Antimicrobial Agents and Chemotherapy最新文献

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Drug-resistant clinical Candida responded to 5-aminolevulinic acid photodynamic therapy (ALA-PDT) in vitro via enhanced ROS release. 耐药临床念珠菌通过增强ROS释放对体外5-氨基乙酰丙酸光动力治疗(ALA-PDT)有反应。
IF 4.5 2区 医学
Antimicrobial Agents and Chemotherapy Pub Date : 2026-05-06 Epub Date: 2026-04-17 DOI: 10.1128/aac.01645-25
Zhiya Yang, Yonghong Zhang, Dongmei Li, Sisi Wang, Ruoyu Shi, Dongmei Shi
{"title":"Drug-resistant clinical <i>Candida</i> responded to 5-aminolevulinic acid photodynamic therapy (ALA-PDT) <i>in vitro</i> via enhanced ROS release.","authors":"Zhiya Yang, Yonghong Zhang, Dongmei Li, Sisi Wang, Ruoyu Shi, Dongmei Shi","doi":"10.1128/aac.01645-25","DOIUrl":"10.1128/aac.01645-25","url":null,"abstract":"<p><p>Photodynamic therapy (PDT) has emerged as a potential strategy to combat drug-resistant fungal infections. This study aimed to evaluate the therapeutic efficacy of 5-aminolevulinic acid PDT (ALA-PDT) against drug-resistant <i>Candida</i> strains isolated from patients with candidiasis and to elucidate its underlying mechanisms. Drug-resistant strains were identified by their reduced antifungal susceptibility to azoles, micafungin, amphotericin B, and terbinafine. RNA sequencing (RNA-seq) was used to assess gene expression related to mycelial formation and fungal growth. Scanning electron microscopy (SEM) was employed to observe cell-wall morphology after ALA-PDT treatment. Biofilm formation and intracellular reactive oxygen species (ROS) levels were also measured to investigate the mechanism of ALA-PDT-mediated fungal killing. <i>Candida albicans</i> and <i>Candida tropicalis</i> accounted for over half, predominantly from male ICU patients aged over 40 years. <i>Candida</i> spp. strains exhibited resistance rates of approximately 69.38% to terbinafine, 40.8% to azole antifungals, and 16.3% to micafungin among 49 drug-resistant isolates. Treatment with 20% ALA-PDT effectively eradicated those azole-resistant <i>C. albicans in vitro</i>, increased fungal killing, and significantly increased intracellular ROS levels. SEM analysis revealed varying degrees of cell-wall disruption, and RNA-seq demonstrated downregulation of mycelia-related genes following ALA-PDT. ALA-PDT effectively inhibits drug-resistant <i>Candida</i> spp. growth by inducing ROS-mediated cell damage and suppressing mycelial gene expression. These findings highlight ALA-PDT as a promising therapeutic approach for refractory candidiasis and provide mechanistic insights into its antifungal activity.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":" ","pages":"e0164525"},"PeriodicalIF":4.5,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13148027/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147715688","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}
引用次数: 0
Identification and characteristics of a novel acquired aminoglycoside phosphotransferase, APH(3')-IVb, from Riemerella anatipestifer. 鸭疫里默氏菌获得性氨基糖苷磷酸转移酶APH(3′)-IVb的鉴定与特性研究
IF 4.5 2区 医学
Antimicrobial Agents and Chemotherapy Pub Date : 2026-05-06 Epub Date: 2026-03-24 DOI: 10.1128/aac.01631-25
Mingkang Zhou, Zhishuang Yang, Mingshu Wang, Renyong Jia, Shun Chen, Mafeng Liu, Xinxin Zhao, Qiao Yang, Ying Wu, Shaqiu Zhang, Juan Huang, Xumin Ou, Di Sun, Bin Tian, Yu He, Zhen Wu, Anchun Cheng, Dekang Zhu
