Antimicrobial Agents and Chemotherapy最新文献

{"title":"Synergistic antibacterial activity and prevention of drug resistance of daptomycin combined with fosfomycin against methicillin-resistant <i>Staphylococcus aureus</i>.","authors":"Qin Ai, Sailan Wang, Ziyan Chen, Shuai Zheng, Zaixing Chen, Na Zhang, Yaowen Li, Huiping Liu, Yanyan Liu, Jiabin Li, Xiaohui Huang","doi":"10.1128/aac.01609-24","DOIUrl":"https://doi.org/10.1128/aac.01609-24","url":null,"abstract":"<p><p>The combination of daptomycin and fosfomycin is attracting attention due to the rising resistance observed in methicillin-resistant <i>Staphylococcus aureus</i> (MRSA). Most studies indicate that this combination exhibits synergistic or additive antimicrobial activity against MRSA. However, its capacity to prevent resistance remains uncertain. In this study, we first investigated the antibacterial effect of daptomycin and fosfomycin on MRSA, followed by predicting MRSA resistance under the influence of different drugs using a resistance mutation selection window. Subsequently, we conducted preliminary analyses of drug resistance gene mutations in resistance mutants through gene sequencing technology. Additionally, we established an <i>in vitro</i> biofilm infection model to explore the internal tolerance associated with phenotypic alterations in biofilms and assess the combination's ability to prevent drug resistance. Combination drug sensitivity experiments demonstrated that daptomycin and fosfomycin synergistically enhanced antimicrobial effects against the tested strains. This combination reduced the mutant prevention concentration of each drug and narrowed the selection window for drug-resistant mutations. Sequencing results indicated that specific resistance genes were mutated in the single-drug mutants, while no mutations were detected in the combination. Furthermore, the combination exhibited stronger inhibition and removal of biofilm compared to single agents. In conclusion, the daptomycin-fosfomycin combination displays a synergistic antibacterial effect against MRSA and shows enhanced capacity to prevent bacterial resistance, likely attributed to its ability to inhibit resistance gene mutations and exhibit superior anti-biofilm activity.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":" ","pages":"e0160924"},"PeriodicalIF":4.1,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144324293","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":"Population pharmacokinetic/pharmacodynamic modeling to optimize aztreonam-avibactam dose regimens for adult patients.","authors":"Rujia Xie, Halley Rogers, Joseph W Chow, Elena Soto, Susan R Raber","doi":"10.1128/aac.01950-24","DOIUrl":"https://doi.org/10.1128/aac.01950-24","url":null,"abstract":"<p><p>Aztreonam-avibactam, a fixed-ratio (3:1) β-lactam/β-lactamase inhibitor combination, was approved in Europe in 2024 for adults with complicated intra-abdominal infection (cIAI), complicated urinary tract infection, hospital-acquired/ventilator-associated pneumonia, and other infections due to aerobic gram-negative organisms with limited treatment options. Pharmacokinetic data from two phase 3 trials were added to previous data to develop a simultaneous aztreonam and avibactam population pharmacokinetic model. The final model was used to simulate exposures by infection type and renal function and estimate the joint probability of pharmacodynamic target attainment (PTA) for phase 3 patients (aztreonam 60% <i>f</i>T >MIC_ATM-AVI of 8 mg/L and avibactam 50% <i>f</i>T >C_T of 2.5 mg/L). Additional simulations evaluated simplified loading doses, regimens for end-stage renal disease, and ceftazidime-avibactam + aztreonam regimens. The final model included 4,914 aztreonam plasma samples (431 subjects) and 18,222 avibactam plasma samples (2,635 subjects). A two-compartment model with zero-order infusion and first-order elimination best fit the data. Time-varying creatinine clearance was a key covariate on clearance for both drugs, whereas infection type was a key covariate on clearance and volume, with the lowest exposures observed in patients with cIAI. Final aztreonam-avibactam dose regimens achieved joint PTA 89% to >99% at steady state across renal function groups. Ceftazidime-avibactam + aztreonam dose regimens proposed by the Infectious Diseases Society of America (IDSA) achieved joint PTA <85% due to insufficient avibactam exposures. Approved aztreonam-avibactam dose regimens (single loading dose and regular maintenance doses, all 3 h intravenous infusions) are optimized for joint PTA across renal function groups and infection types.CLINICAL TRIALSThis study is registered with ClinicalTrials.gov as NCT03329092 and NCT03580044.