Search Results (3,361)

Background: This study aimed to compare mortality rates and treatment efficacy between ceftazidime–avibactam (CAZ/AVI) and meropenem-based combination regimens in critically ill patients with carbapenem-resistant Gram-negative bacteria (CRGNB) infections. Methods: This retrospective study included 135 intensive care unit (ICU) patients diagnosed with CRGNB infections between 2020 and 2024. Patients were categorized on the basis of treatment: CAZ/AVI or alternative combinations that included meropenem with either amikacin or polymyxin. The primary outcomes were 14-day, 30-day, and 90-day all-cause mortality rates. The secondary outcomes included the clinical response on day 14 and the total duration of ICU hospitalization. Results: Among the patients, 74 received CAZ/AVI, whereas 61 were treated with meropenem-based regimens. No significant differences were observed in the baseline characteristics between the groups. There were no statistically significant differences in 14-day (27.0% vs. 31.1%), 30-day (41.9% vs. 47.5%), or 90-day mortality rates (62.2% vs. 65.6%) between the two groups (p = 0.738, 0.511, and 0.818, respectively), including within the pneumonia and bloodstream infection subgroups. Clinical success was observed in 64.9% of the CAZ/AVI group and 65.6% of the other group (p = 0.931), with comparable ICU lengths of stay (44.0 ± 29.1 vs. 41.5 ± 26.4 days, p = 0.974). Multivariate analysis revealed that advanced age, higher Sequential Organ Failure Assessment (SOFA) scores, elevated procalcitonin levels, and prolonged time from culture collection to the initiation of appropriate antibiotic therapy were independent predictors of increased 30-day mortality. Conclusions: CAZ/AVI demonstrated efficacy and mortality outcomes comparable to those of meropenem-based regimens in ICU patients with CRGNB infections. Prompt initiation of appropriate antimicrobial therapy remains critical. Full article

Background: Differentiating between bacterial and viral infections in pediatric emergency care is challenging, often leading to unnecessary antibiotic use. The MeMed BV (MMBV) test is a host-response assay designed to differentiate bacterial from viral infections, but real-world data in pediatric settings remain limited. Methods: We conducted a pragmatic, single-center, prospective cohort study to assess the clinical utility of MMBV in children with acute respiratory infections or fever without source. Patients were assigned to standard of care (SOC) or MMBV testing (SOC+MMBV) based on time of presentation to the emergency department. The primary outcome was antibiotic prescribing. Secondary outcomes included diagnostic test utilization, hospitalization rates, and length of stay. Analyses were stratified by hospitalization status, clinical severity [National Institute for Health and Care Excellence (NICE) traffic light system], and patient age. Results: From July 2023 to April 2024, 343 patients were enrolled (171 SOC, 172 SOC+MMBV). In the SOC+MMBV arm, reduced antibiotic prescribing was observed among outpatients and those with non-severe signs and symptoms. Antibiotic prescribing was significantly reduced in children under five years with a low-risk profile, according to the NICE traffic light system (26.3% vs. 7.5%; p = 0.034). Multiplex PCR testing was significantly reduced in the SOC+MMBV group (28.7% vs. 16.3%; p = 0.006) compared to SOC for both inpatients and outpatients. No significant differences were observed in overall diagnostic test use or length of stay. Conclusions: MMBV improved antibiotic and diagnostic stewardship in a real-world pediatric ED setting, significantly reducing unnecessary antibiotic use among low-risk children under five and minimizing unnecessary multiplex PCR testing across the cohort. Full article

