International Journal of Antimicrobial Agents最新文献

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Clinical emergence of Providencia zhejiangensis sp. nov. and Providencia xihuensis sp. nov.: Genomic insights into antimicrobial resistance and geographical distribution 临床标本中出现的两种普罗维登斯:浙江普罗维登斯和西湖普罗维登斯。
IF 4.9 2区 医学
International Journal of Antimicrobial Agents Pub Date : 2025-02-27 DOI: 10.1016/j.ijantimicag.2025.107484
Xu Dong , Yanghui Xiang , Ping Shen , Yonghong Xiao , Ying Zhang
{"title":"Clinical emergence of Providencia zhejiangensis sp. nov. and Providencia xihuensis sp. nov.: Genomic insights into antimicrobial resistance and geographical distribution","authors":"Xu Dong ,&nbsp;Yanghui Xiang ,&nbsp;Ping Shen ,&nbsp;Yonghong Xiao ,&nbsp;Ying Zhang","doi":"10.1016/j.ijantimicag.2025.107484","DOIUrl":"10.1016/j.ijantimicag.2025.107484","url":null,"abstract":"<div><div>Members of the genus <em>Providencia</em> are typically opportunistic pathogens that can cause severe infections in immunocompromised hosts. This study identified two <em>Providencia</em> strains, SKLX146130 and SKLX074055, representing novel species designated as <em>Providencia zhejiangensis</em> sp. nov. and <em>Providencia xihuensis</em> sp. nov., respectively. Both strains were isolated from clinical samples, with <em>P. zhejiangensis</em> displaying extensive drug resistance. Our analysis revealed that <em>P. xihuensis</em> is predominantly from China, whereas <em>P. zhejiangensis</em> has a global presence. Meanwhile, our analyses resolved <em>Providencia huashanensis</em> as a later heterotypic synonym of <em>Providencia xianensis</em>. Notably, the strain SKLX146130 from <em>P. zhejiangensis</em>, characterized by carrying multiple acquired resistance determinants including the carbapenemase gene <em>bla</em><sub>NDM-1</sub>, belongs to a zoonotic subclade. The genomic analyses of the <em>P. zhejiangensis</em> strain SKLX146130 and <em>Providencia xihuensis</em> strain SKLX074055 showed 79.76–84.55% and 79.85–95.85% average nucleotide identity (ANI), respectively, with other <em>Providencia</em> type strains. In silico DNA-DNA hybridization (dDDH) values ranged from 20.7 to 26.2% and 21.3–64.8%, respectively. These results, along with phenotypic characterization and phylogenetic evidence, confirm that SKLX146130 and SKLX074055 represent two distinct novel species within the genus <em>Providencia</em>. Consequently, we propose the names <em>Providencia zhejiangensis</em> sp. nov. and <em>Providencia xihuensis</em> sp. nov. for these species and call for monitoring these species in clinical infections.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"65 5","pages":"Article 107484"},"PeriodicalIF":4.9,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143537100","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
Posaconazole effectiveness in rare invasive fungal infections: A systematic literature review 泊沙康唑治疗罕见侵袭性真菌感染的有效性:系统文献综述。
IF 4.9 2区 医学
International Journal of Antimicrobial Agents Pub Date : 2025-02-27 DOI: 10.1016/j.ijantimicag.2025.107482
Mark Bernauer , Hetty Waskin , Nicole Cossrow , Allysen Kaminski , Alyssa Simon , Havilland Campbell , Dipen Patel
{"title":"Posaconazole effectiveness in rare invasive fungal infections: A systematic literature review","authors":"Mark Bernauer ,&nbsp;Hetty Waskin ,&nbsp;Nicole Cossrow ,&nbsp;Allysen Kaminski ,&nbsp;Alyssa Simon ,&nbsp;Havilland Campbell ,&nbsp;Dipen Patel","doi":"10.1016/j.ijantimicag.2025.107482","DOIUrl":"10.1016/j.ijantimicag.2025.107482","url":null,"abstract":"<div><h3>Introduction</h3><div>Mucormycosis, hyalohyphomycosis, chromoblastomycosis, and fungal mycetoma are rare invasive fungal infections (IFIs) that cause significant morbidity and mortality in immunocompromised patients. Few effective treatment options are available for these IFIs.