Antibiotics-Basel最新文献

Ellagic acid (EA), a naturally occurring phenolic compound, has garnered significant interest as a potential antifungal agent owing to increasing fungal resistance and a scarce therapeutic pipeline. This review consolidates the evidence of the broad-spectrum activity of EA against critical priority pathogens, including Candida auris and Cryptococcus neoformans. We highlight its multi-target mechanisms of action, such as the impairment of cell wall integrity and plasma membrane disruption resulting from the inhibition of ergosterol biosynthesis, and inhibition of key enzymes, such as laccase. In addition to its direct growth-inhibitory effects, EA exhibits antivirulence properties, reducing biofilm formation and hyphal morphogenesis. Notably, it demonstrates synergistic potential with conventional antifungals, such as fluconazole, enhancing efficacy and potentially hindering the emergence of resistance. Although its poor solubility and bioavailability pose therapeutic challenges, advanced formulations such as liposomal systems show promise for improving its delivery. We conclude that EA is a promising candidate for developing new antifungal strategies, particularly as a synergistic agent or in nanoformulations, warranting further investigation to translate its potential into clinical practice.

Invasive Candida infections in the neonatal intensive care unit (NICU) are associated with significant morbidity and mortality, particularly among extremely preterm neonates. Early treatment with antifungals is critical to improve survival rates and avoid long-term adverse outcomes. Prevention with antifungal prophylaxis in high-risk neonates has been shown to reduce the prevalence of invasive Candida infections effectively. However, the irrational and/or inappropriate use of antifungals has been documented. This narrative review aims to provide an overview of the rationales for the inappropriate use of antifungals in the NICU, the consequences that ensue, and the promising strategy of antifungal stewardship programs to optimize antifungal use. The nonspecific clinical presentation of systemic Candida infections and the lack of rapid, accurate diagnostic techniques for Candida identification and specification in most settings lead to a high rate of empirical treatment in neonates without a proven infection. Moreover, evidence on the optimal dosing of antifungal agents and the treatment duration in the neonatal population is lacking, which may result in excessive or subtherapeutic drug exposure. Antifungal misuse is associated with microbiological consequences, including the emergence of antifungal-resistant Candida strains, and clinical consequences, such as drug toxicities and alterations in the intestinal mycobiome. It is therefore imperative to optimize antifungal use in the NICU. The implementation of antifungal stewardship programs, which, through a multidisciplinary approach, aim to improve diagnosis and guide clinicians on antifungal selection, dosing, and duration for both prevention and treatment according to the local epidemiology, represents a promising strategy for antifungal optimization in the NICU.

Antimicrobial resistance (AMR) represents a significant global concern, undermining the efficacy of treatments in both human and veterinary medicine. Livestock production plays a major role in the emergence and dissemination of AMR, primarily due to the extensive use of antibiotics for therapeutic, prophylactic, and metaphylactic purposes. Addressing this multifaceted issue necessitates a One Health approach. At the international level, regulatory frameworks are predominantly non-binding, relying on soft-law instruments developed by the World Health Organization (WHO), the Food and Agriculture Organization (FAO), and the World Organization for Animal Health (WOAH, formerly OIE), which advocate for harmonized guidelines and national action plans. In contrast, the European Union has implemented binding regulations, including Regulation (EU) 2019/6 and Regulation (EU) 2019/4, which restrict non-essential antimicrobial use (AMU) and reinforce veterinary accountability. Initiatives such as the Farm to Fork Strategy and platforms like ClassyFarm further advance antimicrobial stewardship by integrating animal welfare, sustainability, and access to EU funding. Achieving substantial reductions in AMR within livestock systems requires coordinated, cross-disciplinary, and multi-level governance efforts. The EU model illustrates how enforceable legal frameworks, combined with science-based monitoring and welfare incentives, can facilitate prudent antibiotic use and promote sustainable animal production. This review aims to provide an integrated overview of international and European strategies for regulating antibiotic use in food-producing animals, focusing on how scientific, veterinary and legal perspectives contribute to combating AMR and promoting animal welfare by emphasizing prevention, and a prudent and responsible AMU.

