Search Results (840)

Foodborne illness caused by bacterial pathogens is a global health concern and results in millions of infections annually. Therefore, food products typically undergo several processing stages, including sanitation steps, before being distributed in an attempt to remove pathogens. However, many sanitation methods have compounding effects on the color, texture, flavor, and nutritional quality of the product or do not effectively reduce the pathogens that food can be exposed to. Some bacterial pathogens particularly possess traits and tactics that make them even more difficult to mitigate such as biofilm formation. Non-thermal plasma sanitation techniques, including plasma-treated water (PTW), have proven to be promising methods that significantly reduce pathogenic bacteria that food is exposed to. Published work reveals that PTW can effectively mitigate both gram-positive and gram-negative bacterial biofilms. This study presents a novel analysis of the differences in antimicrobial effects of PTW treatment between biofilm-forming gram-positive bacteria, commonly associated with foodborne illness, that are sporulating (Bacillus cereus) and non-sporulating (Listeria monocytogenes). After treatment with PTW, the results suggest the following hypotheses: (1) that the non-sporulating species experiences less membrane damage but a greater reduction in metabolic activity, leading to a possible viable but non-culturable (VBNC) state, and (2) that the sporulating species undergoes spore formation, which may subsequently convert into vegetative cells over time. PTW treatment on gram-positive bacterial biofilms that persist in food processing environments proves to be effective in reducing the proliferating abilities of the bacteria. However, the variance in PTW’s effects on metabolic activity and cell vitality between sporulating and non-sporulating species suggest that other survival tactics might be induced. This analysis further informs the application of PTW in food processing as an effective sanitation method. Full article

Pressure therapy combined with silicone has a significant effect on scar hyperplasia, but limitations such as long-term wearing of compression garments (CGs) can easily cause bacterial infection, cleanliness, and lifespan problems of CGs caused by the tedious operation of applying silicone. In this study, a compression garment fabric (CGF) with both inhibition of scar hyperplasia and antibacterial function was prepared. A polydimethylsiloxane (PDMS)-loaded microcapsule (PDMS-M) was prepared with chitosan quaternary ammonium salt (HACC) and sodium alginate (SA) as wall materials and PDMS as core materials by the complex coagulation method. The PDMS-Ms were finished on CGF and modified with (3-aminopropyl)triethoxysilane (APTES) to obtain PDMS-M CGF, which was further treated with HACC to produce PDMS-M-HACC CGF. X-ray Photoelectron Spectroscopy(XPS) and Fourier transform infrared spectroscopy (FTIR) analysis confirmed the formation of covalent bonding between PDMS-M and CGF. The PDMS-M CGF exhibited antibacterial rates of 94.2% against Gram-negative bacteria Escherichia coli (E. coli, AATCC 6538) and of 83.1% against Gram-positive bacteria Staphylococcus aureus (S. aureus, AATCC 25922). The antibacterial rate of PDMS-M-HACC CGF against both E. coli and S. aureus reached 99.9%, with wash durability reaching grade AA for E. coli and approaching grade A for S. aureus. The finished CGF maintained good biocompatibility and showed minimal reduction in moisture permeability compared to unfinished CGF, though with decreased elastic recovery, air permeability and softness. The finished CGF of this study is expected to improve the therapeutic effect of hypertrophic scars and improve the quality of life of patients with hypertrophic scars. Full article

