Antibiotics-Basel最新文献

{"title":"Real-World Experience on the Use of Eravacycline at Doses of 1 mg/kg Bodyweight and Fixed Dose Strategy in Two European Tertiary Centers.","authors":"Karin Oberreiter, Miriam M Moser, Lisa Schneider, Heinz Burgmann, Chiara Moreal, Simone Giuliano, Jacopo Angelini, Carlo Tascini, Matthias G Vossen","doi":"10.3390/antibiotics15040421","DOIUrl":"https://doi.org/10.3390/antibiotics15040421","url":null,"abstract":"<p><p><b>Background:</b> Eravaycline is a novel fully synthetic fluorocycline that is currently approved for complicated intra-abdominal infections. However, it is sometimes also used off-label in tertiary care centers for other infection sites as an antibiotic of last resort due to its broad spectrum of activity and efficacy against <i>Enterobacterales</i>, including multidrug-resistant pathogens like extended spectrum β-lactamase (ESBL) producers or carbapenem-resistant <i>Enterobacterales</i>, as well as all Gram-positive organisms including methicillin-resistant <i>Staphylococcus aureus</i> (MRSA) and vancomycin- and linezolid-resistant <i>Enterococcus faecium</i> (VRE). <b>Methods:</b> We retrospectively included a total of 78 patients from Austria and Udine who received eravacycline between April 2023 and August 2024 to evaluate the real-world efficacy of eravacycline in various infection sites and pathogens using descriptive statistics. <b>Results:</b> Eravacycline was most commonly used in intra-abdominal infections (44.9%), followed by pneumonia (12.8%) and infections of unknown origin (7.7%)<i>. Escherichia coli</i>, including ESBL producers, was the most common pathogen (24.4%), followed by <i>Enterococcus</i> spp. (12.8%) and <i>Klebsiella pneumoniae</i> (12.8%). Clinical cure was achieved in 65% of patients, whereas microbiological cure was documented in 46%; source control was attained in 48.7%, and 16.7% died within 30 days. A total of 48% of patients required intensive care. <b>Conclusions:</b> Eravacycline represents a possible therapeutic option for a wide range of pathogens, but its use must be evaluated in the context of infection site and severity.</p>","PeriodicalId":54246,"journal":{"name":"Antibiotics-Basel","volume":"15 4","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13113548/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147788775","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"How Glyphosate and Its Derivatives Influence Antimicrobial Resistance Emergence and Transmission: A One Health Perspective.","authors":"Leticia Malinoski, Gilmar Gonçalves Silva, Larissa Kaniak Ikeda Rodrigues, Leandro Flávio Carneiro, Marcelo Pedrosa Gomes","doi":"10.3390/antibiotics15040419","DOIUrl":"https://doi.org/10.3390/antibiotics15040419","url":null,"abstract":"<p><p><b>Background/Objectives:</b> Glyphosate-based formulations are globally pervasive pollutants increasingly recognized as potential contributors to antimicrobial resistance (AMR) in environmental microbiomes. Although glyphosate is designed to inhibit plant 5-enolpyruvylshikimate-3-phosphate synthase, it also affects microbial metabolism, stress response, and genetic exchange. This review synthesizes the pathways through which glyphosate, its metabolite aminomethylphosphonic acid (AMPA), and commercial mixtures influence resistance-associated phenotypes and the dissemination of antibiotic resistance (ABR). <b>Methods:</b> A critical synthesis of the literature was conducted to evaluate the mechanistic and ecological interactions between glyphosate exposure and bacterial resistance in soil, aquatic, and host-associated microbiomes. <b>Results:</b> Experimental evidence showed that sublethal glyphosate exposure induced oxidative stress, altered membrane permeability, activated multidrug efflux pumps, and promoted tolerance phenotypes that could modify antibiotic susceptibility. It also enhances mutation rates and horizontal gene transfer processes associated with the emergence of resistance under controlled conditions. At the community level, glyphosate exposure is associated with microbiome restructuring and enrichment of resistance determinants, often without major shifts in overall diversity of the microbiome. These effects have been reported at environmentally relevant concentrations, although the evidence remains largely derived from laboratory and mesocosm studies. <b>Conclusions:</b> Glyphosate acts as both a biochemical modulator of resistance-related phenotypes and an environmental selective pressure that shapes microbial communities. Its widespread use and environmental persistence position it as a context-dependent contributor to the emergence and dissemination of AMR through interacting mechanistic and ecological pathways. Integrating AMR endpoints into pesticide risk assessments and surveillance frameworks is warranted, in addition to expanded field-based validation.