Background: Antimicrobial resistance is a major global health threat, particularly from pathogens such as Pseudomonas aeruginosa, known for forming biofilms and producing virulence factors that cause persistent infections. Essential oils (EOs) offer promising alternatives to conventional antimicrobial therapy due to their antimicrobial and antibiofilm properties. This study aimed to investigate the modulatory effects of a thymol-rich EO from Satureja montana L. on planktonic growth, biofilm formation, swarming motility, proteolytic activity and pyocyanin production of P. aeruginosa PAO1. Methods: The essential oil, isolated by hydrodistillation from S. montana aerial parts, was analysed by GC-MS. The minimum inhibitory concentration (MIC) of the EO and thymol was determined using the broth microdilution method. Sub-MICs were tested for planktonic growth and biofilm formation. Virulence was assessed by testing swarming motility, proteolytic activity and pyocyanin production. Results: The EO was characterised by a very high content of monoterpenes, with thymol dominating (56.47%). MIC for both EO and thymol was 4 mg/mL. They showed a biphasic effect: higher concentrations significantly inhibited planktonic growth (36–58% reduction; p < 0.05), while lower concentrations promoted it (10–17% increase; p < 0.05). Biofilm biomass varied, but the biofilm index indicated promotion at higher concentrations (0.125–0.5 mg/mL; p < 0.05). Both inhibited swarming at 0.5 mg/mL (thymol was more effective). Thymol decreased proteolytic activity, while EO increased pyocyanin production. Conclusions: S. montana essential oil and thymol show concentration-dependent modulation of P. aeruginosa growth, biofilms and virulence, suggesting their potential as anti-virulence agents, although the biphasic responses require careful dosing. Full article

Background: Nephrolepis exaltata (sword fern) possesses a considerable amount of phytochemicals and different biological activities. The current study investigates the anti-biofilm potential of greenly synthesized bimetallic nanoparticles of Nephrolepis exaltata leaf methanol extract (NEME-MnO₂-MgO BNPs). Methods: The NEME was subjected to UPLC/MS analysis, followed by characterization of its NPs by size, zeta potential, FTIR, entrapment efficiency, and release. Then, antioxidant, antimicrobial and antibiofilm assays were employed, followed by in silico studies. Results: The UPLC/MS analysis of NEME led to the tentative identification of 27 metabolites, mostly phenolics. The MnO₂-MgO BNPs presented a uniform size and distribution and exhibited IC₅₀ values of 350 and 215.6 μg/mL, in the DPPH and ABTS assays, respectively. Moreover, the NPs exhibited antimicrobial and anti-biofilm efficacies against Pseudomonas aeruginosa, Klebsiella pneumonia (ATCC-9633), Staphylococcus aureus (ATCC-6538), Escherichia coli, Bacillus cereus, and C. albicans, with MIC values of 250–500 μg/mL. The MnO₂-MgO BNPs inhibited Candida albicans biofilms with a % inhibition of 66.83 ± 2.45% at 1/2 MIC. The network pharmacology highlighted epigallocatechin and hyperoside to be the major compounds responsible for the anti-biofilm potential. The ASKCOS facilitated the prediction of the redox transformations that occurred in the green synthesis, while the docking analysis revealed enhanced binding affinities of the oxidized forms of both compounds towards the outer membrane porin OprD of P. aeruginosa, with binding scores of −4.6547 and −5.7701 kcal/mol., respectively. Conclusions: The greenly synthesized Nephrolepis exaltata bimetallic nanoparticles may provide a promising, eco-friendly, and sustainable source for antimicrobial agents of natural origin with potential biofilm inhibition. Full article