Background. The genus Streptomyces is known for its capability to produce a wide range of bioactive secondary metabolites. The enzymes required for their synthesis are encoded within biosynthetic gene clusters (BGCs), whose expression can be influenced by various physical and nutritional factors. Among these nutritional factors, it is worth highlighting carbon catabolic repression (CCR), which prevents the formation of secondary metabolites. It has been shown that transcriptional factors, in turn, regulated by glucose or by the enzyme glucose kinase (Glk), may be involved in this mechanism. It was shown that the expression of some transcriptional factors is regulated by glucose availability and that the enzyme glucose kinase (Glk) may play a role in this process. One of the transcriptional factors most upregulated in the presence of glucose/agar in Streptomyces coelicolor M145 is SCO7424, a member of the MarR family of transcriptional regulators. However, its influence on antibiotic synthesis has never been studied. Objective. In this work, we evaluated the effect of SCO7424 overexpression on the synthesis of actinorhodin (ACT) and undecylprodigiosin (RED), and its impact on growth and glucose consumption. Methods. A copy of the sco7424 gene was cloned into the pIJ702 plasmid, which was then transformed into a wild-type strain of S. coelicolor M145. Growth and antibiotic production were evaluated in the strain with two copies of sco7424 and in the wild-type strain. We also evaluated the expression of the probable target genes by quantitative RT-PCR. Results. We found that overexpression of sco7424 negatively impacts growth, glucose consumption kinetics, and the expression of specific regulators of the ACT and RED biosynthetic pathways, resulting in reduced ACT and RED production. Understanding the function of the regulatory cascades regulated by this family of regulators is crucial for boosting the yields of valuable metabolites produced by industrial strains.

(1) Background: Zinc is an essential micronutrient involved in immune regulation, epithelial barrier integrity, and the host response to bacterial infections. However, the clinical benefits of zinc supplementation across different age groups remain uncertain, with heterogeneous findings and variable dosing strategies reported in the literature. (2) Objectives: To map and summarize randomized controlled trials (RCTs) evaluating zinc supplementation (either as treatment or prophylaxis) for bacterial infection outcomes in neonates, children, and adults, and to identify gaps requiring further research, including the use of zinc-based nanoparticles. (3) Eligibility Criteria: We included English-language RCTs that evaluated zinc supplementation and reported clinical outcomes related to bacterial infections. Observational studies, trials without infection-related outcomes, and studies not involving human participants were excluded. (4) Sources of Evidence: A MEDLINE (PubMed) search was conducted from 2000 to 1 November 2025 using predefined keywords related to zinc supplementation, neonates, children, adults, and bacterial infections. Reference lists of eligible articles were screened to identify additional studies. (5) Charting Methods: Data were charted for each included study, including population characteristics, zinc dosing and regimen, type of supplementation (therapeutic or prophylactic), main infection-related outcomes, and key findings. Data charting was performed independently and verified within the research team. (6) Results: A total of 51 RCTs were included: 10 in neonates, 32 in children, and 9 in adults. In neonates, therapeutic zinc supplementation as an adjunct to antibiotics showed heterogeneous results, with some studies reporting reductions in morbidity, inflammatory markers or mortality, while others found no significant differences in clinical outcomes. In children, zinc supplementation consistently reduced the duration and severity of diarrheal episodes and, in several trials, improved the resolution of respiratory infections. In adults, the evidence was limited but suggested potential benefits in selected populations, such as burn patients or those with zinc deficiency or immunologic dysfunction. Variability in zinc dosage, treatment duration, and outcome definitions limits direct comparison across studies. (7) Conclusions: Zinc supplementation appears to provide benefits in neonates and children, whereas evidence in adults remains mixed and inconclusive. Standardized, well-powered RCTs are needed to define optimal dosing strategies, identify populations most likely to benefit, and clarify the mechanisms underlying zinc's anti-infective effects. Future research should consider the use of zinc oxide nanoparticles (ZnO-NPs) demonstrated broad-spectrum antimicrobial activity and potential synergy with antibiotics, although clinical data remain still limited.

Background/objectives: Antimicrobial peptides (AMPs), evolutionarily conserved components of innate immunity characterized by their broad-spectrum efficacy and minimal resistance development, are increasingly recognized as promising therapeutic candidates. This review aims to integrate current knowledge concerning natural and synthetic antimicrobial peptides and their therapeutic effectiveness in addressing gastrointestinal infections.