{"title":"Identification and characteristics of a novel acquired aminoglycoside phosphotransferase, APH(3')-IVb, from <i>Riemerella anatipestifer</i>.","authors":"Mingkang Zhou, Zhishuang Yang, Mingshu Wang, Renyong Jia, Shun Chen, Mafeng Liu, Xinxin Zhao, Qiao Yang, Ying Wu, Shaqiu Zhang, Juan Huang, Xumin Ou, Di Sun, Bin Tian, Yu He, Zhen Wu, Anchun Cheng, Dekang Zhu","doi":"10.1128/aac.01631-25","DOIUrl":"10.1128/aac.01631-25","url":null,"abstract":"<p><p>A novel acquired aminoglycoside resistance gene, <i>aph(3</i>'<i>)-IVb</i>, was identified via whole-genome sequencing of a multidrug-resistant <i>Riemerella anatipestifer</i> isolate from a duck. The gene encodes a 262-amino-acid phosphotransferase, APH(3')-IVb, sharing only 39.9% amino acid identity with its closest known homolog, APH(3')-IVa. Heterologous expression of <i>aph(3</i>'<i>)-IVb</i> in <i>Escherichia coli</i> and a susceptible <i>R. anatipestifer</i> strain conferred resistance to neomycin, paromomycin, and ribostamycin, a phenotype validated by gene deletion and complementation experiments. Kinetic analysis of the purified APH(3')-IVb enzyme confirmed phosphotransferase activity against these three aminoglycosides, with catalytic efficiencies (<i>k</i><sub>cat</sub>/<i>K<sub>m</sub></i>) ranging from 10⁴ to 10⁵ M⁻¹·s⁻¹. Furthermore, site-directed mutagenesis identified key residues critical for enzymatic function. While the prevalence of <i>aph(3</i>'<i>)-IVb</i> in <i>R. anatipestifer</i> isolates was low (1.6%), analysis of public databases identified 93 <i>aph(3</i>'<i>)-IVb</i>-positive sequences, of which 36.6% originated from human pathogens. Genetic environment analysis revealed that <i>aph(3</i>'<i>)-IVb</i> resides within a genomic resistance island flanked by mobile genetic elements, suggesting its horizontal acquisition. The emergence of this novel enzyme, coupled with its association with mobile elements and distribution among human pathogens, underscores a potential pathway for resistance dissemination across veterinary and clinical environments, posing a significant public health concern.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":" ","pages":"e0163125"},"PeriodicalIF":4.5,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13148043/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147502871","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}
引用次数: 0
Human Dectin-1- and Dectin-2-targeted DectiSomes are effective against diverse pathogenic fungi. 人Dectin-1和dectin -2靶向DectiSomes对多种病原真菌有效。
IF 4.5 2区 医学
Antimicrobial Agents and Chemotherapy Pub Date : 2026-05-06 Epub Date: 2026-03-30 DOI: 10.1128/aac.01689-25
Suresh Ambati, Xiaorong Lin, Zachary A Lewis, Jesse A Peter, Richard B Meagher
{"title":"Human Dectin-1- and Dectin-2-targeted DectiSomes are effective against diverse pathogenic fungi.","authors":"Suresh Ambati, Xiaorong Lin, Zachary A Lewis, Jesse A Peter, Richard B Meagher","doi":"10.1128/aac.01689-25","DOIUrl":"10.1128/aac.01689-25","url":null,"abstract":"<p><p>Annually, aspergillosis, candidiasis, cryptococcosis, and mucormycosis result in approximately 1,500,000, 650,000, 120,000, and 59,000 deaths, respectively. Mortality rates among patients receiving antifungal drug treatment range from 30% to 90%. Therefore, there is an urgent need to improve the efficacy of antifungal drug therapies against infections by these high-priority fungal diseases. <i>Aspergillus fumigatus</i>, <i>Candida albicans</i>, <i>Cryptococcus neoformans</i>, and <i>Rhizopus delemar</i> are the most common causative pathogens. We have previously developed DectiSomes, which are liposomes loaded with antifungal drugs and coated with the carbohydrate recognition domains of mouse Dectin-1 and/or Dectin-2. We demonstrated that the murine DectiSomes efficiently bound