Background and purpose: Vulvovaginal candidiasis (VVC), caused by Candida albicans (C. albicans), is exacerbated by oxidative stress and uncontrolled inflammation. Pathogens like C. albicans generate reactive oxygen species (ROS) to enhance virulence, while host immune responses further amplify oxidative damage. This study investigates the antioxidant and antifungal properties of Hyssopus cuspidatus Boriss volatile extract (SXC), a traditional Uyghur medicinal herb, against fluconazole-resistant VVC. We hypothesize that SXC’s bioactive volatiles counteract pathogen-induced oxidative stress while inhibiting fungal growth and inflammation. Methods: GC-MS identified SXC’s major bioactive components, while broth microdilution assays determined minimum inhibitory concentrations (MICs) against bacterial/fungal pathogens, and synergistic interactions with amphotericin B (AmB) or fluconazole (FLC) were assessed via time–kill kinetics. Anti-biofilm activity was quantified using crystal violet/XTT assays, and in vitro studies evaluated SXC’s effects on C. albicans-induced cytotoxicity (LDH release in A431 cells) and inflammatory responses (cytokine production in LPS-stimulated RAW264.7 macrophages). A murine VVC model, employing estrogen-mediated pathogenesis and intravaginal C. albicans challenge, confirmed SXC’s in vivo effects. Immune modulation was assessed using ELISA and RT-qPCR targeting inflammatory and antioxidative stress mediators, while UPLC-MS was employed to profile metabolic perturbations in C. albicans. Results: Gas chromatography-mass spectrometry identified 10 key volatile components contributing to SXC’s activity. SXC exhibited broad-spectrum antimicrobial activity with MIC values ranging from 0.125–16 μL/mL against bacterial and fungal pathogens, including fluconazole-resistant Candida strains. Time–kill assays revealed that combinations of AmB-SXC and FLC-SXC achieved sustained synergistic bactericidal activity across all tested strains. Mechanistic studies revealed SXC’s dual antifungal actions: inhibition of C. albicans hyphal development and biofilm formation through downregulation of the Ras1-cAMP-Efg1 signaling pathway, and attenuation of riboflavin-mediated energy metabolism crucial for fungal proliferation. In the VVC model, SXC reduced vaginal fungal burden, alleviated clinical symptoms, and preserved vaginal epithelial integrity. Mechanistically, SXC modulated host immune responses by suppressing oxidative stress and pyroptosis through TLR4/NF-κB/NLRP3 pathway inhibition, evidenced by reduced caspase-1 activation and decreased pro-inflammatory cytokines (IL-1β, IL-6, TNF-α). Conclusions: SXC shows promise as a broad-spectrum natural antimicrobial against fungal pathogens. It inhibited C. albicans hyphal growth, adhesion, biofilm formation, and invasion in vitro, while reducing oxidative and preserving vaginal mucosal integrity in vivo. By disrupting fungal metabolic pathways and modulating host immune responses, SXC offers a novel approach to treating recurrent, drug-resistant VVC. Full article

The persistence of pharmaceutical pollutants such as ciprofloxacin (CIP) in aquatic environments represents a critical environmental threat due to their potential to induce antimicrobial resistance. Photocatalysis using TiO₂-based materials offers a promising solution for their mineralization; however, the limited visible-light response of TiO₂ and charge carrier recombination restricts its overall efficiency. In this study, Nb-doped TiO₂ nanoparticles were synthesized via the sol–gel method, incorporating Nb⁵⁺, ions into the TiO₂ lattice to modulate the structural and electronic properties of TiO₂ to enhance its photocatalytic performance for CIP degradation under UV and visible irradiation. Comprehensive structural, morphological, and optical analyses revealed that Nb incorporation stabilizes the anatase phase, reduces particle size (from 21.42 nm to 10.29 nm), and induces a slight band gap widening (from 2.85 to 2.87 eV) due to the Burstein–Moss effect. Despite this blue shift, Nb-TiO₂ exhibited significantly improved photocatalytic activity under visible light, achieving 86% CIP degradation with a reaction rate 16 times higher than that of undoped TiO₂. This enhancement was attributed to improved charge separation and higher hydroxyl radical (^•OH) generation, driven by excess conduction band electrons introduced by Nb doping. Density Functional Theory (DFT) calculations further elucidated the electronic structure modifications responsible for this behavior, offering molecular-level insights into Nb dopant-induced property tuning. These findings demonstrate how targeted doping strategies can engineer multifunctional nanomaterials with superior photocatalytic efficiencies, especially under visible light, highlighting the synergy between experimental design and theoretical modeling for environmental applications. Full article

