Antimicrobial Agents and Chemotherapy最新文献

{"title":"Recent increase in Candida auris frequency in the SENTRY surveillance program: antifungal activity and genotypic characterization","authors":"Mariana CastanheiraLalitagauri M. DeshpandePaul R. RhombergCecilia G. Carvalhaes1Element Iowa City (JMI Laboratories), North Liberty, Iowa, USADamian J. Krysan","doi":"10.1128/aac.00570-24","DOIUrl":"https://doi.org/10.1128/aac.00570-24","url":null,"abstract":"Antimicrobial Agents and Chemotherapy, Ahead of Print. <br/>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142196515","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The OprF porin as a potential target for the restoration of carbapenem susceptibility in Pseudomonas aeruginosa expressing acquired carbapenemases","authors":"Patrice NordmannNicolas HelsensLaurent PoirelMustafa SadekDirk BumannJacqueline Findlay1European Institute for Emerging Antibiotic Resistance, Pasteur Institute, Lille, France2European Institute for Emerging Antibiotic Resistance, University of Fribourg, Fribourg, Switzerland3Medical and Molecular Microbiology, Faculty of Science and Medicine, University of Fribourg, Fribourg, Switzerland4Swiss National Reference Center for Emerging Antibiotic Resistance (NARA), University of Fribourg, Fribourg, Switzerland5Clinical Microbiology Unit, Pasteur Institute of Lille, Lille, France6Biozentrum, University of Basel, Basel, SwitzerlandJared A. Silverman","doi":"10.1128/aac.00761-24","DOIUrl":"https://doi.org/10.1128/aac.00761-24","url":null,"abstract":"Antimicrobial Agents and Chemotherapy, Ahead of Print. <br/>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142196513","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synergistic antimicrobial combination of third-generation cephalosporins and polymyxin B against carbapenem-polymyxin-resistant Klebsiella pneumoniae: an in vitro and in vivo analysis","authors":"Mariana Carvalho SturaroNathalia da Silva DamacenoIzadora Dillis FaccinOsmar Nascimento SilvaThiago Mendonça de AquinoNathalia Monteiro Lins FreireMarcone Gomes dos Santos AlcântaraKadja Luana Chagas MonteiroLuana RossatoGleyce Hellen de Almeida de SouzaSimone Simionatto1Laboratório de Pesquisa em Ciências da Saúde, Universidade Federal da Grande Dourados, Dourados, Brazil2Universidade Católica de Brasília, Brasilia, Brazil3Laboratório de Síntese e Pesquisa em Química Medicinal, Instituto de Química e Biotecnologia, Universidade Federal de Alagoas, Maceió, BrazilAnne-Catrin Uhlemann","doi":"10.1128/aac.00930-24","DOIUrl":"https://doi.org/10.1128/aac.00930-24","url":null,"abstract":"Antimicrobial Agents and Chemotherapy, Ahead of Print. <br/>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142196520","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evolution toward extremely high imipenem resistance in Mycobacterium abscessus outbreak strains","authors":"Eva Le RunHervé TettelinSteven M. HollandAdrian M. Zelazny1Laboratory of Clinical Immunology and Microbiology (LCIM), Immunopathogenesis Section, National Institute of Allergy and Infectious Diseases (NIAID), NIH, Bethesda, Maryland, USA2Department of Microbiology and Immunology, Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, Maryland, USA3Department of Laboratory Medicine (DLM), Microbiology Service, Clinical Center, NIH, Bethesda, Maryland, USAJared A. Silverman","doi":"10.1128/aac.00673-24","DOIUrl":"https://doi.org/10.1128/aac.00673-24","url":null,"abstract":"Antimicrobial Agents and Chemotherapy, Ahead of Print. <br/>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142196519","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular characterization of clinically isolated Pseudomonas aeruginosa with varying resistance to ceftazidime-avibactam and ceftolozane-tazobactam collected as a part of the ATLAS global surveillance program from 2020 to 2021","authors":"H. LiA. OliverR. K. ShieldsS. KamatG. StoneM. Estabrook1IHMA, Schaumburg, Illinois, USA2Microbiology Service, Son Espases University Hospital, IdISBa, CIBERINFEC, Palma, Illes Balears, Spain3Department of Medicine, Division of Infectious Diseases, University of Pittsburgh, Pittsburgh, Pennsylvania, USA4Pfizer, Mumbai, India5Pfizer, Groton, Connecticut, USABoudewijn L. de Jonge","doi":"10.1128/aac.00670-24","DOIUrl":"https://doi.org/10.1128/aac.00670-24","url":null,"abstract":"Antimicrobial Agents and Chemotherapy, Ahead of Print. <br/>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142196517","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A high content imaging assay for identification of specific inhibitors of native Plasmodium