Antibiotics-Basel最新文献

Background/Objectives: Bovine mastitis, a significant global concern in dairy farming, results in substantial economic losses and poses considerable risks to both animal and human health. With the increasing prevalence of antimicrobial resistance (AMR) in mastitis pathogens, the potential for resistant infections to spread from livestock to humans and the environment is becoming a critical public health issue. This narrative review summarizes the current evidence on antimicrobial resistance in pathogens causing bovine mastitis and examines it from a One Health perspective, encompassing animal, human, and environmental interfaces. Results: By examining the complex interplay among animal, human, and environmental health, we highlight key factors that drive resistance, including the overuse of antimicrobials, poor farm management, and environmental contamination. We also discuss innovative strategies, such as enhanced surveillance, pathogen-specific diagnostics, alternatives to antimicrobials, and sustainable farm practices, that can mitigate the emergence of resistance. Key knowledge gaps include a limited understanding of antimicrobial residues, resistant pathogens, and gene transmission pathways and inconsistent implementation of antimicrobial stewardship practices. Conclusions: This review emphasizes the need for a coordinated, multidisciplinary effort to reduce the burden of AMR in bovine mastitis pathogens, ensuring the continued efficacy of antimicrobials and safeguarding public health through responsible management and policy interventions.

Athamanta L. is a small genus of the Apiaceae family, comprising only sixteen species and subspecies, which are distributed in the Canary Islands, Central Europe, and the Mediterranean basin. Background/Objectives: Since the time of Dioscurides, the species of this genus have been reported to have had several ethnopharmacological activities, and some of them are also used currently. Athamanta sicula L., growing in Italy, Tunisia, Algeria, and Morocco, is the only species of this genus present in Sicily. To further explore the phytochemical profile and biological properties of this species, the present study focused on the essential oil (EO) extracted from the aerial parts of wild A. sicula populations collected in central Sicily. Methods: The chemical composition of the EO, obtained by hydrodistillation, was determined by GC-MS analysis. The presence of myristicin was confirmed by isolation and by ¹H-NMR spectroscopic characterization. Results: The EO and its main constituents have been tested for possible antimicrobial properties against several bacterial strains, showing MIC values in the of 15-30 mg/mL range, and the mechanism of action was further investigated, revealing membrane-targeting effects consistent with outer membrane permeabilization. In addition, antibiofilm activity (with up to ~80% inhibition of biofilm formation at sub-MICs), antioxidant potential (demonstrating dose-dependent radical scavenging activity), and biocompatibility with eukaryotic cells were assessed to provide a comprehensive pharmacological profile of A. sicula EO. Specifically, the most abundant constituent was myristicin (62.2%), the principal representative of the phenylpropanoid class (64.4%). Hydrocarbon monoterpenes represented the second class of the EO (27.4%), with β-phellandrene (12.2%) as the main compound. Conclusions: Myristicin emerged as the key contributor to the antimicrobial and antibiofilm activity of the EO. The obtained results highlight the relevance of A. sicula EO as a myristicin-rich essential oil with notable in vitro biological activity.

The increasing problem of antibiotic resistance is a critical global health issue, necessitating the development of alternative therapeutic strategies to manage infections effectively. Among the promising solutions are human antimicrobial peptides (AMPs), naturally occurring molecules known for their broad spectrum of antimicrobial activity. Background/Objectives: This study investigates the potential of some AMPs, selected through a bioinformatic approach, as alternatives to conventional antibiotics, particularly focusing on their efficacy against species within the Bacteroidota phylum. These species, including pathogens such as Porphyromonas gingivalis, Capnocytophaga ochracea, and Capnocytophaga canimorsus, are well known for their roles in various human infections and related diseases. Non-pathogenic environmental species, such as Flavobacterium johnsoniae, are also included in this group, frequently used as a model organism. Methods: By analyzing the antimicrobial efficacy, mechanisms of action, and potential therapeutic applications of human AMPs, this research underscores their significance in addressing the challenge of antibiotic resistance. Results: This study identified three peptides, KTL24, LIR23, and MFP22, as particularly interesting. These peptides are derived from specific human proteins, namely SPI1, NAPSA and SCUB1. Conclusions: Their notable antimicrobial potential suggests that AMPs could serve either as a complementary treatment alongside traditional antibiotics or as a standalone therapy, mitigating the ongoing spread of antibiotic resistance and offering an alternative in global health strategies.

