Antimicrobial Agents and Chemotherapy最新文献

{"title":"Modeling the potential effect of cabamiquine-pyronaridine for chemoprevention against <i>Plasmodium falciparum</i> malaria.","authors":"Lucy C Okell, Perrine Courlet, Filippo Venezia, Claude Oeuvray, Claudia Demarta, Thomas Spangenberg, Joseph Okebe","doi":"10.1128/aac.00434-26","DOIUrl":"https://doi.org/10.1128/aac.00434-26","url":null,"abstract":"<p><p>Preventive treatment (chemoprevention) is a key intervention for reducing the burden of <i>Plasmodium falciparum</i> malaria in children. The impact of the current widely used drug combination, sulfadoxine-pyrimethamine-amodiaquine (SP-AQ), is challenged by emerging drug resistance and adherence to multi-day dosing. Cabamiquine is a novel antimalarial with activity against liver- and blood-stage malaria parasites, administered as a single dose, and under development in combination with pyronaridine. We used mathematical modeling to translate early phase 1 clinical results into estimates of its potential impact as malaria chemoprevention. Pharmacokinetic-pharmacodynamic (PKPD) models of cabamiquine and pyronaridine were combined, assuming Bliss independence, to estimate time-varying protection against infection. PKPD results were incorporated into an established individual-based malaria transmission model to estimate the impact of seasonal malaria chemoprevention (SMC) across settings with differing transmission and seasonality. Cabamiquine-pyronaridine was predicted to provide protection of >95% for approximately 4 weeks, slightly outperforming SP-AQ even in children who fully adhere to SP-AQ treatment. Six weeks after treatment, cabamiquine-pyronaridine protection dropped for the regimens containing <200 mg cabamiquine, but the combination could still outperform SP-AQ at doses ≥200 mg. If deployed as SMC, a longer duration of protection may enable fewer, more widely spaced treatment cycles while maintaining impact, improving projected cost-effectiveness. Cabamiquine-pyronaridine shows strong potential as a next-generation single-dose chemoprevention regimen, supporting continued clinical development and evaluation.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":" ","pages":"e0043426"},"PeriodicalIF":4.2,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149134969","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":"<i>In vitro</i> in-depth characterization of emodepside in combination with key anthelmintic drugs on soil-transmitted helminths.","authors":"Anastasia Schärer, Cécile Häberli, Dominique Schlienger, Jennifer Keiser","doi":"10.1128/aac.00825-26","DOIUrl":"https://doi.org/10.1128/aac.00825-26","url":null,"abstract":"<p><p>Despite the enormous disease burden, treatments are limited for soil-transmitted helminthiasis. The handful of anthelmintic drugs suffer from variable and often insufficient efficacy against the pathogens. Resistance development, caused by high drug pressure, is an ongoing concern. New treatments are needed, and combination therapies may represent a promising therapeutic strategy. We explored emodepside as a partner in combination therapy and characterized drug-interaction effects with key anthelmintics <i>in vitro</i> against different soil-transmitted helminths (STHs). Drug-interaction studies were carried out in human recombinant cytochromes P450 assays. Combination studies revealed species-, stage-, and drug-dependent interaction profiles. For benzimidazole-emodepside combinations, potentiation was only observed against <i>Ancylostoma ceylanicum</i> larvae, while against adult stages, up to threefold potentiation or synergy (ΣFIC < 0.9) was observed for <i>Heligmosomoides polygyrus</i> and <i>Trichuris muris</i>, especially for albendazole and albendazole sulfoxide. Combinations of emodepside with macrocyclic lactones showed mostly strong synergy against <i>H. polygyrus</i> larvae (ΣFIC 0.06-2.52), while other species trended toward antagonism (ΣFIC >1.5). Against adult stages, potentiation or synergism was observed in <i>H. polygyrus</i> and <i>T. muris</i>, while against <i>Strongyloides ratti</i>, only the moxidectin-emodepside combination was synergistic (ΣFIC 0.69-0.99). For nAChR agonists, levamisole showed the strongest effect against <i>Necator americanus</i> larvae, while oxantel pamoate exhibited potentiation or synergistic effects across multiple species and life stages. CYP450 inhibition assays reveal no relevant drug-drug interactions. This study provides a thorough evaluation of emodepside as a combination partner against soil-transmitted helminths <i>in vitro</i>, paving the way for <i>in vivo</i> studies and ultimately a novel combination therapy with emodepside against STH infections.