Journal of Antimicrobial Chemotherapy最新文献

{"title":"Dalbavancin as chronic suppressive therapy in a patient undergoing monthly apheresis: a case report with therapeutic drug monitoring.","authors":"Carlo Pallotto, Margherita Albagini, Antonio D'Avolio, Alice Palermiti, Laura Curci, Daniela Francisci","doi":"10.1093/jac/dkaf173","DOIUrl":"10.1093/jac/dkaf173","url":null,"abstract":"","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":"2323-2324"},"PeriodicalIF":3.6,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144208533","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":"Optimization and improvement of the disc diffusion method for mucoid Pseudomonas aeruginosa.","authors":"Aixin Wang, Pei Liu, Yun Wu, Ruirui Ma, Wei Kang, Yingchun Xu, Yali Liu","doi":"10.1093/jac/dkaf179","DOIUrl":"10.1093/jac/dkaf179","url":null,"abstract":"<p><strong>Objectives: </strong>Antibiotic susceptibility test for mucoid Pseudomonas aeruginosa is challenging to conduct using the disc diffusion method based on Mueller-Hinton agar (MHA) due to its slow growth. The aim of this study is to compare the suitability of blood MHA versus MHA for disc diffusion antimicrobial susceptibility testing of mucoid P. aeruginosa and to determine the optimal reporting time.</p><p><strong>Methods: </strong>The study employed blood MHA for the disc diffusion method, using MHA as a control, and broth microdilution as a reference method. We tested 60 mucoid P. aeruginosa strains on both media types, with results assessed at 16, 18, 20, 24 and 48 hours.</p><p><strong>Results: </strong>The findings indicated that the interpretive categories determined by using blood MHA were comparable to those obtained with standard MHA. Notably, compared with the reference method, the categorical agreement for the blood MHA at multiple time points was significantly better than that for the standard MHA. For most tested antibiotics, results could be reliably interpreted at 20-24 hours by using blood MHA, with 24 hours being the optimal interpretation time. Results for quinolones particularly levofloxacin, were unacceptable when compared with reference methods. Additionally, the study found that blood agar and chocolate agar could help reduce the expression of mucus and accelerate its growth rate.</p><p><strong>Conclusions: </strong>In conclusion, the blood MHA can serve as a substitute for the MHA, with an optimal interpretation time of 24 hours.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":"2117-2125"},"PeriodicalIF":3.6,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144266301","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":"Characterization of Carbapenemase-producing Enterobacterales isolated from patients returning from Sub-Saharan Africa, France, 2015-2022.","authors":"Corentin Poignon, Laurent Dortet, Aurélien Birer, Inès Rezzoug, Cécile Emeraud, Delphine Girlich, Thierry Naas, Rémy A Bonnin, Agnès B Jousset","doi":"10.1093/jac/dkaf206","DOIUrl":"10.1093/jac/dkaf206","url":null,"abstract":"<p><strong>Objectives: </strong>The rise of carbapenemase-producing Enterobacterales (CPE) represents a major public health threat, as highlighted in numerous reports from international health organizations. However, a significant data gap remains for certain regions, particularly Sub-Saharan Africa (SSA). The aim of this study is to characterize CPE isolates from patients returning from SSA at both phenotypic and genomic levels.</p><p><strong>Methods: </strong>This retrospective study analysed 408 CPE received at the French National Reference Center between 2015 and 2022 and collected from patients returning from SSA. Antibiotic susceptibility testing and WGS were performed to assess phenotypic and genomic diversity.</p><p><strong>Results: </strong>Among 408 isolates collected from 29 countries, 55.1% produced oxacillinase-48 (OXA-48)-like carbapenemases, predominantly OXA-181, while 46.3% produced NDM (New Delhi metallo-β-lactamase), with NDM-5 being the major variant despite regional disparities. Temporal analysis revealed a trend shifting from OXA-48-like producers to NDM producers.Ceftazidime-avibactam was effective against 100% of non-metallo-β-lactamase producers. Cefiderocol, amikacin and colistin were effective on 73%, 86.7% and 98.4% of all CPEs respectively. Genomic analysis revealed a polyclonal dissemination among K. pneumoniae strains, whereas three E. coli clonal complexes were dominant (CC410, CC167, CC448).