</div></div><div><h3>Methods</h3><div>We performed a systematic literature review of MEDLINE and Embase to identify studies published from 2005 (year of posaconazole approval) to 22 October 2022, reporting the efficacy/effectiveness of posaconazole monotherapy or combination therapy for treating mucormycosis, hyalohyphomycosis, chromoblastomycosis, and mycetoma. Positive outcomes or positive clinical outcomes were defined as reporting of a positive efficacy/effectiveness measure (i.e. no relapse, response, cure, radiological improvement, clinical/symptom improvement, or survived therapy).</div></div><div><h3>Results</h3><div>Of 3207 articles identified (after removing duplicates), 533 articles (mostly case reports) were included. Positive clinical outcomes with posaconazole therapy were observed in most patients with mucormycosis (74.8%, 1197/1601), hyalohyphomycosis (58.5%, 62/106), chromoblastomycosis (90.5%, 19/21), and mycetoma (100%, 5/5). Overall survival was around 70% or greater across the IFIs examined. Positive response was higher in second-line monotherapy than first-line monotherapy in mucormycosis and chromoblastomycosis. Higher mortality was observed with combination therapy than monotherapy in mucormycosis and hyalohyphomycosis infections (except for first-line use in mucormycosis). Positive clinical outcome was 78.6% and overall survival was 78.6% in 323 coronavirus disease-associated mucormycosis infection cases.</div></div><div><h3>Conclusions</h3><div>Despite the rarity of these IFIs, substantial data have been published since posaconazole was initially approved in 2005, and the real-world case reports demonstrate that posaconazole is an effective therapeutic option alone or in combination for the treatment of these rare IFIs.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"66 1","pages":"Article 107482"},"PeriodicalIF":4.9,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143537120","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
International Society of Antimicrobial Chemotherapy (ISAC) News and Information Page 国际抗微生物化疗学会(ISAC)新闻和信息页面
IF 4.9 2区 医学
International Journal of Antimicrobial Agents Pub Date : 2025-02-27 DOI: 10.1016/j.ijantimicag.2025.107481
{"title":"International Society of Antimicrobial Chemotherapy (ISAC) News and Information Page","authors":"","doi":"10.1016/j.ijantimicag.2025.107481","DOIUrl":"10.1016/j.ijantimicag.2025.107481","url":null,"abstract":"","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"65 4","pages":"Article 107481"},"PeriodicalIF":4.9,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143508858","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
Inhaled alone versus inhaled plus intravenous polymyxin B for the treatment of pneumonia due to carbapenem-resistant gram-negative bacteria: A prospective randomized controlled trial 单独吸入多粘菌素B与吸入加静脉注射多粘菌素B治疗耐碳青霉烯革兰氏阴性菌所致肺炎:一项前瞻性随机对照试验
IF 4.9 2区 医学
International Journal of Antimicrobial Agents Pub Date : 2025-02-27 DOI: 10.1016/j.ijantimicag.2025.107483
Yu Cheng , Lili Zhou , Danjie Wang , Xueyong Li , Rongqi Lin , Junnian Chen , Fuquan Tu , Yiqin Lin , Wenwei Wu , Maobai Liu , Hui Zhang , Hongqiang Qiu