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":" ","pages":"e0082526"},"PeriodicalIF":4.2,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149135039","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":"Development and validation of a cefepime population pharmacokinetic model to guide treatment for patients with hospital-acquired pneumonia requiring renal replacement.","authors":"Adrian Valadez, Emma Harlan, Marc H Scheetz, Michael N Neely, Helen K Donnelly, Richard G Wunderink, Nathaniel J Rhodes","doi":"10.1128/aac.00900-26","DOIUrl":"https://doi.org/10.1128/aac.00900-26","url":null,"abstract":"<p><p>Cefepime is used in critically ill pneumonia patients, but dosing in renal replacement therapy (RRT) is complicated by altered renal function, extracorporeal removal, and variability in pulmonary epithelial lining fluid (ELF) exposure. We sought to develop an integrated model linking systemic, extracorporeal, and pulmonary cefepime pharmacokinetics in RRT. Pharmacokinetic (PK) data from critically ill adults receiving cefepime and requiring RRT were included. In a dedicated continuous RRT (CRRT) cohort (<i>n</i> = 8), pre- and post-filter plasma and effluent PK data were collected. Additional patients (<i>n</i> = 43) requiring RRT also contributed plasma and ELF samples. A non-parametric population PK model was developed using an 80/20 subject-level development-validation split. Covariate models assessed the impact of residual renal function, effluent flow rate, body size, and fixed intradialytic hemodialysis (HD) clearance. Monte Carlo simulations evaluated plasma and ELF target attainment across dosing strategies, weight strata, and minimum inhibitory concentrations (MICs). The final model jointly described systemic, extracorporeal, and pulmonary cefepime disposition using piecewise central volume, native clearance, linear effluent-flow-dependent CRRT clearance, fixed HD clearance, and ELF distribution. Simulations showed adequate plasma target attainment, whereas ELF attainment was sensitive to MIC, target, regimen, and body weight. Continuous infusions of 4 g/day provided adequate ELF attainment at MICs ≤4 mg/L. Plasma-based cefepime target attainment may overestimate pulmonary exposure during RRT, particularly at higher MICs, body weights, and <i>f</i>T>MIC targets. External validation and prospective studies are needed to refine pulmonary target estimates and determine whether plasma-guided Bayesian dosing can reliably ensure site-of-infection exposure.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":" ","pages":"e0090026"},"PeriodicalIF":4.2,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149134989","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":"Rapid broad-spectrum activity of molecular iodine against multidrug-resistant bacterial and fungal pathogens without residual staining.","authors":"Nandhana Nair, Arushi Sangal, Samuel Kim, Ilker Bayer, Victor Nizet, Elisabet Bjånes","doi":"10.1128/aac.00764-26","DOIUrl":"10.1128/aac.00764-26","url":null,"abstract":"<p><p>Povidone iodine (PVP-I) is a widely used topical antiseptic with broad antimicrobial activity, but its clinical utility can be limited by skin irritation, slow drying, and persistent staining of skin, textiles, and surfaces. Here, we evaluated reformulated molecular iodine (I₂) products as potential non-staining alternatives with retained or enhanced antimicrobial efficacy. Three I₂ formulations (soak, nasal antiseptic, and hand ointment) were tested against 17 clinically relevant bacterial and fungal pathogens, including multidrug-resistant organisms and emerging nosocomial pathogens. Antimicrobial performance was assessed by quantitative kill assays, textile staining studies, and persistence testing on dried surfaces. All three I₂ formulations demonstrated broad-spectrum activity