Ceftazidime–avibactam (CAZ-AVI) is a second-generation intravenous β-lactam/β-lactamase inhibitor combination. In recent years, substantial evidence has emerged regarding the efficacy and safety of CAZ-AVI. However, data on its use in critically ill patients remain limited. Background/Objectives: This multicenter, retrospective, observational cohort study was conducted across four Intensive Care Units (ICUs) in three hospitals in the Marche region of Italy. The primary objective was to evaluate the 30-day clinical outcomes and identify risk factors associated with 30-day clinical failure—defined as death, microbiological recurrence, or persistence within 30 days after discontinuation of therapy—in critically ill patients treated with CAZ-AVI. Methods: The study included all adult critically ill patients admitted to the participating ICUs between January 2020 and September 2023 who received CAZ-AVI for at least 72 h for the treatment of a confirmed or suspected Gram-negative bacterial (GNB) infection. Results: Among the 161 patients included in the study, CAZ-AVI treatment resulted in a positive clinical outcome (i.e., clinical improvement and 30-day survival) in 58% of cases (n = 93/161), while the overall mortality rate was 24% (n = 38/161). Relapse or persistent infection occurred in a substantial proportion of patients (25%, n = 41/161). Notably, acquired resistance to CAZ-AVI was observed in 26% of these cases, likely due to suboptimal use of the drug in relation to its pharmacokinetic/pharmacodynamic (PK/PD) properties in critically ill patients. Furthermore, treatment failure was more frequent among immunosuppressed individuals, particularly liver transplant recipients. Conclusions: This study demonstrates that the mortality rate among ICU patients treated with this novel antimicrobial combination is consistent with findings from other studies involving heterogeneous populations. However, the rapid emergence of resistance underscores the need for vigilant surveillance and the implementation of robust antimicrobial stewardship strategies. Full article

The emergence and spread of antimicrobial resistance among pathogens are significantly reducing available therapeutic options, highlighting the urgent need for novel and complementary treatment strategies. Antimicrobial photodynamic therapy (aPDT) is a promising alternative approach that can overcome antimicrobial resistance through a multitarget mechanism of action, exerting direct bactericidal and fungicidal effects with minimal risk of resistance development. Although aPDT has shown efficacy against a variety of pathogens, data on its activity against large collections of clinical multidrug-resistant strains are still limited. In this study, we assessed the antimicrobial activity of the photosensitizer RLP068/Cl combined with a red light-emitting LED source at 630 nm (Molteni Farmaceutici, Italy) against a large panel of Gram-negative and Gram-positive bacterial strains harboring relevant resistance traits and Candida species. Our results demonstrated the significant microbicidal activity of RLP068/Cl against all of the tested strains regardless of their resistance phenotype, with particularly prominent activity against Gram-positive bacteria (range of bactericidal concentrations 0.05–0.1 µM), which required significantly lower exposure to photosensitizer compared to Candida and Gram-negative species (range 5–20 µM). Overall, these findings support the potential use of RLP068/Cl-mediated aPDT as an effective therapeutic strategy for the management of localized infections caused by MDR organisms, particularly when conventional therapeutic options are limited. Full article

Background/Objectives: This study aimed to create a ‘carbapenem resistance score’ with the risk factors of carbapenem-resistant Gram-negative bacterial infections (GNBIs) in patients with hematological malignancies. Methods: Patients with carbapenem-resistant and susceptible GNBIs were included in this study and compared in terms of risk factors. Three models of “carbapenem resistance risk scores” were created with statistically significant variables. Results: The study included 154 patients with hospital-acquired GNBIs, of whom 64 had carbapenem-resistant GNBIs and 90 had carbapenem-susceptible GNBIs. Univariate and multivariate analyses identified several statistically significant risk factors for carbapenem resistance, including transfer from another hospital or clinic (p = 0.038), prior use of antibiotics like fluoroquinolones (p = 0.009) and carbapenems (p = 0.001), a history of carbapenem-resistant infection in the last six months (p < 0.001), rectal Klebsiella pneumoniae colonization (p < 0.001), hospitalization for ≥30 days (p = 0.001), and the presence of a urinary catheter (p = 0.002). Notably, the 14-day mortality rate was significantly higher in the carbapenem-resistant group (p < 0.001). Based on these findings, three risk-scoring models were developed. Common factors in all three models were fluoroquinolone use in the last six months, rectal K. pneumoniae colonization, and the presence of a urinary catheter. The fourth variable was transfer from another hospital (Model 1), a history of carbapenem-resistant infection (Model 2), or hospitalization for ≥30 days (Model 3). All models demonstrated strong discriminative power (AUC for Model 1: 0.830, Model 2: 0.826, Model 3: 0.831). For all three models, a cutoff value of >2.5 was adopted as the threshold to identify patients at high risk for carbapenem resistance, a value which yielded high positive and negative predictive values. Conclusions: This study successfully developed three practical risk-scoring models to predict carbapenem resistance in patients with hematological malignancies using common clinical risk factors. A cutoff score of >2.5 proved to be a reliable threshold for identifying high-risk patients across all models, providing clinicians with a valuable tool to guide appropriate empirical antibiotic therapy. Full article