{"title":"Inhaled alone versus inhaled plus intravenous polymyxin B for the treatment of pneumonia due to carbapenem-resistant gram-negative bacteria: A prospective randomized controlled trial","authors":"Yu Cheng ,&nbsp;Lili Zhou ,&nbsp;Danjie Wang ,&nbsp;Xueyong Li ,&nbsp;Rongqi Lin ,&nbsp;Junnian Chen ,&nbsp;Fuquan Tu ,&nbsp;Yiqin Lin ,&nbsp;Wenwei Wu ,&nbsp;Maobai Liu ,&nbsp;Hui Zhang ,&nbsp;Hongqiang Qiu","doi":"10.1016/j.ijantimicag.2025.107483","DOIUrl":"10.1016/j.ijantimicag.2025.107483","url":null,"abstract":"<div><h3>Objectives</h3><div>Infections due to carbapenem-resistant Gram-negative bacteria (CR-GNB) are associated with considerable morbidity and mortality. Polymyxin B (PMB) is a first-line agent for CR-GNB-associated pneumonia, but limited data exist on the clinical use of inhaled (IH) PMB.</div></div><div><h3>Methods</h3><div>A single-center, prospective randomized controlled trial was conducted in China to compare IH PMB alone with IH plus intravenous (IV) PMB between February 2022 and February 2024. The primary outcome was the clinical cure rate.</div></div><div><h3>Results</h3><div>Twenty-two evaluable patients were assigned to the IH group, and 56 patients were included in the IH+IV group. Baseline characteristics were comparable between the two groups. No significant differences were observed in clinical cure rates, favorable clinical outcomes, microbiological outcomes, all-cause mortality, or pneumonia-related mortality. However, IH PMB alone was associated with a lower incidence of nephrotoxicity (<em>P</em> = 0.030). IH PMB demonstrated significantly higher drug concentrations in the epithelial lining fluid (ELF) compared to systemic administration. Patients with immunosuppressive therapy (OR, 0.066; 95% CI, 0.010–0.433; <em>P</em> = 0.005), malignancies (OR, 0.112; 95% CI, 0.016–0.797; <em>P</em> = 0.029), and higher SOFA scores (OR, 0.693; 95% CI, 0.518–0.929; <em>P</em> = 0.014) were less likely to achieve favorable clinical outcomes. Conversely, higher PMB ELF 1-hour concentrations (OR, 1.085; 95% CI, 1.026–1.148; <em>P</em> = 0.004) were associated with more favorable clinical outcomes. The combination of these four indicators demonstrated excellent diagnostic performance (AUC = 0.882). Plasma 1-hour PMB concentrations showed acceptable predictive performance for nephrotoxicity (AUC = 0.766).</div></div><div><h3>Conclusions</h3><div>The potential benefits of IH PMB outweigh the risks, making it an effective treatment for CR-GNB-associated pneumonia in combination with other empirical antimicrobial agents.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"65 5","pages":"Article 107483"},"PeriodicalIF":4.9,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143537118","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
Title Page & Editorial Board 标题页和编辑委员会
IF 4.9 2区 医学
International Journal of Antimicrobial Agents Pub Date : 2025-02-25 DOI: 10.1016/S0924-8579(25)00031-7
{"title":"Title Page & Editorial Board","authors":"","doi":"10.1016/S0924-8579(25)00031-7","DOIUrl":"10.1016/S0924-8579(25)00031-7","url":null,"abstract":"","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"65 3","pages":"Article 107473"},"PeriodicalIF":4.9,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143478549","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
“Seesaw effect” between daptomycin and ceftobiprole in daptomycin-resistant methicillin-resistant staphylococcus aureus isolates 耐甲氧西林金黄色葡萄球菌耐达托霉素与头孢双普罗的“跷跷板效应”。
IF 4.9 2区 医学
International Journal of Antimicrobial Agents Pub Date : 2025-02-21 DOI: 10.1016/j.ijantimicag.2025.107469
Mengzhen Chen , Shengnan Jiang , Lu Sun , Haiping Wang , Lingfang Di , Yeqiong Liu , Ying Zhang , Hemu Zhuang , Yueqin Hong , Zhengan Wang , Feiteng Zhu , Yiyi Chen , Shujuan Ji , Yunsong Yu , Yan Chen , Xiaoxing Du