Xylella fastidiosa (Xf) is a Gram-negative bacterium responsible for severe diseases in several commercially significant crops, including olive, grapevine, citrus and almond. Its management is particularly challenging due to its transmission via widespread vector insects, its ability to form biofilms, its high genetic diversity and, sometimes, latent symptoms. Current control strategies focus on integrated and preventive approaches, including the use of resistant varieties, agronomic practices, and vector control through chemical and biological methods. Direct control of the bacterium has always been a complex challenge that includes strategies to limit vector presence and activity in the field; however, several compounds have recently been evaluated that are able to inhibit biofilm formation and Xf growth. This review provides an up-to-date summary of studies investigating the efficacy of various treatments based on organic compounds, synthetic molecules and salt- or metal-based formulations. By evaluating the results of in vitro and in vivo experiments, the most promising solutions were identified that address the main challenges and limitations of chemical control strategies. These include N-acetylcysteine and zinc- and copper-based formulations, which are effective and potentially transferable to the field for crops such as citrus and olive trees. Antimicrobial peptides and nanoparticles, on the other hand, have demonstrated high efficacy in vitro, although further studies directly in the field are required. The evidence emerging from the analyzed studies offer insights to guide future research towards more effective and sustainable management approaches to mitigate the spread and impact of Xf. Full article

Antibiotics have dramatically reduced the burden of infectious diseases since their discovery, but the accelerating rise in antimicrobial resistance (AMR) now threatens these gains. AMR was responsible for nearly 5 million deaths in 2023 and continues to undermine the efficacy of existing treatments, particularly in low- and middle-income countries. While efforts to address AMR have focused heavily on antibiotic stewardship and new drug development, vaccines represent a powerful yet underutilized tool for prevention. By reducing the incidence of bacterial infections, vaccines lower antibiotic consumption, interrupt transmission of resistant strains, and minimize the selective pressures that drive resistance. Unlike antibiotics, vaccines offer long-lasting protection, rarely induce resistance, and confer indirect protection through herd immunity. This review examines the global burden and drivers of AMR, highlights the unique advantages of vaccines over antibiotics in mitigating AMR, and surveys the current development pipeline of vaccines targeting key multidrug-resistant bacterial pathogens. Full article

Objectives: To evaluate the in vitro antimicrobial activity of TiAB, a compound based on silver-bound titanium dioxide, against clinical isolates from dermatological infections. Methods: We tested 155 strains clinically isolated from ulcers and skin infections, including MRSA, ESBL-producing Enterobacterales, and P. aeruginosa. MIC and MBC values were determined using broth microdilution according to CLSI guidelines. Time-kill assays were performed at 0.5×, 1×, and 2× MIC. Median values were used to describe susceptibility profiles. Results: TiAB exhibited strong bactericidal activity against Gram-negative bacteria, including ESBL-positive E. coli and K. pneumoniae, with complete killing at 2× MIC (4–8%) within 4–8 h. Gram-positive pathogens exhibited higher MICs (≥8%) and limited response within 24 h; however, extending exposure to 48 h resulted in enhanced activity. Conclusions: TiAB exhibited in vitro bactericidal activity with median MIC values ranging from 1% to 2% (w/v) against Gram-negative clinical isolates such as E. coli and P. aeruginosa, and 2% to 4% against Gram-positive strains including MRSA. Time-kill assays confirmed ≥3 log₁₀ CFU/mL reductions for Gram-negative bacteria at 2× MIC within 24 h. These results suggest TiAB’s potential as a topical antimicrobial agent, though further in vivo studies are needed to validate its safety and efficacy. Full article

