{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T13:07:44Z","timestamp":1784552864466,"version":"3.55.0"},"reference-count":48,"publisher":"Ovid Technologies (Wolters Kluwer Health)","content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Cefepime is widely used in intensive care units for the treatment of complicated gram-negative infections. Owing to its concentration-dependent neurological toxicity, cefepime is a candidate for therapeutic drug monitoring and model-informed precision dosing (MIPD), especially in critically ill patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>\n                      A monocentric, retrospective, before\u2012after study was performed, including all adult patients hospitalized in the intensive care unit who were administered cefepime (prolonged infusion) and for whom at least 2 cefepime plasma trough concentrations (C\n                      <jats:sub>min<\/jats:sub>\n                      ) were measured on separate days. Empirical therapeutic drug monitoring\u2013based dosing optimization was compared with MIPD. The main end point was a C\n                      <jats:sub>min<\/jats:sub>\n                      between 4 \u00d7 MIC (or 10 mg\/L if the MIC was unavailable) and 20 mg\/L. The odds of target attainment were modeled via a mixed-effect logistic model and the rate of target attainment via a spline model.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>A total of 254 patients were studied, of whom 113 were in the MIPD group and 141 in the control group. The proportion of compliance to dosage recommendation in the MIPD group was 70%. A total of 701 cefepime trough concentrations were analyzed. MIPD was nonsignificantly associated with higher odds of achieving concentrations within the therapeutic range (aOR 1.38 [0.87\u20132.19]) and significantly associated with lower odds of overexposure (aOR 0.59 [0.36\u20130.98]). The hazard ratio of target attainment was 1.1 [0.7\u20131.9] on day 1 and 1.6 [0.9\u20132.9] on day 7.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>Cefepime MIPD in the intensive care unit reduces the odds of overexposure when compared with empirical dosing. It may also improve the odds and rate of pharmacokinetic\/pharmacodynamic target attainment. Further research on clinical safety end points is needed to consolidate the present findings on the added value of MIPD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1097\/ftd.0000000000001503","type":"journal-article","created":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T13:00:24Z","timestamp":1784552424000},"update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":0,"title":["Evaluation of Model-Informed Precision Dosing of Cefepime in Critically Ill Patients: A French Before\u2013After Study"],"prefix":"10.1097","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0152-9171","authenticated-orcid":false,"given":"Giuseppe","family":"Balice","sequence":"first","affiliation":[{"name":"Universit\u00e9 Claude Bernard Lyon 1, Laboratoire de Biom\u00e9trie et Biologie Evolutive, CNRS UMR5558, Villeurbanne, France;"},{"name":"Hospices Civils de Lyon, Service Hospitalo-Universitaire de Pharmacotoxicologie, Lyon, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soizic","family":"Percevault","sequence":"additional","affiliation":[{"name":"Hospices Civils de Lyon, Service de Pharmacie, Groupement Hospitalier Nord, Lyon, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabine","family":"Cohen","sequence":"additional","affiliation":[{"name":"Hospices Civils de Lyon, Laboratoire de Pharmacologie, Pharmacog\u00e9n\u00e9tique et Toxicologie, Groupement Hospitalier Sud, Lyon, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Romain","family":"Garreau","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Claude Bernard Lyon 1, Laboratoire de Biom\u00e9trie et Biologie Evolutive, CNRS UMR5558, Villeurbanne, France;"},{"name":"Hospices Civils de Lyon, Service de Pharmacie, Groupement Hospitalier Nord, Lyon, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florent","family":"Wallet","sequence":"additional","affiliation":[{"name":"Hospices Civils de Lyon, Service d\u2019Anesth\u00e9sie-R\u00e9animation et M\u00e9decine Intensive, Groupement Hospitalier