{"title":"“Seesaw effect” between daptomycin and ceftobiprole in daptomycin-resistant methicillin-resistant staphylococcus aureus isolates","authors":"Mengzhen Chen ,&nbsp;Shengnan Jiang ,&nbsp;Lu Sun ,&nbsp;Haiping Wang ,&nbsp;Lingfang Di ,&nbsp;Yeqiong Liu ,&nbsp;Ying Zhang ,&nbsp;Hemu Zhuang ,&nbsp;Yueqin Hong ,&nbsp;Zhengan Wang ,&nbsp;Feiteng Zhu ,&nbsp;Yiyi Chen ,&nbsp;Shujuan Ji ,&nbsp;Yunsong Yu ,&nbsp;Yan Chen ,&nbsp;Xiaoxing Du","doi":"10.1016/j.ijantimicag.2025.107469","DOIUrl":"10.1016/j.ijantimicag.2025.107469","url":null,"abstract":"<div><h3>Objectives</h3><div>This study aimed to investigate the “seesaw effect” of daptomycin (DAP) and ceftobiprole (BPR) on DAP-resistant (DAP-R) methicillin-resistant <em>Staphylococcus aureus</em> (MRSA) isolates.</div></div><div><h3>Methods</h3><div>Broth microdilution minimum inhibitory concentrations (MICs) of DAP and BPR were tested for laboratory-derived and clinical DAP-R MRSA isolates to estimate the “seesaw effect.” Time-kill curves for seven representative DAP-R isolates were obtained using DAP and BPR to validate their synergistic activity <em>in vitro</em>. Whole genome sequencing as well as deletion and complementation of the <em>mprF</em> gene were performed to investigate the mechanisms of the “seesaw effect.”</div></div><div><h3>Results</h3><div>The BPR MICs decreased by half-fold in DAP-R MRSA isolates. The synergistic effect of DAP and BPR against representative clinical and community-associated MRSA (CA-MRSA) isolates was demonstrated in time-kill analyses, showing that synergistic activity was preferred in CA-MRSA compared with hospital-associated MRSA. The <em>mprF</em> mutations were identified in isolates exhibiting the “seesaw effect.” These mutations increased the DAP MIC while decreasing the BPR MIC.</div></div><div><h3>Conclusions</h3><div>The “seesaw effect” between DAP and BPR was prevalent among DAP-R MRSA isolates. This phenomenon was associated with the <em>mprF</em> mutations of MRSA.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"65 5","pages":"Article 107469"},"PeriodicalIF":4.9,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143476571","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
Temporal, regional, and demographic differences among antimicrobial-resistant domestic Campylobacter jejuni human infections across the United States, 2013–2019 2013-2019年美国国内耐药空肠弯曲杆菌人类感染的时间、地区和人口统计学差异
IF 4.9 2区 医学
International Journal of Antimicrobial Agents Pub Date : 2025-02-20 DOI: 10.1016/j.ijantimicag.2025.107467
Hamid Reza Sodagari , Mohammad Nasim Sohail , Csaba Varga
{"title":"Temporal, regional, and demographic differences among antimicrobial-resistant domestic Campylobacter jejuni human infections across the United States, 2013–2019","authors":"Hamid Reza Sodagari ,&nbsp;Mohammad Nasim Sohail ,&nbsp;Csaba Varga","doi":"10.1016/j.ijantimicag.2025.107467","DOIUrl":"10.1016/j.ijantimicag.2025.107467","url":null,"abstract":"<div><div>Human infections with antimicrobial-resistant <em>Campylobacter jejuni</em> increase morbidity, mortality, hospitalization, and treatment costs. Resistance to antimicrobials recommended to treat campylobacteriosis has increased in the United States, despite the mitigating efforts of public health authorities. This study analyzed publicly available antimicrobial resistance (AMR) monitoring data collected by the National Antimicrobial Resistance Monitoring System (NARMS) to assess temporal, regional, and demographic differences in AMR among domestically acquired <em>C. jejuni</em> infections across the United States between 2013 and 2019. Mann–Kendall tests evaluated trends in AMR throughout the study period. Poisson regression models assessed differences in resistance to each antimicrobial class among the years, age groups, and regions. Among the 7624 <em>C. jejuni</em> isolates, high resistance was identified against tetracyclines (n = 3504; 45.96%; 95% CI = 44.84–47.09), and quinolones (n = 2093; 27.45%; 95% CI = 26.45–28.47). An increasing trend in resistance to quinolones (<em>P</em> = 0.07) and a decreasing trend for tetracyclines (<em>P</em> = 0.036) were identified. The rate of isolates that showed resistance to all antimicrobial classes except tetracyclines was significantly higher in the state of Connecticut. Resistance rates for all antimicrobials except aminoglycosides were higher among the 20–39 year age group. Regions and age groups with the greatest AMR rates were identified, which warrants further studies to identify individual and area-level risk factors. To mitigate the burden of antimicrobial-resistant <em>C. jejuni</em> infections, health authorities should focus on regions and age groups with the highest risk.