Methods: A literature review was performed, evaluating recent peer-reviewed studies on AMPs. The research concentrated on their molecular mechanisms of action, antimicrobial spectrum, and their interactions with standard antibiotics. More in detail, the peptide classes examined herein included defensins, cathelicidins, histatins, and various natural peptides such as lactoferricin, protamines, RegIII, and hepcidin, along with synthetic analogs like WR12, D-IK8, MSI-78, and IMX942.

Results: Natural AMPs demonstrated significant antimicrobial and immunomodulatory effects against Escherichia coli, Klebsiella pneumoniae, Salmonella spp., and Shigella spp. Beyond direct antimicrobial activity, antimicrobial peptides act as integrated anti-infective agents not only by modulating host-microbiota interactions, but also preserving epithelial barrier integrity, and limiting inflammation, thereby offering a multifaceted strategy to control gastrointestinal infections. On the other hand, synthetic peptides showed improved stability, reduced cytotoxicity, and synergistic interactions with antibiotics, which suggests that they could be used either alone or in combination with other treatments.

Conclusions: AMPs constitute a promising category endowed with anti-infective activity, especially for therapy of intestinal diseases, which is attributed to their distinctive anti-infective mechanisms, immune-modulating characteristics, and a relatively low propensity for resistance development compared to conventional antibiotics. However, more clinical trials and improvements to their formulation are needed to translate promising in vitro results into reliable patient outcomes.

Background/Objectives: Antimicrobial resistance (AMR) among Enterobacterales poses a major threat to public health in Southern Africa and has led to limited treatment options and increased mortality. Despite Africa bearing the brunt, there is limited data on the epidemiology and molecular epidemiology of the genetic determinants of β-lactam and/or carbapenem resistance. This narrative literature review summarizes the epidemiology and molecular characteristics of extended-spectrum β-lactamase-producing Enterobacterales (ESBL-PE), carbapenem-resistant Enterobacterales (CRE), and carbapenemase-producing Enterobacterales (CPE) in Southern Africa, while identifying data gaps and surveillance challenges. Methods: A comprehensive literature review was conducted using peer-reviewed articles from ten Southern African countries, including South Africa, Lesotho, Eswatini, Botswana, Namibia, Angola, Zambia, Zimbabwe, Mozambique, and Malawi, reporting the epidemiology and/or molecular characterization of ESBL-PE, CRE, and CPE. Results: ESBL-PE, CRE, and CPE pose an increasing healthcare threat in Southern Africa, with prevalence varying widely by source. Klebsiella pneumoniae and E. coli are the predominant ESBL-PE, CRE, and CPE species. The most frequent resistance genes are bla_CTX-M among ESBLs and bla_NDM and bla_OXA among carbapenemases, reflecting global patterns. However, molecular characterization across the region remains limited, with countries such as Botswana, Lesotho, Eswatini, Zambia, and Zimbabwe lacking sufficient data on the prevalence and diversity of these resistance determinants. Conclusions: Despite the paucity of genomic and epidemiological data, Southern Africa faces an urgent AMR challenge. Strengthening laboratory infrastructure, genomic surveillance, and regional coordination is crucial to mitigate AMR and guide antibiotic stewardship policies.