</p>","PeriodicalId":54246,"journal":{"name":"Antibiotics-Basel","volume":"15 4","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13114102/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147788754","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of the Antifungal Activity of the Polyphenol Formulation <i>Viroelixir</i> Against <i>Candida albicans</i>.","authors":"Manal Dahdah, Yasmine Ettouil, Hawraa Issa, Latifa Koussih, Mikhlid H Almutairi, Mahmoud Rouabhia, Abdelhabib Semlali","doi":"10.3390/antibiotics15040420","DOIUrl":"https://doi.org/10.3390/antibiotics15040420","url":null,"abstract":"<p><p><i>Candida albicans</i> (<i>C. albicans</i>) is an opportunistic fungal pathogen capable of causing a wide range of infections, including mucosal and systemic candidiasis. In the oral cavity, fungi represent a minor component of the microbiome but can significantly contribute to morbidity, particularly under conditions of dysbiosis or immunosuppression. Treatment remains challenging due to increasing multidrug resistance. This study investigates the in vitro antifungal potential of <i>Viroelixir</i>, a standardized polyphenol blend derived from green tea and pomegranate and enriched in catechins (including epigallocatechin gallate, EGCG), ellagitannins (notably punicalagin), ellagic acid, and flavonoids, with particular focus on its potential anti-virulence mechanisms.</p><p><strong>Methods: </strong>The effect of <i>Viroelixir</i> on <i>C. albicans</i> growth was assessed using MTT assay, optical density measurements, colony formation, carbohydrate quantification, and pH variation analysis. Biofilm formation, morphological transition, ROS production, necrosis, virulence gene expression, adhesion, and host immune responses were also evaluated.</p><p><strong>Results: </strong><i>Viroelixir</i> significantly inhibited <i>C. albicans</i> growth and reduced colony formation compared with untreated controls. The formulation also inhibited biofilm formation and markedly reduced pseudohyphal development, reaching up to 94% reduction under specific treatment conditions. Flow cytometry analysis showed an increase in dead fungal cells, reaching approximately 88% following exposure to <i>Viroelixir</i> at the highest tested concentration. In addition, <i>Viroelixir</i> reduced the transcript levels of several virulence-associated genes, including SAP1-SAP9 and EAP1. In epithelial cell co-culture models, pre-treatment of <i>C. albicans</i> with <i>Viroelixir</i> reduced fungal adhesion and attenuated epithelial inflammatory responses, including IL-6, IL-8, and hBD-2 production, and was associated with reduced activation of the TLR4-NF-κB signaling pathway.</p><p><strong>Conclusions: </strong>These findings suggest that the antifungal and anti-virulence effects observed may be associated with the polyphenolic compounds present in the <i>Viroelixir</i> formulation, highlighting its potential as a promising in vitro antifungal candidate against <i>C. albicans</i>.</p>","PeriodicalId":54246,"journal":{"name":"Antibiotics-Basel","volume":"15 4","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13113709/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147789215","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cefiderocol Targeted Treatment for Multidrug-Resistant Gram-Negative Infections: An Observational Cohort Study.","authors":"Lourdes García-Carnero, Gabriela Abelenda-Alonso, Marc Santos-Puig, Ariadna Padullés, Clara Ribera, Alberto Lamiel, Rosa Costa-Primo, Manuel González de Aledo, Rosa Granada, Víctor Daniel Gumucio, Eva Santafosta, Marc Gilabert, Alejandro Blanco-Arévalo, Mireia Puig-Asensio, Evelyn Shaw, Jordi Carratalà, Carlota Gudiol","doi":"10.3390/antibiotics15040416","DOIUrl":"https://doi.org/10.3390/antibiotics15040416","url":null,"abstract":"<p><p><b>Background/Objectives</b>: Infections caused by multidrug-resistant Gram-negative bacteria (MDR-GNB) represent a major therapeutic challenge, particularly in hospitalized and critically ill patients with limited treatment