against all organisms tested, with rapid 3-4 log₁₀ reduction in colony-forming units (CFUs) or >99.9% killing commonly achieved within 15 s; selected fungal species required longer contact times or higher concentrations for maximal activity. Potent activity was observed against major healthcare-associated bacterial pathogens, including <i>Staphylococcus aureus</i>, <i>Enterococcus faecalis</i>, <i>Klebsiella pneumoniae</i>, and <i>Pseudomonas aeruginosa</i>, as well as fungal pathogens including <i>Candida albicans</i> and <i>Candidozyma auris</i>. Compared with PVP-I, I₂ exhibited minimal residual staining and was readily removed from porous hospital textiles after brief water rinsing. Surface persistence studies further demonstrated sustained antimicrobial activity after drying. These findings indicate that I₂ retains the broad-spectrum efficacy of traditional iodophors while offering practical advantages in material compatibility and reduced residual staining. I₂ formulations may, therefore, represent useful alternatives for topical antisepsis and environmental decontamination in high-throughput healthcare settings where both antimicrobial performance and staining-related costs are important considerations.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":" ","pages":"e0076426"},"PeriodicalIF":4.2,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148910583","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":"Comparative adjuvant therapy to reduce vancomycin-associated nephrotoxicity in an animal model.","authors":"Yongqi Xiao, Nicholas S Teran, Cole S Hudson, Masayuki Nigo, Vincent H Tam","doi":"10.1128/aac.00887-26","DOIUrl":"10.1128/aac.00887-26","url":null,"abstract":"<p><p>Vancomycin is a mainstay antibiotic for serious gram-positive infections, but nephrotoxicity remains a major barrier to its optimal use. In this study, we compared the effectiveness of montelukast and zileuton as adjuvant strategies to reduce vancomycin-associated nephrotoxicity. Montelukast only had a marginal effect in vancomycin-treated animals, whereas zileuton significantly delayed nephrotoxicity onset. These findings support further formulation and dose-optimization studies to repurpose zileuton as a renal-protective adjuvant.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":" ","pages":"e0088726"},"PeriodicalIF":4.2,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148918363","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":"Effectiveness and safety of cefazolin vs antistaphylococcal penicillins for methicillin-susceptible <i>Staphylococcus aureus</i> bacteremia: a multicenter real-world evaluation using the international TriNetX database.","authors":"Natesan Ramsamy, Maïa Simon, Isabelle Adam, Gema Hernandez, Sarah Williford, Olivier Denquin, Céline Pulcini, Nathalie Thilly, Benjamin Lefèvre","doi":"10.1128/aac.01765-25","DOIUrl":"10.1128/aac.01765-25","url":null,"abstract":"<p><p>This study aimed to evaluate the effectiveness and safety of cefazolin vs antistaphylococcal penicillins (ASPs) in the treatment of methicillin-susceptible <i>Staphylococcus aureus</i> (MSSA) bacteremia. This phase IV, retrospective, comparative-effectiveness, multicenter study used data extracted from the international TriNetX analytics platform. Eligible patients developed monomicrobial MSSA bacteremia during hospitalization between 1 January 2015 and 31 December 2025 and received treatment with either cefazolin or ASPs. The primary outcome was all-cause mortality within 90 days. Safety outcomes included <i>Clostridioides difficile</i> infection within 90 days and renal, liver, allergic, and hematological disorders within 30 days. Survival analyses were conducted after propensity score matching. Among 110,275 patients with MSSA bacteremia identified, 3,908 (3.5%) met the inclusion criteria. After propensity score matching, 1,954 patients were included in each group. Treatment with cefazolin was associated with significantly reduced all-cause mortality within 90 days (9.7% vs 14.7%, HR = 0.620 [0.515-0.748]). Among the safety outcomes, <i>Clostridioides difficile</i> infection occurred less frequently in the cefazolin group (4.9% vs 7.20%, HR = 0.631 [0.482-0.827]). This real-world evaluation using the international TriNetX database suggests that, compared with ASPs, cefazolin is more effective and safer for the management of MSSA bacteremia.CLINICAL TRIALSThis study is registered with ClinicalTrials.gov as NCT07186894.