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":" ","pages":"e0195024"},"PeriodicalIF":4.1,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144324362","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":"Erratum for Singh et al., \"Repurposing drugs to advance the treatment of Buruli ulcer\".","authors":"Sanjay Singh, Rie Yotsu, Eric Nuermberger, Shashikant Srivastava","doi":"10.1128/aac.00724-25","DOIUrl":"https://doi.org/10.1128/aac.00724-25","url":null,"abstract":"","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":" ","pages":"e0072425"},"PeriodicalIF":4.1,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144324361","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":"Treatment of <i>Staphylococcus aureus</i> with environmentally relevant concentrations of triclosan activates SaeRS-dependent virulence factor expression.","authors":"Jeffrey M Boyd, Erin E Price, Franklin Roman Rodriguez, Natalie Burchat, Javiera Norambuena, Ashley L DuMont, Victor J Torres, Harini Sampath","doi":"10.1128/aac.01728-24","DOIUrl":"https://doi.org/10.1128/aac.01728-24","url":null,"abstract":"<p><p>In the human pathogen <i>Staphylococcus aureus</i>, the two-component regulatory system SaeRS contributes to the expression of numerous virulence factors essential for pathogenesis. The kinase and phosphatase activities of SaeS are stimulated by several host and physiological signals, resulting in increased phosphorylation of the transcription factor SaeR and increased transcriptional activity of regulated promoters. It was recently demonstrated that the accumulation of fatty acids negatively impacts SaeS activity, decreasing titers of phosphorylated SaeP and transcriptional output. Triclosan is an effective antimicrobial that has been integrated as an ingredient in a variety of healthcare and consumer products. The chlorinated compound is recalcitrant to natural or biological transformations, resulting in environmental accumulation. At low concentrations, triclosan is a bacteriostatic inhibitor of enoyl-acetyl carrier protein reductase (FabI) of the type II fatty acid synthesis system (FASII), which is necessary for the elongation and synthesis of fatty acids. Herein, we demonstrate that the treatment of <i>S. aureus</i> with a growth-permissive concentration of triclosan alters the titers of cell-associated fatty acids and thereby functions as an activator of SaeRS. Triclosan-dependent activation of SaeRS subsequently resulted in increased transcription and expression of genes that code for virulence factors. These phenotypes are chemically reversed by the exogenous addition of oleic acid, which inactivates SaeRS, and genetically reversed by crippling the FakAB fatty acid kinase system, which generates phosphorylated fatty acids for incorporation into phospholipids. These findings present implications for the widespread use of triclosan as an antimicrobial agent in household products and its role as a persistent environmental pollutant.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":" ","pages":"e0172824"},"PeriodicalIF":4.1,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144324294","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":"Clinically applicable parasite viability assay for rapid assessment of antimalarial pharmacodynamic endpoints.","authors":"Mohamed Maiga, Sebastian G Wicha, Fatoumata Diallo, Issa Traoré, Abdoul Karim Samaké, Fanta Sogore, Ousmaila Diakité, François Dao, Djeneba Diallo, Aliou Traoré, Abdoulaye A Djimde, Thomas Spangenberg, Claudia Demarta-Gatsi, Laurent Dembele","doi":"10.1128/aac.01863-24","DOIUrl":"https://doi.org/10.1128/aac.01863-24","url":null,"abstract":"<p><p>Evaluating the efficacy of antimalarial drugs is crucial in the fight against malaria, as the parasiticidal effectiveness of these drugs often predicts their clinical success. Parasite Reduction Ratio (PRR) assay is the current method of choice for assessing antimalarial's ability to halt parasite recovery after treatment; however, it is time-consuming