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Using BEATLE trial data, a one-compartment model was fitted and clearance was influenced by Cockcroft-Gault creatinine clearance. Monte Carlo simulations compared extended/continuous regimens versus short infusions for achieving 100% ƒT>MIC and safety targets, supporting extended or continuous infusion particularly at higher CrCL or higher-MIC Gram-negative infections.",{"@graph":14,"@context":73},[15,34,56],{"@type":16,"itemListElement":17},"BreadcrumbList",[18,23,27,31],{"item":19,"name":20,"@type":21,"position":22},"https://docshare.wps.com","Home","ListItem",1,{"item":24,"name":25,"@type":21,"position":26},"https://docshare.wps.com/document/","Document",2,{"item":28,"name":29,"@type":21,"position":30},"https://docshare.wps.com/document/healthcare/","Healthcare",3,{"item":32,"name":10,"@type":21,"position":33},"https://docshare.wps.com/document/population-pharmacokinetics-and-optimized-dosing-of-piperacillin-tazobactam-in-hematological-patients-with-febrile-neutropenia/455943/",4,{"url":32,"name":10,"@type":35,"image":36,"author":41,"headline":10,"publisher":44,"fileFormat":47,"inLanguage":8,"description":12,"dateModified":48,"datePublished":49,"encodingFormat":47,"isAccessibleForFree":50,"interactionStatistic":51},"DigitalDocument",{"url":37,"@type":38,"width":39,"height":40},"https://docshare.wps.com/thumbnails/population-pharmacokinetics-and-optimized-dosing-of-piperacillin-tazobactam-in-hematological-patients-with-febrile-neutropenia/455943.png","ImageObject",300,407,{"name":42,"@type":43},"Quinn Holloway","Person",{"url":19,"name":45,"@type":46},"DocShare","Organization","application/pdf","2026-11-07","2026-09-30",true,{"@type":52,"interactionType":53,"userInteractionCount":55},"InteractionCounter",{"@type":54},"ViewAction",11,{"@type":57,"mainEntity":58},"FAQPage",[59,65,69],{"name":60,"@type":61,"acceptedAnswer":62},"What pharmacokinetic problem does this study address in febrile neutropenia patients?","Question",{"text":63,"@type":64},"It addresses pharmacokinetic alterations after piperacillin-tazobactam that may compromise drug exposure. These changes can affect both distribution and clearance, influencing target attainment.","Answer",{"name":66,"@type":61,"acceptedAnswer":67},"How was drug exposure optimized in this research?",{"text":68,"@type":64},"A population pharmacokinetic model of plasma piperacillin was built and Monte Carlo simulations evaluated extended/continuous versus 30-minute infusions. Optimization focused on probability of meeting 100% ƒT>MIC and a toxicity threshold (≥160 mg/L).",{"name":70,"@type":61,"acceptedAnswer":71},"Which patient factors and dosing strategies were most supported by the results?",{"text":72,"@type":64},"Extended or continuous infusions were superior for attaining 100% ƒT>MIC, especially when creatinine clearance was higher (>90 mL/min) or when infections involved less susceptible Gram-negative bacilli with higher MIC (8–16 mg/L). In such cases, continuous infusions of 12–16 g/day were likely needed.","https://schema.org",{"og:url":32,"og:type":75,"og:title":10,"og:site_name":45,"og:description":12},"article",{"robots":77,"canonical":32},"index,follow",{"doc_id":79,"site_id":7},455943,1790792392,{"code":4,"msg":82,"data":83},"success",[84,88,92,96,101,106,110,115,120,123,127],{"id":22,"doc_module":4,"doc_module_name":25,"category_name":85,"show_sort_weight":86,"slug":87},"Story & Novel",90,"story-novel",{"id":26,"doc_module":4,"doc_module_name":25,"category_name":89,"show_sort_weight":90,"slug":91},"Literature",80,"literature",{"id":33,"doc_module":4,"doc_module_name":25,"category_name":93,"show_sort_weight":94,"slug":95},"Exam",70,"exam",{"id":97,"doc_module":4,"doc_module_name":25,"category_name":98,"show_sort_weight":99,"slug":100},5,"Comic",60,"comic",{"id":102,"doc_module":4,"doc_module_name":25,"category_name":103,"show_sort_weight":104,"slug":105},6,"Technology",50,"technology",{"id":107,"doc_module":4,"doc_module_name":25,"category_name":29,"show_sort_weight":108,"slug":109},7,40,"healthcare",{"id":111,"doc_module":4,"doc_module_name":25,"category_name":112,"show_sort_weight":113,"slug":114},8,"Research & Report",30,"research-report",{"id":116,"doc_module":4,"doc_module_name":25,"category_name":117,"show_sort_weight":118,"slug":119},9,"Religion & Spirituality",20,"religion-spirituality",{"id":118,"doc_module":4,"doc_module_name":25,"category_name":121,"show_sort_weight":118,"slug":122},"World Cup","world-cup",{"id":124,"doc_module":4,"doc_module_name":25,"category_name":125,"show_sort_weight":124,"slug":126},10,"Lifestyle","lifestyle",{"id":128,"doc_module":4,"doc_module_name":25,"category_name":129,"show_sort_weight":97,"slug":130},19,"General","general",{"code":4,"msg":82,"data":132},{"doc_id":79,"user_id":133,"nickname":42,"user_avatar":134,"doc_module":4,"category_id":107,"category_name":29,"doc_title":10,"doc_description":12,"doc_content":135,"file_id":136,"file_url":137,"file_type":138,"file_size":139,"view_count":55,"is_deleted":4,"is_public":22,"is_downloadable":22,"audit_status":22,"page_count":140,"language":141,"language_code":8,"site_id":7,"html_lang":8,"table_of_contents":142,"faqs":143,"seo_title":144,"seo_description":12,"update_tm":145,"read_time":146,"preview_page_count":4},2336474466712,"https://ap-avatar.wpscdn.com/davatar_a8503ba1806abce46bf441b54a3ca4cd","| Antimicrobial Chemotherapy | Full-Length Text  \nPopulation pharmacokinetics and optimized dosing of piperacillin-tazobactam in hematological patients with febrile neutropenia  \nJulia Laporte-Amargos,1,2 Marta Ulldemolins,1,3 María Patricia Hernández-Mitre,3 Jason A. Roberts,3,4,5,6,7 Raul Rigo-Bonnin,8 Francisco Carmona-Torre,9 Maria Huguet,10 Pedro Puerta-Alcalde,11 Montserrat Arnan,2,12 Jose Luis del Pozo,9 Anna Torrent,10 Carolina García-Vidal,13 Anna Sureda,12 Alba Bergas,1 Enric Sastre-Escolà,1,2,13 Jordi Carratalà,1,2,13,14 Carlota Gudiol1,2,13,14,15  \nAUTHOR AFFILIATIONS See affiliation list on p. 11.  \nABSTRACT Hematological patients with febrile neutropenia receiving piperacillin-tazobactam may experience pharmacokinetic alterations that compromise drug exposure. We aimed to characterize the population pharmacokinetics of piperacillin in plasma and provide optimized dosing recommendations for this patient population. A population pharmacokinetic analysis was conducted in patients who received piperacillin-tazobactam as part of the BEATLE study, which compared the efficacy, safety, and pharma cokinetic/pharmacodynamic target attainment of β-lactams administered in extended infusion versus short 30 min infusion in adult hematological patients with febrile neutropenia. Monte Carlo simulations were performed to evaluate, for each dosing regimen, the probability of attaining (i) an efficacy target of unbound piperacillin concentrations above the minimum inhibitory concentration (MIC) of the bacteria for the entire dosing interval (100% ƒT>MIC), and (ii) a toxicity threshold of ≥ 160 mg/L. A total of 44 patients and 221 plasma concentrations were included. A one-compartment model best described piperacillin plasma pharmacokinetics, with Cockcroft-Gault creatinine clearance (CrCL) significantly influencing drug clearance. Dosing simulations showed that extended and continuous infusions were superior to short 30 min