Antibiotics-Basel最新文献

{"title":"Potential Synergy of Fluoxetine and Antibacterial Agents Against Skin and Soft Tissue Pathogens and Drug-Resistant Organisms.","authors":"Samar A Ahmed, Rondelle L Jordan, Roslyn Rivkah Isseroff, Justin R Lenhard","doi":"10.3390/antibiotics13121165","DOIUrl":"https://doi.org/10.3390/antibiotics13121165","url":null,"abstract":"<p><p><b>Background/Objectives:</b> The feasibility of repurposing selective serotonin reuptake inhibitors as adjunctive antibacterial agents is an area of current investigation. We sought to evaluate if fluoxetine will achieve synergistic killing with relevant antibacterial drugs against skin and soft tissue pathogens and multidrug-resistant pathogens. <b>Methods</b>: The MIC of fluoxetine was determined using broth microdilution for a diverse isolate collection of 21 organisms. Checkerboard experiments were then conducted using fluoxetine and clinically relevant antibacterial drugs. If fluoxetine and an anti-infective agent achieved synergy denoted by a fractional inhibitory concentration index ≤ 0.5, then the combination was further evaluated in 24 h time-killing experiments. Synergy in time-killing experiments was defined as a ≥2 log₁₀ CFU/mL reduction in fluoxetine combined with an antibacterial agent at any point in the experiment in comparison to whichever agent in the combination resulted in the lowest bacterial counts individually. <b>Results</b>: The fluoxetine MICs ranged from 64 to 128 mcg/mL for Gram-positive isolates and 8-512 mcg/mL for Gram-negative organisms. Against Gram-positive isolates, vancomycin, linezolid, clindamycin, and gentamicin failed to achieve synergy in checkerboard experiments. Levofloxacin and fluoxetine were the only combination that demonstrated synergy against a Gram-positive pathogen in both checkerboard and time-killing experiments (1/6 isolates, 16.7%). Against Gram-negative organisms, the most promising combination was fluoxetine and polymyxin B, which achieved synergistic killing in both checkerboard experiments and time-killing experiments in 12/15 isolates (80%). In comparison, fosfomycin and meropenem achieved synergy in both experiments against 6/15 (40%) and 3/15 (20%) Gram-negative isolates, respectively. <b>Conclusions</b>: The combination of fluoxetine and polymyxin B may be a potential strategy for combatting difficult-to-treat Gram-negative pathogens.</p>","PeriodicalId":54246,"journal":{"name":"Antibiotics-Basel","volume":"13 12","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11672584/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142958954","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":"Rapid Antibacterial Assessments for Plastic and Textile Materials Against <i>Escherichia coli</i>.","authors":"Anson M Y Luk, Adrian M H Luk, Jiachi Amber Chiou, Man-Yi Ho, Chi-Man Ngai, Chi-Wai Kan","doi":"10.3390/antibiotics13121156","DOIUrl":"https://doi.org/10.3390/antibiotics13121156","url":null,"abstract":"<p><p><b>Background</b>: Standard test methods for evaluating the antibacterial performance of plastic (non-porous) and textile (porous) materials are accurate and reliable, but completing a standard assessment generally requires at least several days to a week. Well-trained and experienced technicians are also required to conduct the standard tests consistently and analyse the samples and test results systemically. These costs are often not favourable for the performance assurance of antimicrobial products in industrial production, nor for meeting the fast-return demands in research and development of antimicrobial materials nowadays. <b>Methods</b>: In this study, \"Rapid Tests\" are developed to evaluate the antibacterial activities of plastic and textile materials. <b>Results</b>: The assessment results from Rapid Tests for plastics and textiles are highly correlated to those from the ISO 22196 and the AATCC Test Method 100, respectively, whereas the evaluation operation can be completed within one day. Based on bioluminescence technology, colony-forming units of <i>E. coli</i> from the inoculated specimens are determined via luminometry. Antibacterial efficacy of the treated plastic and textile samples can be examined effectively. <b>Conclusions</b>: By analysing antimicrobial artificial leather samples composed of hydrophilic polyurethane polymer using Rapid Tests for plastics and textiles, the applicability and scope of these tests were remarkedly recognised and verified.