liver stage protein synthesis","authors":"James L. McLellanBeatriz Morales-HernandezSarah SaegerKirsten K. Hanson1Department of Molecular Microbiology and Immunology, and the South Texas Center for Emerging Infectious Diseases, University of Texas at San Antonio, San Antonio, Texas, USAAudrey Odom John","doi":"10.1128/aac.00793-24","DOIUrl":"https://doi.org/10.1128/aac.00793-24","url":null,"abstract":"Antimicrobial Agents and Chemotherapy, Ahead of Print. <br/>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142196518","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Zebrafish as an effective model for evaluating phage therapy in bacterial infections: a promising strategy against human pathogens.","authors":"Lucile Plumet, Denis Costechareyre, Jean-Philippe Lavigne, Karima Kissa, Virginie Molle","doi":"10.1128/aac.00829-24","DOIUrl":"https://doi.org/10.1128/aac.00829-24","url":null,"abstract":"<p><p>The escalating prevalence of antibiotic-resistant bacterial infections necessitates urgent alternative therapeutic strategies. Phage therapy, which employs bacteriophages to specifically target pathogenic bacteria, emerges as a promising solution. This review examines the efficacy of phage therapy in zebrafish models, both embryos and adults, which are proven and reliable for simulating human infectious diseases. We synthesize findings from recent studies that utilized these models to assess phage treatments against various bacterial pathogens, including <i>Enterococcus faecalis</i>, <i>Pseudomonas aeruginosa</i>, <i>Mycobacterium abscessus</i>, <i>Staphylococcus aureus</i>, <i>Klebsiella pneumoniae</i>, <i>Acinetobacter baumannii</i>, and <i>Escherichia coli</i>. Methods of phage administration, such as circulation injection and bath immersion, are detailed alongside evaluations of survival rates and bacterial load reductions. Notably, combination therapies of phages with antibiotics show enhanced efficacy, as evidenced by improved survival rates and synergistic effects in reducing bacterial loads. We also discuss the transition from zebrafish embryos to adult models, emphasizing the increased complexity of immune responses. This review highlights the valuable contribution of the zebrafish model to advancing phage therapy research, particularly in the face of rising antibiotic resistance and the urgent need for alternative treatments.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142153035","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Polymyxins retain <i>in vitro</i> activity and <i>in vivo</i> efficacy against \"resistant\" <i>Acinetobacter baumannii</i> strains when tested in physiological conditions.","authors":"Jennifer Rubio, Jun Yan, Sarah Miller, Jiaqi Cheng, Rachel Li, Zac Builta, Kari Aoyagi, Mark Fisher, Rosemary She, Brad Spellberg, Brian Luna","doi":"10.1128/aac.00725-24","DOIUrl":"https://doi.org/10.1128/aac.00725-24","url":null,"abstract":"<p><p>The emergence of plasmid-mediated resistance threatens the efficacy of polymyxins as the last line of defense against pan-drug-resistant infections. However, we have found that using Mueller-Hinton II (MHII), the standard minimum inhibitory concentration (MIC) medium, results in MIC data that are disconnected from <i>in vivo</i> treatment outcomes. We found that culturing putative colistin-resistant <i>Acinetobacter baumannii</i> clinical isolates, as defined by MICs of >2 mg/L in standard MHII testing conditions, in bicarbonate-containing media reduced MICs to the susceptible range by preventing colistin resistance-conferring lipopolysaccharide modifications from occurring. Furthermore, the lower MICs in bicarbonate-containing media accurately predicted <i>in vivo</i> efficacy of a human-simulated dosing strategy of colistin and polymyxin B in a lethal murine infection model for some polymyxin-resistant <i>A. baumannii</i> strains. Thus, current polymyxin susceptibility testing methods overestimate the contribution of polymyxin resistance-conferring mutations and incorrectly predict antibiotic activity <i>in vivo</i>. Polymyxins may remain a viable therapeutic option against <i>Acinetobacter baumannii</i> strains heretofore determined to be \"pan-resistant.