Pediococcus pentosaceus, which often occurs in fermented foods, is characterized by numerous positive effects on the human health, such as the presence of possible probiotic abilities, the reduction of cholesterol levels, satisfactory antimicrobial activity, and certain therapeutic functions. This study was conducted with the goal of describing the genomic content of Pediococcus pentosaceus ENM104, a strain known for its inhibitory effects against pathogenic bacteria and its remarkable probiotic potential, including the induction of significant reductions in cholesterol levels and the production of γ-aminobutyric acid (GABA). The P. pentosaceus ENM104 chromosome is circular. The chromosome is 1,734,928 bp with a GC content of 37.2%. P. pentosaceus also harbors a circular plasmid, pENM104, that is 71,811 bp with a GC content of 38.1%. Functional annotations identified numerous genes associated with probiotic traits, including those involved in stress adaptation (e.g., heat stress: htpX, dnaK, and dnaJ), bile tolerance (e.g., ppaC), vitamin biosynthesis (e.g., ribU, ribZ, ribF, and btuD), immunomodulation (e.g., dltA, dltC, and dltD), and bacteriocin production (e.g., pedA). Notably, genes responsible for lowering cholesterol levels (bile salt hydrolase, bsh) and GABA synthesis (glutamate/GABA antiporter, gadC) were also identified. The in vitro assay results using cell-free supernatants of P. pentosaceus ENM104 revealed antibacterial activity against carbapenem-resistant bacteria, such as Pseudomonas aeruginosa, Klebsiella pneumoniae, and Acinetobacter baumannii, and the inhibition zone diameter increased progressively over time. This comprehensive study provides valuable insights into the molecular characteristics of P. pentosaceus ENM104, emphasizing its potential as a probiotic. Its notable cholesterol-lowering, GABA-producing, and antimicrobial capabilities suggest promising applications in the pharmaceutical and food industries. Future research should focus on further exploring these functional properties and assessing the strain's efficacy in clinical settings.
{"title":"Genomic Insights into <i>Pediococcus pentosaceus</i> ENM104: A Probiotic with Potential Antimicrobial and Cholesterol-Reducing Properties.","authors":"Siriwan Kompramool, Kamonnut Singkhamanan, Rattanaruji Pomwised, Nattarika Chaichana, Sirikan Suwannasin, Monwadee Wonglapsuwan, Jirayu Jitpakdee, Duangporn Kantachote, Thunchanok Yaikhan, Komwit Surachat","doi":"10.3390/antibiotics13090813","DOIUrl":"https://doi.org/10.3390/antibiotics13090813","url":null,"abstract":"<p><p><i>Pediococcus pentosaceus</i>, which often occurs in fermented foods, is characterized by numerous positive effects on the human health, such as the presence of possible probiotic abilities, the reduction of cholesterol levels, satisfactory antimicrobial activity, and certain therapeutic functions. This study was conducted with the goal of describing the genomic content of <i>Pediococcus pentosaceus</i> ENM104, a strain known for its inhibitory effects against pathogenic bacteria and its remarkable probiotic potential, including the induction of significant reductions in cholesterol levels and the production of γ-aminobutyric acid (GABA). The <i>P. pentosaceus</i> ENM104 chromosome is circular. The chromosome is 1,734,928 bp with a GC content of 37.2%. <i>P. pentosaceus</i> also harbors a circular plasmid, pENM104, that is 71,811 bp with a GC content of 38.1%. Functional annotations identified numerous genes associated with probiotic traits, including those involved in stress adaptation (e.g., heat stress: <i>htpX</i>, <i>dnaK</i>, and <i>dnaJ</i>), bile tolerance (e.g., <i>ppaC</i>), vitamin biosynthesis (e.g., <i>ribU</i>, <i>ribZ</i>, <i>ribF</i>, and <i>btuD</i>), immunomodulation (e.g., <i>dltA</i>, <i>dltC</i>, and <i>dltD</i>), and bacteriocin production (e.g., <i>pedA</i>). Notably, genes responsible for lowering cholesterol levels (bile salt hydrolase, <i>bsh</i>) and GABA synthesis (glutamate/GABA antiporter, <i>gadC</i>) were also identified. The in vitro assay results using cell-free supernatants of <i>P. pentosaceus</i> ENM104 revealed antibacterial activity against carbapenem-resistant bacteria, such as <i>Pseudomonas aeruginosa</i>, <i>Klebsiella pneumoniae</i>, and <i>Acinetobacter baumannii</i>, and the inhibition zone diameter increased progressively over time. This comprehensive study provides valuable insights into the molecular characteristics of <i>P. pentosaceus</i> ENM104, emphasizing its potential as a probiotic. Its notable cholesterol-lowering, GABA-producing, and antimicrobial capabilities suggest promising applications in the pharmaceutical and food industries. Future research should focus on further exploring these functional properties and assessing the strain's efficacy in clinical settings.</p>","PeriodicalId":54246,"journal":{"name":"Antibiotics-Basel","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11428213/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142332285","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}