and killed these pathogens growing <i>in vitro</i> and/or in mouse disease models. With the plan to move DectiSomes into the clinic with the human Dectin orthologs, we were concerned that the significant sequence divergence between mouse and human Dectin-1 and Dectin-2 carbohydrate recognition domains could have altered pathogen specificity. Herein, we compared the functionality of the human and mouse Dectin-1 and Dectin-2 orthologs in targeting DectiSomes to these pathogens. Binding and growth inhibition data on <i>A. fumigatus</i> and <i>C. neoformans</i> supported their functional similarity, while results with <i>C. albicans</i> and <i>R. delemar</i> indicated some functional divergence. Despite these differences, our results demonstrate that both human and mouse DectiSomes are effective at binding and killing all four diverse fungal pathogens.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":" ","pages":"e0168925"},"PeriodicalIF":4.5,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13148054/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147571955","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}
引用次数: 0
Leveraging the global genomic epidemiology of carbapenemase-producing Klebsiella pneumoniae to inform infection prevention in Tunisian hospitals. 利用产生碳青霉烯酶的肺炎克雷伯菌的全球基因组流行病学为突尼斯医院的感染预防提供信息。
IF 4.5 2区 医学
Antimicrobial Agents and Chemotherapy Pub Date : 2026-05-06 DOI: 10.1128/aac.00142-26
Basma Menif, Jay N Worley, Noura Ben Mansour, Faouzia Mahjoubi, Adnene Hammami, Lynn Bry
{"title":"Leveraging the global genomic epidemiology of carbapenemase-producing <i>Klebsiella pneumoniae</i> to inform infection prevention in Tunisian hospitals.","authors":"Basma Menif, Jay N Worley, Noura Ben Mansour, Faouzia Mahjoubi, Adnene Hammami, Lynn Bry","doi":"10.1128/aac.00142-26","DOIUrl":"https://doi.org/10.1128/aac.00142-26","url":null,"abstract":"<p><p>Carbapenemase-producing <i>Klebsiella pneumoniae</i> (CPK) is a major threat in North Africa, yet long-term genomic surveillance efforts remain scarce. To address this, we analyzed 1,013 CPK clinical isolates collected at Habib Bourguiba Hospital (Sfax, Tunisia) from 2009 to 2022. Given limited genomic resources, clinical microbiologic and pulse-field gel electrophoresis (PFGE) profiles identified representative isolates for genomic analyses to resolve transmission dynamics and plasmid dissemination over time. Hospital-acquired CPK increased >10-fold, from 0.95 to 9.59 per 10,000 patient-days. OXA-48-like enzymes predominated, followed by NDMs and dual producers. Genomic analyses identified 23 sequence types, with ST101, ST147, and ST383 accounting for 70% of isolates. ST383 strains carrying <i>bla</i><sub>OXA-204</sub> on IncC plasmids occurred first, followed by ST101 with <i>bla</i><sub>OXA-48</sub> on IncL replicons and ST147 with <i>bla</i><sub>NDM-1</sub> on IncFIB/IncFII multi-replicons. Since 2019, epidemic ST383 co-harboring <i>bla</i><sub>OXA-48</sub> on IncL plasmids and <i>bla</i><sub>NDM-5</sub> with <i>rmpA/iuc</i> on hybrid IncFIB/IncHI1B plasmids became dominant. Comparison with 80,252 global genomes in NCBI Pathogen Detection showed that 82% of study isolates clustered with Mediterranean/global lineages, demonstrating frequent international dissemination. Findings reveal both local and international reservoirs driving CPK introductions, informing targeted infection-control strategies in regional hospitals.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":" ","pages":"e0014226"},"PeriodicalIF":4.5,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147832431","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}