</p><p><strong>Conclusion: </strong>This study provides a comprehensive characterization of CPE isolated from patients returning from SSA. WGS allowed the identification of major circulating clones, their associated resistance genes, and their susceptibility to last-resort antibiotics.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":"2285-2294"},"PeriodicalIF":3.6,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144575467","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":"Outcomes of ceftriaxone 2 g versus 1 g daily in hospitalized patients with pneumonia: a nationwide retrospective cohort study.","authors":"Jumpei Taniguchi, Shotaro Aso, Hiroki Matsui, Kiyohide Fushimi, Hideo Yasunaga","doi":"10.1093/jac/dkaf189","DOIUrl":"10.1093/jac/dkaf189","url":null,"abstract":"<p><strong>Objectives: </strong>Ceftriaxone is widely used for hospitalized patients with community-acquired pneumonia, but its optimal dosage remains unclear.</p><p><strong>Methods: </strong>We retrospectively identified patients diagnosed with pneumonia between July 2010 and March 2022 from the Diagnosis Procedure Combination inpatient database in Japan. They were categorized into those receiving 2 or 1 g/day of ceftriaxone within the first 2 days of hospitalization. The primary outcome was 30-day in-hospital mortality. The secondary outcomes included overall adverse events (composite of biliary tract infection, Clostridioides difficile infection and allergic reactions) and each adverse event. A subgroup analysis was conducted for patients requiring mechanical ventilation. Propensity-score overlap-weighting analysis was used for comparisons.</p><p><strong>Results: </strong>Among the 471 694 eligible patients, 63.3% received 2 g/day and 36.7% received 1 g/day of ceftriaxone. Propensity-score analysis showed no significant difference in 30-day in-hospital mortality between the two groups [4.5% versus 4.6%; risk difference (RD), -0.1%; 95% confidence interval (CI), -0.3% to 0.1%; P = 0.219]. Overall adverse events were slightly higher in the 2 g/day group (1.9% versus 1.8%; RD, 0.1%; 95% CI, 0.0%-0.2%; P = 0.007), particularly the proportion of C. difficile infection. In the subgroup analysis of patients requiring mechanical ventilation, the 2 g/day regimen was associated with lower 30-day mortality (17.2% versus 20.4%; RD, -3.2%; 95% CI, -5.6% to -0.9%; P = 0.006).</p><p><strong>Conclusions: </strong>While a ceftriaxone dose exceeding 1 g/day may not be necessary for routine pneumonia treatment, a 2 g/day regimen may be considered for patients with severe pneumonia requiring mechanical ventilation.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":"2194-2202"},"PeriodicalIF":3.6,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12313466/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144258114","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}

{"title":"HIV-1 drug resistance among people living with HIV receiving dolutegravir-based anti-retroviral regimens in Uganda: a national laboratory-based survey using remnant viral load samples, 2022.","authors":"Christine Watera, Juliana de Fatima Da Silva, Grace Namayanja, Juliet Nkugwa Asio, Deogratius Ssemwanga, Sherri Pals, Miriam Nabukenya, Elliot Raizes, Maria Nanyonjo, Bill Elur, Esther Nazziwa, Grace Sanyu, Alisen Ayitewala, Mina Ssali, Cordelia Katureebe, Hudson Balidawa, Du-Ping Zheng, Clement Zeh, Stephanie Hackett, Christina Mwangi, Mary Naluguza, Jonathan Ntale, Edward Katongole Mbidde, Pontiano Kaleebu","doi":"10.1093/jac/dkaf180","DOIUrl":"10.1093/jac/dkaf180","url":null,"abstract":"<p><strong>Background and objectives: </strong>Uganda adopted dolutegravir as its preferred HIV treatment regimen in the national guidelines for treatment of HIV and AIDS in 2018. We conducted a survey to estimate dolutegravir resistance 4 years post-dolutegravir introduction in routine clinical settings. This was a cross-sectional survey to estimate the prevalence of HIV drug resistance (HIVDR) to dolutegravir among children and adults with viral non-suppression (VNS; ≥1000 copies/mL) receiving dolutegravir-based antiretroviral therapy for at least 9 months.