Hypervirulent carbapenem-resistant Acinetobacter baumannii (hv-CRAB) has emerged in bloodstream infections (BSI). Cases of BSI caused by hv-CRAB (hv-CRAB-BSI) had posed a significant threat to hospitalized patients. In this study, 31 CRAB strains isolated from Chinese BSI patients were analyzed, of which 24 were identified as hv-CRAB-BSI and 7 as non-hv-CRAB-BSI, using the Galleria mellonella infection model. Patients with hv-CRAB-BSI had higher rates of septic shock (79.2% vs. 14.3%, p = 0.004) and mortality (66.7% vs. 14.3%, p = 0.028). All strains were resistant to most antibiotics but sensitive to colistin. Hv-CRAB-BSI showed lower resistance to minocycline than non-hv-CRAB-BSI (54.2% vs. 100%, p = 0.03). Whole-genome sequencing revealed that the detection rates of immune modulation genes ptk and epsA in hv-CRAB-BSI were significantly higher than in non-hv-CRAB-BSI (91.7% vs. 28.6%, p = 0.002). Additionally, all ST457 hv-CRAB-BSI lacked abaR, and all ST1486 non-hv-CRAB-BSI lacked adeG. The checkerboard dilution method assessed the efficacies of various antibiotic combinations, revealing that although synergism was rarely observed, the combination of colistin and minocycline showed the best efficacy for treating CRAB-BSI, regardless of whether the infections were hv-CRAB-BSI or non-hv-CRAB-BSI. These findings highlight the importance of analyzing molecular characteristics and exploring effective treatment strategies for hv-CRAB-BSI.
{"title":"Comparison of Hypervirulent and Non-Hypervirulent Carbapenem-Resistant <i>Acinetobacter baumannii</i> Isolated from Bloodstream Infections: Mortality, Potential Virulence Factors, and Combination Therapy In Vitro.","authors":"Likang Yao, Ningjing Liu, Yingyi Guo, Chuyue Zhuo, Xu Yang, Yijing Wang, Jiong Wang, Feifeng Li, Jiahui Li, Nanhao He, Jiakang Chen, Yexin Lin, Shunian Xiao, Chao Zhuo","doi":"10.3390/antibiotics13090807","DOIUrl":"https://doi.org/10.3390/antibiotics13090807","url":null,"abstract":"<p><p>Hypervirulent carbapenem-resistant <i>Acinetobacter baumannii</i> (hv-CRAB) has emerged in bloodstream infections (BSI). Cases of BSI caused by hv-CRAB (hv-CRAB-BSI) had posed a significant threat to hospitalized patients. In this study, 31 CRAB strains isolated from Chinese BSI patients were analyzed, of which 24 were identified as hv-CRAB-BSI and 7 as non-hv-CRAB-BSI, using the <i>Galleria mellonella</i> infection model. Patients with hv-CRAB-BSI had higher rates of septic shock (79.2% vs. 14.3%, <i>p</i> = 0.004) and mortality (66.7% vs. 14.3%, <i>p</i> = 0.028). All strains were resistant to most antibiotics but sensitive to colistin. Hv-CRAB-BSI showed lower resistance to minocycline than non-hv-CRAB-BSI (54.2% vs. 100%, <i>p</i> = 0.03). Whole-genome sequencing revealed that the detection rates of immune modulation genes <i>ptk</i> and <i>epsA</i> in hv-CRAB-BSI were significantly higher than in non-hv-CRAB-BSI (91.7% vs. 28.6%, <i>p</i> = 0.002). Additionally, all ST457 hv-CRAB-BSI lacked <i>abaR</i>, and all ST1486 non-hv-CRAB-BSI lacked <i>adeG</i>. The checkerboard dilution method assessed the efficacies of various antibiotic combinations, revealing that although synergism was rarely observed, the combination of colistin and minocycline showed the best efficacy for treating CRAB-BSI, regardless of whether the infections were hv-CRAB-BSI or non-hv-CRAB-BSI. These findings highlight the importance of analyzing molecular characteristics and exploring effective treatment strategies for hv-CRAB-BSI.</p>","PeriodicalId":54246,"journal":{"name":"Antibiotics-Basel","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11428969/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142332275","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}
Pub Date : 2024-08-26DOI: 10.3390/antibiotics13090811
Patricia Otero-Batán, Guillermo Lens-Perol, Olalla Vázquez-Cancela, Angel Salgado-Barreira, Juan Manuel Vazquez-Lago
Background: Antimicrobial resistance is a major public health issue today. Therefore, it is essential to focus on the education of pharmacists as future dispensers. The objective of this study was to validate a questionnaire that assesses the knowledge, attitudes, and perceptions of pharmacy students regarding the education received during their university degree on the use and dispensation of antibiotics, as well as bacterial resistance.