</p>","PeriodicalId":54246,"journal":{"name":"Antibiotics-Basel","volume":"13 12","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11672696/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142958960","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":"A Convenient One-Pot Synthesis of Novel Benzimidazole-Thiazinone Derivatives and Their Antimicrobial Activity.","authors":"Sabahat Samreen, Asghar Ali, Saiema Ahmedi, Mohammad Raghib, Anzarul Haque, Nikhat Manzoor, Afzal Hussain, Mohammad Abid, Afreen Inam","doi":"10.3390/antibiotics13121155","DOIUrl":"https://doi.org/10.3390/antibiotics13121155","url":null,"abstract":"<p><p><b>Background:</b> The increasing prevalence of antimicrobial resistant highlights the urgent need for the new therapeutic agents. This study aimed to design and synthesize fused tricyclic benzimidazole-thiazinone derivatives (<b>CS1</b>-<b>CS10</b>) through a convenient method and evaluate their antimicrobial activity against various microorganisms. <b>Methods:</b> A series of fused tricyclic benzimidazole-thiazinone derivatives was rationally designed and synthesized in one pot by the reaction between trans substituted acrylic acids and 1<i>H</i>-benzo[d]imidazole-2-thiol using coupling reagent TBTU (2-(1<i>H</i>-benzotriazol-1-yl)-1,1,3,3-tetramethyluronium tetrafluoroborate). The structure of these compounds was confirmed through various spectroscopic techniques like IR, ¹H and ¹³C NMR, the DEPT and 2D-HMQC NMR techniques were also performed to confirm the relation of both carbon and proton. Further, the compounds were in vitro evaluated for their effectiveness against the <i>Candida</i> species and a panel of standard bacterial isolates. <b>Results:</b> The synthesized compounds showed moderate antimicrobial activity. Among all of the compounds, <b>CS4</b> exhibited potent inhibition against <i>Pseudomonas aeruginosa</i> and <i>Escherichia coli</i> at 256 and 512 μg/mL concentrations, respectively. Additional research indicated that compound <b>CS4</b> demonstrated a synergistic effect after combining with the standard antibacterial drug ciprofloxacin. <b>Conclusions:</b> These results suggest that <b>CS4</b> is the best-synthesized antibacterial agent particularly in combination therapies. These findings highlight its promise for further development as a novel antibacterial agent.</p>","PeriodicalId":54246,"journal":{"name":"Antibiotics-Basel","volume":"13 12","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11672583/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142958741","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":"Local Electric Field-Incorporated In-Situ Copper Ions Eliminating Pathogens and Antibiotic Resistance Genes in Drinking Water.","authors":"Ruiqing Li, Haojie Dai, Wei Wang, Rulin Peng, Shenbo Yu, Xueying Zhang, Zheng-Yang Huo, Qingbin Yuan, Yi Luo","doi":"10.3390/antibiotics13121161","DOIUrl":"https://doi.org/10.3390/antibiotics13121161","url":null,"abstract":"<p><strong>Background/objectives: </strong>Pathogen inactivation and harmful gene destruction from water just before drinking is the last line of defense to protect people from waterborne diseases. However, commonly used disinfection methods, such as chlorination, ultraviolet irradiation, and membrane filtration, experience several challenges such as continuous chemical dosing, the spread of antibiotic resistance genes (ARGs), and intensive energy consumption.</p><p><strong>Methods: </strong>Here, we perform a simultaneous elimination of pathogens and ARGs in drinking water using local electric fields and in-situ generated trace copper ions (LEF-Cu) without external chemical dosing. A 100-μm thin copper wire placed in the center of a household water pipe can generate local electric fields and trace copper ions near its surface after an external low voltage is applied.