引用次数: 0
Rise of Neisseria gonorrhoeae with mosaic penA-34, France, 2018-2023. 淋病奈瑟菌的崛起与马赛克penA-34,法国,2018-2023。
IF 4.5 2区 医学
Antimicrobial Agents and Chemotherapy Pub Date : 2026-05-06 DOI: 10.1128/aac.01919-25
François Camelena, Manel Merimèche, Mary Mainardis, Aymeric Braille, Béatrice Bercot
{"title":"Rise of <i>Neisseria gonorrhoeae</i> with mosaic <i>penA-34,</i> France, 2018-2023.","authors":"François Camelena, Manel Merimèche, Mary Mainardis, Aymeric Braille, Béatrice Bercot","doi":"10.1128/aac.01919-25","DOIUrl":"https://doi.org/10.1128/aac.01919-25","url":null,"abstract":"<p><p>Surveillance of antimicrobial resistance in <i>Neisseria gonorrhoeae</i> was conducted in France from 2018 to 2023. The proportion of isolates with cefixime MIC ≥ 0.032 mg/L increased from 8.1% in 2018-2022 to 23.5% in 2023. This sharp rise was driven by the expansion of two clones, ST1580 and ST16676, carrying the mosaic <i>penA-34.001</i> and <i>penA-34.007</i> alleles, respectively. These findings highlight the essential role of genomic surveillance in monitoring the evolution of resistance determinants in <i>N. gonorrhoeae</i>.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":" ","pages":"e0191925"},"PeriodicalIF":4.5,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147832432","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}
引用次数: 0
Optimizing target inactivation to treat multidrug-resistant Escherichia coli with NDM and PBP3 mutations: "going the extra mile". 优化靶失活以治疗具有NDM和PBP3突变的多重耐药大肠杆菌:“加倍努力”。
IF 4.5 2区 医学
Antimicrobial Agents and Chemotherapy Pub Date : 2026-05-06 Epub Date: 2026-02-20 DOI: 10.1128/aac.00887-25
Claudia Fabrizio, Felice Valzano, Simone Giuliano, Elisabetta Morelli, Daniela Serio, Giovanni Battista Buccoliero, Maurizio Cervellera, Gianfranco La Bella, Fabio Arena, Andrea M Hujer, Magdalena A Taracila, Steven H Marshall, Robert A Bonomo, Carlo Tascini
{"title":"Optimizing target inactivation to treat multidrug-resistant <i>Escherichia coli</i> with NDM and PBP3 mutations: \"going the extra mile\".","authors":"Claudia Fabrizio, Felice Valzano, Simone Giuliano, Elisabetta Morelli, Daniela Serio, Giovanni Battista Buccoliero, Maurizio Cervellera, Gianfranco La Bella, Fabio Arena, Andrea M Hujer, Magdalena A Taracila, Steven H Marshall, Robert A Bonomo, Carlo Tascini","doi":"10.1128/aac.00887-25","DOIUrl":"10.1128/aac.00887-25","url":null,"abstract":"<p><p>A 65-year-old man without identifiable risk factors for multidrug-resistant pathogens was admitted with peritonitis, isolating NDM-producing <i>Escherichia coli</i> from a rectal swab and intraoperative samples. After surgery, ceftazidime-avibactam/aztreonam was administered. Due to poor clinical response, he was switched to imipenem-relebactam/aztreonam, resulting in a successful outcome. Whole-genome sequencing detected <i>bla</i><sub>NDM-5</sub> and <i>bla</i><sub>CMY-148</sub> β-lactamases, PBP3 YRIN insertion, and mutated <i>cirA</i> gene. This case illustrates the importance of considering different mechanisms of resistance when choosing combination therapy.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":" ","pages":"e0088725"},"PeriodicalIF":4.5,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13148025/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146256965","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}
引用次数: 0
Multifunctional ACE2-nanobody fusion design for pan-specific neutralization and cardiovascular protection in SARS coronavirus infection. SARS冠状病毒感染中泛特异性中和和心血管保护的多功能ace2纳米体融合设计