Methods: An online questionnaire was developed and distributed via RedCap v.13.7.1 to pharmacy students at the University of Santiago de Compostela using the WhatsApp social network. The questionnaire consisted of 28 items evaluating 5 dimensions: "quality of care", "communication skills", "antibiotic resistance", "teaching methodology", and "education on antibiotics at the faculty". The questionnaire validation was conducted in 2 steps: Step 1 involved content and appearance validation, and Step 2 involved reliability analysis.
Results: A total of 61 completed questionnaires were received. The mean age was 21.82 ± 3.81 years, with 20 males (32.8%) and 41 females (67.2%). Content validation was performed through a nominal group of 5 experts, and appearance validation was conducted by a focus group of 6 university pharmacy students. The questionnaire demonstrated a Cronbach's alpha value of 0.80 and adequate item discrimination capability. Confirmatory factor analysis was performed to assess construct validity, confirming the 5 predefined dimensions.
Conclusions: A questionnaire has been developed and validated with high reliability and validity. Its use will help identify areas for improvement in the university education of pharmacy students, ultimately contributing to better use and dispensation of antibiotics and thereby improving antimicrobial resistance.
{"title":"Validity and Reliability of a Questionnaire on Attitudes, Knowledge, and Perceptions of Pharmacy Students Regarding the Training Received on Antibiotics and Antimicrobial Resistance during Their University Studies.","authors":"Patricia Otero-Batán, Guillermo Lens-Perol, Olalla Vázquez-Cancela, Angel Salgado-Barreira, Juan Manuel Vazquez-Lago","doi":"10.3390/antibiotics13090811","DOIUrl":"https://doi.org/10.3390/antibiotics13090811","url":null,"abstract":"<p><strong>Background: </strong>Antimicrobial resistance is a major public health issue today. Therefore, it is essential to focus on the education of pharmacists as future dispensers. The objective of this study was to validate a questionnaire that assesses the knowledge, attitudes, and perceptions of pharmacy students regarding the education received during their university degree on the use and dispensation of antibiotics, as well as bacterial resistance.</p><p><strong>Methods: </strong>An online questionnaire was developed and distributed via RedCap v.13.7.1 to pharmacy students at the University of Santiago de Compostela using the WhatsApp social network. The questionnaire consisted of 28 items evaluating 5 dimensions: \"quality of care\", \"communication skills\", \"antibiotic resistance\", \"teaching methodology\", and \"education on antibiotics at the faculty\". The questionnaire validation was conducted in 2 steps: Step 1 involved content and appearance validation, and Step 2 involved reliability analysis.</p><p><strong>Results: </strong>A total of 61 completed questionnaires were received. The mean age was 21.82 ± 3.81 years, with 20 males (32.8%) and 41 females (67.2%). Content validation was performed through a nominal group of 5 experts, and appearance validation was conducted by a focus group of 6 university pharmacy students. The questionnaire demonstrated a Cronbach's alpha value of 0.80 and adequate item discrimination capability. Confirmatory factor analysis was performed to assess construct validity, confirming the 5 predefined dimensions.</p><p><strong>Conclusions: </strong>A questionnaire has been developed and validated with high reliability and validity. Its use will help identify areas for improvement in the university education of pharmacy students, ultimately contributing to better use and dispensation of antibiotics and thereby improving antimicrobial resistance.</p>","PeriodicalId":54246,"journal":{"name":"Antibiotics-Basel","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11428262/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142332302","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}
Pub Date : 2024-08-26DOI: 10.3390/antibiotics13090809
Amyleigh Watts, Paul Wigley
Avian Pathogenic Escherichia coli (APEC) is an extraintestinal pathotype of E. coli that leads to a range of clinical manifestations, including respiratory, systemic and reproductive infections of chickens in both egg and meat production. Unlike most E. coli pathotypes, APEC is not defined by specific virulence genes but rather is a collection of several distinct genotypes that can act as both primary and secondary pathogens leading to colibacillosis. Recent measures to reduce antimicrobials both as growth promoters and as flock-level therapeutics are considered to have led to increased numbers of animals affected. Nevertheless, antimicrobial resistance is a considerable problem in APEC, with resistance to third and fourth-generation cephalosporins via extended-spectrum beta-lactamases (ESBLs), fluoroquinolones and colistin seen as a particular concern. The need to control APEC without antimicrobial use at the flock level has seen an increased focus on vaccination. Currently, a few commercial vaccines are already available, and a range of approaches are being applied to develop new vaccines, and other controls, such as bacteriophage or probiotics, are attracting interest. The lack of a single defined APEC genotype presents challenges to these approaches.