</p><p><strong>Results: </strong>The local electric field rapidly damages the outer structure of microorganisms through electroporation, and the trace copper ions can effectively permeate the electroporated microorganisms, successfully damaging their nucleic acids. The LEF-Cu disinfection system achieved complete inactivation (>6 log removal) of <i>Escherichia coli</i> O157:H7, <i>Pseudomonas aeruginosa</i> PAO1, and bacteriophage MS2 in drinking water at 2 V for 2 min, with low energy consumption (10^-2 kWh/m³). Meanwhile, the system effectively damages both intracellular (0.54~0.64 log) and extracellular (0.5~1.09 log) ARGs and blocks horizontal gene transfer.</p><p><strong>Conclusions: </strong>LEF-Cu disinfection holds promise for preventing horizontal gene transfer and providing safe drinking water for household applications.</p>","PeriodicalId":54246,"journal":{"name":"Antibiotics-Basel","volume":"13 12","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11672500/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142958944","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":"Assessing the Theoretical Efficacy of Combination Therapy Against Gram-Negative Infections in Neutropenic Pediatric Cancer Patients: Insights from the Statistical Analysis of Survey Data.","authors":"Elio Castagnola, Francesca Bagnasco, Alessio Mesini, Philipp K A Agyeman, Roland A Ammann, Marta Arrabito, Fabianne Carlesse, Maria Rosaria D'Amico, Giovanna Giagnuolo, Gabrielle M Haeusler, Evgeny A Idelevich, Christa Koenig, Thomas Lehrnbecher, Marie Luckowitsch, Mariaclaudia Meli, Giuseppe Menna, Giovanna Russo, Maria Elena Santolaya de Pablo, Arne Simon, Galina Solopova, Lillian Sung, Annalisa Tondo, Andreas H Groll","doi":"10.3390/antibiotics13121160","DOIUrl":"https://doi.org/10.3390/antibiotics13121160","url":null,"abstract":"<p><p><b>Background</b>: Empirical antibacterial therapy for febrile neutropenia reduces mortality due to Gram-negative blood stream infections (BSIs). Pediatric guidelines recommend monotherapy with an antipseudomonal beta-lactam or a carbapenem and to add a second anti-Gram-negative agent in selected situations. We evaluated the changes in the proportions of resistance of beta-lactam monotherapies vs. their combination with amikacin, and the possible impact on ICU admission or death. <b>Results</b>: 797 BSIs due to Gram-negative bacteria in 685 patients were included. Combination therapies with amikacin had a lower percentage of isolates resistant to one or to both drugs compared with the respective monotherapy. The highest OR for ICU admission was observed when both drugs of the combination of meropenem-amikacin were resistant. Mortality was significantly associated with relapse or the progression of the underlying malignancy, and resistance to both drugs of the combinations of cefepime-amikacin or meropenem-amikacin. <b>Methods</b>: This study was based on data collected for a large multinational study, in which the susceptibility of Gram-negative bloodstream isolates was categorized following either EUCAST or CLSI according to local laboratory standards. An escalation antibiogram was generated for each selected drug. For resistant bacteria, the conditional susceptibility probability on resistance was calculated. <b>Conclusions</b>: In pediatric cancer patients with Gram-negative BSIs, the proportion of the resistant organism correlates with ICU admission or death, which may be reduced by combination therapy. In patients with suspected or confirmed Gram-negative BSIs that are not-improving or deteriorating under monotherapy, escalation to meropenem may represent the best option. Amikacin should be preferred when combination therapy is considered with ciprofloxacin as an alternative in the case of impaired renal function.</p>","PeriodicalId":54246,"journal":{"name":"Antibiotics-Basel","volume":"13 12","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11672620/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142958700","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":"Accelerated Bacterial Identification with MALDI-TOF MS Leads to Fewer Diagnostic Tests and Cost Savings.","authors":"Miriam Uzuriaga, Francisco Guillén-Grima, Marta Rua, José Leiva, José R Yuste","doi":"10.3390/antibiotics13121163","DOIUrl":"https://doi.org/10.3390/antibiotics13121163","url":null,"abstract":"<p><strong>Introduction: </strong>Rapid microbiology reporting can enhance both clinical and economic outcomes.