation for the development of photocatalytic materials aimed at controlling MRSA and other drug-resistant bacteria. Full article

Background/Objectives: Implant-associated infections are challenging conditions in orthopedic surgery. This experimental study aimed to evaluate phage localization within infected tissues following different routes of administration. Methods: An implant-related infection model was created using methicillin-resistant Staphylococcus aureus (MRSA) in twenty-four rats. Subjects were randomly divided into four groups depending on the bacteriophage administration route. Three rats were designated as the control group. Phage suspension was applied intraperitoneally, intravenously, orally and locally at 0.1 mL/day of 1 × 10⁸ PFU/mL suspension for three consecutive days. In the control group, intravenous, intraperitoneal and oral phage suspensions were administered separately at the same dose for 3 days. After completion of the experiment, tibia samples were taken in the experimental group. Additionally, liver, kidney, stomach, brain, heart muscle and striated muscle tissue samples were taken from the three subjects in the control group. Results: In the control group, unconfirmed phage-like structures were incidentally observed in some mitochondria of renal proximal tubular epithelial cells on transmission electron microscopy. In the experimental group, there was a strong positive linear relationship between the total number of bacteria and the number of bacteriophage clusters, independent of the groups. Conclusions: Bacteriophage clusters were detected in infected tibial tissues after all administration routes, suggesting phage localization at the infection site. Unexpected phage-like clusters were observed within mitochondria of proximal tubular epithelial cells in the control animals. This finding should be regarded as an unconfirmed incidental finding requiring further validation. Full article

Buffalo meat is widely consumed in Egypt; however, it may pose serious food safety risks due to microbial contamination during handling, preparation, and processing. This study investigated the prevalence and characterization of multidrug-resistant (MDR) enterotoxigenic Staphylococcus aureus in raw ground buffalo meat and ready-to-eat (RTE) kofta and liver sandwiches marketed in Mansoura, Egypt. S. aureus was detected in 62% (62/100) of raw buffalo ground meat, 41% (41/100) of RTE kofta, and 60% (60/100) of RTE liver samples, with an overall prevalence of 54.3% (163/300). All 660 isolates were confirmed as S. aureus via nuc gene detection, among which 46.8% (309/660) were mecA-positive and verified as methicillin-resistant (MRSA), and 21.8% (144/660) were vanA-positive and verified as vancomycin-resistant (VRSA). Enterotoxigenic strains were identified in 42.7% (282/660) of isolates, with the sea gene being most prevalent (67.7%; 191/282), followed by seb (58.2%; 164/282) and sec (39.7%; 112/282). The highest frequency of enterotoxigenic strains occurred in raw ground meat (47.2%), followed by kofta (45.1%) and liver (36%). Antimicrobial susceptibility testing against 15 antibiotics revealed that 7.6% (50/660) of isolates were extensively drug-resistant (XDR) with a MAR index of 0.9, while 82.9% (547/660) were MDR with MAR values between 0.3 and 0.7, indicating exposure to environments of intensive antibiotic use. The present findings highlight a high contamination level of buffalo meat products with MDR enterotoxigenic MRSA and VRSA, representing a significant public health hazard. Implementation of strict hygiene measures, wise antibiotic usage, and continuous surveillance is essential to control their dissemination through the food chain. Full article