options. Cefiderocol, a novel siderophore cephalosporin, has demonstrated activity against a broad range of resistant Gram-negative pathogens. We aimed to evaluate the effectiveness and safety of cefiderocol for the treatment of MDR-GNB infection. <b>Methods</b>: We conducted a retrospective observational study including all adult patients who received ≥72 h of cefiderocol between November 2020 and October 2024 at a Spanish tertiary-care hospital. The primary outcome was clinical success, defined as survival and absence of clinical recurrence 30 days after cefiderocol initiation. Secondary outcomes included 30- and 90-day mortality, clinical and microbiological recurrence, emergence of resistance, and adverse events. <b>Results</b>: Eighty patients were included (median age 64 years [IQR 56-72]; 81.3% male). Respiratory (26.2%) and abdominal (22.5%) infections were the most common, and 20% presented with bacteremia. At infection onset, 26.2% had septic shock and 45% required intensive care unit admission. The three most frequently isolated pathogen was <i>Pseudomonas aeruginosa</i> (33.9%), followed by Enterobacterales (33%) and <i>Stenotrophomonas maltophilia</i> (30.1%). Clinical success was achieved in 67.5% of patients. Thirty and 90-day mortality rates were 27.5% and 36.5%, respectively. Recurrence within 90 days occurred in 5% of cases. Emergence of resistance was detected in one <i>Klebsiella pneumoniae</i> ST147 isolate, and serious adverse events occurred in 5% of patients. <b>Conclusions</b>: In a cohort including a substantial proportion of critically ill patients, cefiderocol was associated with favorable clinical outcomes and an acceptable safety profile. These findings suggest that cefiderocol may represent a useful therapeutic option for severe MDR-GNB infections in patients with limited treatment alternatives.</p>","PeriodicalId":54246,"journal":{"name":"Antibiotics-Basel","volume":"15 4","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13113607/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147789098","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mobile Genetic Elements as Central Drivers of Antimicrobial Resistance: Molecular Mechanisms, Evolutionary Ecology, One Health Implications and Control Strategies.","authors":"Hemayet Hossain, Md Hasan Ali, Tanvir Ahmad, Snigdha Sharmin Binte Sayeed, Md Abdur Nur Sakib, Khadiza Akter Brishty, Md Shah Jahan Saleh, Md Mosharof Hosen, Shahabuddin Ahmed, Shihab Ahmed, Md Shahidur Rahman Chowdhury, Md Mahfujur Rahman","doi":"10.3390/antibiotics15040418","DOIUrl":"https://doi.org/10.3390/antibiotics15040418","url":null,"abstract":"<p><p>Antimicrobial resistance (AMR) represents a global health crisis, driven largely by the mobility of resistance determinants through mobile genetic elements (MGEs). These include plasmids, integrons, insertion sequences, transposons, integrative and conjugative elements (ICEs), and prophages, which together facilitate horizontal gene transfer (HGT) across bacterial species and ecosystems. This review aims to provide a comprehensive synthesis of current knowledge on the types, mechanisms, ecological drivers, and impacts of MGEs in the dissemination of antibiotic resistance genes (ARGs). Methods involved critical evaluation of recent genomic, epidemiological, and ecological studies, alongside case studies of clinically significant resistance outbreaks. Findings highlight how MGEs function as hubs for ARG capture, recombination, and stabilization, enabling the emergence of multidrug-resistant (MDR) and extensively drug-resistant (XDR) pathogens. We also explored their interactions with ecological pressures such as antibiotics, heavy metals, and biocides, as well as their role in One Health transmission pathways. The significance of this study lies in linking molecular insights with applied strategies, including genomic surveillance, MGE-targeted inhibitors, phage therapy, and CRISPR-based interventions. Understanding MGEs is essential for designing effective interventions to mitigate AMR and protect global health.