International Journal of Antimicrobial Agents最新文献

{"title":"High-level ceftazidime-avibactam resistance by in-host evolution of blaKPC genes: Emergence of a novel blaKPC-102 variant and increase of blaKPC-33 copy number in Klebsiella pneumoniae strains from a lung transplantation recipient","authors":"Yulin Zhang ,&nbsp;Ziyao Li ,&nbsp;Huihui Shi ,&nbsp;Zichen Lei ,&nbsp;Dongya Pu ,&nbsp;Qi Liu ,&nbsp;Feilong Zhang ,&nbsp;Jiankang Zhao ,&nbsp;Xinmeng Liu ,&nbsp;Binghuai Lu ,&nbsp;Bin Cao","doi":"10.1016/j.ijantimicag.2025.107521","DOIUrl":"10.1016/j.ijantimicag.2025.107521","url":null,"abstract":"<div><h3>Objective</h3><div>KPC-producing <em>Klebsiella pneumoniae</em> (Kp) infections have become one of the major threats to public health in China. Recently, the emergence of ceftazidime-avibactam (CZA) resistance due to the <em>bla</em>_KPC mutations has been increasingly reported.</div></div><div><h3>Methods</h3><div>Two CZA-susceptible Kp strains (Kp36854 carrying <em>bla</em>_KPC-2 and Kp37523 without <em>bla</em>_KPC) and two CZA-resistant Kp strains (Kp38935 carrying double copies of <em>bla</em>_KPC-33 and Kp38097 carrying a newly identified <em>bla</em>_KPC-102 gene) were isolated from a lung-transplanted patient during CZA treatment. This study analyzed the within-host evolutionary dynamics of <em>bla</em>_KPC in KPC-Kp strains.</div></div><div><h3>Results</h3><div>Compared with KPC-2, KPC-33 possessed only a D179Y substitution while KPC-102 harbored both D179Y and Y241D substitutions. We constructed KPC-δ33 with only a Y241D substitution, which means the correction of the first mutation that is also present in KPC-33 (D179Y). Cloning and expression experiments showed that CZA-MIC value of <em>E. coli</em> DH5α/pKPC102 was 512 mg/L, while CZA-MIC values of both <em>E. coli</em> DH5α/pKPC-33 and <em>E. coli</em> DH5α/pKPC-δ33 were 32/4 mg/L. Enzymatic kinetic analysis revealed that KPC-2 demonstrated the highest catalytic efficiency to nitrocefin and meropenem, whereas KPC-33 displayed higher catalytic efficiency against ceftazidime compared to other tested KPC variants. Regarding avibactam, KPC-2 showed the highest sensitivity, while KPC-δ33 and KPC-102 were less sensitive.</div></div><div><h3>Conclusion</h3><div>High-level CZA resistance was mediated by the novel <em>bla</em>_KPC-102 and double copies of <em>bla</em>_KPC-33 gene, respectively, in two porin-deficient Kp strains from one patient. The CZA resistance resulting from <em>bla</em>_KPC mutation could be selected and evolved to be more diverse and heterogeneous within the host after CZA therapy. It is very essential to perform the surveillance of CZA-resistance for clinicians during treatment.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"66 2","pages":"Article 107521"},"PeriodicalIF":4.9,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143935608","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":"Synergistic activity of menadione in combination with colistin against colistin-susceptible and colistin-resistant Gram-negative bacteria","authors":"Jun Yang ,&nbsp;Huiying Yue ,&nbsp;Weifeng Wang ,&nbsp;Caiying Lin ,&nbsp;Chenchen Li ,&nbsp;Jiakuo Chen ,&nbsp;Jian-Hua Liu ,&nbsp;Yi-Yun Liu","doi":"10.1016/j.ijantimicag.2025.107523","DOIUrl":"10.1016/j.ijantimicag.2025.107523","url":null,"abstract":"<div><h3>Objective</h3><div>Antibiotic resistance poses a formidable challenge, especially with the emergence of multidrug-resistant Gram-negative bacteria. Colistin serves as a last-resort antibiotic to combat multidrug-resistance, but it is limited by its nephrotoxicity and rising resistance. This study introduces menadione, a synthetic form of vitamin K, as a potential adjuvant to enhance colistin's efficacy against both susceptible and resistant strains of Gram-negative bacteria.</div></div><div><h3>Methods</h3><div>Through checkerboard dilution assays, we demonstrate that menadione significantly lowers the MICs of colistin, with fractional inhibitory concentration indices ranging from 0.031 to 0.375. Furthermore, synergistic effects were confirmed via time–kill kinetics, indicating effective bacterial growth inhibition. The study also explores the mechanism underlying this synergy, revealing that menadione in combination with colistin disrupts the bacterial outer membrane, reduces the proton motive force and adenosine triphosphate content, and amplify the production of reactive oxygen species, contributing to bacterial cell death.