{"title":"Avian Pathogenic <i>Escherichia coli</i>: An Overview of Infection Biology, Antimicrobial Resistance and Vaccination.","authors":"Amyleigh Watts, Paul Wigley","doi":"10.3390/antibiotics13090809","DOIUrl":"https://doi.org/10.3390/antibiotics13090809","url":null,"abstract":"<p><p>Avian Pathogenic <i>Escherichia coli</i> (APEC) is an extraintestinal pathotype of <i>E. coli</i> that leads to a range of clinical manifestations, including respiratory, systemic and reproductive infections of chickens in both egg and meat production. Unlike most <i>E. coli</i> pathotypes, APEC is not defined by specific virulence genes but rather is a collection of several distinct genotypes that can act as both primary and secondary pathogens leading to colibacillosis. Recent measures to reduce antimicrobials both as growth promoters and as flock-level therapeutics are considered to have led to increased numbers of animals affected. Nevertheless, antimicrobial resistance is a considerable problem in APEC, with resistance to third and fourth-generation cephalosporins via extended-spectrum beta-lactamases (ESBLs), fluoroquinolones and colistin seen as a particular concern. The need to control APEC without antimicrobial use at the flock level has seen an increased focus on vaccination. Currently, a few commercial vaccines are already available, and a range of approaches are being applied to develop new vaccines, and other controls, such as bacteriophage or probiotics, are attracting interest. The lack of a single defined APEC genotype presents challenges to these approaches.</p>","PeriodicalId":54246,"journal":{"name":"Antibiotics-Basel","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11429189/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142332267","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}
Pub Date : 2024-08-26DOI: 10.3390/antibiotics13090808
Alessandra Piccirillo, Roberta Tolosi, Lapo Mughini-Gras, Jannigje G Kers, Andrea Laconi
Drinking water distribution systems (DWDSs) represent an ideal environment for biofilm formation, which can harbor pathogenic and antimicrobial-resistant bacteria. This study aimed to assess longitudinally the microbial community composition and antimicrobial resistance (AMR), as determined by 16S rRNA NGS and qPCR, respectively, in drinking water (DW) and biofilm from DWDSs, as well as faeces, of free-range organic broiler farms. The role of DWDSs in AMR gene (ARG) dissemination within the farm environment and transmission to animals, was also assessed. DW and biofilm microbial communities differed from those of faecal samples. Moreover, potentially pathogenic and opportunistic bacteria (e.g., Staphylococcaceae) were identified in water and biofilms. High prevalence and abundance of ARGs conferring resistance to carbapenems (i.e., blaNDM), 3rd and 4th generation cephalosporins (i.e., blaCMY-2), (fluoro)quinolones (i.e., qnrS), and polymyxins (i.e., mcr-3 and mcr-5) were detected in DW, biofilm, and faecal samples, which is of concern for both animal and human health. Although other factors (e.g., feed, pests, and wildlife) may contribute to the dissemination of AMR in free-range organic poultry farms, this study indicates that DWDSs can also play a role.