and resource-intensive, making it less ideal for low-resource or clinical settings. Recent advancements in parasite viability assessment, such as use of the MitoTracker (MT) which probes stain active mitochondria in live cells, provide a faster way to distinguish live from dead parasites using the flow cytometry, providing, thus, timely insights to inform treatment outcomes in clinical trials. In this study, the accuracy of direct viability assessment (DVA) of the parasite using MT staining was compared with the previously established PRR assay to evaluate the efficacy of four reference antimalarial drugs (dihydroartemisinin, chloroquine, atovaquone, and pyrimethamine) using <i>P. falciparum</i> 3D7 strain. Additionally, a mathematical model was developed to estimate key parameters, such as maximum killing rate and lag phase. The model yielded comparable values for these compounds across both assays reinforcing the reliability of the DVA assay for rapidly assessing antimalarial drug efficacy. In conclusion, the DVA relies on specialized equipment and technical expertise. However, it can emerge as an alternative to the PRR, offering a faster and more clinically suited approach for studies.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":" ","pages":"e0186324"},"PeriodicalIF":4.1,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144315825","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":"Cethromycin pharmacokinetics and pharmacodynamics for single dose cure of <i>Plasmodium berghei</i> liver stages.","authors":"Grace Kennedy, Rachel M West, Kristin Poti, Bryce Bobb, Matthew M Ippolito, Mark A Marzinke, Nikola Kaludov, David J Sullivan","doi":"10.1128/aac.00215-25","DOIUrl":"https://doi.org/10.1128/aac.00215-25","url":null,"abstract":"<p><p>Cethromycin combines a quinoline nucleus and a macrolide for broad-spectrum antibacterial and antiprotozoan activity. Here, we characterized the murine pharmacokinetics and <i>Plasmodium berghei</i> lifecycle stage pharmacodynamics for the cethromycin base. Liver pharmacokinetic studies in mice show peak mM drug concentrations in the liver with 20 hour sustained levels above 10 μM. Peak concentrations in the liver were double the lung and about 440 times that of plasma. Immunofluorescence imaging of <i>in vitro</i> cethromycin-treated infected hepatocytes shows complete ablation of the apicoplast. We observed complete cure of <i>P. berghei</i> liver-stage infection by a single oral dose of 60 mg/kg in mice, which is equivalent to the 5 mg/kg human dose of 300 mg a day used in bacterial pneumonia studies. Cethromycin at 60 mg/kg daily for 7 days was curative in the high parasitemic <i>P. berghei</i> mouse model. Both mosquito membrane feeding of <i>Plasmodium falciparum</i> gametocytes incubated with 20 μM cethromycin and oral dosing in mice demonstrated no decrease in oocyst numbers. Cethromycin has been evaluated for efficacy against bacterial pneumonia in more than 5,000 patients with good safety profiles. Cethromycin has potential for rapid clinical development for casual malaria prophylaxis and possibly radical cure of dormant liver <i>Plasmodium vivax</i>.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":" ","pages":"e0021525"},"PeriodicalIF":4.1,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144309471","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":"Combination of mitomycin C and low-dose metronidazole synergistically against <i>Clostridioides difficile</i> infection and recurrence prevention.","authors":"Jun-Jia Gong, I-Hsiu Huang, Yuan-Pin Hung, Yi-Wei Chen, Yun-Chien Lin, Jenn-Wei Chen","doi":"10.1128/aac.00515-25","DOIUrl":"https://doi.org/10.1128/aac.00515-25","url":null,"abstract":"<p><p><i>Clostridioides difficile</i> is an anaerobic, spore-forming pathogen responsible for illnesses ranging from mild diarrhea to life-threatening colitis. Current treatments rely on antibiotics such as vancomycin and metronidazole (MTZ), but high doses can disrupt gut microbiota, contributing to recurrent infections. Mitomycin C (MMC), a Food and Drug Administration-approved anticancer agent, is known to induce prophage activation in lysogenic bacteria. Given that over 70% of <i>C. difficile</i> strains harbor prophages, we evaluated MMC's potential to enhance antibiotic efficacy against <i>C. difficile</i> infection (CDI). <i>In