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"65 5","pages":"Article 107467"},"PeriodicalIF":4.9,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143476560","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
The efficacy and underlying mechanisms of berberine in the treatment of recurrent Clostridioides difficile infection 小檗碱治疗复发性难辨梭菌感染的疗效及潜在机制。
IF 4.9 2区 医学
International Journal of Antimicrobial Agents Pub Date : 2025-02-20 DOI: 10.1016/j.ijantimicag.2025.107468
Li Wang , Teng Xu , Shi Wu , Chao Zhao , Haihui Huang
{"title":"The efficacy and underlying mechanisms of berberine in the treatment of recurrent Clostridioides difficile infection","authors":"Li Wang ,&nbsp;Teng Xu ,&nbsp;Shi Wu ,&nbsp;Chao Zhao ,&nbsp;Haihui Huang","doi":"10.1016/j.ijantimicag.2025.107468","DOIUrl":"10.1016/j.ijantimicag.2025.107468","url":null,"abstract":"<div><div>Recurrent <em>Clostridioides difficile</em> infection (rCDI) is a global health threat that has received considerable attention. Berberine (BBR), a natural pentacyclic isoquinoline alkaloid, has been used as a cost-effective treatment for intestinal infections in Asia for many years. However, the effect of BBR on rCDI is not clear. The efficacy and underlying mechanisms of BBR were evaluated in a vancomycin-dependent rCDI mouse model and an intestinal organoids model. The study findings showed that BBR treatment alleviated the severity of infection and increased survival rate in rCDI mice. Mechanistically, BBR alleviated intestinal epithelial damage with higher <em>Occludin</em> expression, suppressed some inflammatory pathways and reduced the level of inflammatory factors in both the caecum and serum. Moreover, 16S rRNA sequencing analysis indicated that BBR reshaped the gut microbiota by increasing the abundance of <em>Firmicutes</em> and reducing the abundance of <em>Proteobacteria</em>. At genus level, BBR treatment increased levels of <em>Blautia</em> and <em>Bilophila</em>, and reduced levels of <em>Proteus</em>. In addition, acetic acid, one of the short-chain fatty acids (SCFAs), was also increased after BBR treatment in rCDI mice. Collectively, BBR exerted a protective effect in rCDI via multiple underlying mechanisms and is a potential drug candidate for alleviating rCDI, but further research is needed in this area.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"65 5","pages":"Article 107468"},"PeriodicalIF":4.9,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143476575","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
Elimination of intracellular microbes using drug combination therapy and unveiling survival mechanism of host cells upon microbial invasion 利用药物联合治疗消除细胞内微生物,揭示微生物入侵后宿主细胞的生存机制。
IF 4.9 2区 医学
International Journal of Antimicrobial Agents Pub Date : 2025-02-20 DOI: 10.1016/j.ijantimicag.2025.107471
Zara Ahmad Khan , Sha-sha Song , Hongquan Xu , Mashaal Ahmad , Aiting Wang , Aynur Abdullah , Lai Jiang , Xianting Ding
