Search Results (2,408)

The increasing prevalence of antibiotic-resistant microbes necessitates new antimicrobial strategies. In this study, the antibacterial activity of leaf extracts from a number of plants, Pistacia lentiscus, Laurus nobilis, Solanum lycopersicum, Ruta chalepensis, Inula viscosa, Myrtus communis, and Ficus carica, under photodynamic and sonodynamic activation was evaluated against S. aureus (methicillin-susceptible Staphylococcus aureus, MSSA), methicillin-resistant S. aureus (MRSA), and E. coli. Crude extracts of all the plants exhibited antibacterial activity against S. aureus, eradicating bacterial cells in 2–20 min. However, none of the extracts was active against E. coli. The most active extracts from P. lentiscus, L. nobilis, I. viscosa, and F. carica were tested against two clinical MRSA strains, and all inhibit cells within 5 to 40 min. These four active extracts were separated by reversed-phase chromatography, yielding fractions of varying polarity that exhibited dark activity (more hydrophilic fractions) or photodynamic properties (more hydrophobic fractions) when tested against S. aureus. Two extracts (from P. lentiscus and I. viscosa) exhibited sonodynamic activity against S. aureus, and only one (from P. lentiscus) against E. coli. Full article

Background: Antimicrobial resistance complicates the management of skin and soft tissue infections (SSTIs), particularly in low- and middle-income countries where microbiological surveillance remains limited. We compared the microbiological spectrum and antimicrobial resistance patterns of wound-associated SSTIs between tertiary-care hospitals in Ghana and Germany. Methods: This retrospective bicentric cohort study analysed routine microbiological data from 309 patients in Ghana and 294 patients in Germany. 329 bacterial isolates from Ghana and 816 bacterial isolates from Germany were included. Pathogen distribution, antimicrobial susceptibility, and the prevalence of methicillin-resistant Staphylococcus aureus (MRSA), third-generation cephalosporin-resistant (3GC-R) Enterobacterales, and carbapenem-resistant Gram-negative bacteria were compared descriptively. Results: The microbiological spectrum differed markedly between the two cohorts. Gram-negative bacteria predominated in Ghana (83.9%), whereas Gram-positive organisms predominated in Germany (62.9%). Escherichia coli, Pseudomonas aeruginosa, and Klebsiella spp. were the leading pathogens in Ghana, while Staphylococcus aureus was the predominant pathogen in Germany. Compared with Germany, Ghanaian isolates exhibited substantially higher resistance to third-generation cephalosporins, fluoroquinolones and aminoglycosides. 3GC-R Enterobacterales were identified in 52.8% and 15.6% of evaluable isolates in Ghana and Germany, respectively. Carbapenem resistance among evaluable Gram-negative isolates was detected in 15.2% and 11.2%, respectively. MRSA prevalence (45.2% vs. 4.1%) was also considerably higher in Ghana than in Germany. Conclusions: Wound-associated SSTIs in Ghana and Germany differ substantially in pathogen distribution and antimicrobial resistance profiles. The predominance of Gram-negative pathogens and the high resistance burden observed in the Ghanaian cohort highlight the need for strengthened microbiological surveillance and antimicrobial stewardship. Institution-specific resistance data are essential to optimize empirical antimicrobial therapy across different healthcare settings. Full article