Background: Unambiguous clinical interpretation of PCR results for urinary tract infections (UTIs) remains a challenge. Here we compare and correlate multiplex qPCR results (quantification cycle values) with traditional microbial culture results (colony forming units) for clinical samples. Methods: Serial dilutions [10⁸ to 10⁰ colony forming units (CFU)/mL] were performed on five Gram-negative and two Gram-positive UTI-causing bacterial pathogens. For each dilution, quantitative cultures on solid media to confirm CFU/mL values and a real-time PCR UTI panel employing a nanofluidic Open Array^TM platform producing quantification cycle (Cq) values were performed. Cq values were correlated with CFU/mL values, generating a semi-quantitative interpretive scale for clinical samples. The clinical utility of the scale was then assessed using PCR and culture data from 168 clinical urine samples. Results: For Gram-negative bacteria, Cq values of <23, 23 to 28, and >28 corresponded with ≥10⁵ CFU/mL, <10⁵ CFU/mL and negative cultures, respectively. For Gram-positive bacteria, Cq values of <26, 26 to 30, and >30 corresponded with ≥10⁵ CFU/mL, <10⁵ CFU/mL and negative cultures, respectively. Among 168 urine specimens (including 138 Gram-negative and 30 Gram-positive bacteria), there was 83.3% agreement (n = 140/168) and 16.6% non-agreement (n = 28/168) between culture CFU/mL and qPCR Cq. Gram-negative bacteria had higher agreement (87.6%, 121/138) than Gram-positive bacteria (63.3%, 19/30). Conclusions: This study demonstrates that qPCR Cq results can be directly correlated with traditional urine quantitative culture results and reliably identify the clinically relevant cutoff of 10⁵ CFU/mL for detected uropathogens. Full article

Feline urinary tract infections (UTIs) present a common challenge in veterinary practice, underscoring the importance of understanding local bacterial pathogens and antimicrobial resistance (AMR). This study determined bacterial prevalence and antimicrobial susceptibility in cats at Kasetsart University’s Veterinary Teaching Hospital in Bangkok, Thailand. Of the 543 cystocentesis urine samples collected from 428 cats, 115 (21.2%) tested positive for bacterial cultures, leading to a diagnosis of UTIs in 95 cats (22.2%). The most prevalent isolates included Escherichia coli (24.8%), Staphylococcus species (19.2%), Proteus mirabilis (13.6%), Pseudomonas aeruginosa (12.0%), and Enterococcus species (12.0%). Staphylococcus felis (8.8%) and Staphylococcus pseudintermedius (5.6%) were the predominant Staphylococcus species. Rare pathogens such as Corynebacterium urealyticum and Lactococcus garvieae were also identified. Antimicrobial testing revealed alarming resistance, with 69.2% of isolates exhibiting multidrug resistance (MDR). Escherichia coli and Proteus mirabilis showed high resistance to amoxicillin/clavulanic acid (AMC) (45.2–70.6%) and sulfamethoxazole/trimethoprim (SXT) (51.6–52.9%). Enterococcus faecium exhibited 85.7% resistance to AMC. Methicillin resistance was identified in 41.7% of Staphylococcus isolates, particularly high in Staphylococcus epidermidis (75.0%) and Staphylococcus pseudintermedius (71.4%). High fluoroquinolone resistance among MDR isolates further exacerbates AMR concerns. These results indicate that MDR Gram-negative, Staphylococcus, and Enterococcus species complicate the empirical treatment of feline UTIs, highlighting significant implications for AMR in veterinary practice. Full article