Background/Objectives: The rise in urinary tract infections caused by multidrug-resistant (MDR) bacteria presents a serious public health challenge across the Balkans, a region already burdened by aging populations, healthcare resource limitations, and fragmented antimicrobial surveillance systems. Methods: This review explores the epidemiology, risk factors, and consequences of MDR UTIs, particularly in the context of the COVID-19 pandemic, which significantly accelerated antimicrobial resistance (AMR) due to widespread, inappropriate antibiotic use. Results: The paper discusses region-specific data on resistance trends, highlights the gaps in diagnostic infrastructure, and evaluates emerging clinical strategies including antimicrobial stewardship (AMS), rapid diagnostic technologies, novel antibiotics, and non-antibiotic alternatives such as bacteriophage therapy and vaccines. Conclusions: Policy recommendations are provided to strengthen surveillance, promote evidence-based treatment, and ensure equitable access to diagnostic and therapeutic tools. A multidimensional and regionally coordinated response is essential to curb the MDR UTI burden and safeguard public health across the Balkans. Full article

Psoriasis is a chronic inflammatory skin disease driven by genetic, environmental, and immune factors. While biologics like adalimumab (anti-TNFα) and risankizumab (anti-IL-23) have improved outcomes, patient response variability remains unclear. This study examined immune-related transcriptomic differences between lesional (L) and non-lesional (NL) psoriatic skin, focusing on immune-related hub genes, their plasma levels, and their correlations with severity and treatment response. Patients with moderate-to-severe psoriasis were enrolled before treatment with anti-TNFα (n = 16) or anti-IL-23 (n = 18). Plasma and paired L and NL skin biopsies were collected for RNA sequencing. Gene ontology enrichment analysis found four immune-related terms enriched in L skin: T-helper 17, granulocyte and lymphocyte chemotaxis, and antimicrobial humoral response. A protein–protein interaction network identified ten immune-related hub genes upregulated in L skin that correlated with clinical severity. Patients with prior treatments expressed distinctive gene profiles. Plasma levels of CCL20 strongly correlated with disease severity. Decision tree models identified CCL20 expression in skin and plasma levels of IL-6 and CXCL8 as candidate predictors for anti-TNFα response. Similarly, skin expression of CXCL8, IL-6, and CXCL10, alongside plasma levels of CCL20, IL-6, and CXCL8, may predict anti-IL-23 response. Ten immune-related hubs may serve as possible biomarkers for disease severity and therapeutic response in psoriasis. Full article

The increasing global burden of mosquito-borne diseases and the widespread development of insecticide resistance in mosquitoes have fueled renewed interest in entomopathogenic fungi as effective tools that are compatible with existing mosquito control strategies. These fungi produce different types of infective propagules, including hydrophobic conidia and yeast-like blastospores, which differ in structure, mode of infection, and virulence. In this study, we evaluated the larvicidal activity of conidial and blastospore propagules from Beauveria bassiana MBC076 and Beauveria brongniartii MBC397 against Aedes aegypti. Conidia exhibited more rapid and more potent larvicidal effects compared to blastospores, but the overall survival at seven days post-infection was similar between the two types of propagules. Interestingly, B. brongniartii blastospore infections resulted in a significantly higher proportion of pupal mortality, suggesting a delayed mode of action. Immune profiling of infected larvae indicated significant induction of antimicrobial effectors such as cecropin, defensin, and attacin, primarily in response to conidial infection. In contrast, blastospore infections were associated with reduced expression of several prophenoloxidase genes, particularly during infection with B. brongniartii blastospores. These findings indicate that different fungal species and their propagule types exert varying levels of virulence and immune modulation in mosquito larvae. This study provides insights into the infection dynamics of fungal propagules and identifies immune markers that can be leveraged to enhance the efficacy of fungal-based larvicides. Full article