Sud, Lyon, France; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arnaud","family":"Friggeri","sequence":"additional","affiliation":[{"name":"Hospices Civils de Lyon, Service d\u2019Anesth\u00e9sie-R\u00e9animation et M\u00e9decine Intensive, Groupement Hospitalier Sud, Lyon, France; and"},{"name":"Universit\u00e9 Claude Bernard Lyon 1, ENS Lyon, Centre international de recherche en infectiologie, Inserm U1111, CNRS UMR5308, Lyon, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylvain","family":"Goutelle","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Claude Bernard Lyon 1, Laboratoire de Biom\u00e9trie et Biologie Evolutive, CNRS UMR5558, Villeurbanne, France;"},{"name":"Hospices Civils de Lyon, Service de Pharmacie, Groupement Hospitalier Nord, Lyon, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2026,7,20]]},"reference":[{"key":"R1-20260720","doi-asserted-by":"crossref","first-page":"471","DOI":"10.2165\/00003495-199447030-00007","article-title":"Cefepime. A review of its antibacterial activity, pharmacokinetic properties and therapeutic use","volume":"47","author":"Barradell","year":"1994","journal-title":"Drugs"},{"key":"R2-20260720","doi-asserted-by":"crossref","first-page":"2908","DOI":"10.1093\/jac\/dkac271","article-title":"Cefepime-induced neurotoxicity: systematic review","volume":"77","author":"Maan","year":"2022","journal-title":"J Antimicrob Chemother"},{"key":"R3-20260720","doi-asserted-by":"crossref","first-page":"929","DOI":"10.1007\/s40262-022-01137-y","article-title":"Clinical pharmacokinetics and pharmacodynamics of cefepime","volume":"61","author":"Pais","year":"2022","journal-title":"Clin Pharmacokinet"},{"key":"R4-20260720","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/j.ijantimicag.2011.11.002","article-title":"How to optimise antimicrobial prescriptions in the intensive care unit: principles of individualised dosing using pharmacokinetics and pharmacodynamics","volume":"39","author":"Roberts","year":"2012","journal-title":"Int J Antimicrob Agents"},{"key":"R5-20260720","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.ccc.2010.09.006","article-title":"Antimicrobial pharmacokinetic and pharmacodynamic issues in the critically ill with severe sepsis and septic shock","volume":"27","author":"Varghese","year":"2011","journal-title":"Crit Care Clin"},{"key":"R6-20260720","doi-asserted-by":"crossref","first-page":"1072","DOI":"10.1093\/cid\/ciu027","article-title":"DALI: defining antibiotic levels in intensive care unit patients: are current \u03b2-lactam antibiotic doses sufficient for critically ill patients?","volume":"58","author":"Roberts","year":"2014","journal-title":"Clin Infect Dis"},{"key":"R7-20260720","doi-asserted-by":"crossref","first-page":"1853","DOI":"10.1128\/AAC.47.6.1853-1861.2003","article-title":"Pharmacokinetics and pharmacodynamics of cefepime in patients with various degrees of renal function","volume":"47","author":"Tam","year":"2003","journal-title":"Antimicrob Agents Chemother"},{"key":"R8-20260720","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1016\/j.ijantimicag.2007.12.009","article-title":"Evaluation of area under the inhibitory curve (AUIC) and time above the minimum inhibitory concentration (T>MIC) as predictors of outcome for cefepime and ceftazidime in serious bacterial infections","volume":"31","author":"McKinnon","year":"2008","journal-title":"Int J Antimicrob Agents"},{"key":"R9-20260720","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1016\/j.ijantimicag.2017.04.023","article-title":"Defining the impact of severity of illness on time above the MIC threshold for cefepime in Gram-negative bacteraemia: a \u2018Goldilocks\u2019 window","volume":"50","author":"Miglis","year":"2017","journal-title":"Int J Antimicrob Agents"},{"key":"R10-20260720","doi-asserted-by":"crossref","first-page":"1127","DOI":"10.1007\/s00134-020-06050-1","article-title":"Antimicrobial therapeutic drug monitoring in critically ill adult patients: a Position Paper","volume":"46","author":"Abdul-Aziz","year":"2020","journal-title":"Intensive Care Med"},{"key":"R11-20260720","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1186\/s13054-024-04911-5","article-title":"Impact of attaining aggressive vs. conservative PK\/PD target on the clinical efficacy of beta-lactams for the treatment of gram-negative infections in the critically ill patients: a systematic review and meta-analysis","volume":"28","author":"Gatti","year":"2024","journal-title":"Crit Care"},{"key":"R12-20260720","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1002\/phar.2744","article-title":"Use of therapeutic drug monitoring to characterize cefepime-related neurotoxicity","volume":"43","author":"Venugopalan","year":"2023","journal-title":"Pharmacotherapy"},{"key":"R13-20260720","doi-asserted-by":"crossref","first-page":"4360","DOI":"10.1128\/AAC.01595-08","article-title":"High cefepime plasma concentrations and neurological toxicity in febrile neutropenic patients with mild impairment of renal function","volume":"54","author":"Lamoth","year":"2010","journal-title":"Antimicrob Agents Chemother"},{"key":"R14-20260720","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1186\/s13054-017-1856-1","article-title":"Cefepime-induced neurotoxicity: a systematic review","volume":"21","author":"Payne","year":"2017","journal-title":"Crit Care"},{"key":"R15-20260720","doi-asserted-by":"crossref","first-page":"106443","DOI":"10.1016\/j.ijantimicag.2021.106443","article-title":"Assessment of cefepime toxicodynamics: comprehensive examination of pharmacokinetic\/pharmacodynamic targets for cefepime-induced neurotoxicity and evaluation of current dosing guidelines","volume":"58","author":"Lau","year":"2021","journal-title":"Int J Antimicrob Agents"},{"key":"R16-20260720","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1016\/j.cmi.2019.06.028","article-title":"Cefepime neurotoxicity: thresholds and risk factors. A retrospective cohort study","volume":"26","author":"Boschung-Pasquier","year":"2020","journal-title":"Clin Microbiol Infect"},{"key":"R17-20260720","doi-asserted-by":"crossref","first-page":"928","DOI":"10.1002\/cpt.2202","article-title":"From therapeutic drug monitoring to model-informed precision dosing for antibiotics","volume":"109","author":"Wicha","year":"2021","journal-title":"Clin Pharmacol Ther"},{"key":"R18-20260720","doi-asserted-by":"crossref","first-page":"115421","DOI":"10.1016\/j.addr.2024.115421","article-title":"Model-informed precision dosing: state of the art and future perspectives","volume":"215","author":"Minichmayr","year":"2024","journal-title":"Adv Drug Deliv Rev"},{"key":"R19-20260720","doi-asserted-by":"crossref","first-page":"e02042-17","DOI":"10.1128\/AAC.02042-17","article-title":"Prospective trial on the use of trough concentration versus area under the curve to determine therapeutic vancomycin dosing","volume":"62","author":"Neely","year":"2018","journal-title":"Antimicrob Agents Chemother"},{"key":"R20-20260720","doi-asserted-by":"crossref","first-page":"ofae002","DOI":"10.1093\/ofid\/ofae002","article-title":"Model-informed precision dosing improves outcomes in patients receiving vancomycin for gram-positive infections","volume":"11","author":"Hall","year":"2024","journal-title":"Open Forum Infect Dis"},{"key":"R21-20260720","doi-asserted-by":"crossref","first-page":"1760","DOI":"10.1007\/s00134-022-06921-9","article-title":"Model-informed precision dosing of beta-lactam antibiotics and ciprofloxacin in critically ill patients: a multicentre randomised clinical trial","volume":"48","author":"Ewoldt","year":"2022","journal-title":"Intensive Care Med"},{"key":"R22-20260720","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1007\/s00134-023-06990-4","article-title":"Individualised dosing of antibiotics in ICU patients: timing, target and model selection matter","volume":"49","author":"Liebchen","year":"2023","journal-title":"Intensive Care Med"},{"key":"R23-20260720","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1007\/s00134-022-06969-7","article-title":"Advancing precision-based antimicrobial dosing in critically ill patients","volume":"49","author":"Cotta","year":"2023","journal-title":"Intensive Care Med"},{"key":"R24-20260720","doi-asserted-by":"crossref","first-page":"e00309-23","DOI":"10.1128\/aac.00309-23","article-title":"Cefepime population pharmacokinetics, antibacterial target attainment, and estimated probability of neurotoxicity in critically ill patients","volume":"67","author":"Bilal","year":"2023","journal-title":"Antimicrob Agents Chemother"},{"key":"R25-20260720","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1002\/jcph.1967","article-title":"Evaluation