</div></div><div><h3>Results</h3><div>Menadione was shown to prevent the evolution of colistin resistance.</div></div><div><h3>Conclusions</h3><div>This research highlights the potential of using menadione as a colistin adjuvant to combat antibiotic-resistant Gram-negative bacteria, providing a promising approach to extend the utility of existing antibiotics in clinical settings.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"66 2","pages":"Article 107523"},"PeriodicalIF":4.9,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144015028","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":"The potential of RNA-binding proteins as host-targeting antivirals against RNA viruses","authors":"Cleo Anastassopoulou ,&nbsp;Antonios-Periklis Panagiotopoulos ,&nbsp;Nikolaos Siafakas ,&nbsp;Athanasios Tsakris","doi":"10.1016/j.ijantimicag.2025.107522","DOIUrl":"10.1016/j.ijantimicag.2025.107522","url":null,"abstract":"<div><div>RNA-binding proteins (RBPs) are essential regulators of cellular RNA processes, including RNA stability, translation, and post-translational regulation. During viral infections, RBPs are key regulators of the viral cycle due to their interaction with both host and viral RNAs. Herein, we initially explore the roles of specific RBP families, namely heterogeneous nuclear ribonucleoproteins (hnRNPs), DEAD-box helicases, human antigen R (HuR), and the eukaryotic initiation factors of the eIF4F complex, in viral RNA replication, translation, and assembly. Next, we examine the potential of these RBPs as host-targeting antivirals against pandemic-prone RNA viruses that have been gaining momentum in recent years. Targeting RBPs could disrupt cellular homeostasis, leading to unintended effects on host cells; however, RBPs have been successfully targeted mainly in anticancer therapies, showcasing that their modulation can be safely achieved by drug repurposing. By disrupting key viral-RBP interactions or modulating RBP functions, such therapeutic interventions aim to inhibit viral propagation and restore normal host processes. Thus, conceivable benefits of targeting RBPs as alternative antiviral strategies include their broad-spectrum activity and potential for combination therapies with conventional antivirals, reduced or delayed resistance development, and concomitant enhancement of host immune responses. Our discussion also highlights the broader implications of leveraging host-directed therapies in an attempt to overcome viral resistance. Finally, we emphasise the need for continued innovation to refine these strategies for broad-spectrum antiviral applications.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"66 2","pages":"Article 107522"},"PeriodicalIF":4.9,"publicationDate":"2025-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143935953","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":"Drug resistance phenotypes of clinical Klebsiella pneumoniae isolates in the past 20 years in China: A systematic review and meta-analysis","authors":"Wei Wei ,&nbsp;Yueran Lian ,&nbsp;Yao Peng ,&nbsp;Biao Kan ,&nbsp;Zhenpeng Li ,&nbsp;Xin Lu","doi":"10.1016/j.ijantimicag.2025.107520","DOIUrl":"10.1016/j.ijantimicag.2025.107520","url":null,"abstract":"<div><h3>Objectives</h3><div>Monitoring the drug resistance phenotypes of <em>Klebsiella pneumoniae</em> is crucial in clinical practice. This study aims to evaluate the prevalence of drug resistance of clinical <em>K. pneumoniae</em> isolates in China over the past two decades using a systematic review and meta-analysis.</div></div><div><h3>Methods</h3><div>We systematically searched five databases for relevant articles published between January 1, 2003 and November 21, 2023. We assessed the resistance of clinical <em>K. pneumoniae</em> strains isolated in China over the past 20 years to 15 antibiotics, which were divided into three subgroups.