IF 4.5 2区 医学
Antimicrobial Agents and Chemotherapy Pub Date : 2026-05-06 Epub Date: 2026-03-23 DOI: 10.1128/aac.00024-26
Traian Sulea, Matthew Stuible, Maria Moreno, Alex Pelletier, Martin A Rossotti, Yuneivy Cepero-Donates, Jacqueline Slinn, Patrick Salois, Anh Tran, Melissa Hewitt, Alvaro Yogi, Nazanin Rohani, Brian Cass, Anne E G Lenferink, Jamshid Tanha, Binbing Ling, Etienne Lessard, Laurence Delafosse, Jagdeep K Sandhu, Danica Stanimirovic
{"title":"Multifunctional ACE2-nanobody fusion design for pan-specific neutralization and cardiovascular protection in SARS coronavirus infection.","authors":"Traian Sulea, Matthew Stuible, Maria Moreno, Alex Pelletier, Martin A Rossotti, Yuneivy Cepero-Donates, Jacqueline Slinn, Patrick Salois, Anh Tran, Melissa Hewitt, Alvaro Yogi, Nazanin Rohani, Brian Cass, Anne E G Lenferink, Jamshid Tanha, Binbing Ling, Etienne Lessard, Laurence Delafosse, Jagdeep K Sandhu, Danica Stanimirovic","doi":"10.1128/aac.00024-26","DOIUrl":"10.1128/aac.00024-26","url":null,"abstract":"<p><p>Severe acute respiratory syndrome coronaviruses use the ACE2 receptor for viral entry while downregulating its activity, potentially leading to hypertension and major organ injuries. Dual-action technologies based on soluble ACE2 aimed to neutralize the virus while restoring ACE2's normal enzymatic activity. Here, we describe a novel general molecular design, VHH<sub>Spike</sub>-ACE2<sub>ECD</sub>-VHH<sub>Albumin</sub>, in the toolbox of ACE2-centric therapeutic modalities. The optimized nanobody module VHH<sub>Spike</sub> afforded strong pan-specific binding against the entire sarbecoviral clade. This correlated with potent <i>in vitro</i> neutralization of pseudotyped virus variants of concern, with IC<sub>50</sub> values in the picomolar range. Exogenous enzymatic activity was provided by the ACE2<sub>ECD</sub> module, which also contributed binding avidity via intrinsic homodimerization. Persistence of enzymatic activity in circulation was increased <i>in vivo</i> via the nanobody module VHH<sub>Albumin</sub> optimized for serum albumin binding. Single-dose therapeutic administration of lead compound 72opt-ACE2-R28 demonstrated virus neutralization in lungs of hamsters at day 5 post-infection with SARS-CoV-2. In hypertensive mice maintained under continuous injection of angiotensin II, a single dose of 72opt-ACE2-R28 normalized systolic blood pressure, maintaining a 30 mmHg reduction after 24 h. Overall, encouraging coronavirus neutralization and hypertension reduction showed magnitudes and timeframes appropriate for treatment of typical acute infections. We discuss molecular bases of interactions with coronavirus spike protein molecules and future scale-up manufacturability toward clinical development of this modular design scaffold with high potential against emerging SARS-CoV-2 variants.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":" ","pages":"e0002426"},"PeriodicalIF":4.5,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13148018/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147497552","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}
引用次数: 0
Polygenic, cell-envelope adaptations drive high-frequency daptomycin resistance in Staphylococcus capitis NRCS-A from neonatal sepsis and NEC. 新生儿败血症和NEC引起的冠状葡萄球菌NRCS-A的多基因细胞包膜适应驱动高频达托霉素耐药。
IF 4.5 2区 医学
Antimicrobial Agents and Chemotherapy Pub Date : 2026-05-06 Epub Date: 2026-03-24 DOI: 10.1128/aac.01414-25
Lara Kränkel, Janna Hauser, Jessica Slavetinsky, Alina Zinser, Annika Schmidt, Mulugeta Nega, Ahmed M A Elsherbini, Tanja Schneider, Christian Gille, Martin Schaller, Jörg Fuchs, Andreas Peschel, Christoph Slavetinsky