Background: The effect of antibiotics can be severely affected by external factors. Combining the oxidative impact of photodynamic therapy with antibiotics is largely unexplored, which may result in positive results with great impact on clinical applications. In particular, that can be relevant in the case of antibiotic resistance. Objectives: In this study, we examined the effects of aPDT using the photosensitizers (PSs), methylene blue (MB) or Photodithazine (PDZ), both alone and in combination with the antibiotics ciprofloxacin (CIP), gentamicin (GEN), and ceftriaxone (CEF), against the Gram-negative bacterium Klebsiella pneumoniae. Methods: A standard suspension of K. pneumoniae was subjected to PDT with varying doses of MB and PDZ solutions, using a 75 mW/cm² LED emitting at 660 nm with an energy of 15 J/cm². The MICs of CIP, GEN, and CEF were determined using the broth dilution method. We also tested the photosensitizers MB or PDZ as potentiating agents for synergistic combinations with antibiotics CIP, GEN, and CEF against K. pneumoniae. Results: The results showed that MB was more effective in inhibiting survival and killing K. pneumoniae compared to PDZ. The tested antibiotics CIP, GEN, and CEF suppressed bacterial growth (as shown by reduced MIC values) and effectively killed K. pneumoniae (reduced Log CFU/mL). While antibiotic treatment or aPDT alone showed a moderate effect (1 Log₁₀ to 2 Log₁₀ CFU reduction) on killing K. pneumoniae, the combination therapy significantly increased bacterial death, resulting in a ≥3 Log₁₀ to 6 Log₁₀ CFU reduction. Conclusions: Our study indicates that pre-treating bacteria with PDT makes them more susceptible to antibiotics and could serve as an alternative for treating local infections caused by resistant bacteria or even reduce the required antibiotic dosage. This work explores numerous possible combinations of PDT and antibiotics, emphasizing their interdependence in controlling infections and the unique properties each PS-antibiotic combination offers. Clinical application for the combination is a promising reality since both are individually already adopted in clinical use. Full article

Background/Objectives: Limited robust data support the use of antibiotic combinations in the treatment of orthopedic infections. However, in certain situations, the combination of antibiotics seems to be beneficial. This review aims to outline the circumstances under which a combination of antibiotics may be utilized in the treatment of orthopedic infections. Methods: We reviewed the existing guidelines on orthopedic infections and focused on situations where antibiotic combinations are recommended or proposed optionally. We chose vitro and animal studies that provide evidence for the effectiveness of several widely recommended combinations. Results: The combinations serve multiple purposes: they provide empirical coverage while awaiting microbiological results, offer targeted treatment for difficult-to-treat infections, and facilitate oral treatment primarily for staphylococcal infections. The objectives include enhancing bacterial coverage against Gram-positive and Gram-negative bacteria, achieving synergistic effects with bactericidal agents, and reducing the risk of antibiotic resistance. The review outlines specific combinations for fracture-related infections, periprosthetic joint infections, spinal infections, and anterior cruciate ligament reconstruction infections, emphasizing the importance of tailoring antibiotic choices based on local epidemiology and patient history. The review also addresses potential drawbacks of combination therapy, such as toxicity, higher costs, and drug interactions, underscoring the complexity of managing orthopedic infections effectively. Conclusions: According to the guidelines, several different proposals are made, depending in part on the countries’ epidemiology. In a well-defined situation, various authors propose either monotherapy or a combination of antibiotics. When a combination is suggested, the choice of antibiotics is based on the expected effect: broadening the spectrum, enhancing bactericidal activity, achieving a synergistic effect, or reinforcing biofilm activity to optimize the treatment. Full article

The global antimicrobial resistance crisis demands innovative strategies to combat bacterial infections, including those caused by drug-sensitive pathogens that evade treatment through biofilm formation or metabolic adaptations. Here, we demonstrate that Squama Manitis extract (SME)—a traditional Chinese medicine component—exhibits broad-spectrum bactericidal activity against clinically significant pathogens, including both Gram-positive (Staphylococcus aureus) and Gram-negative (Escherichia coli) species (MIC = 31.25 mg/mL), achieving significant reduction in bacterial viability within 24 h. Through integrated multi-omics analysis combining scanning electron microscopy and RNA sequencing, we reveal SME’s unprecedented tripartite mechanism of action: (1) direct membrane disruption causing cell envelope collapse, (2) metabolic paralysis through coordinated suppression of TCA cycle and fatty acid degradation pathways, and (3) inhibition of DNA repair systems (SOS response and recombination downregulation). Despite its potent activity, SME shows low cytotoxicity toward mammalian cells (>90% viability) and can penetrate Gram-negative outer membranes. These features highlight SME’s potential to address drug-resistant infections through synthetic lethality across stress response, energy metabolism, and DNA integrity pathways. While advocating for synthetic alternatives to endangered animal products, this study establishes SME as a polypharmacological template for resistance-resilient antimicrobial design, demonstrating how traditional knowledge and modern systems biology can converge to guide sustainable anti-infective development. Full article