</div></div><div><h3>Results</h3><div>A total of 177 studies derived from 160 articles were eligible for meta-analysis. The pooled antibiotic resistance rate ranged from 5.01% (for imipenem) to 96.03% (for ampicillin). The pooled rate of resistance to the carbapenem antibiotics imipenem and meropenem was relatively low, and subgroup analyses showed that these rates increased over time. The antibiotic resistance rate showed a geographic trend, being highest in central China and lowest in northwest China. The drug resistance rate was highest in strains isolated from specimens from patients with urinary tract infections.</div></div><div><h3>Conclusion</h3><div>This meta-analysis provides reliable data on the rate of antibiotic resistance of <em>K. pneumoniae</em> grouped according to isolation region, time, and source, which may be helpful for the selection of antibiotics for clinical treatment. Areas requiring specific attention include management of the use of carbapenem, improving the prevention and treatment of <em>K. pneumoniae</em> in patients with urinary tract infections, and control of transmission of strains from one region to another.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"66 2","pages":"Article 107520"},"PeriodicalIF":4.9,"publicationDate":"2025-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143964213","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":"Cellular and genetic changes during and after fluconazole exposure in Cryptococcus neoformans","authors":"Samah H. Albehaijani ,&nbsp;Tien Huynh ,&nbsp;Kylie J. Boyce","doi":"10.1016/j.ijantimicag.2025.107519","DOIUrl":"10.1016/j.ijantimicag.2025.107519","url":null,"abstract":"<div><div>The validity of genome replication is fundamental to fungal survival, and errors in this process can result in ploidy changes. These changes can have negative effects, such as developmental defects or reduced fitness, or positive effects such as fungal adaptation and resilience. In the fungal pathogen <em>Cryptococcus neoformans</em>, ploidy changes have been consistently observed in clinical populations, and isolates exposed to the antifungal drug fluconazole commonly exhibit chromosome 1 aneuploidy. Chromosomal and putative metabolic function changes due to drug exposure are not well studied and are important for understanding resistance. Objectives: This study examined the fluconazole influence on <em>C. neoformans</em> transient aneuploidy and identified any potential genetic pathways that may be implicated. Methods: The study investigated 30 genes predicted to have a role in transient aneuploidy, which are related to chromosome organisation, DNA damage checkpoints and stress signalling. Other factors including ploidy status (haploid, diploid, polyploid) and species were also investigated to observe commonalities for a universal drug treatment strategy. Results: Fluconazole treatment increased DNA content, cell size and chromosomal changes in the wildtype and mutants. When fluconazole was removed, permanent changes were observed and were highly variable in the wildtypes and the 30 mutants. Additionally, some mutants lacked chromosomal changes such as <em>tel1∆, mrc1∆</em> and <em>hog1∆</em>, highlighting the potential involvement in the aneuploidy process. Conclusions: These findings highlight that fluconazole influences the entire genome rather than specific chromosomes, which increases the heterogeneity in permanent changes after fluconazole removal. This heterogeneity may result in long–term consequences, including drug resistance.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"66 2","pages":"Article 107519"},"PeriodicalIF":4.9,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143935954","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":"Characterisation of the genome of a Klebsiella pneumoniae clinical strain carrying a novel KPC-205 variant associated with resistance to ceftazidime/avibactam and cefiderocol","authors":"Stefano Amadesi ,&nbsp;Annarita Mazzariol ,&nbsp;Gabriele Bianco ,&nbsp;Davide Gibellini ,&nbsp;Cristina Costa ,&nbsp;Paolo Gaibani","doi":"10.1016/j.ijantimicag.2025.107514","DOIUrl":"10.1016/j.ijantimicag.2025.107514","url":null,"abstract":"","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"66 2","pages":"Article 107514"},"PeriodicalIF":4.9,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143917774","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":"Rising threat of metallo-β-lactamase-producing Klebsiella oxytoca complex