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. 2023 Sep 5;78(9):2140-2147.
doi: 10.1093/jac/dkad192.

Cefepime pharmacokinetics in critically ill children and young adults undergoing continuous kidney replacement therapy

Kathryn Pavia  1   2 , H Rhodes Hambrick  2   3 , Kelli Paice  1   2 , Peter Tang  4   5 , Nieko Punt  6   7 , Jennifer Kaplan  1   5 , Stuart L Goldstein  3   5 , Alexander A Vinks  2   5 , Tomoyuki Mizuno  2   5 , Sonya Tang Girdwood  2   5   8
Affiliations

Cefepime pharmacokinetics in critically ill children and young adults undergoing continuous kidney replacement therapy

Kathryn Pavia et al. J Antimicrob Chemother. .

Abstract

Objectives: Cefepime is an antibiotic commonly used to treat sepsis and is cleared by renal excretion. Cefepime dosing requires adjustment in patients with decreased kidney function and in those receiving continuous kidney replacement therapy (CKRT). We aimed to characterize cefepime PK in a diverse cohort of critically ill paediatric patients on CKRT.

Methods: Patients were identified from an ongoing pharmacokinetic/pharmacodynamic (PK/PD) study of beta-lactam antibiotics, and were included if they had received at least two cefepime doses in the ICU and were on CKRT for at least 24 h. PK parameters were estimated using MwPharm++ with Bayesian estimation and a paediatric population PK model. Target attainment was assessed as time of free cefepime concentrations above minimum inhibitory concentration (fT > 1× or 4 × MIC).

Results: Seven patients were included in the study (ages 2 to 20 years). CKRT indications included liver failure (n = 1), renal failure (n = 4) and fluid overload (n = 2). Total effluent flow rates ranged from 1833 to 3115 (mean 2603) mL/1.73 m2/h, while clearance was 2.11-3.70 (mean 3.0) L/h/70 kg. Effluent flows were lower, but clearance and fT > MIC were similar to paediatric data published previously. Using Pseudomonas aeruginosa MIC breakpoints, all patients had 100% of dosing interval above MIC, but only one had 100% of dosing interval above 4× MIC.

Conclusions: Since most patients failed to attain stringent targets of 100% fT > 4× MIC, model-informed precision dosing may benefit such patients.

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Figures

Figure 1.
Figure 1.
Correlation between total effluent flow rates and cefepime clearance. Linear regression model of the relationship between total effluent flow rate and total cefepime clearance. Model described as CL = 1.00 × Qef + 0.020; adjusted R2 = 0.77, P = 0.005. Qef = total effluent flow. Total effluent flow rate is the sum of dialysate flow rate, total substitution fluid rate and net ultrafiltrate rate. This figure appears in colour in the online version of JAC and in black and white in the print version of JAC.
See this image and copyright information in PMC

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