Resistance of various bacterial pathogens to the activity of clinically approved drugs currently leads to serious infections, rapid spread of difficult-to-treat diseases, and even death. Taking the threats for human health in mind, researchers are focused on the isolation and characterization of novel natural products, including plant secondary metabolites. These molecules serve as inspiration and a suitable structural platform in the design and development of novel semi-synthetic and synthetic derivatives. All considered compounds have to be adequately evaluated in silico, in vitro, and in vivo using relevant approaches. The current review paper briefly focuses on the chemical and metabolic properties of resveratrol (1), as well as its oligomeric structures, viniferins, and viniferin-based molecules. The core scaffolds of these compounds contain so-called privileged structures, which are also present in many clinically approved drugs, indicating that those natural, properly substituted semi-synthetic, and synthetic molecules can provide a notably broad spectrum of beneficial pharmacological activities, including very impressive antimicrobial efficiency. Except for spectral verification of their structures, these compounds suffer from the determination or prediction of other structural and physicochemical characteristics. Therefore, the structure–activity relationships for specific dihydrodimeric and dimeric viniferins, their bioisosteres, and derivatives with notable efficacy in vitro, especially against chosen Gram-positive bacterial strains, are summarized. In addition, a set of descriptors related to their structural, physicochemical, pharmacokinetic, and toxicological properties is generated using various computational tools. The obtained values are compared to those of clinically approved drugs. The particular relationships between these in silico parameters are also explored. Full article

Background/Objectives: The liver, the body’s primary detoxifying organ, is often affected by various inflammatory diseases, including hepatitis, cirrhosis, and non-alcoholic fatty liver disease (NAFLD), many of which can be exacerbated by secondary infections such as spontaneous bacterial peritonitis, bacteremia, and sepsis—particularly in patients with advanced liver dysfunction. The global rise in these conditions underscores the need for effective interventions. Natural products have attracted attention for their potential to support liver health, particularly through synergistic combinations of plant extracts. Epavin, a dietary supplement from Erbenobili S.r.l., formulated with plant extracts like Taraxacum officinale (L.), Silybum marianum (L.) Gaertn., and Cynara scolymus (L.), known for their liver-supporting properties, has been proposed as adjuvant for liver functions. The aim of this work was to evaluate of Epavin’s antioxidant, anti-inflammatory, and protective effects against heavy metal-induced toxicity. In addition, the antibacterial effect of Epavin against a panel of bacterial strains responsible for infections associated with liver injuries has been evaluated. Methods: The protection against oxidative stress induced by H₂O₂ was evaluated in HepG2 and BALB/3T3 cells using the dichlorofluorescein diacetate (DCFH-DA) assay. Its anti-inflammatory activity was investigated by measuring the reduction in nitric oxide (NO) production in LPS-stimulated RAW 264.7 macrophages using the Griess assay. Additionally, the cytoprotecting of Epavin against heavy metal-induced toxicity and oxidative stress were evaluated in HepG2 cells using the [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide] (MTT) and DCFH-DA assays. The antibacterial activity of Epavin was assessed by determining the minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC) against Gram-positive (Enterococcus faecalis ATCC 29212, and BS, Staphylococcus aureus 25923, 29213, 43300, and BS) and Gram-negative (Escherichia coli 25922, and BS, Klebsiella pneumoniae 13883, 70063, and BS) bacterial strains using the microdilution method in broth, following the Clinical and Laboratory Standards Institute’s (CLSI) guidelines. Results: Epavin effectively reduced oxidative stress in HepG2 and BALB/3T3 cells and decreased NO production in LPS-stimulated RAW 264.7 macrophages. Moreover, Epavin demonstrated a protective effect against heavy metal-induced toxicity and oxidative damage in HepG2 cells. Finally, it exhibited significant antibacterial activity against both Gram-positive and Gram-negative bacterial strains, with MIC values ranging from 1.5 to 6.0 mg/mL. Conclusions: The interesting results obtained suggest that Epavin may serve as a valuable natural adjuvant for liver health by enhancing detoxification processes, reducing inflammation, and exerting antibacterial effects that could be beneficial in the context of liver-associated infections. Full article

