ArticleThe Journal of antimicrobial chemotherapy2023
Making the case for precision dosing: visualizing the variability of cefepime exposures in critically ill adults.
Article in The Journal of antimicrobial chemotherapy, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed, 4 citations in OpenAlex.
- Article
- Individualizing beta-lactam dosing in real-world patients: lessons from a pharmacist-led programme implementation and evaluation.JAC-antimicrobial resistance · 2026Article
- Cefepime Combined with Late-Generation β-Lactamase Inhibitors: Mechanisms of Action, In Vitro Activity, PK/PD Characteristics, Clinical Evidence and Resistance Mechanisms.Antibiotics (Basel, Switzerland) · 2026Review
- Cefepime and New Cefepime/Beta-Lactamase Inhibitor Combination for the Treatment of Gram-Negative Bacteria: Chemical Structure and Mechanism of Action, Microbiological Target, Clinical Use and PK/PD Characteristics.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Cystatin C-Guided Dosing Nomogram Improves Target Attainment for Cefepime in the Critically Ill.Critical care medicine · 2025Article
- Role of therapeutic drug monitoring in the treatment of multi-drug resistant tuberculosis.Journal of clinical tuberculosis and other mycobacterial diseases · 2024Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
objectiveTo investigate and describe the variability in cefepime exposures among 'real-world', critically ill patients by using population pharmacokinetic modelling and simulations, and with translation of these findings to visualizations.
methodsA cohort of adult medical ICU patients who received cefepime with therapeutic drug monitoring was studied. Two compartment models were developed to estimate cefepime clearance (Model 1) and simulate cefepime exposures among 1000 patients, each with identical creatinine clearance of 60 mL/min and receiving a regimen of cefepime 1 gram IV over 30 minutes, every 8 hours (Model 2). Variability in the relationship between cefepime clearance and creatinine clearance (CrCL) was visualized, and a random, representative sample of 10 simulated patients was utilized to illustrate variability in cefepime exposures.
resultsA total of 75 adult medical ICU patients (52% female) and 98 serum cefepime samples were included in the study. Population parameter estimates for cefepime displayed a wide range of variation in Model 1 (CV: 45% to 95%), with low bias at the individual level at 0.226 mg/L but high bias in the population model 10.6 mg/L. Model 2 displayed similar fits, demonstrating that correcting for individual patient creatinine clearance slightly improves the bias of the population model (bias = 4.31 mg/L). Among 10 simulated patients that a clinician would deem similar from a dosing perspective (i.e. equivalent creatinine clearance), maximum concentrations after three simulated doses varied more than 8-fold from 41.2 to 339 mg/L at the 5th and 95th percentiles, and clearance profiles were highly different.
conclusionCreatinine clearance estimates alone are inadequate for predicting cefepime exposures. Wide variations in cefepime exposure exist among ICU patients, even for those with similar kidney function estimates. Current population adjustment schemes based solely on creatinine clearance will result in unintended high and low exposures leading to safety and efficacy concerns, respectively.
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