</p><p><strong>Methods: </strong>We used remnant specimens from routine viral load monitoring stored at Central Public Health Laboratories during February-April 2022. Genotyping of the protease, reverse transcriptase and integrase regions of the HIV-1 pol gene was done using Thermo Fisher® kits and analysed using the Stanford HIVDR database. Weighted prevalences of HIVDR with 95% confidence intervals (CI) were estimated for adults (≥15 years) and children (0-14 years).</p><p><strong>Results: </strong>We randomly selected 857 specimens including 457 from adults and 400 from children for HIVDR testing from 3578 eligible specimens collected during February-April 2022. Five hundred and eleven (59.6%) were successfully genotyped in the integrase region. Intermediate- to high-level dolutegravir HIVDR prevalence was 3.9% (CI: 0.7, 7.1) for adults and 6.6% (CI: 3.5, 9.6) for children.</p><p><strong>Conclusion: </strong>HIVDR to dolutegravir was uncommon but present among both children and adults with VNS after 9 months or more of exposure to dolutegravir. Additional longitudinal outcomes data are needed to determine if adherence counselling for patients with VNS on dolutegravir regimens might improve outcomes.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":"2126-2134"},"PeriodicalIF":3.6,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12313458/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144248028","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}

{"title":"Evaluation of amoxicillin and benzylpenicillin therapy in early-onset neonatal sepsis: a pharmacometric external validation and simulation study.","authors":"Tom C Zwart, Dimitra Eleftheriou, Sophie J Jansen, Martha T van der Beek, Dirk Jan A R Moes, Swantje Völler, Vincent Bekker","doi":"10.1093/jac/dkaf191","DOIUrl":"10.1093/jac/dkaf191","url":null,"abstract":"<p><strong>Background and objectives: </strong>Early-onset sepsis (EOS) poses a significant morbidity and mortality risk in neonates, for which early diagnosis and adequate antibiotic therapy is crucial. Amoxicillin and benzylpenicillin combined with aminoglycosides are often prescribed empirically for neonatal EOS but optimal dosing regimens are lacking. To evaluate the pharmacokinetics (PK), PTA and toxicity of amoxicillin and benzylpenicillin in (pre)term neonates with EOS, and define optimal dosing regimens.</p><p><strong>Methods: </strong>One hundred forty-five neonates [gestational age (GA): 24-42 weeks] with EOS treated with intravenous amoxicillin or benzylpenicillin, dosed as per the Dutch Pediatric Formulary (DPF), were included. Amoxicillin and benzylpenicillin were quantified in left-over samples during the first 48 h of life. First, the performance of nine paediatric amoxicillin and benzylpenicillin population PK models was evaluated. Second, the most appropriate models were used for simulation-based PTA and toxicity analyses, evaluating eight international neonatal dosing regimens. Third, simulation-based dose optimization was conducted.</p><p><strong>Results: </strong>The Bijleveld (amoxicillin) and Padari (benzylpenicillin) models adequately described the obtained PK data (N = 252). For amoxicillin, all regimens showed >90% PTA up to 100%fT > MIC but displayed GA-dependent toxicity potential (concentrations >110 mg/L), the DPF regimen excepted. By contrast, all benzylpenicillin regimens showed suboptimal PTA, often accompanied with GA-dependent toxicity potential (concentrations >50 mg/L). Simulations indicated GA-based intermittent dosing or continuous infusion as options to further optimize benzylpenicillin therapy.</p><p><strong>Conclusions: </strong>(Pre)term neonates with EOS can be adequately treated with amoxicillin dosed as per the DPF regimen. By contrast, further optimization is warranted for benzylpenicillin, for which GA-based intermittent dosing or continuous infusion pose potential alternatives.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":"2214-2225"},"PeriodicalIF":3.6,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12313450/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144309948","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}