Background/Objectives: Ascites is a major complication in patients with decompensated cirrhosis. Spontaneous bacterial peritonitis (SBP), an infection of the ascitic fluid, is a life-threatening condition in patients with cirrhosis. This study aimed to assess the utility of Tm mapping, a novel high-efficacy method for bacterial detection and quantification, in the early diagnosis of SBP and its pathogenesis. Methods: Ascitic fluid samples from 29 patients with cirrhosis were analyzed using Tm mapping for bacterial identification. Inflammatory cytokine and pathogen-associated molecular pattern levels in ascitic fluid were measured and correlated with SBP pathophysiology. Additionally, the role of ascitic macrophages was investigated in vitro. Results: Tm mapping detected bacteria more effectively than conventional culture methods. In samples where bacteria were identified, ascitic interleukin (IL)-6 levels were elevated. A positive correlation was observed between extracellular vesicle (EV) levels and IL-6, suggesting a role for EVs in peritoneal inflammation. Furthermore, EVs derived from Gram-negative bacteria induced M1 macrophage differentiation via the signal transducer and activator of transcription 1 signaling pathway. Conclusions: Tm mapping is a valuable tool for the early detection of bacteria in ascitic fluid. Additionally, EVs promote M1 macrophage differentiation, implicating them in the pathogenesis of cirrhotic complications, including SBP. Full article

Honey, propolis or royal jelly are considered natural remedies with therapeutic properties since antiquity. Many papers explore the development of antimicrobial biomaterials based on individual bee products, but there is a lack of studies on their synergistic effects. Combining honey, propolis and royal jelly with silver nanoparticles in a biopolymer matrix offers a synergistic strategy to combat antibiotic-resistant bacterial infections. This approach supports progress in wound healing, soft tissue engineering and other domains where elimination of the microorganisms is needed like food packaging. In this study we have obtained antimicrobial films based on bee products and silver nanoparticles (AgNPs) incorporated in an alginate–chitosan blend. The novel biomaterials were analyzed by UV-Vis, fluorescence and FTIR spectroscopy or microscopy, SEM and thermal analysis. Antibacterial tests were conducted against both Gram-positive and Gram-negative bacteria, while the antifungal properties were tested against Candida albicans. The diameters for growth inhibition zones were up to 10 mm for bacterial strains and 8 mm for the fungal strain. Additionally, cytotoxicity assays were performed to evaluate the biocompatibility of the materials, the results indicating that the combination of honey, propolis, royal jelly and AgNPs does not produce synergistic toxicity. Full article

Nocardia spp. are opportunistic pathogens of humans, domestic animals, and wildlife that can cause high levels of morbidity and mortality. Here, we present a unique case of nocardial airsacculitis in a free-ranging mallard (Anas platyrhynchos) from Arizona, USA, and compare it to the hosts, geographic distribution, diagnostic methodology, and infection site of known nocardiosis cases in birds. A gross necropsy, histopathology, and bacterial culture were performed. There were no gross findings associated with the nocardiosis. Histopathology showed multiple granulomas expanding the air sac with intralesional filamentous bacteria that were Grocott’s methenamine silver-positive, Fite–Faraco and Ziehl–Neelsen acid-fast, positive with the Periodic acid–Schiff reaction, and variably Gram-positive. The organism was isolated in culture and identified as Nocardia cyriacigeorgica based on the sequencing of a 463 bp portion of the 16S rRNA gene. While reports of nocardiosis in the class Aves are rare and some are possibly misdiagnosed due to limited diagnostics, cases are reported globally, sometimes resulting in epizootics. More information is needed to understand whether immunosuppression plays a role in disease development in birds. Known to be an emerging pathogen in humans, N. cyriacigeorgica can be considered as a differential diagnosis for pulmonary and potentially cutaneous or disseminated infections in birds. Full article