Background: Hajj is an international mass gathering in which infection prevention and antimicrobial stewardship intersect. Methicillin-resistant Staphylococcus aureus (MRSA) was selected as the organism-specific focus because it is a clinically important antimicrobial-resistant pathogen associated with skin and soft-tissue infections, wound care, and transmission through close contact and sharing of personal items. Hajj studies have also documented MRSA-related carriage and broader antimicrobial-resistance concerns among pilgrims and other mass-gathering populations. However, the relation between general infection awareness, MRSA-specific knowledge, and self-reported antibiotic-use behaviour remains less well described. This study assessed these three domains among Hajj pilgrims arriving in Madinah, Saudi Arabia. Methods: A questionnaire-based cross-sectional study was conducted during Hajj 1446H (2025). The study dataset comprised 342 completed questionnaires. Item-level descriptive analyses were used because no validated composite scoring algorithm was documented in the available study records. The primary exploratory outcome was an undated, self-reported history of taking antibiotics without consulting a doctor. Modified Poisson regression with robust variance estimated adjusted prevalence ratios (aPRs), with sex, age group, education, healthcare employment, and MRSA awareness entered simultaneously as prespecified covariates. Results: Among 342 respondents, 213 (62.3%) were male, 155 (45.3%) were aged 46–60 years, 181 (52.9%) reported postgraduate education, and 51 (14.9%) worked in healthcare. General awareness of crowding-related bacterial-infection risk was high (256/342, 74.9%), whereas MRSA-specific knowledge was lower: 110 (32.2%) had heard of MRSA, 137 (40.1%) identified personal-item sharing as a transmission route, and 124 (36.3%) recognised that MRSA can cause serious or fatal infection. Handwashing ≥ 3 times/day was reported by 310 respondents (90.6%), and 327 (95.6%) reported not sharing personal items. However, 143 respondents (41.8%) reported taking antibiotics without consulting a doctor. In the adjusted model, the prevalence of this outcome was higher among participants aged > 60 years than among those aged < 46 years (aPR 1.86, 95% CI 1.35–2.56) and among those who had not heard of MRSA (aPR 3.60, 95% CI 2.10–6.18) or did not know whether they had heard of MRSA (aPR 3.40, 95% CI 1.84–6.30), compared with those who had heard of MRSA. Conclusions: Among pilgrims arriving in Madinah, general infection-prevention awareness and self-reported hygiene practices coexisted with limited MRSA-specific knowledge, and a substantial proportion of respondents reported taking antibiotics without consulting a doctor. The observed associations are cross-sectional and non-causal; they neither establish the timing or appropriateness of antibiotic use nor demonstrate that an education intervention would change behaviour. They identify a hypothesis for prospective evaluation of multilingual Hajj education linking MRSA transmission, wound care, and antibiotic stewardship. Full article

Osteomyelitis involving the pediatric growth plate is uncommon and potentially serious. We present a rare case of methicillin-resistant Staphylococcus aureus (MRSA) osteomyelitis affecting the distal physis of the hallux in a 9-year-old boy occurring after a routine permanent partial nail avulsion for an ingrown toenail. Approximately one month after the procedure, the patient developed persistent pain, erythema, and swelling of the hallux. Imaging confirmed osteomyelitis involving the distal phalanx and growth plate. Surgical incision and drainage were performed and cultures confirmed MRSA. The patient was treated with intravenous vancomycin followed by an early transition to oral clindamycin. Symptoms resolved within two weeks and he returned to full activity without evidence of growth disturbance. This case highlights the potential for direct inoculation osteomyelitis following minor toenail procedures and supports evolving approaches to pediatric osteomyelitis treatment, which was historically managed with prolonged IV antibiotics via PICC lines. Recent studies support shorter courses and early transition to oral therapy in uncomplicated cases. This approach reduces hospital stays, avoids PICC-related complications, and has shown comparable outcomes in large pediatric cohorts. Although rare, growth plate osteomyelitis can occur after routine nail procedures. Early recognition, early imaging and combined surgical and medical management are essential for preventing long-term sequelae. This case reinforces the safety and efficacy of early oral antibiotic transition in selected pediatric osteomyelitis cases consistent with current evidence-based guidelines. Full article

Veterinary practice faces rising antimicrobial resistance, driving interest in plant-derived alternatives. Purslane (Portulaca oleracea L.), a medicinal edible herb with antimicrobial, anti-inflammatory, and immunomodulatory properties, is a promising candidate. This narrative review synthesizes 160 studies into a unified framework linking chemical composition (flavonoids, alkaloids, polysaccharides, organic acids), pharmacological activities (12 major effects), and veterinary applications. Mechanistically, polysaccharides act as immunomodulators via the TLR4/MyD88 pathway; flavonoids (quercetin, kaempferol) exert antioxidant/anti-inflammatory effects through NF-κB/MAPK inhibition and Nrf2 activation; organic acid extracts show potent anti-MRSA activity (MIC 0.5–1.0 mg/mL); and alkaloids enhance insulin secretion. In vivo, dietary purslane at 2–3% improves broiler growth performance and feed conversion, while supplementation enriches omega-3 fatty acids in eggs and meat. However, translational barriers persist, including limited pharmacokinetic data, lack of large-scale field trials, and insufficient safety and residue-depletion information for food-producing animals. We outline future priorities, including species-specific pharmacokinetic studies, field efficacy trials, and quality-control standards, positioning purslane as a mechanism-rich, antibiotic-sparing candidate for further investigation in veterinary therapeutics and functional feed additives. Full article

