Cefepime Precision Dosing Tool: from Standard to Precise Dose Using Nonparametric Population Pharmacokinetics

Cefepime is the second most common cephalosporin used in U.S. hospitals. We aim to develop and validate a cefepime population pharmacokinetic (PK) model and integrate it into a precision dosing tool for implementation. Two data sets (680 patients) were used to build the cefepime PK model in Pmetrics...

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Bibliographic Details
Published in:Antimicrobial agents and chemotherapy 2022-02, Vol.66 (2), p.e0204621
Main Authors: Alshaer, Mohammad H, Goutelle, Sylvain, Santevecchi, Barbara A, Shoulders, Bethany R, Venugopalan, Veena, Cherabuddi, Kartikeya, Liu, Jiajun, Kiel, Patrick J, Roberts, Jason A, Sime, Fekade Bruck, Scheetz, Marc H, Neely, Michael N, Peloquin, Charles A
Format: Article
Language:English
Subjects:
Adult
Anti-Bacterial Agents
Antimicrobial Chemotherapy
Cefepime
Cephalosporins
Child
Clinical Therapeutics
Humans
Life Sciences
Microbial Sensitivity Tests
Pharmaceutical sciences
Pharmacology
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Summary:Cefepime is the second most common cephalosporin used in U.S. hospitals. We aim to develop and validate a cefepime population pharmacokinetic (PK) model and integrate it into a precision dosing tool for implementation. Two data sets (680 patients) were used to build the cefepime PK model in Pmetrics, and three data sets (34 patients) were used for the validation. A separate application data set (115 patients) was used for the implementation and validation of a precision dosing tool. The model support points and covariates were used to generate the optimal initial dose (OID). Cefepime PK was described by a two-compartment model including weight and creatinine clearance (CrCl) as covariates. The median rate of elimination was 0.30 h (adults) and 0.96 h (children), the central volume of distribution was 13.85 L, and the rate of transfer from the central to the peripheral compartments was 1.22 h and from the peripheral to the central compartments was 1.38 h . After integration in BestDose, the observed versus predicted cefepime concentration fit using the application data set was excellent ( > 0.98), and the median difference between what was observed and what BestDose predicted on a second occasion was 4%. For the OID, cefepime at a 0.5- to 1-g 4-h infusion every 8 to 24 h (q8 to 24 h) with a CrCl of
ISSN:0066-4804
1098-6596
DOI:10.1128/aac.02046-21