{"title":"Drinking Water and Biofilm as Sources of Antimicrobial Resistance in Free-Range Organic Broiler Farms.","authors":"Alessandra Piccirillo, Roberta Tolosi, Lapo Mughini-Gras, Jannigje G Kers, Andrea Laconi","doi":"10.3390/antibiotics13090808","DOIUrl":"https://doi.org/10.3390/antibiotics13090808","url":null,"abstract":"<p><p>Drinking water distribution systems (DWDSs) represent an ideal environment for biofilm formation, which can harbor pathogenic and antimicrobial-resistant bacteria. This study aimed to assess longitudinally the microbial community composition and antimicrobial resistance (AMR), as determined by 16S rRNA NGS and qPCR, respectively, in drinking water (DW) and biofilm from DWDSs, as well as faeces, of free-range organic broiler farms. The role of DWDSs in AMR gene (ARG) dissemination within the farm environment and transmission to animals, was also assessed. DW and biofilm microbial communities differed from those of faecal samples. Moreover, potentially pathogenic and opportunistic bacteria (e.g., Staphylococcaceae) were identified in water and biofilms. High prevalence and abundance of ARGs conferring resistance to carbapenems (i.e., <i>bla<sub>NDM</sub></i>), 3rd and 4th generation cephalosporins (i.e., <i>bla<sub>CMY-2</sub></i>), (fluoro)quinolones (i.e., <i>qnrS</i>), and polymyxins (i.e., <i>mcr-3</i> and <i>mcr-5</i>) were detected in DW, biofilm, and faecal samples, which is of concern for both animal and human health. Although other factors (e.g., feed, pests, and wildlife) may contribute to the dissemination of AMR in free-range organic poultry farms, this study indicates that DWDSs can also play a role.</p>","PeriodicalId":54246,"journal":{"name":"Antibiotics-Basel","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11429059/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142332277","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}
Pub Date : 2024-08-26DOI: 10.3390/antibiotics13090806
Nuchpicha Intakhan, Atiporn Saeung, Sonia M Rodrigues Oliveira, Maria de Lourdes Pereira, Wetpisit Chanmol
Leishmaniasis is a tropical infectious disease caused by Leishmania parasites. The disease can be spread by the bite of an infected sand fly. Currently, five chemotherapeutic drugs are available in leishmaniasis treatment. However, these drugs exhibit toxicity and serious adverse effects on infected individuals, necessitating alternative treatment strategies. One such strategy involves using combinations of existing antileishmanial drugs. In this study, we evaluated the interaction between artesunate (AS) and three antileishmanial drugs-amphotericin B (AmB), miltefosine (MF), and paromomycin (PM) against Leishmania infantum. This evaluation marks the first time such an assessment has been conducted. The Chou-Talalay combination index method was employed to analyze the drug interaction. The findings revealed that the interaction between AS and AmB ranged from antagonistic to synergistic, while the interaction between AS and MF showed moderate to strong synergism. In contrast, the interaction between AS and PM resulted in an antagonistic interaction, which differs from the combinations with AmB or MF. This study provides valuable insights for developing novel drug regimens for leishmaniasis treatment, emphasizing the potential of AS and its combination with existing antileishmanial drugs. Further research is necessary to optimize drug combinations and minimize adverse effects, leading to more effective therapeutic outcomes.
利什曼病是一种由利什曼寄生虫引起的热带传染病。该病可通过被感染的沙蝇叮咬传播。目前,治疗利什曼病的化疗药物有五种。然而,这些药物对受感染者有毒性和严重的不良影响,因此需要采取其他治疗策略。其中一种策略就是将现有的抗利什曼病药物组合使用。在这项研究中,我们评估了青蒿琥酯(AS)与三种抗利什曼病药--两性霉素 B(AmB)、米替福星(MF)和副黏菌素(PM)--在抗婴儿利什曼病方面的相互作用。这是首次进行此类评估。采用 Chou-Talalay 组合指数法分析了药物相互作用。结果显示,AS 与 AmB 之间的相互作用从拮抗到协同不等,而 AS 与 MF 之间的相互作用则表现出中等到强的协同作用。与此相反,AS 与 PM 的相互作用为拮抗作用,这与与 AmB 或 MF 的组合不同。这项研究为开发治疗利什曼病的新型药物方案提供了有价值的见解,强调了 AS 及其与现有抗利什曼病药物组合的潜力。有必要开展进一步研究,以优化药物组合,尽量减少不良反应,从而取得更有效的治疗效果。
{"title":"Synergistic Effects of Artesunate in Combination with Amphotericin B and Miltefosine against <i>Leishmania infantum</i>: Potential for Dose Reduction and Enhanced Therapeutic Strategies.","authors":"Nuchpicha Intakhan, Atiporn Saeung, Sonia M Rodrigues Oliveira, Maria de Lourdes Pereira, Wetpisit Chanmol","doi":"10.3390/antibiotics13090806","DOIUrl":"https://doi.org/10.3390/antibiotics13090806","url":null,"abstract":"<p><p>Leishmaniasis is a tropical infectious disease caused by <i>Leishmania</i> parasites. The disease can be spread by the bite of an infected sand fly. Currently, five chemotherapeutic drugs are available in leishmaniasis treatment. However, these drugs exhibit toxicity and serious adverse effects on infected individuals, necessitating alternative treatment strategies. One such strategy involves using combinations of existing antileishmanial drugs. In this study, we evaluated the interaction between artesunate (AS) and three antileishmanial drugs-amphotericin B (AmB), miltefosine (MF), and paromomycin (PM) against <i>Leishmania infantum</i>. This evaluation marks the first time such an assessment has been conducted. The Chou-Talalay combination index method was employed to analyze the drug interaction. The findings revealed that the interaction between AS and AmB ranged from antagonistic to synergistic, while the interaction between AS and MF showed moderate to strong synergism. In contrast, the interaction between AS and PM resulted in an antagonistic interaction, which differs from the combinations with AmB or MF. This study provides valuable insights for developing novel drug regimens for leishmaniasis treatment, emphasizing the potential of AS and its combination with existing antileishmanial drugs. Further research is necessary to optimize drug combinations and minimize adverse effects, leading to more effective therapeutic outcomes.</p>","PeriodicalId":54246,"journal":{"name":"Antibiotics-Basel","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11428804/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142336636","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}
Pseudomonas aeruginosa is a multidrug-resistant Gram-negative pathogen and one of the leading causes of ventilator-associated pneumonia and infections in patients with chronic obstructive pulmonary disease and cystic fibrosis. Murepavadin is a peptidomimetic that specifically targets outer-membrane lipopolysaccharide transport protein LptD of P. aeruginosa. In this study, we find that murepavadin enhances the bactericidal efficacy of ciprofloxacin. We further demonstrate that murepavadin increases intracellular accumulation of ciprofloxacin by suppressing drug efflux. In addition, the murepavadin-ciprofloxacin combination exhibits a synergistic bactericidal effect in an acute murine pneumonia model. In conclusion, our results identify an effective drug combination for the treatment of P. aeruginosa infections.