Background/Objectives: Tallaga cheese is an artisanal form of traditional Egyptian soft white Damietta cheese, characterized by high moisture, elevated salinity, and a limited shelf life, which collectively increase its vulnerability to microbial contamination. Typically produced from raw or minimally heated cow or buffalo milk, Tallaga cheese represents a relevant model for studying emerging food safety challenges. Methods/Results: This study revealed marked variability among commercial samples and, unexpectedly, a general absence of typical lactic acid bacteria (LAB) such as Lactococcus spp. Instead, enterococci, microorganisms increasingly associated with antimicrobial resistance and virulence traits, emerged as the dominant LAB group, with the detection of Enterococcus faecium strains posing particular concern for dairy safety. To address these challenges, the antimicrobial potential of isolated LAB was evaluated against Latilactobacillus sakei (CECT 906). Twelve bacteriocin-producing strains were identified: ten Enterococcus faecalis, one E. faecium, and one Lactococcus lactis. Enterococci demonstrated robust tolerance to stress conditions, including high salt concentrations, emphasizing their persistence in dairy environments. Given the relevance of controlling resistant and potentially virulent strains such as E. faecium, the bioprotective capacity of two bacteriocinogenic L. lactis strains (IPLA 1064 and AHRI ST9) was assessed using a laboratory-scale cheese model. Both strains effectively inhibited E. faecium AHRI CH4, achieving reductions of 2.6 and 3.6 log units (99.9%). Conclusions: These findings underscore the relevance of bacteriocin-producing L. lactis as natural biopreservatives to mitigate emerging threats related to antimicrobial-resistant food-borne pathogens in dairy products.

The growing global threat of antimicrobial resistance (AMR), particularly in cutaneous wound infections, represents a significant clinical and economic challenge. Biofilm formation by multidrug-resistant pathogens, such as Acinetobacter baumannii, often complicates healing and leads to therapeutic failure. Antimicrobial peptides (AMPs) are a promising alternative to conventional antibiotics due to their potent membrane-disrupting mechanism of action and lower propensity to induce resistance. Background/Objectives: This study aimed to evaluate the antibacterial, antibiofilm, and in vivo efficacy of four snake venom-derived cathelicidin-like peptides-Btn (15-34) and BotrAMP14 from Bothrops atrox, and Ctn (15-34) and CrotAMP14 from Crotalus durissus-against multidrug-resistant A. baumannii, Escherichia coli, and Pseudomonas aeruginosa clinical isolates from skin infections, with emphasis on A. baumannii, a WHO priority pathogen. Methods: Minimal Inhibitory Concentration (MIC), Minimal Bactericidal Concentration (MBC), and Minimal Biofilm Inhibitory Concentration (MBIC) were determined against A. baumannii, Escherichia coli, and Pseudomonas aeruginosa. Time-kill kinetics, hemolytic activity, and cytotoxicity assays were performed. A murine skin wound infection model was established to evaluate in vivo antibacterial efficacy and safety. Results: MIC/MBC values ranged from 0.78 to 25 µM against planktonic cells. In comparison, MBIC ranged from 1.56 to 12.5 µM against biofilms. BotrAMP14 eradicated A. baumannii within 4 min, while CrotAMP14 achieved bactericidal action in 20 min at 1.56 µM. Both peptides exhibited no hemolytic activity up to 128 µM and low cytotoxicity (IC₅₀ > 128 µM). In vivo, BotrAMP14 and CrotAMP14 demonstrated significant antibacterial activity at 24 h and 48 h post-infection, respectively, surpassing that of meropenem. Conclusions: These findings suggest that BotrAMP14 and CrotAMP14 are promising topical antimicrobial agents for managing multidrug-resistant skin infections and may help address the urgent need for alternative therapies against antibiotic-resistant pathogens.