</p>","PeriodicalId":54246,"journal":{"name":"Antibiotics-Basel","volume":"15 4","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13113465/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147789195","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gut Microbiota and Acute Myeloid Leukemia: State of the Art, Clinical Signals, and Translational Opportunities.","authors":"Maria Eugenia Alvaro, Santino Caserta, Enrica Antonia Martino, Mamdouh Skafi, Antonella Bruzzese, Nicola Amodio, Eugenio Lucia, Virginia Olivito, Caterina Labanca, Francesco Mendicino, Ernesto Vigna, Fortunato Morabito, Massimo Gentile","doi":"10.3390/antibiotics15040417","DOIUrl":"https://doi.org/10.3390/antibiotics15040417","url":null,"abstract":"<p><p>Acute myeloid leukemia (AML) remains a highly morbid malignancy in which outcomes are constrained not only by disease refractoriness and relapse, but also by therapy-related toxicity-particularly infections, mucosal injury, and delayed hematopoietic reconstitution. The gut microbiota has emerged as a potentially modifiable layer of host vulnerability and resilience during AML treatment. Microbiome disruption is detectable already at diagnosis, even in antibiotic-naïve patients, and is often characterized by reduced community diversity, depletion of anaerobic taxa linked to short-chain fatty acids (SCFAs) production, and enrichment of pathobiont-associated profiles. During induction, cytotoxic therapy and antimicrobials precipitates diversity loss, domination events, and persistent shifts beyond discharge. Clinically, the most consistent translational signal is the association between baseline or early-treatment microbiome features and infectious outcomes, while emerging data suggest that diagnosis-time microbiome structure may also relate to hematologic recovery kinetics. Mechanistic models converge on pathways linking barrier integrity, microbial metabolites (notably butyrate and other SCFAs), immune calibration, and inflammatory translocation of microbial products. These insights support hypotheses: antimicrobial stewardship may preserve microbiome function; ecosystem repair strategies such as autologous fecal microbiota transfer (A-FMT) are feasible and can restore community structure; and metabolite or nutritional interventions merit evaluation in immunocompromised hosts. Regimen-specific microbiome effects and microbiome-drug interactions suggest that treatment choice could have downstream microbiome-mediated consequences. We synthesize evidence, outline interventional concepts, and define methodological priorities for next-generation trials assessing causality and clinical benefit. Progress will require longitudinal sampling, multi-omic integration (metabolomics, resistomics, and barrier/inflammatory biomarkers), and interventional designs linking microbiome dynamics to clinically meaningful outcomes.</p>","PeriodicalId":54246,"journal":{"name":"Antibiotics-Basel","volume":"15 4","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13113732/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147788762","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sialoendoscopy with Intraductal Irrigation in Chronic Salivary Gland Disease: A Minimally Invasive, Antibiotic-Sparing Strategy.","authors":"Riccardo Manzella, Palmira Immordino, Francesco Lorusso, Francesco Dispenza, Federico Sireci, Cosimo Galletti, Salvatore Gallina, Angelo Immordino","doi":"10.3390/antibiotics15040415","DOIUrl":"https://doi.org/10.3390/antibiotics15040415","url":null,"abstract":"<p><p><b>Background/Objectives</b>: Chronic and recurrent sialadenitis are inflammatory disorders of the major salivary glands often managed with repeated courses of systemic antibiotics, despite limited long-term efficacy and growing concerns regarding antimicrobial resistance. Minimally invasive intraductal therapies, including sialoendoscopy with irrigation, have emerged as effective alternatives aimed at addressing ductal obstruction and chronic inflammation while reducing antibiotic exposure. This study aimed to systematically review the available evidence on the effectiveness and safety of sialoendoscopy with intraductal irrigation in the management of chronic and recurrent sialadenitis, with particular attention to its potential antibiotic-sparing role. <b>Methods</b>: A literature review was conducted in accordance with PRISMA guidelines. Major scientific databases were searched to identify studies evaluating sialoendoscopy with intraductal irrigation in patients with chronic or recurrent sialadenitis. Study characteristics, patient populations, irrigation protocols, and clinical outcomes were extracted and qualitatively analyzed. <b>Results</b>: Sialoendoscopy with intraductal irrigation was associated with significant clinical improvement in more than two-thirds of patients, with complete