Staphylococcus aureus is a leading cause of bacterial keratitis and antimicrobial resistance-associated death globally. This study aimed to evaluate the efficacy of CaD23, a human-derived hybrid antimicrobial peptide (AMP), in combination with antibiotics in treating S. aureus infections. The efficacy of CaD23 and six medically important antibiotics (amikacin, cefuroxime, chloramphenicol, fosfomycin, vancomycin and levofloxacin) was examined against six strains of methicillin-sensitive and methicillin-resistant S. aureus using a minimum inhibitory concentration (MIC) assay. CaD23–antibiotic interactions were evaluated using checkerboard and time–kill kinetics assays. 3,3′-dipropylthiadicarbocyanine iodide (DiSC_3,5) cytoplasmic membrane depolarisation assay was performed to examine the mechanism of action. Overall, CaD23 exhibited good efficacy against all MSSA and MRSA (MIC = 16–32 μg/mL [6.7–13.3 μM]). Of 20 peptide–antibiotic–organism combinations, 19 (95%) combinations demonstrated positive interactions, with six (31.6%) and 13 (68.4%) exhibiting synergistic (FICI = 0.293–0.412) and additive effects (FICI = 0.521–0.890), respectively. CaD23 was able to achieve complete bacterial eradication significantly faster than cefuroxime and levofloxacin (15 min vs. 8–24 h). When used at a sub-MIC concentration, CaD23 could accelerate the killing of S. aureus of cefuroxime from 8–24 h to within 1 h and enhance the activity of levofloxacin by 90%. CaD23 was shown to rapidly depolarise the inner membrane of S. aureus within seconds of the treatment. In conclusion, CaD23–antibiotic combination therapy serves as a useful strategy for tackling drug-resistant ocular and systemic S. aureus infections. Full article

Methicillin-resistant Staphylococcus aureus (MRSA) remains a significant multidrug-resistant pathogen, frequently associated with persistent infections and biofilm formation, underscoring the urgent need for alternative antimicrobial strategies. Bioactive compounds derived from fungi have attracted considerable attention due to their structural diversity and demonstrated antibacterial activity against MRSA. This study employed a scientometric approach to assess global research trends, thematic evolution, and collaborative networks concerning fungi-derived anti-MRSA compounds. Bibliographic data were collected from the Scopus database, and a total of 1666 English-language articles and reviews published up to 2025 were analyzed using Bibliometrix/Biblioshiny and VOSviewer. The findings indicate a marked increase in research output after 2010, reflecting heightened scientific interest in fungal natural products for MRSA management. China and the United States emerged as leading contributors in terms of publication volume and international collaboration. Thematic analysis revealed a shift from broad antimicrobial screening to more specialized investigations, including antibiofilm activity, secondary metabolites, endophytic fungi, molecular docking, and antimicrobial resistance. Nonetheless, several challenges persist, such as insufficient mechanistic validation, limited toxicity and pharmacokinetic assessments, and a lack of clinically relevant in vivo studies. Overall, the field is increasingly multidisciplinary, integrating microbiology, natural product chemistry, and computational methodologies to advance the discovery of anti-MRSA agents. Full article

Antimicrobial resistance (AMR) is a growing global public health challenge. Its development is strongly associated with the inappropriate and excessive use of antimicrobial agents, leading to reduced treatment effectiveness, limited availability of therapeutic options, constraints on medical procedures, and an increasing economic burden. This narrative review synthesizes current knowledge on antibiotic-resistant bacteria detected in airborne samples from healthcare environments and examines their reported resistance profiles. The review focused on the bacterial species identified, methods used for antimicrobial susceptibility assessment, types of healthcare facilities investigated, and environmental and behavioral factors influencing the occurrence and dissemination of airborne antibiotic-resistant bacteria. The clinical relevance of the reported pathogens was discussed in the context of the WHO Bacterial Priority Pathogens List (BPPL), while the WHO AWaRe classification and TrACSS framework were used as complementary interpretative tools to contextualize resistance patterns and their implications for antimicrobial stewardship and AMR surveillance. The reviewed studies showed that airborne bacterial communities in healthcare settings were dominated by Gram-positive bacteria, particularly Staphylococcus spp. and Bacillus spp., while clinically relevant pathogens such as methicillin-resistant Staphylococcus aureus (MRSA), Pseudomonas aeruginosa, and Acinetobacter baumannii were also frequently detected. Resistance to β-lactam antibiotics was the most frequently reported resistance pattern. Considerable heterogeneity in sampling strategies, antimicrobial susceptibility testing methods, and interpretive criteria limited direct comparison among studies. The findings highlight the need for standardized monitoring methods, long-term surveillance, and integrated environmental and clinical research to support infection prevention strategies and mitigate antimicrobial resistance. Full article