Background: Methicillin-resistant Staphylococcus aureus (MRSA) urinary tract infections (UTIs), while relatively uncommon, pose a unique challenge in treatment as only specific intravenous (IV) options are typically utilized, with the efficacy of oral antimicrobials being poorly defined. Methods: The multi-site retrospective cohort study described herein therefore aims to characterize outcomes associated with oral administration of linezolid, trimethoprim-sulfamethoxazole (TMP-SMX), or doxycycline for the treatment of MRSA UTIs. Study participants were adults with culture-positive MRSA UTIs receiving one of the three oral therapies. Exclusion criteria included polymicrobial UTI, concomitant MRSA outside the urinary tract, receipt of non-study anti-MRSA agents for greater than or equal to 50% of treatment, less than 48 h of the oral study drug, and/or prostatitis. The primary outcome was clinical cure defined as a composite of symptom resolution, no readmission within 30 days of discharge attributable to UTI, and no change in therapy due to treatment failure. Secondary outcomes included antibiotic discontinuation because of adverse effects (AEs). Results: Overall, patients attained a clinical cure rate from MRSA UTI of 78.8%, 80.0%, and 94.4% when treated with linezolid, TMP-SMX, or doxycycline, respectively. Conclusions: While there were no observed differences between the clinical cure rates of the three antimicrobials studied, the high clinical cure rate coupled with low rates of AEs may support these oral therapies for the treatment of MRSA UTIs, but further investigation is required. Full article

Vancomycin (VCN) is a glycopeptide antibiotic widely used to treat Gram-positive infections such as those caused by methicillin-resistant Staphylococcus aureus (MRSA). Its narrow therapeutic window, high interindividual pharmacokinetic variability, and dose-dependent nephrotoxicity support the need for therapeutic drug monitoring (TDM). In this study, a UHPLC-UV method for VCN quantification in human plasma was developed and validated according to ICH M10 guidelines, using a one-step protein precipitation requiring only 100 µL of plasma. Clinical applicability was preliminarily explored in three hospitalized patients, where the area under the concentration-time curve over 24 h to minimum inhibitory concentration ratio (AUC₂₄/MIC) was estimated using PrecisePK, NextDose, and TDMx Bayesian software platforms before and after dose adjustment. The method showed linearity from 0.5 to 100 µg/mL (r² > 0.99), with accuracy within ±7% and precision below 11%. Acceptance criteria for selectivity and matrix effect were met, and stability was confirmed under multiple conditions, including clinically relevant storage and transport. Pre-adjustment AUC₂₄/MIC values were outside the target window of 400–600 in all patients, confirming the pertinence of implementing model-informed precision dosing as a routine TDM practice in Colombian health institutions. Full article

Optimizing hop (Humulus lupulus L.) extraction protocols for maximum antibacterial efficacy remains an open methodological challenge in developing plant-based natural antimicrobials. We compared five extraction protocols—hot ethanol, cold ethanol, espresso/steam, hot water, and cold water—applied to four hop varieties (Citra, Lubelski, Magnat and Marynka), with a commercial supercritical CO₂ extract as a reference preparation. We characterized extracts by HPLC (α-acids, β-acids, iso-α-acids) and GC-MS (volatile profile of cold ethanol extracts) and determined antibacterial activity as minimum inhibitory concentration (MIC) against reference and clinically relevant multidrug-resistant (MDR) strains of Escherichia coli and Staphylococcus aureus. Friedman tests confirmed a statistically significant effect of extraction method on MIC values (p ≤ 0.004 for E. coli ATCC 25922, S. aureus ATCC 29213, and clinical MRSA). Ethanol-based protocols consistently produced the highest hop acid concentrations and the lowest MICs against S. aureus ATCC 29213 (0.125–0.250 mg/mL) and against clinical MRSA (as low as 0.016 mg/mL), compared with 1.0–15.0 mg/mL for aqueous and steam-based extracts. Clinical MRSA demonstrated increased susceptibility to selected ethanol extracts and to the CO₂ reference. MDR uropathogenic E. coli (UPEC) maintained high-level resistance (MIC 15 mg/mL) to all preparations except the CO₂ reference (MIC 6 mg/mL). Spearman correlation identified α-acid content as the dominant predictor of antibacterial activity (ρ = −0.927, p < 0.001 for S. aureus ATCC 29213). These results suggest ethanol-based and supercritical CO₂ extraction as optimal protocols for producing hop extracts with antibacterial properties targeting Gram-positive pathogens, including MRSA, and provide a rationale for their use as natural antimicrobials. Full article

