{"doi":"10.1093/jac/dkad106","title":"Population pharmacokinetics and target attainment analyses to identify a rational empirical dosing strategy for cefepime in critically ill patients","abstract":"OBJECTIVES: We aimed to identify rational empirical dosing strategies for cefepime treatment in critically ill patients by utilizing population pharmacokinetics and target attainment analysis. PATIENTS AND METHODS: A prospective and opportunistic pharmacokinetic (PK) study was conducted in 130 critically ill patients in two ICU sites. The plasma concentrations of cefepime were determined using a validated LC-MS/MS method. All cefepime PK data were analysed simultaneously using the non-linear mixed-effects modelling approach. Monte Carlo simulations were performed to evaluate the PTA of cefepime at different MIC values following different dose regimens in subjects with different renal functions. RESULTS: The PK of cefepime in critically ill patients was best characterized by a two-compartment model with zero-order input and first-order elimination. Creatinine clearance and body weight were identified to be significant covariates. Our simulation results showed that prolonged 3 h infusion does not provide significant improvement on target attainment compared with the traditional intermittent 0.5 h infusion. In contrast, for a given daily dose continuous infusion provided much higher breakpoint coverage than either 0.5 h or 3 h intermittent infusions. To balance the target attainment and potential neurotoxicity, cefepime 3 g/day continuous infusion appears to be a better dosing regimen than 6 g/day continuous infusion. CONCLUSIONS: Continuous infusion may represent a promising strategy for cefepime treatment in critically ill patients. With the availability of institution- and/or unit-specific cefepime susceptibility patterns as well as individual patients' renal function, our PTA results may represent useful references for physicians to make dosing decisions.","journal":"Journal of Antimicrobial Chemotherapy","year":2023,"id":362029,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":8,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9508,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":103450,"name":"C. Buddy Creech","orcid":"0000-0002-8276-9053","position":1,"is_corresponding":false},{"id":387420,"name":"Nan Wu","orcid":"0000-0002-1475-4503","position":2,"is_corresponding":false},{"id":350711,"name":"Roger L. Nation","orcid":"0000-0003-1492-8590","position":3,"is_corresponding":false},{"id":971992,"name":"Kenan Gu","orcid":"0009-0001-9621-8439","position":4,"is_corresponding":false},{"id":386446,"name":"Demet Nalbant","orcid":null,"position":5,"is_corresponding":false},{"id":663420,"name":"Natalia Jimenez‐Truque","orcid":"0000-0002-3065-9127","position":6,"is_corresponding":false},{"id":426896,"name":"William H. Fissell","orcid":"0000-0002-3960-3998","position":7,"is_corresponding":false},{"id":751947,"name":"Pratish C Patel","orcid":"0000-0001-8660-1023","position":8,"is_corresponding":false},{"id":1079113,"name":"Nicholas Fishbane","orcid":null,"position":9,"is_corresponding":false},{"id":1079112,"name":"Amy Watanabe","orcid":null,"position":10,"is_corresponding":false},{"id":1078581,"name":"Stephanie Rolsma","orcid":"0000-0002-7636-2222","position":11,"is_corresponding":false},{"id":1078582,"name":"Carl M. J. Kirkpatrick","orcid":"0000-0002-5715-1534","position":12,"is_corresponding":false},{"id":350709,"name":"Cornelia B. Landersdorfer","orcid":"0000-0003-0928-4743","position":13,"is_corresponding":false},{"id":332255,"name":"Patricia Winokur","orcid":"0000-0002-4826-1790","position":14,"is_corresponding":false},{"id":336076,"name":"Guohua An","orcid":"0000-0002-6498-7663","position":0,"is_corresponding":true}],"reference_count":24,"raw_metadata":null,"created_at":"2026-07-19T01:14:19.266946Z","pmid":"37071586","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}