{"title":"Development of a ribavirin dosing regimen in transplant recipients with chronic hepatitis E virus infection: a population pharmacokinetic and -dynamic model.","authors":"Midas B Mulder, Martijn van Noort, Robert A de Man, Nassim Kamar, Joep de Bruijne, Marjolein Knoester, Hans Blokzijl, Thomas Vanwolleghem, Laurence Roosens, Jacques Izopet, Peggy Gandia, Annemiek A van der Eijk, Herold J Metselaar, Maurice J Ahsman, Tamara J van Steeg, Dennis A Hesselink, Brenda C M de Winter","doi":"10.1093/jac/dkaf183","DOIUrl":"10.1093/jac/dkaf183","url":null,"abstract":"<p><strong>Objectives: </strong>The optimal ribavirin dosing regimen for the treatment of chronic hepatitis E virus (HEV) infection in solid organ transplant (SOT) is unknown. We modelled ribavirin plasma concentrations versus virologic response and haemoglobin concentrations.</p><p><strong>Patients and methods: </strong>Data were collected in a retrospective, multicentre study of adult SOT recipients with chronic HEV infection treated with ribavirin between September 2009 and November 2019. Population pharmacokinetic and pharmacodynamic analyses were conducted using nonlinear mixed-effects modelling. Simulations were performed to select the most suitable RBV dosing regimen considering efficacy and safety.</p><p><strong>Results: </strong>In total, 107 chronically HEV-infected SOT recipients with 305 ribavirin plasma levels, 592 viral load and 443 haemoglobin concentrations were included. Sustained virologic response was achieved in 68.2% of the subjects. Owing to a low IC50, the decline in viral load was independent of ribavirin concentration and dose, whereas haemoglobin decreased with increasing ribavirin concentration and dose. A model-supported ribavirin dose for 180 days of 600 mg/day and kidney function (eGFR) ≥ 60 mL/min/1.73 m2, 400 mg/day and eGFR 30-59 mL/min/1.73 m2 and 200 mg/day and eGFR ≤30 mL/min/1.73 m2 showed good efficacy and low toxicity.</p><p><strong>Conclusions: </strong>This study constitutes a valuable first step in determining the optimal ribavirin treatment regimen for chronic HEV infections in SOT recipients. Our model suggests a lower dose of ribavirin and longer treatment duration compared to the suggested dosing regimen in the EASL Clinical Practice Guidelines on HEV infection. Implementing our dosing regimen in clinical practice will allow for lower toxicity rates, improved tolerability and equal efficacy in chronically HEV-infected SOT recipients.</p><p><strong>Clinical trial number: </strong>MEC-2018-1326.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":"2158-2168"},"PeriodicalIF":3.6,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12313452/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144528089","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}

{"title":"Clinical outcomes and the impact of treatment modalities in children with carbapenem-resistant Enterobacteriaceae bloodstream infections: a retrospective cohort study from a Tertiary University Hospital-right to reply-author's response.","authors":"Gulhadiye Avcu","doi":"10.1093/jac/dkaf201","DOIUrl":"10.1093/jac/dkaf201","url":null,"abstract":"","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":"2332-2333"},"PeriodicalIF":3.6,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144484476","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":"Penicillin-susceptible ST398 with strong biofilm-forming ability poses a significant threat to osteoarticular infections.","authors":"Ye Jin, Wangxiao Zhou, Weiwei Chen, Yonghong Xiao","doi":"10.1093/jac/dkaf208","DOIUrl":"10.1093/jac/dkaf208","url":null,"abstract":"<p><strong>Background: </strong>Osteoarticular infections (OAIs), primarily caused by Staphylococcus aureus (both MSSA and MRSA), pose significant clinical challenges due to their heterogeneity and complexity.</p><p><strong>Objective: </strong>To investigate the epidemiology, clinical characteristics and bacterial features of S. aureus strains isolated from OAI patients treated at a major tertiary hospital in China over a 9-year period, with a focus on biofilm formation and colonization potential.