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":" ","pages":"e0176525"},"PeriodicalIF":4.2,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148944260","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":"Reply to Srivastava and Gumbo, \"Rigor and reproducibility of hollow-fiber infection model for antiviral pharmacokinetics/pharmacodynamics studies\".","authors":"Lalitya M Sudarsono, Suzanne A M Wenker, Xuanlin Liu, Jorn Brink, Dirk-Jan van den Berg, J G C van Hasselt, Anne-Grete Märtson","doi":"10.1128/aac.00980-26","DOIUrl":"10.1128/aac.00980-26","url":null,"abstract":"","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":" ","pages":"e0098026"},"PeriodicalIF":4.2,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148886002","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":"Fluoroquinolone resistance-conferring <i>gyrA</i> variants alter the fitness cost and potentiate the resistance of the zoliflodacin resistance mutation <i>gyrB</i>^D429N in <i>Neisseria gonorrhoeae</i>.","authors":"Aditi Mukherjee, Sofia O P Blomqvist, David Helekal, Daniel H F Rubin, Bailey Bowcutt, Samantha G Palace, Yonatan H Grad","doi":"10.1128/aac.00766-26","DOIUrl":"10.1128/aac.00766-26","url":null,"abstract":"<p><p><i>Neisseria gonorrhoeae</i> is a major public health concern due to its high global prevalence and rapid evolution of antibiotic resistance. A first-in-class topoisomerase inhibitor, zoliflodacin (a spiropyrimidinetrione), recently received FDA approval for treatment of gonorrhea, but its potential for cross-resistance with another topoisomerase inhibitor, the fluoroquinolone antibiotic ciprofloxacin, remains poorly understood. Here, we investigated how genetic diversity in the fluoroquinolone target <i>gyrA</i> influences the resistance and fitness effects of the zoliflodacin resistance mutation <i>gyrB</i>^D429N. We constructed an isogenic panel of <i>N. gonorrhoeae</i> to determine how the resistance and fitness effects of the <i>gyrB</i>^D429N mutation are modulated by the most common ciprofloxacin resistance-associated variants in <i>gyrA</i>. In the presence of <i>gyrB</i>^D429N, the zoliflodacin minimum inhibitory concentration (MIC) was two- to fourfold higher in strains that also contained ciprofloxacin resistance-associated <i>gyrA</i> alleles, and the <i>gyrB</i>^D429N mutation reciprocally increased ciprofloxacin MICs of these strains three- to sixfold. The fitness cost of the <i>gyrB</i>^D429N mutation varied from modest to severe across <i>gyrA</i> backgrounds, with the largest cost in ciprofloxacin-resistant <i>gyrA</i>^91F/95G and <i>gyrA</i>^91F/95N backgrounds and comparatively minimal cost in the ciprofloxacin-resistant <i>gyrA</i>^91F/95A background. These results demonstrate the capacity for epistatic interactions among resistance-associated <i>gyrA</i> and <i>gyrB</i> mutations, underscoring the need for genomic surveillance to monitor high-risk combinations of resistance determinants as new therapies are deployed.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":" ","pages":"e0076626"},"PeriodicalIF":4.2,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148787607","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":"Development of a dosing algorithm integrating pharmacogenetic markers and inflammation for individualization of initial voriconazole maintenance doses.","authors":"Elodie Gautier-Veyret, Othilie Giannoni, Marc Manceau, Capucine Arrive, Sylvia Klomp, Matthieu Roustit, Fabien Lamoureux, Benjamin Hennart, Caroline Solas, Sarah Baklouti, Celine Verstuyft, Christelle Boglione-Kerrien, Jesse J Swen, Nicolas Pallet, Anette Veringa, Jan Willem C Alffenaar, Takahiro Yamada, Takafumi Naito, Françoise Stanke-Labesque, Charles Khouri","doi":"10.1128/aac.00278-26","DOIUrl":"10.1128/aac.00278-26","url":null,"abstract":"<p><p>Achieving early therapeutic trough concentrations (Cmin) of voriconazole (VRC) is crucial for treatment efficacy and to avoid side effects. Since VRC Cmin are influenced by numerous determinants, this multicenter retrospective study aimed to develop a