Introduction: Haemolytic Escherichia coli (E. coli) is commonly associated with enteric disease in pigs and is frequently used as a phenotypic marker for enterotoxigenic E. coli (ETEC). This study aimed to characterise the resistance and virulence profiles of haemolytic E. coli isolated from Colombian pig farms. Methods: A total of 367 faecal samples from sows and pigs across all production stages were collected and analysed for the presence of haemolytic E. coli. Resistance and virulence genes associated with ETEC was detected by multiplex PCR, and antimicrobial susceptibility profiles were determined using broth microdilution and disc diffusion. Results: Haemolytic E. coli were identified in 40.3% of samples (n = 148 non-duplicate isolates), with the highest prevalence observed in growing piglets (47.1%). ETEC occurred in 5.4% of isolates. All isolates exhibited resistance to at least three antimicrobial classes (MDR), with high levels of resistance to tetracycline (98.0%), neomycin (97.3%), chloramphenicol (95.9%), sulfamethoxazole (93.9%), trimethoprim (91.9%), ampicillin (91.9%), nalidixic acid (82.4%), and ciprofloxacin (79.7%). Colistin resistance was observed in 5.4% of isolates, mediated by mcr1 or mcr3, while cefotaxime resistance (8.8%) was extensively associated with blaCTX-M. Conclusions: These findings reveal a concerning burden of MDR E. coli in Colombia's pig-producing regions and indicate that haemolysis alone is a poor indicator of ETEC. Integrating farm-level antimicrobial use data with genomic analyses will be essential to identify drivers of AMR and guide effective stewardship in the Colombian pig industry.

Background/Objectives: Emerging biofilms of uropathogenic bacteria, particularly P. aeruginosa, on medical devices such as urinary catheters, lead to complications in the treatment of urinary tract infections (UTI). Considering the spread of antibiotic resistance, the search for alternative efficient control options for biofilms is of great medical interest. Methods: Curcumin, 1-monolaurin, n-undecyl-α/β-l-fucopyranoside, and the fungal metabolite terrein were investigated for their influence on biofilm formation by P. aeruginosa on latex catheter pieces in artificial urine (AU), monitoring the number of colony-forming units per cm Latex-Catheter (CFU/cm Latex-Catheter). Results: Significant inhibition of P. aeruginosa biofilm formation [55.6% CFU reduction/cm²] was observed with the fungal metabolite terrein at 256 µg/mL AU. At a concentration of 512 µg/mL AU, terrein achieved almost complete inhibition of biofilm formation. n-undecyl-α/β-l-fucopyranoside inhibited biofilm formation [58.3% CFU reduction/cm²] by P. aeruginosa ATCC 27853 at 512 µg/mL AU. Compared to that, it caused an increase in biofilm formation [87.0% CFU increase/cm²] by P. aeruginosa PA 01 at 256 µg/mL AU. This study is limited by the fact that no investigations into the possible cytotoxicity of the two active substances, terrein and n-undecyl-α/β-l-fucopyranoside, on healthy eukaryotic cells have been carried out. Conclusions: Natural substances may be a promising approach to prevent the formation of P. aeruginosa biofilms. For antibacterial applications, fungal metabolites, such as terrein, offer a novel approach to prevent biofilms in urological practice.