A sustainable method has been developed to produce multi-walled carbon nanotubes (MWCNTs) that are adorned with a unique silver nanoparticle, using a plant extract (Origanum dubium) as a mediator. Gas chromatography/mass spectrometry (GC/MS) technique was used to investigate the chemical components of the plant extract. Silver nanoparticles (AgNPs) have been deposited on the MWCNTs as well as acid-functionalized MWCNTs (f-MWCNTs) via an in situ solution method. The present study presents a sustainable and economical approach to the synthesis of AgNPs. The biosynthesis of Ag nanoparticles has been optimized by varying several parameters, including pH, temperature, reaction time, concentration of plant extract, and duration of UV exposure. The nanohybrids composed of AgNPs, MWCNTs, acid-treated MWCNTs, and AgNP-decorated MWCNT nanocomposites were successfully synthesized and evaluated for their antibacterial potential against the Gram-positive methicillin-resistant Staphylococcus aureus (MRSA) and the Gram-negative Escherichia coli (E. coli) strains. Their radical scavenging activities were also evaluated against DPPH and hydrogen peroxide. X-ray diffraction (XRD) analysis, Fourier transform infrared spectroscopy (FTIR), and UV–vis spectroscopy were used to investigate the structure and nature of f-MWCNT and decorated nanocomposites. The scanning electron microscopy (SEM) technique was used to analyze the dispersion state of carbon nanotubes and the immobilization of AgNPs. The study reveals that the modified AgNPs possess viable antimicrobial and antioxidant activities. Full article

Background: Methicillin-resistant Staphylococcus aureus (MRSA) wound infections are a major clinical concern due to their high prevalence and the growing risk of antimicrobial resistance. Therefore, it is imperative to develop safe and effective therapeutic strategies. Methods: Herein, we fabricated a novel antibiotic-free nanodrug delivery system (HNK/DG-COS NPs) by loading honokiol (HNK), a hydrophobic natural antimicrobial agent, onto a dual-polysaccharide carrier composed of chitosan (COS) and β-D-glucan (DG), for the treatment of MRSA-infected wounds. COS endows the nanoparticles with synergistic antibacterial activity together with HNK, while DG improves their anti-inflammatory and tissue repair capacities. The physicochemical characteristics of nanoparticles, as well as their in vitro antibacterial and anti-inflammatory activities, were systematically evaluated. Furthermore, an MRSA-infected wound model was constructed to verify their therapeutic efficacy. Results: HNK/DG-COS NPs exhibited a spherical morphology with a uniform particle size of approximately 200 nm. In vitro experiments have shown that HNK/DG-COS NPs can significantly kill MRSA and inhibit biofilm formation. Scanning electron microscopy further revealed that the nanoparticles exerted antibacterial effects by disrupting the integrity of bacterial cell membranes. In LPS-stimulated RAW264.7 macrophages, treatment with HNK/DG-COS NPs significantly mitigated pro-inflammatory cytokine levels. Cell migration assays confirmed that nanoparticles effectively enhanced L929 cell migration. In vivo, treatment with HNK/DG-COS NPs significantly accelerated MRSA-infected wound healing in mice, mitigated inflammatory damage, stimulated collagen production and repaired damaged tissues. Conclusions: HNK/DG-COS NPs represent a promising antibiotic-free candidate for intervention against early-stage MRSA-infected wounds. Full article