The native fruits of the Cerrado have an interesting composition of bioactive compounds responsible for antioxidant, anti-inflammatory, and antimicrobial activities, with technological potential for functional industries. This study investigated the extraction of bioactive compounds in cagaita and mamacadela fruits, under different conditions, using eutectic solvents based on choline chloride (CC) with citric acid (CA) or tartaric acid (TA), plus ethanol as reference. For a better understanding of the extracts, their antioxidant capacity was assessed by the DPPH^•, FRAP, ABTS^•+, and total phenolic compounds and flavonoids assays, as well as for color, water activity, and identification of bioactive compounds by mass spectrometry. Additionally, the carotenoid contents were evaluated in the ethanolic extracts. The results showed that ethanol was efficient for the extraction of flavonoids and presented advantages demonstrated in the antioxidant analyses of ABTS^•+ and FRAP. However, eutectic solvents stood out in the extraction of phenolic compounds, with yields 14.0 and 4.5 times higher than ethanol for mamacadela and cagaita, respectively. In addition, when compared to cagaita, mamacadela had twice the carotenoid content. Furthermore, the CC:TA solvent was the most efficient, demonstrating, by DI-ESI-MS, 29 phenolic compounds in mamacadela and 27 in cagaita. Therefore, the extracts obtained present potential for use as natural pigments, adding value to the fruits and encouraging their exploration by industries. Full article

Propolis is a complex, resinous substance originating from plant exudates and processed by bees, e.g., Apis mellifera L. Propolis is rich in flavonoids, phenolic acids, and terpenoids. It exhibits broad biological activities, including antimicrobial, anti-inflammatory, immunomodulatory, and anticancer effects. This review summarizes recent findings on the therapeutic potential of propolis in preclinical models of cancer and infectious diseases, with a focus on its molecular mechanisms of action. Experimental data indicate that propolis and its active constituents can induce apoptosis, inhibit proliferation, angiogenesis, and metastasis of cancer cells, and modulate immune responses and microbial virulence. Despite promising in vitro results, in vivo studies remain limited, and their results are often inconsistent. The variability in chemical composition due to geographical and botanical factors, as well as the lack of standardized extracts, further impedes translational research. We highlight key molecular pathways affected by propolis and propose directions for future studies, including improved standardization and more rigorous in vivo results description. These efforts are essential to validate propolis as a potential booster or alternative therapeutic strategy in oncology and infectious diseases treatment. Full article

Hydrogel materials have become an efficient, bioactive, and multifunctional alternative with great potential for biomedical applications. In this work, photoactive films were successfully designed for optical processing, and their photoactivity was tested in photodynamic therapy (PDT), such as antimicrobial patches. The stimulus-response hydrogel films are made of a hydrophilic polymer based on vinyl monomers, specifically 2-hydroxyethyl methacrylate (HEMA) and acrylamide (AAm), in a 1:1 molar ratio, along with the photochromic agent, 3,3-dimethylindolin-6′-nitrobenzoespiropirano (BSP), and a crosslinking agent, N,N’-methylenebisacrylamide (MBA). These hydrogel films were successfully created using the photoinitiator 2-hydroxy-4′-(2-hydroxyethoxy)-2-methylpropiophenone (IRGACURE 2959), MBA, and BSP in different concentrations (0.1, 0.3, and 0.5 mol%), which were later tested in photodynamic therapy (PDT) with the photosensitizer Ru(bpy)₂²⁺ against Staphylococcus aureus. The results showed that, while free Ru(bpy)₂²⁺ needed concentrations of 4–8 µg/mL to eliminate methicillin-sensitive (MSSA) strains, only partial inactivation was achieved for methicillin-resistant (MRSA) strains. The addition of the hydrogel films with BSP improved their effectiveness, lowering the minimum inhibitory concentration (MIC) to 2 µg/mL to fully inactivate MSSA and MRSA strains. These findings demonstrate that the combined use of hydrogel films containing BSP and Ru(bpy)₂²⁺ within a hydrogel matrix not only boosts antimicrobial activity but also highlights the potential of these photoactive films as innovative photosensitive antimicrobial coatings. This synergistic effect of BSP and Ru(bpy)₂²⁺ indicates that these materials are promising candidates for next-generation antimicrobial coatings and creative photosensitive materials. Full article