{"title":"Murepavadin Enhances the Killing Efficacy of Ciprofloxacin against <i>Pseudomonas aeruginosa</i> by Inhibiting Drug Efflux.","authors":"Xiaoya Wei, Dandan Zhou, Congjuan Xu, Ping Chen, Shuiping Chen, Zhihui Cheng, Yongxin Jin, Shouguang Jin, Weihui Wu","doi":"10.3390/antibiotics13090810","DOIUrl":"https://doi.org/10.3390/antibiotics13090810","url":null,"abstract":"<p><p><i>Pseudomonas aeruginosa</i> is a multidrug-resistant Gram-negative pathogen and one of the leading causes of ventilator-associated pneumonia and infections in patients with chronic obstructive pulmonary disease and cystic fibrosis. Murepavadin is a peptidomimetic that specifically targets outer-membrane lipopolysaccharide transport protein LptD of <i>P. aeruginosa</i>. In this study, we find that murepavadin enhances the bactericidal efficacy of ciprofloxacin. We further demonstrate that murepavadin increases intracellular accumulation of ciprofloxacin by suppressing drug efflux. In addition, the murepavadin-ciprofloxacin combination exhibits a synergistic bactericidal effect in an acute murine pneumonia model. In conclusion, our results identify an effective drug combination for the treatment of <i>P. aeruginosa</i> infections.</p>","PeriodicalId":54246,"journal":{"name":"Antibiotics-Basel","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11429200/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142332293","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}
Pub Date : 2024-08-25DOI: 10.3390/antibiotics13090805
Ionela-Anca Pintea-Simon, Ligia Bancu, Anca Delia Mare, Cristina Nicoleta Ciurea, Felicia Toma, Adrian Man
With approximately half a billion events per year, lower respiratory tract infections (LRTIs) represent a major challenge for the global public health. Among LRTI cases, those caused by Gram-negative bacteria (GNB) are associated with a poorer prognostic. Standard-of-care etiologic diagnostics is lengthy and difficult to establish, with more than half of cases remaining microbiologically undocumented. Recently, syndromic molecular diagnostic panels became available, enabling simultaneous detection of tens of pathogen-related and antimicrobial-resistance genetic markers within a few hours. In this narrative review, we summarize the available data on the performance of molecular diagnostics in GNB pneumonia, highlighting the main strengths and limitations of these assays, as well as the main factors influencing their clinical utility. We searched MEDLINE and Web of Science databases for relevant English-language articles. Molecular assays have higher analytical sensitivity than cultural methods, and show good agreement with standard-of-care diagnostics regarding detection of respiratory pathogens, including GNB, and identification of frequent patterns of resistance to antibiotics. Clinical trials reported encouraging results on the usefulness of molecular assays in antibiotic stewardship. By providing early information on the presence of pathogens and their probable resistance phenotypes, these assays assist in the choice of targeted therapy, in shortening the time from sample collection to appropriate antimicrobial treatment, and in reducing unnecessary antibiotic use.