Over the past few years, considerable scholarly interest has been directed toward the synergistic application of natural compounds alongside conventional antibiotics to address infections stemming from multidrug-resistant (MDR) pathogens. The primary objective of this research is to investigate the efficacy of baicalin (BA), an extract obtained from Scutellaria baicalensis, when used in conjunction with oxacillin sodium (OXS). Specifically, the study evaluates their combined impact on biofilm formation and toxicity reduction in methicillin-resistant Staphylococcus aureus (MRSA) strain USA300. Furthermore, a murine peritonitis model induced by MRSA USA300 was developed to determine the therapeutic potential of this combination therapy against infection. Experimental data indicate that the co-administration of BA and OXS does not induce hemolysis in vitro. In comparison to treatments involving either BA or OXS alone, the combined regimen significantly enhances the accumulation of intracellular reactive oxygen species (ROS) within MRSA USA300. Additionally, this synergistic approach suppresses the production of extracellular polymeric substances (EPSs), decreases the overall protein content within the biofilm matrix, and impairs the metabolic functions of biofilm cells. The investigation also revealed that the synergistic application of BA and OXS intensifies the suppression of key virulence determinants, specifically lipase activity and staphyloxanthin production, while simultaneously downregulating the transcription of sarA (a global regulator of virulence). These findings substantiate the anti-virulence efficacy of the BA-OXS combination. In a murine model of peritonitis established using MRSA USA300, the healthy mice group, the MRSA USA300 group, the BA group, the OXS group, the combined group of BA and OXS, and the VAN group were set up, with eight mice in each group. The results showed that the combined therapy significantly mitigated body weight reduction, decreased the circulating counts of inflammatory cells, including leukocytes and lymphocytes, and suppressed the secretion of pro-inflammatory mediators such as TNF-α, IL-6, and IL-1β, thereby demonstrating potent anti-inflammatory properties. Furthermore, the co-administration of BA and OXS reduced bacterial burden in the abdominal organs of infected mice and alleviated associated histopathological injuries. Importantly, the treatment regimen exhibited no hepatorenal toxicity in the peritonitis mice, effectively maintaining normal levels. In the plasma of mice suffering from peritonitis, the concentration of malondialdehyde (MDA), a marker of oxidative stress, was reduced, while the activities of catalase (CAT) and superoxide dismutase (SOD) were elevated. This modulation contributes to anti-infective effects. These findings offer a theoretical foundation for subsequent investigations into the synergistic application of natural compounds and conventional antibiotics against MRSA. Full article

Background: Antimicrobial resistance is at alarming levels. Methicillin-resistant Staphylococcus aureus is a clinical concern and has been classified as one of the so-called ESKAPE pathogens. The increase in resistance coupled with the lack of new agents in development requires innovative ways of developing new antimicrobials. Methods: Here, we investigate an approved drug (Zafirlukast), which has been previously reported to have activity against Mycobacterium, for activities against other bacterial strains. Antibacterial activity was assessed using standard MIC testing along with checkerboard analysis to investigate potential synergies/antagonisms. In order to define the mechanism of action (MOA), a number of Zafirlukast-resistant mutant strains of MRSA (generated via serial passage) were sequenced. Biochemical analysis was performed on the target pathway to confirm the putative target of Zafirlukast in Staphylococcus aureus. Results: Zafirlukast showed modest direct-acting antimicrobial activity (0.5–32 μg/mL) against a panel of Gram-positive bacteria, including MRSA. It was also found that Zafirlukast synergised with a number of existing antibiotics. Remarkably, mutants forced to be resistant to Zafirlukast became resensitised to the β-lactams that they were originally resistant to. This is potentially a very useful property of a potentiator drug. Mutational analysis suggested the target of Zafirlukast in Staphylococci is LtaS (Lipoteichoic acid synthase), of which there are no currently approved inhibitors. Teichoic acid pathway involvement was further confirmed via biochemical analysis. Conclusions: Here, we establish that Zafirlukast has activities beyond Mycobacterium and Gingivalis, encompassing many Gram-positive bacteria including MRSA, and, for the first time, we report its putative target as LtaS. The repurposing of safe-to-use drugs is an attractive strategy to derisk drug discovery programmes. Zafirlukast has many attractive antimicrobial activities, which may encourage further investigations in this field. However, it should be noted that it may represent a safe starting scaffold, and further chemistry is likely to be needed for it to be used in the antimicrobial setting. Full article