of individualized cefepime dosing strategy using population pharmacokinetics","volume":"62","author":"Mo","year":"2022","journal-title":"The J Clin Pharmacol"},{"key":"R26-20260720","doi-asserted-by":"crossref","first-page":"e00745-20","DOI":"10.1128\/AAC.00745-20","article-title":"Population pharmacokinetics and target attainment of cefepime in critically ill patients and guidance for initial dosing","volume":"64","author":"Al-Shaer","year":"2020","journal-title":"Antimicrob Agents Chemother"},{"key":"R27-20260720","doi-asserted-by":"crossref","first-page":"e02046-21","DOI":"10.1128\/aac.02046-21","article-title":"Cefepime precision dosing tool: from standard to precise dose using nonparametric population pharmacokinetics","volume":"66","author":"Alshaer","year":"2022","journal-title":"Antimicrob Agents Chemother"},{"key":"R29-20260720","doi-asserted-by":"crossref","first-page":"1027","DOI":"10.1007\/s40262-020-00873-3","article-title":"Development of population and bayesian models for applied use in patients receiving cefepime","volume":"59","author":"Liu","year":"2020","journal-title":"Clin Pharmacokinet"},{"key":"R30-20260720","doi-asserted-by":"crossref","first-page":"1066","DOI":"10.1002\/phar.2332","article-title":"Pharmacokinetics and pharmacodynamics of extended-infusion cefepime in critically ill patients receiving continuous renal replacement therapy: a prospective, open-label study","volume":"39","author":"Philpott","year":"2019","journal-title":"Pharmacother The J Hum Pharmacol Drug Ther"},{"key":"R31-20260720","doi-asserted-by":"crossref","first-page":"3148","DOI":"10.1128\/AAC.45.11.3148-3155.2001","article-title":"Pharmacokinetics of cefepime during continuous renal replacement therapy in critically ill patients","volume":"45","author":"Malone","year":"2001","journal-title":"Antimicrob Agents Chemother"},{"key":"R33-20260720","doi-asserted-by":"crossref","first-page":"e15059","DOI":"10.1111\/ctr.15059","article-title":"Impact of weight and creatinine adjustments on the accuracy of Cockcroft-gault equation in hematopoietic cell transplant patients","volume":"37","author":"Emanuel","year":"2023","journal-title":"Clin Transplant"},{"key":"R35-20260720","doi-asserted-by":"crossref","first-page":"1","DOI":"10.18637\/jss.v067.i01","article-title":"Fitting linear mixed-effects models using lme4","volume":"67","author":"Bates","year":"2015","journal-title":"J Stat Softw"},{"key":"R37-20260720","doi-asserted-by":"crossref","first-page":"1434","DOI":"10.21105\/joss.01434","article-title":"survPen: an R package for hazard and excess hazard modelling with multidimensional penalized splines","volume":"4","author":"Fauvernier","year":"2019","journal-title":"J Open Source Softw"},{"key":"R38-20260720","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1007\/s00134-013-3187-2","article-title":"Therapeutic drug monitoring-based dose optimisation of piperacillin and meropenem: a randomised controlled trial","volume":"40","author":"De Waele","year":"2014","journal-title":"Intensive Care Med"},{"key":"R39-20260720","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1007\/s00134-021-06609-6","article-title":"Effect of therapeutic drug monitoring-based dose optimization of piperacillin\/tazobactam on sepsis-related organ dysfunction in patients with sepsis: a randomized controlled trial","volume":"48","author":"Hagel","year":"2022","journal-title":"Intensive Care Med"},{"key":"R40-20260720","doi-asserted-by":"crossref","first-page":"7793","DOI":"10.1038\/s41598-024-58200-w","article-title":"Assessment of the practical impact of adjusting beta-lactam dosages based on therapeutic drug monitoring in critically ill adult patients: a systematic review and meta-analysis of randomized clinical trials and observational studies","volume":"14","author":"Guly\u00e1s","year":"2024","journal-title":"Sci Rep"},{"key":"R41-20260720","doi-asserted-by":"crossref","first-page":"1848","DOI":"10.1093\/cid\/ciac506","article-title":"Beta-lactam antibiotic therapeutic drug monitoring in critically ill patients: a systematic review and meta-analysis","volume":"75","author":"Pai Mangalore","year":"2022","journal-title":"Clin Infect Dis"},{"key":"R42-20260720","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1186\/s13054-022-04098-7","article-title":"Right dose, right now: bedside, real-time, data-driven, and personalised antibiotic dosing in critically ill patients with sepsis or septic shock \u2013 a two-centre randomised clinical trial","volume":"26","author":"Roggeveen","year":"2022","journal-title":"Crit Care"},{"key":"R43-20260720","doi-asserted-by":"crossref","first-page":"780","DOI":"10.1016\/j.clinbiochem.2012.03.030","article-title":"Population pharmacokinetics of four \u03b2-lactams in critically ill septic patients comedicated with amikacin","volume":"45","author":"Delattre","year":"2012","journal-title":"Clin Biochem"},{"key":"R44-20260720","doi-asserted-by":"crossref","first-page":"1171","DOI":"10.1177\/0091270006291035","article-title":"Population pharmacokinetic analysis and dosing regimen optimization of meropenem in adult patients","volume":"46","author":"Li","year":"2006","journal-title":"The J Clin Pharmacol"},{"key":"R45-20260720","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1093\/jac\/dkx330","article-title":"Maximally effective dosing regimens of meropenem in patients with septic shock","volume":"73","author":"Sj\u00f6vall","year":"2018","journal-title":"J Antimicrob Chemother"},{"key":"R46-20260720","doi-asserted-by":"crossref","first-page":"1281","DOI":"10.1007\/s00228-020-02922-z","article-title":"External evaluation of population pharmacokinetic models for continuous administration of meropenem in critically ill adult patients","volume":"76","author":"Wang","year":"2020","journal-title":"Eur J Clin Pharmacol"},{"key":"R47-20260720","doi-asserted-by":"crossref","first-page":"838205","DOI":"10.3389\/fphar.2022.838205","article-title":"External evaluation of population pharmacokinetic models to inform precision dosing of meropenem in critically ill patients","volume":"13","author":"Yang","year":"2022","journal-title":"Front Pharmacol"},{"key":"R48-20260720","doi-asserted-by":"crossref","first-page":"e02478-16","DOI":"10.1128\/AAC.02478-16","article-title":"Pilot study of a bayesian approach to estimate vancomycin exposure in obese patients with limited pharmacokinetic sampling","volume":"61","author":"Carreno","year":"2017","journal-title":"Antimicrob Agents Chemother"},{"key":"R49-20260720","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1097\/FTD.0000000000000490","article-title":"Hospitalized patients with and without hemodialysis have markedly different vancomycin pharmacokinetics: a population pharmacokinetic model-based analysis","volume":"40","author":"Goti","year":"2018","journal-title":"Ther Drug Monit"},{"key":"R50-20260720","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/j.jcrc.2021.12.013","article-title":"Therapeutic drug monitoring of meropenem and piperacillin-tazobactam in the Singapore critically ill population \u2013 a prospective, multi-center, observational study (BLAST 1)","volume":"68","author":"Chua","year":"2022","journal-title":"J Crit Care"},{"key":"R51-20260720","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1007\/s00134-014-3641-9","article-title":"Comparison of different equations to assess glomerular filtration in critically ill patients","volume":"41","author":"Carlier","year":"2015","journal-title":"Intensive Care Med"},{"key":"R52-20260720","doi-asserted-by":"crossref","first-page":"e00810-23","DOI":"10.1128\/aac.00810-23","article-title":"Population pharmacokinetic model of cefepime for critically ill adults: a comparative assessment of eGFR equations","volume":"67","author":"Barreto","year":"2023","journal-title":"Antimicrob Agents Chemother"}],"container-title":["Therapeutic Drug Monitoring"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.lww.com\/10.1097\/FTD.0000000000001503","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T13:00:30Z","timestamp":1784552430000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.lww.com\/10.1097\/FTD.0000000000001503"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,20]]},"references-count":48,"URL":"https:\/\/doi.org\/10.1097\/ftd.0000000000001503","relation":{},"ISSN":["0163-4356","1536-3694"],"issn-type":[{"value":"0163-4356","type":"print"},{"value":"1536-3694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,20]]},"assertion":[{"value":"2026-01-21","name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-05-13","name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}}]}}