</p><p><strong>Material and methods: </strong>This three-year, quasi-experimental study, single-group pretest-posttest study, conducted at a university medical center, aimed to evaluate the clinical and economic impact of rapid microbiological identification reporting using MALDI-TOF MS. A total of 363 consecutive hospitalized patients with bacterial infections were evaluated, comparing a historical control group (CG, n = 183) with an intervention group (IG, <i>n</i> = 180). In the CG, microbiological information (bacterial identification and antibiotic susceptibility) was provided between 18:00 and 22:00 h, while in the IG, bacterial identification was reported between 12:00 and 14:00 h, and antibiotic susceptibility was reported between 18:00 and 22:00 h.</p><p><strong>Results: </strong>The IG demonstrated a significant reduction in the number of patients undergoing Microbiology (<i>p</i> = 0.01), Biochemistry (<i>p</i> = 0.05), C-Reactive Protein (<i>p</i> = 0.02), Radiological Tests (<i>p</i> = 0.05), Computed Tomography Tests (<i>p</i> = 0.04), and Pathology (<i>p</i> = 0.01). However, no statistically significant reduction was observed in economic costs related to microbiological testing (<i>p</i> = 0.76) or antibiotic consumption (<i>p</i> = 0.59). The timely reporting of microbiological identification to clinicians resulted in fewer patients undergoing additional diagnostic tests, ultimately contributing to reduced healthcare resource utilization without adversely affecting clinical outcomes.</p>","PeriodicalId":54246,"journal":{"name":"Antibiotics-Basel","volume":"13 12","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11672624/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142958754","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":"Novel Variant of New Delhi Metallo-Beta-Lactamase (<i>bla</i>_NDM-60) Discovered in a Clinical Strain of <i>Escherichia coli</i> from the United Arab Emirates: An Emerging Challenge in Antimicrobial Resistance.","authors":"Farah Al-Marzooq, Akela Ghazawi, Mushal Allam, Timothy Collyns, Aqeel Saleem","doi":"10.3390/antibiotics13121158","DOIUrl":"https://doi.org/10.3390/antibiotics13121158","url":null,"abstract":"<p><p><b>Background/Objectives:</b> Carbapenem resistance poses a significant health threat. This study reports the first detection and characterization of a novel variant of New Delhi metallo-β-lactamase (<i>bla</i>_NDM-60) in <i>Escherichia coli</i> from the United Arab Emirates (UAE), including its genetic context and relationship to global strains. <b>Methods:</b> NDM-60-producing <i>E. coli</i> was isolated from a rectal swab during routine screening. Characterization involved whole-genome sequencing, antimicrobial susceptibility testing, and comparative genomic analysis with 66 known NDM variants. Core genome analysis was performed against 42 global <i>E. coli</i> strains, including the single other reported NDM-60-positive isolate. <b>Results:</b> The strain demonstrated extensive drug resistance, including resistance to novel β-lactam/β-lactamase inhibitor combinations, notably taniborbactam. NDM-60 differs from the closely related NDM-5 by a single amino acid substitution (Asp202Asn) and two amino acid substitutions (Val88Leu and Met154Leu) compared to NDM-1. NDM-60 is located on a nonconjugative IncX3 plasmid. The strain belongs to sequence type 940 (ST940). Phylogenetic analysis revealed high diversity among the global ST940 strains, which carry a plethora of resistance genes and originated from humans, animals, and the environment from diverse geographic locations. <b>Conclusions:</b> NDM-60 emergence in the UAE represents a significant evolution in carbapenemase diversity. Its presence on a nonconjugative plasmid may limit spread; however, its extensive resistance profile is concerning. Further studies are needed to determine the prevalence, dissemination, and clinical impact of NDM-60. NDM evolution underscores the ongoing challenge in managing antimicrobial resistance and the critical importance of vigilant molecular surveillance. It also highlights the pressing demand to discover new antibiotics to fight resistant bacteria.