With the continuous escalation of antimicrobial resistance, drug repurposing based on approved drugs has emerged as a promising strategy for the development of novel anti-infective agents. This study aimed to evaluate the antibacterial effect of the FDA-approved drug Ponatinib hydrochloride against multidrug-resistant S. aureus. Broth microdilution assay showed that ponatinib hydrochloride exhibited potent activity against Gram-positive bacteria, while the MICs against Gram-negative bacteria were all >100 μM. In addition, the MICs against 15 clinical multidrug-resistant S. aureus isolates ranged from 6.25 to 25 μM. Time-kill assay further revealed a pronounced concentration- and time-dependent bactericidal effect, with bacterial viability reduced to nearly the detection limit within 24 h at 4 × MIC. Anti-biofilm assays showed that ponatinib hydrochloride significantly inhibited S. aureus biofilm formation and disrupted mature biofilms. Moreover, serial passaging for 30 days did not induce an obvious increase in resistance. Mechanistic investigations demonstrated that ponatinib hydrochloride increased membrane permeability, induced intracellular reactive oxygen species (ROS) accumulation, and markedly reduced ATP levels. Finally, in a mouse infection model, ponatinib hydrochloride significantly improved the survival of infected mice, with a survival rate of 70% observed in the 15 mg/kg treatment group, while also reducing bacterial burdens and pro-inflammatory cytokine levels in tissues. Collectively, ponatinib hydrochloride exhibits potent antibacterial activity against multidrug-resistant S. aureus both in vitro and in vivo and represents a promising candidate for anti-MRSA therapy. Full article

Background/Objectives: Prompt initiation of appropriate antibiotics is essential for sepsis management. While early anti-methicillin-resistant Staphylococcus aureus (MRSA) therapy benefits confirmed cases, unnecessary use in low-risk patients promotes antimicrobial resistance. Current guidelines recommend risk-based empiric coverage, but specific predictors in the emergency department (ED) remain poorly defined. Therefore, this study aims to identify clinical factors independently associated with MRSA infection in ED patients with sepsis. Methods: This retrospective analysis used data from a prospective, nationwide, multicenter cohort in the Korean Sepsis Alliance registry. The study included 11,477 adults with sepsis from 16 tertiary or university-affiliated EDs between September 2019 and December 2022. Factors independently associated with MRSA infection were identified with multivariable logistic regression. Results: MRSA infection occurred in 189 of 11,477 patients (1.65%; 95% confidence interval [CI], 1.43–1.90%), representing 2.86% (95% CI, 2.49–3.29%) of patients with a microbiologically identified causative pathogen. Catheter-related infection showed the strongest association (odds ratio [OR], 5.98; 95% CI, 1.93–18.49). Other factors independently associated with MRSA included hospitalization within 90 days (OR, 1.65; 95% CI, 1.14–2.39) and elevated C-reactive protein ≥ 6 mg/dL (data-derived cutoff; OR, 2.18; 95% CI, 1.43–3.38). Conversely, abdominal (OR, 0.19; 95% CI, 0.09–0.43) and urinary (OR, 0.40; 95% CI, 0.21–0.77) sources were linked to significantly lower risk. Conclusions: MRSA infection was uncommon (1.65%) among ED patients with sepsis. Catheter-related infection was most strongly associated with MRSA, whereas abdominal and urinary sources were associated with lower odds. These findings may help inform risk stratification and support antimicrobial stewardship in the ED. Full article

The increasing prevalence of antimicrobial resistance has stimulated interest in non-antibiotic small molecules that can restore or potentiate the activity of established antibacterial agents. In this study, a focused series of low-molecular-weight chromene derivatives was synthesized, structurally characterized, and evaluated primarily as antibacterial adjuvants rather than as stand-alone antibiotics. The experimental strategy was designed to distinguish intrinsic antibacterial activity from potentiating activity in combination with a partner antibiotic. Initial susceptibility testing was followed by combination experiments in selected bacterial strains, with particular emphasis on changes in the minimum inhibitory concentration (MIC) of meropenem or doripenem in the presence of each test compound. Broth microdilution combination assays demonstrated that compound 3a significantly reduced the MIC of meropenem and doripenem against methicillin-resistant Staphylococcus aureus (MRSA). The observed adjuvant effect suggests that chromene scaffolds may serve as promising candidates for the development of next-generation β-lactam enhancers aimed at overcoming carbapenem resistance. Full article