in Taiwan, 2013–2022","authors":"Yu-Tsung Huang ,&nbsp;Carl Jay Ballena Bregente ,&nbsp;Wei-Yu Hsu ,&nbsp;Chun-Hsing Liao ,&nbsp;Yao-Wen Kuo ,&nbsp;Jia-Arng Lee ,&nbsp;Tai-fen Lee ,&nbsp;Cheng-Yen Kao ,&nbsp;Po-Ren Hsueh","doi":"10.1016/j.ijantimicag.2025.107515","DOIUrl":"10.1016/j.ijantimicag.2025.107515","url":null,"abstract":"<div><h3>Objectives</h3><div>The emergence of metallo-beta-lactamases (MBLs) within the <em>Klebsiella oxytoca</em> complex (CRKO) poses a significant challenge in Taiwan, with so far incomplete characterization of species distribution and carbapenemase variants. This study aimed to elucidate the diversity, variants, and clinical presentations of CRKO isolates collected from 2013 to 2022.</div></div><div><h3>Methods</h3><div>We analyzed production of carbapenemases by the modified carbapenem inhibitory method (mCIM) and the NG test^TM CARBA-5. Confirmation of five common carbapenemases and multilocus sequence typing were determined by polymerase chain reaction and sequencing. Nanopore whole-genome sequencing was used for the species differentiation and plasmids analysis. We also evaluated the clinical characteristics of the CRKO-infected patients.</div></div><div><h3>Results</h3><div>Three species were identified: <em>K. michiganensis</em> (n = 102), <em>K. pasteurii</em> (n = 13), and <em>K. oxytoca</em> (n = 3). A majority of isolates (91.5%, n = 108) harbored at least one MBL gene, including <em>bla</em>_VIM-1 (n = 56), <em>bla</em>_IMP-8 (n = 26), and <em>bla</em>_NDM-1 (n = 19), with six isolates carrying dual carbapenemase genes. The <em>bla</em>_NDM-1 and <em>bla</em>_IMP-8 genes were located on IncFII(Yp) and IncA/C2 plasmids, respectively. Notably, 34.7% of isolates carried kleboxymycin gene clusters (KGC). Using CLSI and EUCAST criteria, 92.4% and 82.4% of isolates, respectively, were susceptible to cefiderocol. Among 92 infected patients, the 30-day mortality rate was 21.7%, associated with female gender, higher Charlson Comorbidity Index, higher Pitt bacteremia scores, presence of bacteremia, and inversely associated with KGC.</div></div><div><h3>Conclusion</h3><div>The high prevalence of CRKO carrying MBLs and the recent surge of the ST27-<em>bla</em>_NDM-1 genotype, poses significant treatment challenges and underscores the urgent need for enhanced surveillance in Taiwan.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"66 2","pages":"Article 107515"},"PeriodicalIF":4.9,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143917775","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":"Restoring tigecycline efficacy with lysine supplementation in tmexCD-toprJ-positive bacteria","authors":"Fulei Li ,&nbsp;Tianqi Xu ,&nbsp;Dan Fang ,&nbsp;Zhiqiang Wang ,&nbsp;Yuan Liu","doi":"10.1016/j.ijantimicag.2025.107511","DOIUrl":"10.1016/j.ijantimicag.2025.107511","url":null,"abstract":"<div><h3>Objectives</h3><div>Antimicrobial resistance is one of the most pressing challenges to global public health. Tigecycline, a last-resort antibiotic, has been undermined by the emergence of the <em>tmexCD1-toprJ1</em> gene cluster, a transferable RND-type efflux pump that confers resistance. Metabolite-enabled killing of antibiotic-resistant pathogens by antibiotics is an attractive strategy to tackle antibiotic resistance.</div></div><div><h3>Methods</h3><div>The potentiation of lysine to tigecycline was evaluated through a series of <em>in vitro</em> studies, including bacterial viability assays, time-kill kinetics analysis, persister assays, and biofilm eradication experiments, as well as <em>in vivo</em> assessment using a murine systemic infection model. The underlying mechanisms of action were further explored through transcriptomic profiling and biochemical validation.</div></div><div><h3>Results</h3><div>Herein, we show that lysine synergistically enhances the antibacterial efficacy of tigecycline against <em>tmexCD-toprJ</em>-positive bacteria. Mechanistic studies indicate that lysine supplementation promotes tigecycline uptake by upregulating ∆pH and disrupting membrane permeability. Transcriptomic analysis, coupled with phenotypic experiments, indicates that lysine not only triggers the generation of reactive oxygen species (ROS) by inhibiting hydrogen sulfide (H₂S) production but also downregulates energy metabolism pathways essential for efflux pump function. These effects promote intracellular accumulation of tigecycline, thereby overcoming <em>tmexCD-toprJ</em>-mediated resistance. In mouse infection models, the combination of lysine and tigecycline shows improved therapeutic efficacy compared to tigecycline monotherapy.