or partial symptom resolution. The procedure demonstrated high technical feasibility and a favorable safety profile. Symptom control was maintained across most etiological subgroups. The need for prolonged or repeated systemic antibiotic treatment decreased following endoscopic intervention. <b>Conclusions</b>: Sialoendoscopy with intraductal irrigation may represent a promising and minimally invasive therapeutic option for chronic and recurrent sialadenitis and may contribute to improved antibiotic stewardship by reducing unnecessary systemic antibiotic use. These findings suggest that intraductal therapeutic strategies could be considered within evolving care pathways for chronic salivary gland disorders, aligning clinical management with broader public health efforts to combat antimicrobial resistance.</p>","PeriodicalId":54246,"journal":{"name":"Antibiotics-Basel","volume":"15 4","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13114244/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147789040","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In Vitro Restoration of Colistin Susceptibility by Ivacaftor Synergy with Limited Reproducibility in a Murine Pneumonia Model.","authors":"Ana Verónica Halperin, Franziska Schwartz, Lars Christophersen, José Pérez-Del Palacio, Manuel Ponce-Alonso, José Avendaño-Ortiz, Juan de Dios Caballero, Rafael Cantón, Claus Moser, Rosa Del Campo","doi":"10.3390/antibiotics15040414","DOIUrl":"https://doi.org/10.3390/antibiotics15040414","url":null,"abstract":"<p><p><b>Background:</b> We aimed to investigate the potential synergistic effect of ivacaftor combined with colistin against <i>Pseudomonas aeruginosa</i> and <i>Klebsiella pneumoniae</i>, and to elucidate the underlying molecular mechanisms through metabolomic analysis and its reproducibility in a murine model. <b>Methods:</b> Six colistin-susceptible and 2 colistin-resistant cystic fibrosis <i>P. aeruginosa</i> isolates, along with two colistin-resistant <i>K. pneumoniae</i> clinical isolates, were studied. Antimicrobial susceptibility was assessed by broth microdilution, and synergy by checkerboard assay. Metabolomic profiling was conducted via LC-HRMS with statistical analysis. A murine pneumonia model, induced by intranasal administration of colistin-resistant strains, was used to validate in vivo ivacaftor and colistin synergy after 24 h. <b>Results:</b> No previously described colistin resistance mutations were identified in <i>P. aeruginosa</i> strains, whereas <i>K. pneumoniae</i> carried <i>mgrB</i> variations. Ivacaftor restored colistin susceptibility at 16 mg/L concentration, and at 1-2 mg/L led to at least a twofold reduction in colistin MIC. Metabolomic analysis of colistin-resistant <i>P. aeruginosa</i> strains revealed that ivacaftor induced modifications in phosphoethanolamine groups of lipid A. However, no synergistic effects were observed in the short-term in vivo pneumonia model, regardless of the administration route. <b>Conclusions:</b> Ivacaftor exhibited no direct antimicrobial activity against <i>P. aeruginosa</i> and <i>K. pneumoniae</i> isolates in vitro but restored colistin susceptibility through synergistic interactions. The lack of synergy in the murine pneumonia model may reflect treatment time and challenges in standardizing in vivo conditions. These findings highlight the potential of ivacaftor as an adjunct to colistin therapy, warranting further investigation into its clinical applicability.</p>","PeriodicalId":54246,"journal":{"name":"Antibiotics-Basel","volume":"15 4","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13113029/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147789026","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Two Shorter Variants of the Proline-Rich Antimicrobial Peptide B7-005 Scaffold Active Against Clinical Isolates of <i>Pseudomonas aeruginosa</i> and <i>Staphylococcus aureus</i>.","authors":"Giacomo Cappella, Adriana Di Stasi, Clelia Cortese, Luisa Torrini, Agnese D'Amore, Virginia Niccolini, Luigi de Pascale, Bruno Casciaro, Mario Mardirossian, Alessandro Pini, Maria Luisa Mangoni, Marco Scocchi","doi":"10.3390/antibiotics15040412","DOIUrl":"https://doi.org/10.3390/antibiotics15040412","url":null,"abstract":"<p><p><b>Background/Objectives:</b> Developing novel strategies to combat respiratory infections caused by multidrug-resistant \"priority pathogens\" like the ESKAPEE <i>Pseudomonas aeruginosa</i> and <i>Staphylococcus