Allium sativum is widely consumed and studied plant for its potential health-promoting effects. Despite its widespread use, the impact of different extraction methods on the biological efficacy and specific phytochemical composition of garlic has not yet been fully elucidated. This study investigated the phytochemical profile, antibacterial, antioxidant, and anti-inflammatory properties of ethanolic and aqueous extracts of Moroccan-grown A. sativum using in vitro assays and in silico analyses. Total phenolic and flavonoid contents were determined by colorimetric methods, while phenolic aglycones were identified by HPLC. Antibacterial activity was evaluated by disc diffusion and determined the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values, antioxidant capacity by DPPH, TAC, and FRAP assays, and anti-inflammatory activity through protein denaturation inhibition. ADMET profiling was performed to predict pharmacokinetic and toxicological properties of the identified compounds. The ethanolic extract exhibited higher flavonoid and phenolic contents, reaching 13.27 ± 0.01 mg quercetin/_gextract and 1.57 ± 0.02 mg GAE/_gextract, respectively. HPLC analysis identified syringic, caffeic, ferulic, p-coumaric, and chlorogenic acids, as well as kaempferol and quercetin, whereas apigenin was detected only in the ethanolic extract under the present extraction and analytical conditions. Both extracts inhibited MRSA and E. coli but showed no activity against Pseudomonas aeruginosa. Docking analyses suggested favorable interactions between the identified compounds and bacterial target proteins. The ethanolic extract displayed stronger antioxidant activity, with DPPH IC₅₀ and TAC EC₅₀ values of 1.134 and 2.527 mg/mL, respectively. No ferric reducing activity was detected under the tested conditions. Protein denaturation inhibition ranged from 30.68% to 90.37%, with the aqueous extract showing significantly greater activity (p < 0.003). Overall, extraction-dependent differences in phenolic composition appear to influence the biological properties of A. sativum extracts, warranting further mechanistic and in vivo investigations. Full article

Background/Objectives: Antimicrobial resistance in pediatric infections presents a worsening global public health challenge, with antimicrobial resistance (AMR) accounting for more than one million deaths annually and disproportionately affecting children younger than 5 years of age. Neonates and critically ill children face heightened risk owing to immature immunity, frequent healthcare exposures, and limited therapeutic options. This review synthesizes evidence on the epidemiology, mechanisms of resistance, clinical outcomes, and management of AMR across the full pediatric age range. Methods: PubMed/MEDLINE and Google Scholar were searched for literature from 2014 to 2026 using terms covering antibiotic resistance, pediatric populations, and key pathogens. Approximately 1840 records were screened; 69 sources met all inclusion criteria. A narrative synthesis approach was used, given heterogeneity across study designs and outcomes. Results: Extended-spectrum β-lactamase (ESBL)-producing Enterobacterales, carbapenem-resistant pathogens, and methicillin-resistant Staphylococcus aureus drive substantial morbidity and mortality in children. Approximately one in five pediatric Gram-negative bloodstream isolates are resistant to third-generation cephalosporins, a phenotype independently associated with a roughly three-fold increase in adjusted mortality. Carbapenem-resistant Klebsiella pneumoniae bacteremia carries a 30-day mortality approaching 40%, and isolates in low- and middle-income countries (LMICs) frequently harbor multiple resistance genes. Pneumococcal conjugate vaccine implementation was associated with absolute reductions of 7–11% in the proportion of pediatric pneumococcal isolates that were penicillin-non-susceptible or penicillin-resistant, largely by preventing infections caused by resistant serotypes and by reducing antibiotic selection pressure, rather than through a direct effect on resistance mechanisms; global AMR mortality in children younger than 5 years of age fell by more than 50% between 1990 and 2021. Conclusions: Pediatric AMR reflects intersecting microbiological, clinical, and health-system challenges. Priority actions include scaling antimicrobial stewardship programs, expanding access to rapid molecular diagnostics, integrating whole-genome sequencing into surveillance, conducting pediatric-inclusive randomized trials, and deploying vaccines as primary prevention tools, with particular emphasis on LMICs where the burden is greatest. Full article