</div></div><div><h3>Conclusion</h3><div>Collectively, our findings indicate that lysine can serve as a promising tigecycline booster to tackle infections caused by <em>tmexCD-toprJ</em>-positive bacteria.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"66 2","pages":"Article 107511"},"PeriodicalIF":4.9,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143929117","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":"Individualised amoxicillin-clavulanate dosing recommendations for critically ill children with augmented clearance after cardiac surgery","authors":"Evelyn Dhont ,&nbsp;Joseph F. Standing ,&nbsp;Emma Beel ,&nbsp;Thi V.A. Nguyen ,&nbsp;Ingrid Herck ,&nbsp;Harlinde Peperstraete ,&nbsp;Wim Vandenberghe ,&nbsp;Thierry Bové ,&nbsp;Kristof Vandekerckhove ,&nbsp;Nick Verougstraete ,&nbsp;Veronique Stove ,&nbsp;Johan Vande Walle ,&nbsp;Peter De Paepe ,&nbsp;Pieter A. De Cock","doi":"10.1016/j.ijantimicag.2025.107513","DOIUrl":"10.1016/j.ijantimicag.2025.107513","url":null,"abstract":"<div><h3>Objective</h3><div>Children who undergo cardiac surgery are prone to postoperative infections for which amoxicillin-clavulanate is a cornerstone antibiotic. Nevertheless, amoxicillin-clavulanate pharmacokinetics have not been studied in infants and children after cardiac surgery so far. Antibiotic exposure might be highly variable in this population due to the impact of growth, maturation, and specific pathophysiological and surgery-induced alterations. The objective of this study was to develop evidence-based amoxicillin-clavulanate dosing recommendations based on population pharmacokinetic analysis and probability of target attainment simulations in children after cardiac surgery.</div></div><div><h3>Methods</h3><div>Critically ill children (aged 1 day to 15 y) who underwent cardiac surgery and who were treated postoperatively with amoxicillin-clavulanate (30–60 mg/kg/6 h based on the amoxicillin component, infused in 30 min) were included. Up to five amoxicillin and clavulanate blood samples were collected per dose at predefined sampling times. Population pharmacokinetics analysis was performed using nonlinear mixed effects modelling software NONMEM.</div></div><div><h3>Results</h3><div>We collected 316 amoxicillin and 287 clavulanate blood samples from 37 patients. A three-compartment model for amoxicillin and a two-compartment model for clavulanate best described pharmacokinetics, with allometric weight scaling and maturation functions added a priori to scale for size and age. Clearance estimates were remarkably high, except in patients receiving vasopressors, which decreased clearance of amoxicillin-clavulanate by a third. Using a pharmacokinetic/pharmacodynamic target of 50%<em>f</em>T&gt;MIC of 8 mg/L, patients not on vasopressors warranted 4-hourly dosing to achieve adequate drug exposure due to augmented amoxicillin clearance. Only in patients treated with vasopressors was the standard 6-hourly dosing regimen sufficient to attain amoxicillin concentrations above the MIC for half of the dosing interval.</div></div><div><h3>Conclusions</h3><div>Current amoxicillin-clavulanate dosing regimens for critically ill children after cardiac surgery need to be updated to avoid subtherapeutic concentrations and clinical failure due to augmented clearance (ClinicalTrials.gov NCT02456974).</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"66 2","pages":"Article 107513"},"PeriodicalIF":4.9,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143922108","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":"Title Page & Editorial Board","authors":"","doi":"10.1016/S0924-8579(25)00073-1","DOIUrl":"10.1016/S0924-8579(25)00073-1","url":null,"abstract":"","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"65 6","pages":"Article 107516"},"PeriodicalIF":4.9,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143825414","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}