{"title":"Polygenic, cell-envelope adaptations drive high-frequency daptomycin resistance in <i>Staphylococcus capitis</i> NRCS-A from neonatal sepsis and NEC.","authors":"Lara Kränkel, Janna Hauser, Jessica Slavetinsky, Alina Zinser, Annika Schmidt, Mulugeta Nega, Ahmed M A Elsherbini, Tanja Schneider, Christian Gille, Martin Schaller, Jörg Fuchs, Andreas Peschel, Christoph Slavetinsky","doi":"10.1128/aac.01414-25","DOIUrl":"10.1128/aac.01414-25","url":null,"abstract":"<p><p><i>Staphylococcus capitis</i> NRCS-A is a major cause of neonatal sepsis worldwide and exhibits resistance to multiple antibiotics. We assessed the prevalence and mechanisms of daptomycin resistance (DAP-R) in bloodstream isolates from a German neonatal intensive care unit. Ten of 11 NRCS-A isolates (91%) were resistant to daptomycin, and 18% displayed decreased susceptibility to vancomycin. Genomic analysis revealed diverse polymorphisms in genes associated with DAP-R in <i>Staphylococcus aureus,</i> but no single amino acid variant explained resistance. Phospholipid composition remained unchanged, whereas isolates displayed increased cell surface charge and cell wall thickening. Consistently, BODIPY-labeled daptomycin binding was reduced and more diffusely distributed in DAP-R NRCS-A with weaker septal enrichment. In serial passaging experiments, <i>S. capitis</i> acquired DAP-R more rapidly and robustly than <i>S. aureus</i> or <i>S. epidermidis</i> under subinhibitory concentrations of either daptomycin or vancomycin. Resequencing after <i>in vitro</i> DAP-R evolution in <i>S. capitis</i> identified newly acquired mutations in cell envelope-associated genes, including <i>walK</i> and <i>mprF</i>. These results indicate that <i>S. capitis</i> NRCS-A rapidly evolves resistance via polygenic, cell-envelope-driven mechanisms distinct from those in <i>S. aureus</i>. The high prevalence and adaptive capacity of DAP-R in neonatal isolates raise concern for therapeutic failure in neonatal intensive care.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":" ","pages":"e0141425"},"PeriodicalIF":4.5,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13148029/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147502949","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}
引用次数: 0
Sulbactam-durlobactam plus ceftriaxone dosing and novel treatment regimens for Mycobacterium abscessus lung disease. 舒巴坦-杜氯巴坦加头孢曲松治疗脓肿分枝杆菌肺病的新方案。
IF 4.5 2区 医学
Antimicrobial Agents and Chemotherapy Pub Date : 2026-05-06 Epub Date: 2026-04-09 DOI: 10.1128/aac.01437-25
Sanjay Singh, Avneesh Shrivastava, Gunavanthi D Boorgula, Mary C Long, Brian Robbins, Pamela J McShane, Tawanda Gumbo, Shashikant Srivastava
{"title":"Sulbactam-durlobactam plus ceftriaxone dosing and novel treatment regimens for <i>Mycobacterium abscessus</i> lung disease.","authors":"Sanjay Singh, Avneesh Shrivastava, Gunavanthi D Boorgula, Mary C Long, Brian Robbins, Pamela J McShane, Tawanda Gumbo, Shashikant Srivastava","doi":"10.1128/aac.01437-25","DOIUrl":"10.1128/aac.01437-25","url":null,"abstract":"<p><p>The guideline-based therapy achieves sputum culture conversion rates in 20%-34% of patients with <i>Mycobacterium abscessus</i> (MAB) lung disease (LD). Double-β-lactam combinations have been proposed to improve cure based on time-kill curves. We tested MICs followed by hollow fiber system model of MAB (HFS-MAB) exposure-effect studies with sulbactam-durlobactam administered every 8 h (q8h), q12h, and q24h, to identify target