{"doi":"10.1002/phar.2766","title":"Adequacy of cefepime concentrations in the early phase of critical illness: A case for precision pharmacotherapy","abstract":"STUDY OBJECTIVE: In critically ill patients, adequacy of early antibiotic exposure has been incompletely evaluated. This study characterized factors associated with inadequate cefepime exposure in the first 24 h of critical illness. DESIGN: Prospective cohort study. SETTING: Academic Medical Center. PATIENTS: Critically ill adults treated with cefepime. Patients with acute kidney injury or treated with kidney replacement therapy or extracorporeal membrane oxygenation were excluded. INTERVENTION: None. MEASUREMENTS: A nonlinear mixed-effects pharmacokinetic (PK) model was developed to estimate cefepime concentrations for each patient over time. The percentage of time the free drug concentration exceeded 8 mg/L during the first 24 h of therapy was calculated (%ƒT>8; appropriate for the susceptible breakpoint for Pseudomonas aeruginosa). Factors predictive of low %ƒT>8 were explored with multivariable regression. MAIN RESULTS: In the 100 included patients, a one-compartment PK model was developed with first-order elimination with covariates for weight and estimated glomerular filtration rate based on creatinine and cystatin C (eGFRSCr-CysC). The median (interquartile range) %ƒT>8 for cefepime in the first 24 h of therapy based on this model was 85% (66%, 100%). Less than 100% ƒT>8 during first 24 h of therapy occurred in 70 (70%) individuals. Lower Sequential Organ Failure Assessment score (p = 0.032) and higher eGFRSCr-CysC (p < 0.001) predicted a lower %ƒT>8. Central nervous system infection source was protective (i.e., associated with a higher %ƒT>8; p = 0.008). CONCLUSIONS: During early critical illness, cefepime concentrations were inadequate in a significant proportion of patients. Antimicrobial optimization is needed to improve the precision of pharmacotherapy in the critically ill patients.","journal":"Pharmacotherapy The Journal of Human Pharmacology and Drug Therapy","year":2023,"id":340571,"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":15,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9507,"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":536554,"name":"Jack Chang","orcid":"0000-0002-5645-0014","position":1,"is_corresponding":false},{"id":1076175,"name":"Matthew W. Bjergum","orcid":null,"position":2,"is_corresponding":false},{"id":309513,"name":"Ognjen Gajić","orcid":null,"position":3,"is_corresponding":false},{"id":738292,"name":"Paul J. Jannetto","orcid":"0000-0002-5629-439X","position":4,"is_corresponding":false},{"id":275035,"name":"Kristin C. Mara","orcid":"0000-0002-8783-0191","position":5,"is_corresponding":false},{"id":1075378,"name":"Laurie A. Meade","orcid":null,"position":6,"is_corresponding":false},{"id":339336,"name":"Andrew D. Rule","orcid":"0000-0003-0338-7784","position":7,"is_corresponding":false},{"id":1076176,"name":"Kathryn J. Vollmer","orcid":null,"position":8,"is_corresponding":false},{"id":339323,"name":"Marc H. Scheetz","orcid":"0000-0002-1091-6130","position":9,"is_corresponding":false},{"id":1075380,"name":"for the BLOOM Study Group","orcid":null,"position":10,"is_corresponding":false},{"id":307082,"name":"Erin F. Barreto","orcid":"0000-0002-0996-1487","position":0,"is_corresponding":true}],"reference_count":48,"raw_metadata":null,"created_at":"2026-07-19T01:10:58.548803Z","pmid":"36648390","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":[]}