{"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}
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 , Lili Zhou , Danjie Wang , Xueyong Li , Rongqi Lin , Junnian Chen , Fuquan Tu , Yiqin Lin , Wenwei Wu , Maobai Liu , Hui Zhang , 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}
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 , 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","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}
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 , Mohammad Nasim Sohail , 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}
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 , Teng Xu , Shi Wu , Chao Zhao , 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}
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 , Sha-sha Song , Hongquan Xu , Mashaal Ahmad , Aiting Wang , Aynur Abdullah , Lai Jiang , 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}
{"title":"Interspecies differences in plasma protein binding of beta-lactam antibiotics","authors":"Hifza Ahmed , Christoph Dorn , 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}
Yan Li , Xu Liu , Hong Yao , XiaoYu Zhao , Leizi Chi , Cheng Yun Jin , Shangshang Qin
{"title":"The evolution of carbapenem-resistant Pseudomonas aeruginosa in the COVID-19 era: A global perspective and regional insights","authors":"Yan Li , Xu Liu , Hong Yao , XiaoYu Zhao , Leizi Chi , Cheng Yun Jin , Shangshang Qin","doi":"10.1016/j.ijantimicag.2025.107466","DOIUrl":"10.1016/j.ijantimicag.2025.107466","url":null,"abstract":"<div><h3>Objective</h3><div>Carbapenem-resistant <em>Pseudomonas aeruginosa</em> (CRPA) is a major contributor to healthcare-associated infections globally. The aim of this study was the impact of the COVID-19 pandemic on the genomic characteristics of <em>P. aeruginosa</em>, particularly clinical CRPA isolates.</div></div><div><h3>Methods</h3><div>Clinical data of each patient were collected from the clinical and medical record system. Whole-genome sequencing and bioinformatics analyses were performed to characterize the antibiotic resistance genes (ARGs) and evolutionary dynamics of these isolates. Furthermore, big data analysis was employed to elucidate the genomic characteristics of <em>P. aeruginosa</em> genomes across different periods on a global scale. Statistical analyses were applied to ensure the reliability of the findings.</div></div><div><h3>Results</h3><div>A total of 628 non-duplicate CRPA isolates were collected, with 256 isolates from before the COVID-19 pandemic and 372 during the pandemic. Only 26.59% of isolates carried carbapenemases, predominantly GES-14, and carbapenemase diversity decreased during the pandemic. However, the diversity of CRPA sequence types (STs) increased, with ST235 and ST244 emerging as the most prevalent clones. The Antibiotic resistance genes (ARGs) number carried by CRPA isolates significantly decreased during the pandemic (P < 0.05), with notable differences in 24 ARGs and 14 virulence factors (VFs) between prepandemic and pandemic periods (<em>χ</em><sup>2</sup> test, P < 0.05). O11 was the predominant serotype across all periods. Global analysis revealed a significant reduction in ARGs in strains from China and Australia (P < 0.01) during the pandemic. Analysis of the global epidemic clones ST244 and ST235 indicated that ARGs in ST244 <em>P. aeruginosa</em> increased significantly during the pandemic.</div></div><div><h3>Conclusions</h3><div>Our study highlights the critical need for ongoing surveillance of the evolutionary effects of the COVID-19 pandemic on clinical CRPA isolates, offering an essential theoretical basis for the development of effective and rational control strategies in clinical settings.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"65 5","pages":"Article 107466"},"PeriodicalIF":4.9,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143457676","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}
Christina Koenig , Andrew J. Fratoni , Yasmeen Abouelhassan , Jason A. Gluck , David P. Nicolau , Joseph L. Kuti
{"title":"Cefiderocol pharmacokinetics in critically-ill patients receiving extra-corporeal membrane oxygenation (ECMO)","authors":"Christina Koenig , Andrew J. Fratoni , Yasmeen Abouelhassan , Jason A. Gluck , David P. Nicolau , Joseph L. Kuti","doi":"10.1016/j.ijantimicag.2025.107465","DOIUrl":"10.1016/j.ijantimicag.2025.107465","url":null,"abstract":"<div><h3>Objective</h3><div>Critical illness and organ support such as extracorporeal membrane oxygenation (ECMO) may influence antimicrobial pharmacokinetics. This study investigated cefiderocol pharmacokinetics in critically-ill patients receiving ECMO to understand if standard dosing achieves optimal exposure.</div></div><div><h3>Methods</h3><div>Cefiderocol was prescribed according to approved package insert recommendations based on creatinine clearance (CL). Blood sampling was performed at steady-state. Protein binding was determined by ultrafiltration. Concentrations were fitted using the non-parametric adaptive grid algorithm in Pmetrics for R. The <em>f</em>T > MIC for each patient was assessed at MICs of 4, 8, and 16 mg/L. Total AUC<sub>24h</sub> was calculated to evaluate comparative exposure to non-ECMO patients.</div></div><div><h3>Results</h3><div>Five patients receiving 1.5 g q8h to 2 g q6h dosing regimens were enrolled. Three patients received venous-arterial and two veno-venous ECMO (mean flow rate of 3.9 [range: 2.7–4.9] L/min). A two-compartment model fitted the data best with mean ± standard deviation estimates for CL, volume of the central compartment (V), K<sub>12</sub>, and K<sub>21</sub> of 2.3 ± 0.5 L/h, 4.8 ± 2.3 L, 5.1 ± 2.8 h<sup>–1</sup>, and 3.9 ± 3.3 h<sup>–1</sup>, respectively. Mean protein binding was 41% (range: 31%–50%). Prescribed dosing regimens achieved 100% <em>f</em>T > MIC up to 16 mg/L for all patients, with a total steady-state AUC<sub>24h</sub> of 2501 (range: 1631–3276) mg/L·h.</div></div><div><h3>Conclusions</h3><div>These are the first data to describe cefiderocol pharmacokinetics in critically-ill patients undergoing ECMO. The currently labelled dosing recommendations based on creatinine CL in these patients were well tolerated and achieved 100% <em>f</em>T > MIC against susceptible bacteria and AUC exposures similar to values in non-ECMO patients.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"65 5","pages":"Article 107465"},"PeriodicalIF":4.9,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143457644","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}