下呼吸道感染(LRTI)每年约有 5 亿例,是全球公共卫生面临的一大挑战。在下呼吸道感染病例中,由革兰氏阴性菌(GNB)引起的病例预后较差。标准病原学诊断耗时长且难以确定,半数以上的病例仍无微生物学记录。最近,综合征分子诊断面板问世,可在数小时内同时检测数十种病原体相关基因标记和抗菌药耐药性基因标记。在这篇叙述性综述中,我们总结了有关 GNB 肺炎分子诊断性能的现有数据,强调了这些检测方法的主要优势和局限性,以及影响其临床实用性的主要因素。我们在 MEDLINE 和 Web of Science 数据库中检索了相关的英文文章。分子检测法的分析灵敏度高于培养法,在检测呼吸道病原体(包括 GNB)和识别抗生素耐药性的常见模式方面与常规诊断法有很好的一致性。临床试验报告显示,分子检测在抗生素管理中的作用令人鼓舞。通过提供病原体存在及其可能耐药表型的早期信息,这些检测有助于选择有针对性的治疗方法,缩短从样本采集到适当抗菌治疗的时间,并减少不必要的抗生素使用。
{"title":"Rapid Molecular Diagnostics of Pneumonia Caused by Gram-Negative Bacteria: A Clinician's Review.","authors":"Ionela-Anca Pintea-Simon, Ligia Bancu, Anca Delia Mare, Cristina Nicoleta Ciurea, Felicia Toma, Adrian Man","doi":"10.3390/antibiotics13090805","DOIUrl":"https://doi.org/10.3390/antibiotics13090805","url":null,"abstract":"<p><p>With approximately half a billion events per year, lower respiratory tract infections (LRTIs) represent a major challenge for the global public health. Among LRTI cases, those caused by Gram-negative bacteria (GNB) are associated with a poorer prognostic. Standard-of-care etiologic diagnostics is lengthy and difficult to establish, with more than half of cases remaining microbiologically undocumented. Recently, syndromic molecular diagnostic panels became available, enabling simultaneous detection of tens of pathogen-related and antimicrobial-resistance genetic markers within a few hours. In this narrative review, we summarize the available data on the performance of molecular diagnostics in GNB pneumonia, highlighting the main strengths and limitations of these assays, as well as the main factors influencing their clinical utility. We searched MEDLINE and Web of Science databases for relevant English-language articles. Molecular assays have higher analytical sensitivity than cultural methods, and show good agreement with standard-of-care diagnostics regarding detection of respiratory pathogens, including GNB, and identification of frequent patterns of resistance to antibiotics. Clinical trials reported encouraging results on the usefulness of molecular assays in antibiotic stewardship. By providing early information on the presence of pathogens and their probable resistance phenotypes, these assays assist in the choice of targeted therapy, in shortening the time from sample collection to appropriate antimicrobial treatment, and in reducing unnecessary antibiotic use.</p>","PeriodicalId":54246,"journal":{"name":"Antibiotics-Basel","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2024-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11429159/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142332299","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}
Pub Date : 2024-08-25DOI: 10.3390/antibiotics13090804
Yuichi Shibata, Jun Hirai, Nobuaki Mori, Nobuhiro Asai, Mao Hagihara, Hiroshige Mikamo
The present study aimed to evaluate the impact of prospective audit and feedback (PAF) on the use of inpatient broad-spectrum antibiotics for more than 10 days using days of therapy (DOT) and a novel metric called days of antibiotic spectrum coverage (DASC) to assess whether the antimicrobial spectrum was narrowed. Conducted at Aichi Medical University Hospital in Japan, the study compared a six-month baseline period (April to September 2022) with a six-month intervention period (April to September 2023). The primary outcome measures were changes in DOT/patient and DASC/patient for broad-spectrum antibiotics. Propensity score matching was performed between two periods and a total of 172 patients were included in the study (pre-intervention, n = 86; intervention, n = 86). The DASC/patient of broad-spectrum antibiotics was statistically decreased in the intervention period compared to that in the baseline period (153.3 vs. 122.7, p < 0.05). Additionally, our PAF intervention led to a switch to narrow-spectrum antimicrobial therapy without increasing all-cause 30-day mortality (5.8% vs. 5.8%, p = 1.0). However, the DOT/patient, DASC/patient, and DASC/DOT of all antimicrobials were not significantly changed. Our study concluded that we should reconsider the timing of PAF intervention by evaluating the effort of PAF by using DOT and DASC.