</p>","PeriodicalId":54246,"journal":{"name":"Antibiotics-Basel","volume":"13 12","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11672588/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142958847","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":"Future Challenge: Assessing the Antibiotic Susceptibility Patterns of <i>Staphylococcus</i> Species Isolated from Canine Otitis Externa Cases in Western Romania.","authors":"János Dégi, Sorin Morariu, Florin Simiz, Viorel Herman, Florin Beteg, Diana Maria Dégi","doi":"10.3390/antibiotics13121162","DOIUrl":"https://doi.org/10.3390/antibiotics13121162","url":null,"abstract":"<p><strong>Introduction: </strong>Antimicrobial resistance (AMR) has surfaced as a critical challenge to public health on a global scale. The precise and swift identification of resistance to antimicrobial agents, along with timely and suitable antimicrobial therapy paired with effective stewardship practices, is crucial for managing the rise and dissemination of antimicrobial resistance. The objective of our investigation was to outline the antimicrobial resistance profile of <i>Staphylococcus</i> spp., a significant contributor to canine otitis, a prevalent condition in dogs, isolated in Western Romania.</p><p><strong>Methods and materials: </strong>All data were collected from clinical cases of canine otitis externa which presented at the University Clinic of the Faculty of Veterinary Medicine in Timișoara/Romania. A clinical evaluation was conducted, from which era swabs are usually collected and sent for analysis at the laboratory. Laboratory analysis included the microbiological examination for identifying <i>Staphylococcus</i> spp. and determining antibiotic susceptibility phenotypes. Statistical analysis was implemented on all data that were collected. The ear swabs were processed with standard procedures for cultivating and identifying bacteria. The resulting subcultures were processed to determine the staphylococcal species on the GP ID Cards of the Vitek^® 2 automatic system. The antimicrobial susceptibility profiles were detected by the Vitek^® 2 system using an AST-GP80 card. These isolated <i>Staphylococcus</i> spp. strains were further processed by real-time PCR and PCR-RFLP.</p><p><strong>Results: </strong>Of all the auricular exudate samples analyzed, 76 were positive for <i>Staphylococcus</i> spp. (59.38%). Within these, in 82% of auricular samples, six distinct <i>Staphylococcus</i> spp. were identified (<i>Staphylococcus (S.) pseudintermedius, S. intermedius</i>, <i>S. hyicus</i>, <i>S. delphiny</i>, <i>S. shleiferi,</i> and <i>S. aureus</i>). Our data indicate that the PCR-RFLP assay is a practical approach to <i>S. pseudintermedius</i> identification, allowing for discrimination from the other <i>Staphylococcus Intermedius Group</i> (SIG) species and important staphylococcal pathogens of dogs. The highest frequency of resistant <i>S. pseudintermedius</i> isolates was detected against tetracycline (21/34; 61.76%; <i>p</i>-value 0.003), gentamicin (20/34; 58.82%), and kanamycin (20/34; 58.82%).</p><p><strong>Conclusions: </strong>These results are essential to guide the prudent use of antibiotics in veterinary medicine. They will also help design efficient control strategies and measure their effectiveness.</p>","PeriodicalId":54246,"journal":{"name":"Antibiotics-Basel","volume":"13 12","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11672840/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142958918","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":"Isolation and Characterization of Lytic Phages Infecting Clinical <i>Klebsiella pneumoniae</i> from Tunisia.","authors":"Donia Mourali, Rahma Kazdaghli, Marwa Gara-Ali, Houda Ben-Miled, Lucas Mora-Quilis, Pilar Domingo-Calap, Kamel Ben-Mahrez","doi":"10.3390/antibiotics13121154","DOIUrl":"https://doi.org/10.3390/antibiotics13121154","url":null,"abstract":"<p><p><b>Background</b>: <i>Klebsiella pneumoniae</i> is an opportunistic pathogen that causes a wide range of infections worldwide. The