vitro</i>, MMC synergized with MTZ to inhibit strain R20291 and clinical isolates of RT027 and RT078 while reducing the minimum bactericidal concentration of MTZ against biofilm-associated cells. Ex vivo assays using mouse fecal suspensions confirmed the enhanced killing effect of the combination. In a murine recurrence model, low-dose MTZ + MMC treatment significantly improved survival and reduced fecal spore counts compared to monotherapies or vancomycin. Importantly, the combination did not cause greater liver or kidney toxicity than other antibiotics and resulted in less colonic epithelial damage. Microbiota profiling revealed that MTZ + MMC better preserved gut microbial composition than standard treatments. These findings suggest that low-dose MTZ combined with MMC enhances antimicrobial efficacy while reducing toxicity and microbiota disruption, offering a promising strategy for CDI management.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":" ","pages":"e0051525"},"PeriodicalIF":4.1,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144309472","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":"Antimicrobial stewardship interventions reduce the time to the first antibiotic administration in septic patients in ICUs: regional multicenter study in 7 Latin American high-complexity hospitals.","authors":"Juan Carlos García-Betancur, Christian José Pallares, Natalia Restrepo-Arbeláez, Elsa De La Cadena, Wanda Cornistein, Paula Susana Byró, Diogo Boldim-Ferreira, Rodrigo Ahumada, Nicolás Valdebenito, Jorge Chaverri-Murillo, Paulo Castañeda-Méndez, Itaivet Toledo, Elsa Yasmín Vente, Luis Hercilla, Vanessa Moreno, Debra A Goff, María Virginia Villegas","doi":"10.1128/aac.01850-24","DOIUrl":"https://doi.org/10.1128/aac.01850-24","url":null,"abstract":"<p><p>Delay in the initial administration of antimicrobials is one of the strongest predictors for mortality for septic patients in the intensive care unit (ICU). Given the different logistics among hospitals for antibiotic administration, this delay can take hours. As antibiotic administration involves care coordination and the participation of different team members, education and the antimicrobial stewardship (AMS) program play a key role in reducing these times. This study evaluated the time between the initial prescription and the effective administration of antibiotics for ICU patients in seven Latin American hospitals, before (pre-) and after (post-I and post-II) the implementation of a tailored educational approach. After establishing a baseline measurement (pre-), we implemented a tailored educational intervention directed to the ICU team including nurses, specialists, pharmacists, and the members of the AMS team. Then, we conducted a post-intervention measurement after a 3 month period (post-I) and repeated it after a 1 year period (post-II). During the pre-interventional phase, the hang time varied between 88 and 178 min, reporting an adherence to the 1 hour bundle of 33.8%. For the post-I, it significantly reduced with time variations between 46 and 104 min, showing an increase of 54.9% in adherence. After 1 year, in post-II, a persistent effect of shorter administration time was observed, varying between 49 and 109 min, increasing the adherence to 59.6%. Our results highlight that an active and tailored multidisciplinary AMS educational process incorporating antibiotic hang time protocols and including multidisciplinary healthcare teams involved in coordinating sepsis care decreases the administration time of antibiotics in Latin American hospitals with limited resources.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":" ","pages":"e0185024"},"PeriodicalIF":4.1,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144315824","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":"Expression of 1,3-β-glucan synthase subunits in <i>Candida glabrata</i> is regulated by the cell cycle and growth conditions and at both transcriptional and post-transcriptional levels.","authors":"Irene Gonzalez-Jimenez, Mikhail V Keniya, Ariel A Aptekmann, Christopher Quinteros, Alexis Wilkerson, Amir Arastehfar, Farnaz Daneshnia, David S Perlin, Erika Shor","doi":"10.1128/aac.00500-25","DOIUrl":"https://doi.org/10.1128/aac.00500-25","url":null,"abstract":"<p><p>Fungal cell wall-synthesizing enzyme 1,3-β-glucan synthase (GS) is the target of the