{"title":"Days of Antibiotic Spectrum Coverage (DASC) as a Metric for Evaluating the Impact of Prospective Audit and Feedback (PAF) against Long-Term Broad-Spectrum Antibiotic Use.","authors":"Yuichi Shibata, Jun Hirai, Nobuaki Mori, Nobuhiro Asai, Mao Hagihara, Hiroshige Mikamo","doi":"10.3390/antibiotics13090804","DOIUrl":"https://doi.org/10.3390/antibiotics13090804","url":null,"abstract":"<p><p>The present study aimed to evaluate the impact of prospective audit and feedback (PAF) on the use of inpatient broad-spectrum antibiotics for more than 10 days using days of therapy (DOT) and a novel metric called days of antibiotic spectrum coverage (DASC) to assess whether the antimicrobial spectrum was narrowed. Conducted at Aichi Medical University Hospital in Japan, the study compared a six-month baseline period (April to September 2022) with a six-month intervention period (April to September 2023). The primary outcome measures were changes in DOT/patient and DASC/patient for broad-spectrum antibiotics. Propensity score matching was performed between two periods and a total of 172 patients were included in the study (pre-intervention, n = 86; intervention, n = 86). The DASC/patient of broad-spectrum antibiotics was statistically decreased in the intervention period compared to that in the baseline period (153.3 vs. 122.7, <i>p</i> < 0.05). Additionally, our PAF intervention led to a switch to narrow-spectrum antimicrobial therapy without increasing all-cause 30-day mortality (5.8% vs. 5.8%, <i>p</i> = 1.0). However, the DOT/patient, DASC/patient, and DASC/DOT of all antimicrobials were not significantly changed. Our study concluded that we should reconsider the timing of PAF intervention by evaluating the effort of PAF by using DOT and DASC.</p>","PeriodicalId":54246,"journal":{"name":"Antibiotics-Basel","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2024-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11428810/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142332276","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}
Pub Date : 2024-08-25DOI: 10.3390/antibiotics13090803
Simona Liliana Iconaru, Daniela Predoi, Carmen Steluta Ciobanu, Catalin Constantin Negrila, Roxana Trusca, Steinar Raaen, Krzysztof Rokosz, Liliana Ghegoiu, Monica Luminita Badea, Carmen Cimpeanu
In this paper, we present for the first time the development of zinc-doped hydroxyapatite enriched with tetracycline (ZnHApTe) powders and provide a comprehensive evaluation of their physico-chemical and biological properties. Various techniques such as X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM), and Fourier transform infrared spectroscopy (FTIR) were used for the sample's complex evaluation. Moreover, the biocompatibility of zinc-doped hydroxyapatite (ZnHAp) and ZnHApTe nanoparticles was evaluated with the aid of human fetal osteoblastic cells (hFOB 1.19 cell line). The results of the biological assays suggested that these nanoparticles hold great promise as potential candidates for the future development of novel biocompatible and antimicrobial agents for biomedical applications. The antimicrobial properties of the ZnHAp and ZnHApTe nanoparticles were assessed using the standard reference microbial strains Staphylococcus aureus ATCC 25923, Escherichia coli ATCC 25922, and Candida albicans ATCC 10231. The results of the in vitro antimicrobial assay demonstrated that both tested materials exhibited good antimicrobial activity. Additionally, these data also indicated that the antimicrobial effects of the ZnHAp nanoparticles were intensified by the presence of tetracycline (Te). Furthermore, the results also suggested that the antimicrobial activity of the samples increased with the incubation time.
{"title":"Novel Antimicrobial Agents Based on Zinc-Doped Hydroxyapatite Loaded with Tetracycline.","authors":"Simona Liliana Iconaru, Daniela Predoi, Carmen Steluta Ciobanu, Catalin Constantin Negrila, Roxana Trusca, Steinar Raaen, Krzysztof Rokosz, Liliana Ghegoiu, Monica Luminita Badea, Carmen Cimpeanu","doi":"10.3390/antibiotics13090803","DOIUrl":"https://doi.org/10.3390/antibiotics13090803","url":null,"abstract":"<p><p>In this paper, we present for the first time the development of zinc-doped hydroxyapatite enriched with tetracycline (ZnHApTe) powders and provide a comprehensive evaluation of their physico-chemical and biological properties. Various techniques such as X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM), and Fourier transform infrared spectroscopy (FTIR) were used for the sample's complex evaluation. Moreover, the biocompatibility of zinc-doped hydroxyapatite (ZnHAp) and ZnHApTe nanoparticles was evaluated with the aid of human fetal osteoblastic cells (hFOB 1.19 cell line). The results of the biological assays suggested that these nanoparticles hold great promise as potential candidates for the future development of novel biocompatible and antimicrobial agents for biomedical applications. The antimicrobial properties of the ZnHAp and ZnHApTe nanoparticles were assessed using the standard reference microbial strains <i>Staphylococcus aureus</i> ATCC 25923, <i>Escherichia coli</i> ATCC 25922, and <i>Candida albicans</i> ATCC 10231. The results of the in vitro antimicrobial assay demonstrated that both tested materials exhibited good antimicrobial activity. Additionally, these data also indicated that the antimicrobial effects of the ZnHAp nanoparticles were intensified by the presence of tetracycline (Te). Furthermore, the results also suggested that the antimicrobial activity of the samples increased with the incubation time.</p>","PeriodicalId":54246,"journal":{"name":"Antibiotics-Basel","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2024-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11428947/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142332294","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}