emergence and spread of multidrug-resistant clones requires the implementation of novel therapeutics, and phages are a promising approach. <b>Results</b>: In this study, two <i>Klebsiella</i> phages, KpTDp1 and KpTDp2, were isolated from wastewater samples in Tunisia. These phages had a narrow host range and specifically targeted the hypervirulent K2 and K28 capsular types of <i>K. pneumoniae</i>. Both phages have double-stranded linear DNA genomes of 49,311 and 49,084 bp, respectively. Comparative genomic and phylogenetic analyses placed phage KpTDp2 in the genus <i>Webervirus</i>, while phage KpTDp1 showed some homology with members of the genus <i>Jedunavirus</i>, although its placement in a new undescribed genus may be reconsidered. The replication efficiency and lytic ability of these phages, combined with their high stability at temperatures up to 70 °C and pH values ranging from 3.5 to 8.2, highlight the potential of these phages as good candidates for the control of hypervirulent multidrug-resistant <i>K. pneumoniae</i>. <b>Methods</b>: Phage isolation, titration and multiplicity of infection were performed. The stability of KpTDp1 and KpTDp2 was tested at different pH and temperatures. Genomic characterization was done by genome sequencing, annotation and phylogenetic analysis. <b>Conclusions</b>: The ability of KpTDp1 and KpTDp2 to lyse one of the most virulent serotypes of <i>K. pneumoniae</i>, as well as the stability of their lytic activities to pH and temperature variations, make these phages promising candidates for antibacterial control.</p>","PeriodicalId":54246,"journal":{"name":"Antibiotics-Basel","volume":"13 12","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11672853/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142958942","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":"Development of a Stringent Ex Vivo-Burned Porcine Skin Wound Model to Screen Topical Antimicrobial Agents.","authors":"Ping Chen, Eliza A Sebastian, S L Rajasekhar Karna, Kai P Leung","doi":"10.3390/antibiotics13121159","DOIUrl":"https://doi.org/10.3390/antibiotics13121159","url":null,"abstract":"<p><p><b>Background</b>: Due to rising antibiotic-resistant microorganisms, there is a pressing need to screen approved drugs for repurposing and to develop new antibiotics for controlling infections. Current in vitro and ex vivo models have mostly been unsuccessful in establishing in vivo relevance. In this study, we developed a stringent ex vivo-burned porcine skin model with high in vivo relevance to screen topical antimicrobials. <b>Methods</b>: A 3 cm-diameter thermal injury was created on non-sterilized porcine skin using a pressure-monitored and temperature-controlled burn device. Commensals were determined pre- and post-burn. The burn wound was inoculated with a target pathogen, and efficacies of Silvadene, Flammacerium, Sulfamylon, and Mupirocin were determined. The in vivo relevance of this platform was evaluated by comparing the ex vivo treatment effects to available in vivo treatment outcomes (from our laboratory and published reports) against selective burn pathogens. <b>Results</b>: Approximately 1% of the commensals survived the skin burn, and these commensals in the burn wounds affected the treatment outcomes in the ex vivo screening platform. When tested against six pathogens, both Silvadene and Flammacerium treatment exhibited ~1-3 log reduction in viable counts. Sulfamylon and Mupirocin exhibited higher efficacy than both Silvadene and Flammacerium against <i>Pseudomonas</i> and <i>Staphylococcus,</i> respectively. The ex vivo treatment outcomes of Silvadene and Flammacerium against <i>Pseudomonas</i> were highly comparable to the outcomes of the in vivo (rats). <b>Conclusions</b>: The ex vivo model developed in our lab is a stringent and effective platform for antimicrobial activity screening. The outcome obtained from this ex vivo model is highly relevant to in vivo.</p>","PeriodicalId":54246,"journal":{"name":"Antibiotics-Basel","volume":"13 12","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11672622/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142958837","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}