Adequacy of cefepime concentrations in the early phase of critical illness: A case for precision pharmacotherapy.

Autor: Barreto EF; Department of Pharmacy, Mayo Clinic, Rochester, Minnesota, USA., Chang J; Department of Pharmacy Practice, Chicago College of Pharmacy, Pharmacometrics Center of Excellence, Midwestern University, Downers Grove, Illinois, USA.; Department of Pharmacy, Northwestern Medicine, Chicago, Illinois, USA., Bjergum MW; Department of Laboratory Medicine & Pathology, Mayo Clinic, Rochester, Minnesota, USA., Gajic O; Division of Pulmonary Medicine, Mayo Clinic, Rochester, Minnesota, USA., Jannetto PJ; Department of Laboratory Medicine & Pathology, Mayo Clinic, Rochester, Minnesota, USA., Mara KC; Division of Clinical Trials and Biostatistics, Mayo Clinic, Rochester, Minnesota, USA., Meade LA; Anesthesia Clinical Research Unit, Mayo Clinic, Rochester, Minnesota, USA., Rule AD; Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota, USA.; Division of Epidemiology, Mayo Clinic, Rochester, Minnesota, USA., Vollmer KJ; Rutgers Institute for Pharmaceutical Industry Fellowships, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, New Jersey, USA., Scheetz MH; Department of Pharmacy Practice, Chicago College of Pharmacy, Pharmacometrics Center of Excellence, Midwestern University, Downers Grove, Illinois, USA.; Department of Pharmacy, Northwestern Medicine, Chicago, Illinois, USA.
Jazyk: angličtina
Zdroj: Pharmacotherapy [Pharmacotherapy] 2023 Nov; Vol. 43 (11), pp. 1112-1120. Date of Electronic Publication: 2023 Feb 02.
DOI: 10.1002/phar.2766
Abstrakt: 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.
(© 2023 Pharmacotherapy Publications, Inc.)
Databáze: MEDLINE
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