{"title":"Elimination of intracellular microbes using drug combination therapy and unveiling survival mechanism of host cells upon microbial invasion","authors":"Zara Ahmad Khan ,&nbsp;Sha-sha Song ,&nbsp;Hongquan Xu ,&nbsp;Mashaal Ahmad ,&nbsp;Aiting Wang ,&nbsp;Aynur Abdullah ,&nbsp;Lai Jiang ,&nbsp;Xianting Ding","doi":"10.1016/j.ijantimicag.2025.107471","DOIUrl":"10.1016/j.ijantimicag.2025.107471","url":null,"abstract":"<div><div>Intracellular microbes are actively present in various tumor types in low biomass and play a major role in metastasis. Eliminating intracellular microbes on a cellular level with precision remains a challenge. To address this issue, we designed a screening pipeline to characterize intracellular microbes and their interaction with host cells. We used host and microbial in vitro lab-based constant and reproducible model, host as (mammalian cancer HeLa), and microbial strain as (Escherichia coli 25922). To study the pharmacological impact on intracellular bacterial load, we used antibiotics (ampicillin, roxithromycin, and ciprofloxacin) and chemotherapy drugs (doxorubicin and cisplatin) as external stimuli for both host and microbes. We found that increasing pharmacological stress does not increase microbial load inside the host cells. Eliminations of intracellular bacteria was done by using permutation orthogonal arrays (POA), whereby we acquired optimal drug combination in particular sequence of drugs, which reduced 90%–95% of the intracellular microbial load. Proteomic analysis revealed that upon invasion of Escherichia coli 25922, HeLa cells enriched ATP production pathways to activate intermediate filaments, which should be investigated closely via in vivo models.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"65 5","pages":"Article 107471"},"PeriodicalIF":4.9,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143476556","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
Interspecies differences in plasma protein binding of beta-lactam antibiotics β -内酰胺类抗生素血浆蛋白结合的种间差异。
IF 4.9 2区 医学
International Journal of Antimicrobial Agents Pub Date : 2025-02-20 DOI: 10.1016/j.ijantimicag.2025.107476
Hifza Ahmed , Christoph Dorn , Markus Zeitlinger
{"title":"Interspecies differences in plasma protein binding of beta-lactam antibiotics","authors":"Hifza Ahmed ,&nbsp;Christoph Dorn ,&nbsp;Markus Zeitlinger","doi":"10.1016/j.ijantimicag.2025.107476","DOIUrl":"10.1016/j.ijantimicag.2025.107476","url":null,"abstract":"<div><h3>Background</h3><div>Plasma protein binding (PPB) is a critical factor in drug therapy and understanding free compound exposure across preclinical and clinical species is vital for developing new antibiotics. Optimising beta-lactam dosing based on unbound drug concentrations has garnered significant interest, yet there are few data on how interspecies differences in protein binding affect the attainment of targeted unbound concentrations.</div></div><div><h3>Methods</h3><div>The aim of this study was to examine the protein binding of three beta-lactams, cefiderocol, ceftriaxone, and temocillin, using human, bovine, and rat plasma. Total and unbound beta-lactam concentrations were measured using ultrafiltration. An interspecies comparison of PPB was conducted to evaluate variability in protein binding across the different species.</div></div><div><h3>Results</h3><div>The study data showed that PPB was highest in human plasma for all three beta-lactam antibiotics tested. PPB for cefiderocol and ceftriaxone was higher in rat plasma than in bovine plasma, whereas PPB for temocillin was higher in bovine plasma than in rat plasma.</div></div><div><h3>Conclusion</h3><div>The study highlights substantial interspecies differences in the PPB of cefiderocol, ceftriaxone, and temocillin. The findings indicate the need for careful consideration of species-specific PPB in the optimisation of beta-lactam dosing and the development of new pharmaceuticals.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"65 5","pages":"Article 107476"},"PeriodicalIF":4.9,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143476559","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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