</p><p><strong>Methods: </strong>A total of 178 S. aureus isolates (56.8% MSSA and 43.2% MRSA) were analyzed using whole-genome sequencing, antibiotic susceptibility testing, biofilm formation assays and phylogenetic analysis. A murine nasal colonization model and in vitro adhesion assays using A549 human epithelial cells were employed to evaluate colonization and adherence capabilities.</p><p><strong>Results: </strong>Penicillin-susceptible Staphylococcus aureus (PSSA) showed a significant rise during the study period, particularly within clonal complex ST398, which exhibited enhanced biofilm-forming capabilities. Phylogenetic analysis revealed minimal transmission events, suggesting independent cases. Comparative genetic analysis demonstrated distinct human-adaptive features in MRSA and MSSA-ST398 strains. PSSA-ST398 strains exhibited superior biofilm formation and increased adherence to human epithelial cells and murine nasal cavities compared with penicillin-resistant counterparts, indicating a potential advantage in colonization and persistence.</p><p><strong>Conclusions: </strong>Penicillin-susceptible ST398 strains, particularly those with strong biofilm-forming capabilities, which increase their persistence in clinical settings, complicating treatment and eradication efforts, represent a significant threat to OAIs. Despite being penicillin-susceptible, these strains may still pose challenges due to their biofilm-mediated resistance and potential for chronic infection.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":"2295-2304"},"PeriodicalIF":3.6,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144540322","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":"Establishment and validation of downsized hollow-fibre infection model and pharmacokinetics/pharmacodynamics analysis of VAN on Enterococcus faecium.","authors":"Yukitaka Hayashi, Mishu Takahashi, Moe Sasaki, Kenta Suzuki, Yuki Mizukami, Xiaoxi Liu, Yuki Enoki, Kazuaki Taguchi, Tetsuo Yamaguchi, Kazuhiro Tateda, Kazuaki Matsumoto","doi":"10.1093/jac/dkaf175","DOIUrl":"10.1093/jac/dkaf175","url":null,"abstract":"<p><strong>Objectives: </strong>This study clarified the target values of VAN against Enterococcus faecium using pharmacokinetics/pharmacodynamics (PK/PD) analysis and compared a downsized hollow fibre infection model (HFIM) with a conventional HFIM.</p><p><strong>Methods: </strong>VAN was administered subcutaneously and blood concentrations were measured to calculate the PK parameters. PD studies were performed in an infected mouse model by administering VAN at doses ranging from 25 to 400 mg/kg based on PK parameters. PK/PD parameters correlated with antimicrobial efficacy were determined, and a target value of 2 log10 kills was calculated. The efficacy of VAN against E. faecium was evaluated by reproducing the VAN PK in the plasma at doses that achieved the target value using conventional and novel downsized HFIMs.</p><p><strong>Results: </strong>PK/PD analysis showed that fAUC/minimum inhibitory concentration (MIC) demonstrated the most relevant index, with a target value of 249 to achieve a 2 log10 kill. Blood concentrations of 750 mg VAN every 12 h (equivalent to 260 fAUC/MIC) were simulated well with both HFIMs. Changes in E. faecium caused by continuous exposure to VAN resulted in a reduction in bacterial counts by ∼6.0 log10 kill 168 h after the start of treatment in both models. Downsizing reduced the extracapillary space volume, circulating medium, amount of drugs used and infectious waste. The total cost of the downsized cartridge system was approximately half that of the conventional model system.</p><p><strong>Conclusions: </strong>We established a downsized HFIM and demonstrated its viability as a cost-effective and environmentally sustainable in vitro PK/PD. The findings highlighted its potential as a future PK/PD analysis standard.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":"2092-2099"},"PeriodicalIF":3.6,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12313456/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144173851","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}