infusions in the attainment of 100% ƒT>MIC, even for bacteria with low to intermediate MIC (≤2–4 mg/L) . In patients with higher CrCL (>90 mL/min) or infections caused by less susceptible Gram-negative bacilli (MIC: 8–16 mg/L), only continuous infusions of 12–16 g/day were likely to achieve 100% ƒT>MIC. These findings support the use of extended or continuous infusions of piperacillin in the initial management of patients with febrile neutropenia, particularly in patients with higher CrCL or when infections caused by less susceptible pathogens, such as Pseudomonas aeruginosa, are suspected.  \nKEYWORDS febrile neutropenia, piperacillin-tazobactam, extended infusion, continuous infusion, pharmacokinetics, pharmacokinetics/pharmacodynamics, creatinine clearance  \nP iperacillin-tazobactam is frequently used as empirical treatment for febrile  \nneutropenia, in accordance with current international clinical guidelines (1, 2) . As a β-lactam antibiotic, piperacillin-tazobactam exhibits optimal bactericidal activity when free (unbound) drug concentrations are maintained above the minimum inhibitory concentration (MIC) of the bacteria for a specific percentage of the dosing interval (%ƒT>MIC) (3) . In the treatment of patients with severe infections, the β-lactam pharma cokinetic-pharmacodynamic (PK/PD) target associated with the best clinical outcomes remains debated, but emerging evidence suggests that a 100% ƒT>MIC may be necessary for the treatment of severe infections (4–6) . This 100% ƒT>MIC may also be necessary for  \nEditor James E. Leggett, Providence Portland Medical Center, Portland, Oregon, USA  \nAddress correspondence to Julia Laporte-Amargos, [j.laporte@bellvitgehospital.cat](j.laporte@bellvitgehospital.cat), or Marta Ulldemolins, [m.ulldemolinsgomez@uq.edu.au](m.ulldemolinsgomez@uq.edu.au).  \nThe authors declare no conflict of interest.  \nSee the funding table on p. 11.  \nThis study was presented at ESCMID Global 2025, Vienna, Austria and SEIMC (Spanish Society of Infectious Diseases and Clinical Microbiol","cbCaihXXzNS8eHBN","https://ap.wps.com/l/cbCaihXXzNS8eHBN","pdf",883276,13,"English","# Abstract\n# Key findings\n## Population pharmacokinetic model\n## Monte Carlo dosing simulations\n# Background and rationale\n## PK/PD targets (%ƒT>MIC, %ƒT>4×MIC)\n## Pathophysiology in febrile neutropenia\n# Aim of the study\n# Materials and methods\n## Study design, setting, and participants","[{\"question\":\"What pharmacokinetic problem does this study address in febrile neutropenia patients?\",\"answer\":\"It addresses pharmacokinetic alterations after piperacillin-tazobactam that may compromise drug exposure. These changes can affect both distribution and clearance, influencing target attainment.\"},{\"question\":\"How was drug exposure optimized in this research?\",\"answer\":\"A population pharmacokinetic model of plasma piperacillin was built and Monte Carlo simulations evaluated extended/continuous versus 30-minute infusions. Optimization focused on probability of meeting 100% ƒT\\u003eMIC and a toxicity threshold (≥160 mg/L).\"},{\"question\":\"Which patient factors and dosing strategies were most supported by the results?\",\"answer\":\"Extended or continuous infusions were superior for attaining 100% ƒT\\u003eMIC, especially when creatinine clearance was higher (\\u003e90 mL/min) or when infections involved less susceptible Gram-negative bacilli with higher MIC (8–16 mg/L). In such cases, continuous infusions of 12–16 g/day were likely needed.\"}]","Population pharmacokinetics and optimized dosing of piperacillin-tazobactam in hematological patients with febrile neutropenia | PDF",1790744741,33]