exposures. Next, the sulbactam-durlobactam target exposure plus ceftriaxone was administered in the HFS-MAB inoculated with three different MAB isolates, as was the sulbactam-durlobactam-ceftriaxone combination with epetraborole and omadacycline (SDCEO). <i>γ</i>-slopes (kill-speed) were calculated for all regimens. The minimal sulbactam-durlobactam clinical doses that achieved target exposure were identified using Monte Carlo experiments. Ceftriaxone reduced sulbactam-durlobactam MICs by eight-tube dilutions. In the HFS-MAB, sulbactam-durlobactam microbial kill and antimicrobial resistance were linked to % time concentration persists above MIC (%T<sub>MIC</sub>), with target exposure of 50%T<sub>MIC</sub>. Sulbactam-durlobactam killed 3.85 log<sub>10</sub> CFU/mL below day 0 burden (<i>B<sub>0</sub></i>) with regrowth. Sulbactam-durlobactam plus ceftriaxone killed without regrowth and demonstrated Bliss additivity. The kill slope of bacterial population in >95% of virtual subjects was 2.28 (0.97-4.80) log<sub>10</sub> CFU/mL/day for sulbactam-durlobactam-ceftriaxone and 2.91 (1.65-4.93) log<sub>10</sub> CFU/mL/day for SDCEO. The optimal sulbactam-durlobactam dose co-administered with ceftriaxone was 2G q8h for creatinine clearance >90 mL/min (or 4G q12h for outpatients), 2G q12h for 60-90 mL/min, 1G q12h for ≥30 to <60 mL/min, and 1G q24h for <30 mL/min. Sulbactam-durlobactam-ceftriaxone achieved the highest microbial kill encountered so far in the HFS-MAB. Sulbactam-durlobactam-ceftriaxone should be tested as the backbone for novel treatment shortening regimens.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":" ","pages":"e0143725"},"PeriodicalIF":4.5,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13148024/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147637787","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}
引用次数: 0
Seminal plasma concentrations of long-acting cabotegravir in men receiving HIV pre-exposure prophylaxis. 长效卡博特韦在接受HIV暴露前预防的男性中的精浆浓度。
IF 4.5 2区 医学
Antimicrobial Agents and Chemotherapy Pub Date : 2026-05-06 Epub Date: 2026-04-15 DOI: 10.1128/aac.00165-26
Davide Moschese, Chiara Fusetti, Samuel Lazzarin, Andrea Giacomelli, Valentina Mazzotta, Dario Cattaneo, Antonio D'Avolio, Francesco Caruso, Donatella Maddalena, Francesco Petri, Andrea Antinori, Cristina Gervasoni, Andrea Gori, Maria Vittoria Cossu
{"title":"Seminal plasma concentrations of long-acting cabotegravir in men receiving HIV pre-exposure prophylaxis.","authors":"Davide Moschese, Chiara Fusetti, Samuel Lazzarin, Andrea Giacomelli, Valentina Mazzotta, Dario Cattaneo, Antonio D'Avolio, Francesco Caruso, Donatella Maddalena, Francesco Petri, Andrea Antinori, Cristina Gervasoni, Andrea Gori, Maria Vittoria Cossu","doi":"10.1128/aac.00165-26","DOIUrl":"10.1128/aac.00165-26","url":null,"abstract":"<p><p>To address the lack of data on male genital tract penetration of CAB-LA PrEP, seminal plasma was collected at days 3, 7, 28, 84, and 140 and analyzed by LC-MS/MS. CAB was detectable in 71% of samples at day 3, 73% at day 7, and 92% at day 28, with all samples quantifiable at days 84 and 140. Seminal-to-blood plasma ratios remained low but proportional to systemic exposure, indicating sustained seminal CAB exposure.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":" ","pages":"e0016526"},"PeriodicalIF":4.5,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13148058/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147687559","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}
引用次数: 0
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