echinocandins, a frontline antifungal drug class. However, increasing echinocandin resistance due to mutations in GS has been observed in certain fungal pathogens, notably <i>Candida glabrata</i>, where GS is encoded by two homologous genes, <i>FKS1</i> and <i>FKS2</i>. Despite the importance of GS in the fungal life cycle and as a drug target, the regulation of its expression in culture and in the host is still poorly understood. In this study, we used a fluorescent transcriptional reporter, quantitative reverse-transcriptase PCR, protein analysis, and mining of RNA-seq data sets to examine the regulation of <i>C. glabrata</i> GS expression. We determined that <i>FKS1</i> and <i>FKS2</i> promoter activities peak during S-phase and that during exponential growth in culture, <i>FKS1</i> is expressed at higher levels than <i>FKS2</i>. Interestingly, although <i>FKS</i>2 mRNA expression appeared to be strongly induced in an <i>fks1∆</i> mutant, this calcineurin-mediated induction was not accompanied by increased <i>FKS2</i> promoter activity, suggesting post-transcriptional regulation. Examination of <i>FKS2</i> transcript across the ORF as well as Fks2 protein levels was consistent with post-transcriptional regulation. Finally, RNA-seq data mining revealed that, in contrast to vegetative growth, during the stationary phase and under host conditions, <i>FKS2</i> is expressed at equivalent or higher levels than <i>FKS1</i>. Together, these experiments revealed that in <i>C. glabrata,</i> the expression of both GS subunits is regulated transcriptionally by the cell cycle, that <i>FKS2</i> expression is regulated post-transcriptionally by calcineurin and <i>fks1∆</i>, and that in the host, <i>FKS2</i> may be the more abundant subunit.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":" ","pages":"e0050025"},"PeriodicalIF":4.1,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144309473","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":"No two are alike: on the role of <i>Klebsiella pneumoniae</i> permeability barriers in antibiotic susceptibility and persistence.","authors":"Inga V Leus, Helen I Zgurskaya","doi":"10.1128/aac.00085-25","DOIUrl":"https://doi.org/10.1128/aac.00085-25","url":null,"abstract":"<p><p><i>Klebsiella pneumoniae</i> and <i>Escherichia coli</i> cause a broad range of human infections with multidrug-resistant strains presenting serious therapeutic challenges in clinics. The discovery of new antibiotics effective against these pathogens is hindered because of effective drug permeability barriers comprising active efflux pumps acting synergistically with the low-permeability outer membrane. In this study, we characterized these barriers in <i>K. pneumoniae</i> American Type Culture Collection (ATCC) 43816, a hypervirulent strain broadly used in infection models. For this purpose, we constructed an efflux-deficient strain lacking the outer membrane channel TolC, which is required for activities of most resistance-nodulation-division efflux pumps, a hyperporinated strain producing a large non-specific pore in the outer membrane, and a double-compromised strain combining these two features. We next compared the contributions of the permeability barriers of ATCC 43816 to those of the laboratory <i>E. coli</i> BW25113 in antibiotic susceptibilities and persistence and in the intracellular accumulation of fluorescent probes. We identified significant differences between these two related species. Our results show that the outer membranes of <i>K. pneumoniae</i> and <i>E. coli</i> differ in their permeability to fluorescent probes and antibiotics and that <i>K. pneumoniae</i> is more effective in efflux of various compounds. We further found that nutrient-rich and minimal growth media do not affect permeation of all antibiotics in the same way and that the mechanism of antibiotic action and specific physicochemical properties of each compound play a defining role. Likewise, the roles of permeability barriers in the persistence of <i>K. pneumoniae</i> and <i>E. coli</i> vary, depending on the mechanism of antibiotic action, its external concentration, and the affected barrier.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":" ","pages":"e0008525"},"PeriodicalIF":4.1,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144309474","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}