Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 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.

PubMed Disclaimer

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

Similar articles

See all similar articles

Cited by

References

    1. Balamuth F, Weiss SL, Neuman MIet al. . Pediatric severe sepsis in US children’s hospitals. Pediatr Crit Care Med 2014; 15: 798–805. 10.1097/PCC.0000000000000225 - DOI - PMC - PubMed
    1. Gijsen M, Vlasselaers D, Spriet Iet al. . Pharmacokinetics of antibiotics in pediatric intensive care: fostering variability to attain precision medicine. Antibiotics 2021; 10: 1182. 10.3390/antibiotics10101182 - DOI - PMC - PubMed
    1. Hartman SJF, Brüggemann RJ, Orriëns Let al. . Pharmacokinetics and target attainment of antibiotics in critically ill children: a systematic review of current literature. Clin Pharmacokinet 2020; 59: 173–205. 10.1007/s40262-019-00813-w - DOI - PMC - PubMed
    1. Uchino S, Kellum JA, Bellomo Ret al. . Acute renal failure in critically ill patients: a multinational, multicenter study. JAMA 2005; 294: 813–8. 10.1001/jama.294.7.813 - DOI - PubMed
    1. Brivet FG, Kleinknecht DJ, Loirat Pet al. . Acute renal failure in intensive care units—causes, outcome, and prognostic factors of hospital mortality; a prospective, multicenter study. French study group on acute renal failure. Crit Care Med 1996; 24: 192–8. 10.1097/00003246-199602000-00003 - DOI - PubMed

Publication types