\"</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142139118","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oral pharmacokinetics and efficacy of oral phospholipid remdesivir nucleoside prodrugs against SARS-CoV-2 in mice.","authors":"Aaron F Carlin, James R Beadle, Jeremy Ardanuy, Alex E Clark, Victoria Rhodes, Aaron F Garretson, Joyce A Murphy, Nadejda Valiaeva, Robert T Schooley, Matthew B Frieman, Karl Y Hostetler","doi":"10.1128/aac.01039-24","DOIUrl":"https://doi.org/10.1128/aac.01039-24","url":null,"abstract":"<p><p>Oral broad-spectrum antivirals are urgently needed for the treatment of many emerging and contemporary RNA viruses. We previously synthesized 1-<i>O</i>-octadecyl-2-<i>O</i>-benzyl-<i>sn</i>-glyceryl-P-RVn (ODBG-P-RVn, V2043), a phospholipid prodrug of GS-441524 (remdesivir nucleoside, RVn), and demonstrated its <i>in vivo</i> efficacy in a SARS-CoV-2 mouse model. Structure-activity relationship studies focusing on the prodrug scaffold identified two modifications, 3-fluoro-4-methoxy-benzyl (V2053) and 4-cyano-benzyl (V2067), that significantly enhanced the <i>in vitro</i> broad-spectrum antiviral activity against multiple RNA viruses when compared to V2043. Here, we demonstrate that V2043, V2053, and V2067 are all orally bioavailable, well-tolerated, and achieve high sustained plasma levels after single oral daily dosing. All three phospholipid prodrugs are significantly more active than RVn <i>in vitro</i> and significantly reduce SARS-CoV-2 lung titers in prophylaxis and treatment mouse models of SARS-CoV-2 B.1.351 infection. On a molar basis, V2043 and V2067 are substantially more active than obeldesivir/GS-5245 and molnupiravir <i>in vivo</i>. Together, these data support the continued development of phospholipid RVn prodrugs for the treatment of SARS-CoV-2 and other RNA viruses of clinical concern.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142139117","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"High salt condition alters LPS synthesis and induces the emergence of drug resistance mutations in <i>Helicobacter pylori</i>.","authors":"Hongming Huang, Huang Yang, Shunhang Feng, Xiaoyan Zhang, Chu Chen, Hongyu Yan, Rui Li, Mengxin Liu, Juan Lin, Yancheng Wen, Feifei She","doi":"10.1128/aac.00587-24","DOIUrl":"https://doi.org/10.1128/aac.00587-24","url":null,"abstract":"<p><p>The burgeoning emergence of drug-resistant <i>Helicobacter pylori</i> strains poses a significant challenge to the clinical success of eradication therapies and is primarily attributed to mutations within drug-targeting genes that lead to antibiotic resistance. This study investigated the effect of high salt conditions on the occurrence of drug-resistance mutations in <i>H. pylori</i>. We found that high salt condition significantly amplifies the frequency of drug resistance mutations in <i>H. pylori</i>. This can be chiefly attributed to our discovery indicating that high salt concentration results in elevated reactive oxygen species (ROS) levels, initiating DNA damage within <i>H. pylori</i>. Mechanistically, high salt condition suppresses lipopolysaccharide (LPS) synthesis gene expression, inducing alterations in the LPS structure and escalating outer membrane permeability. This disruption of LPS synthesis attenuates the expression and activity of SodB, facilitates increased ROS levels, and consequently increases the drug resistance mutation frequency. Impairing LPS synthesis engenders a reduction in intracellular iron levels, leading to diminished holo-Fur activity and increased apo-Fur activity, which represses the expression of SodB directly. Our findings suggest a correlation between high salt intake and the emergence of drug resistance in the human pathogen <i>H. pylori</i>, implying that dietary choices affect the risk of emergence of antimicrobial resistance.IMPORTANCEDrug resistance mutations mainly contribute to the emergence of clinical antibiotic-resistant <i>Helicobacter pylori,</i> a bacterium linked to stomach ulcers and cancer. In this study, we explored how elevated salt conditions influence the emergence of drug resistance in <i>H. pylori</i>. We demonstrate that <i>H. pylori</i> exhibits an increased antibiotic resistance mutation frequency when exposed to a high salt environment. We observed an increase in reactive oxygen species (ROS) under high salt conditions, which can cause DNA damage and potentially lead to mutations. Moreover, our results showed that high salt condition alters the bacterium's lipopolysaccharide (LPS) synthesis, leading to a reduced expression of SodB in a Fur-dependent manner. This reduction, in turn, elevates ROS levels, culminating in a higher frequency of drug-resistance mutations. Our research underscores the critical need to consider environmental influences, such as diet and lifestyle, in managing bacterial infections and combating the growing challenge of antibiotic resistance.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142139116","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}