aureus</i> is an urgent priority. <b>Methods:</b> We investigated two shortened variants of the proline-rich antimicrobial peptide (PrAMP) B7-005, B7-006 (15-mer) and B7-007 (13-mer). Evaluation included MIC assays against laboratory and clinical multidrug-resistant isolates, mechanistic studies of membrane permeabilization, cytotoxicity testing on BEAS-2B bronchial epithelial cells, and proteolytic stability assays in human elastase and sputum. <b>Results:</b> Despite their reduced size, lower positive charge, and decreased proline content, both variants retained full antimicrobial activity against clinical pathogens with consistent MIC values ≤ 25 µM. These variants exhibit membrane permeabilization in <i>P. aeruginosa</i> but may also relay on a hybrid mode of action involving also intracellular targets. Notably, B7-006 and B7-007 displayed low cytotoxicity compared to the lytic peptide BMAP-18. While B7-007 showed greater susceptibility to proteolytic degradation than its parent B7-005, it preserved partial integrity during the initial hours of exposure. <b>Conclusions:</b> Overall, these findings demonstrate that the B7 scaffold tolerates substantial truncation while preserving potency and selectivity, identifying a minimal 13-amino-acid active core. This work provides critical insights into structure-activity relationships and supports the development of compact, mechanistically versatile antimicrobial peptides to address the growing threat of multidrug-resistant respiratory pathogens.</p>","PeriodicalId":54246,"journal":{"name":"Antibiotics-Basel","volume":"15 4","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13114054/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147789233","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinically Significant Carbapenemases in Gram-Negative Pathogens: Molecular Diversity and Advances in β-Lactamase Inhibitor Therapy.","authors":"Jessi M Grossman, Dorothea K Thompson","doi":"10.3390/antibiotics15040413","DOIUrl":"https://doi.org/10.3390/antibiotics15040413","url":null,"abstract":"<p><p>Carbapenems comprise a class of β-lactam antibiotics with broad-spectrum hydrolytic activity and are often reserved as last-line agents for the treatment of serious multidrug-resistant (MDR) bacterial infections. Clinically important nosocomial MDR Gram-negative bacteria (GNB) include <i>Klebsiella pneumoniae</i>, <i>Pseudomonas aeruginosa</i>, and <i>Acinetobacter baumannii</i>. Carbapenem resistance among these organisms is predominantly mediated by the production of β-lactamases called carbapenemases, such as <i>K. pneumoniae</i> carbapenemase (KPC), New Delhi metallo-β-lactamase (NDM), imipenemase (IMP), Verona integron-encoded metallo-β-lactamase (VIM), and selected oxacillinase (OXA)-type carbapenemases. These enzymes degrade carbapenems, significantly compromising their clinical efficacy. To address escalating antimicrobial resistance, novel next-generation β-lactamase inhibitors (BLIs), partnered with established β-lactams (BLs), have been approved or are currently under development to inhibit carbapenemase activity. The present narrative review aims to synthesize the most current information on the major carbapenemases and discusses recently approved and investigational BL/BLI combination therapies in terms of their mechanisms of action, spectrum of activity, gaps in coverage, and available clinical and in vitro evidence. Development of resistance to novel BL/BLI combinations is also examined. Comparative analysis of inhibitory spectra and microbiological coverage indicates a continued need for metallo-β-lactamase inhibitors with direct pan-inhibitory activity, pathogen-specific BL/BLI regimens for carbapenem-resistant <i>A. baumannii</i>, and carbapenemase-targeted agents effective in the context of non-enzymatic resistance mechanisms. Treatment-emergent resistance to novel BL/BLIs and limitations in activity profiles underscore the critical need for continued innovation in pipeline development, vigilant global and local surveillance of carbapenemase epidemiology, and robust antimicrobial stewardship strategies to aid in preserving the efficacy of the antibacterial drug armamentarium.</p>","PeriodicalId":54246,"journal":{"name":"Antibiotics-Basel","volume":"15 4","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13113064/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147789071","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}