Background/Objectives: Phages show efficacy against multidrug-resistant Pseudomonas aeruginosa, but limited host ranges require combining them in cocktails. In this work, we characterized 25 P. aeruginosa phages, developed therapeutic cocktails active against diverse clinical isolates, and tested phage efficacy in a mouse incisional wound model. Methods/Results: These phages represent seven genera, and genomic and phenotypic analyses indicate that 24/25 are lytic and suitable for phage therapy. Phage host ranges on a diversity panel of 156 P. aeruginosa strains that included 106 sequence types varied from 8% to 54%, and together the 24 lytic phages were active against 133 strains (85%). All of the phages reduced bacterial counts in biofilms. A cocktail of five lytic phages, WRAIR_PAM1, covered 56% of the strain panel, protected 100% of mice from lethal systemic infection (vs. 20% survival in the saline-treated group), and accelerated healing of infected wounds. An improved five-phage cocktail, WRAIR_PAM2, was formulated by a rational design approach (using phages with broader host ranges, more complementing activity, relatively low resistance background, and compatibility in mixes). Conclusions: WRAIR_PAM2 covered 76% of highly diverse clinical isolates and demonstrated significant efficacy against topical and systemic P. aeruginosa infection, indicating that it is a promising therapeutic candidate.

The Emergency Department (ED) represents an ideal location for antimicrobial stewardship (AMS) intervention, given the large volume of antibiotics seen prescribed to a wide variety of patients. This is particularly true in paediatrics, where most infectious presentations are viral in nature. A recent European Society of Clinical Microbiology and Infectious Diseases (ESCMID) position paper addressed four key areas affecting adult ED. This included: (1) the utility of biomarkers or rapid pathogen tests, (2) the impact of blood cultures on antibiotic prescribing, (3) the effect of watchful waiting on clinical outcomes, and (4) the potential for structured follow-up programmes within the ED to impact prescribing. Comparatively, the paediatric ED remains underrepresented in the literature with regard to AMS interventions. In this review article, we review the evidence surrounding the above four key areas as they relate to the paediatric population.

Introduction: The appropriate use of antibiotic prophylaxis (AP) in surgical procedures is an ongoing debate. There is a lack of evidence, and urological guidelines provide limited, procedure-specific recommendations. Our aim was to develop a generic model of an audit to define the need for AP in urological procedures, as well as in other surgical specialties. Material and Methods: Based on our experience with the Global Prevalence of Infections in Urology (GPIU) study and a literature review, we defined benchmark standards for 30-day infection rates, including sepsis, and estimated the number of patients needed to be included in a comparative study of AP versus no AP for a surgical procedure within one year. The generic study model was developed during a modified consensus process within the UTISOLVE research group. Urology departments giving and not giving AP were invited to join our development project as an extension of GPIU. Results: Radical prostatectomy was used as a model procedure. Ca. 60 urology centers performing more than 50 radical prostatectomies per year signed up. There was variation in AP practice among sites. Our own review showed that infection rates were ca. 5%, with severe infections, including sepsis, occurring in <0.5% of cases. A sample of 1825 patients would be required to achieve a 95% confidence interval half-width of ±1.0% for general infections. For sepsis, assuming an incidence of 0.5%, a sample of 2124 patients would be needed to reach a 95% confidence interval precision of ±0.30%. Enrollment of 2070 consecutive procedures would be needed to yield precisions of ±0.94% for infection and ±0.30% for sepsis. Based on the number of procedures performed and the number of interested study sites, we agreed on a prospective, multi-center, non-interventional service evaluation, expected to collect standardized data over a 3-month period. The primary outcome was defined as the 30-day incidence of infectious complications. All patients will undergo 30-day post-procedure follow-up through routine clinical care pathways. Conclusions: Our audit model is based on benchmarking of relevant outcomes. It defines how to assess AP in surgical procedures and clarifies a series of issues necessary to defend the status of a generic study model. We regard DEEP-URO to be a comprehensive, multi-center-based initiative that will help balance infection prevention with antimicrobial stewardship and improve the quality of clinical practice and personalized medicine.