Background/Objectives: Antimicrobial resistance (AMR) in wildlife is an emerging public health concern due to the risk of zoonotic transmission, especially through the food chain, yet data on free-ranging animals remain scarce. This study examined the presence and patterns of AMR among bacteria isolated from hunted wild boars in the Campania region of Italy. Methods: Matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF MS) was used to identify bacterial isolates from wild boar meat and carcass swabs to the species level, and the Kirby-Bauer disk diffusion test was applied to screen 205 isolates, spanning 20 bacterial genera, against a panel of clinically relevant antibiotics. Resistance metrics were analyzed at genus and antibiotic levels, and patterns were visualized using a hierarchically clustered heatmap. Results: Resistance was detected in 15 of the 20 genera, with full susceptibility observed in Acinetobacter, Arthrobacter, Glutamicibacter, Leclercia, and Rahnella. Overall, 67.3% (138/205) of the isolates showed resistance to at least one antibiotic, with 33.7% (69/205) classified as multidrug-resistant (MDR). Carbapenems retained the highest activity (≥95% susceptibility) among all genera tested, while amoxicillin/clavulanate (78.4%) and aztreonam (57.4%) exhibited the highest mean resistance. Among potential pathogens, Escherichia coli exhibited an extended-spectrum β-lactamase (ESBL)-like phenotype, with resistance to amoxicillin/clavulanate (67%), aztreonam (54%), and ceftazidime (47%) but preserved carbapenem susceptibility. Staphylococcus spp. showed pronounced resistance to linezolid (57%) and erythromycin (52%), whereas Pseudomonas isolates demonstrated elevated resistance to aztreonam and ceftazidime (57% each). Opportunistic pathogens such as Alcaligenes faecalis and Pantoea agglomerans showed peak resistance to ciprofloxacin and amoxicillin/clavulanate. Pathogens and opportunistic pathogens demonstrated higher mean resistance (>30%) than commensals (≤32%), but the difference in mean and median resistance levels was not statistically significant (Mann-Whitney's U test, W = 4, p = 0.39). Conclusions: These findings highlight the widespread occurrence of AMR and MDR phenotypes, with clinically significant resistance patterns in wild-boar-associated bacteria, including non-pathogenic strains, highlighting their role in the amplification of AMR. Although the preservation of carbapenem susceptibility underscores their potential as last-line antibiotics, the high resistance to commonly used antibiotics raises concerns for zoonotic transmission. Surveillance of wildlife reservoirs therefore remains critical for integrated AMR control.

Background/objectives: Antimicrobial resistance (AMR) is a major global health threat that reduces antibiotic effectiveness and increases healthcare burdens. Countries in the Asia-Pacific region face a particularly high AMR burden, necessitating international collaboration, education, and practical training to combat this growing crisis. This study describes the design, implementation, and educational outcomes of the Infection Diagnosis Workshop, a short-term international program primarily targeting undergraduate medical sciences students that integrates AMR-focused hands-on clinical microbiology training and lectures, alongside cross-cultural collaboration and scientific English communication.

Methods: The Infection Diagnosis Workshop was implemented as a four-day program combining lectures with hands-on laboratory activities. Training emphasizes the detection and analysis of antibiotic-resistant bacteria through environmental sampling, bacterial culturing, phenotypic and genotypic resistance detection, and species identification, core components that have remained consistent since the workshop's establishment. Students also attended lectures on AMR science, global impact, and management strategies. Group discussions and collaborative tasks encouraged interdisciplinary learning. A thematic analysis of student feedback essays from previous workshop cohorts was conducted to identify key concepts, learning outcomes, and shared experiences. All participants provided informed consent for the use of their written feedback.

Results: Thematic analysis revealed key learning outcomes categorized into three themes: (1) Knowledge, Awareness, and Technical Skills; (2) Cultural Understanding and Cross-Cultural Collaboration; and (3) English Language and Communication Skills. Students reported increased AMR knowledge, improved laboratory proficiency, enhanced cultural adaptability, and greater confidence in English communication. They also expressed a deeper appreciation for interdisciplinary and international approaches to AMR.

Conclusions: The Infection Diagnosis Workshop effectively integrated practical laboratory training with international and cross-cultural engagement. The program strengthened student competencies and contributed to building global partnerships essential for combating AMR.

The OrgTRx platform is a system designed in Queensland, Australia, for the capture of Antimicrobial Resistance (AMR) surveillance data. The data is captured directly from Microbiology Laboratory Information Systems. The most common use of this data is to create facility-specific antibiograms for hospitals and other healthcare facilities. We report on the methods adopted to extract susceptibility results from participating pathology services for AMR surveillance across Australia. OrgTRx receives standardised extracts of antimicrobial susceptibility data from laboratory information systems. This data is validated, verified and incorporated into a database each month. For visualisation by clinical users, the data is displayed in a data cube. The data that is received in this standardised format can be used to review trends in resistance by organism and geographical location of patients presenting with a wide range of infections across Australia. This information can be used to identify areas that require additional resources to combat AMR. The OrgTRx data cube provides clinicians with the tools to create facility-specific antibiograms as well as monitor trends in resistance in pathogens of interest. Increased laboratory capacity and capability, along with adequate funding of surveillance systems, will provide high-quality information to inform the implementation of strategies to prevent the spread of AMR.