multiparametric dosing algorithm for individualizing initial VRC maintenance doses. Individual data regarding VRC Cmin from adult patients and associated parameters (age, sex, underlying disease [presence of hematological disease/other], weight, dose, route of administration, indication: curative/prophylactic, cytochrome [CYP]2C19 and 3A genotypes, C-reactive protein [CRP], transaminases, bilirubin, and proton pump inhibitor treatment) were collected from six previously published studies and routine care data from seven laboratories (building cohort). A mixed-effects model predicting VRC Cmin was developed on this building cohort using a stepwise cross-validation procedure and then externally validated on an independent cohort (validation cohort). The building and validation cohorts included 977 VRC Cmin in 277 patients and 47 VRC Cmin in 33 patients, respectively. The initial model, which integrated VRC daily dose, CYP2C19 genotype, and CRP, was enriched by two additional covariates: age and underlying disease. The final model had an <i>R</i>² of 0.69 but tended to underestimate low VRC Cmin and overestimate high VRC Cmin. Finally, a formula derived from this final model was proposed and integrated into an Excel sheet to individualize initial VRC maintenance doses. The developed predictive model allowed for the creation of a multiparametric dosing algorithm for the individualization of initial VRC maintenance doses. The benefit of this algorithm will soon be evaluated in a prospective pilot study to improve initial VRC exposure.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":" ","pages":"e0027826"},"PeriodicalIF":4.2,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148944329","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 pharmacokinetics of piperacillin/tazobactam in critically ill pediatric patients.","authors":"Tavey Dorofaeff, María Patricia Hernández-Mitre, Xin Liu, Yarmarly C Guerra Valero, Mark G Coulthard, Jeffrey Lipman, Steven C Wallis, Diane L Maresco-Pennisi, Suzane L Parker, Jason A Roberts","doi":"10.1128/aac.00272-26","DOIUrl":"10.1128/aac.00272-26","url":null,"abstract":"<p><p>Piperacillin-tazobactam is commonly used in critically ill pediatric patients; however, standard dosing regimens may not reliably achieve maximally effective exposures in this population. To characterize the population pharmacokinetics of piperacillin-tazobactam in critically ill pediatric patients and evaluate the adequacy of commonly used dosing regimens, plasma concentrations were obtained around a single dose of piperacillin-tazobactam in critically ill pediatric patients aged 1 month to 12 years. A simultaneous population pharmacokinetic model for piperacillin and tazobactam was developed using nonlinear mixed-effects modeling. Monte Carlo simulations were performed to assess the probability of target attainment (PTA) for short, extended, and continuous infusion regimens across a range of ages and renal function states. Dosing adequacy was defined by simultaneous attainment of target drug exposures for piperacillin (100%fT > MIC) and tazobactam (85%fT > 2 mg/L). Thirty-one patients contributed 102 plasma samples, of which only 22.6% of patients achieved simultaneous piperacillin-tazobactam target exposures, considering a piperacillin MIC of 16 mg/L. Renal function and infusion duration were the primary determinants of attainment of target attainment. Standard short infusions frequently failed to achieve combined target exposures, particularly in patients with preserved renal function or augmented renal clearance (ARC). Extended infusions improved PTA, but remained suboptimal at higher MICs. Continuous infusion consistently achieved the highest target drug exposures across all simulated scenarios. Short intermittent piperacillin-tazobactam infusions and even extended infusions often result in suboptimal exposure in critically ill pediatric patients. Continuous infusion represents a rational dosing strategy to improve combined target attainment, particularly in children with preserved or ARC.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":" ","pages":"e0027226"},"PeriodicalIF":4.2,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148886034","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}