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

Author:

Pavia Kathryn12,Hambrick H Rhodes23,Paice Kelli12,Tang Peter45,Punt Nieko67,Kaplan Jennifer15,Goldstein Stuart L35,Vinks Alexander A25,Mizuno Tomoyuki25,Tang Girdwood Sonya258ORCID

Affiliation:

1. Division of Critical Care Medicine, Cincinnati Children’s Hospital Medical Center , Cincinnati, OH , USA

2. Division of Clinical Pharmacology, Cincinnati Children’s Hospital Medical Center , Cincinnati, OH , USA

3. Division of Nephrology and Hypertension, Cincinnati Children’s Hospital Medical Center , Cincinnati, OH , USA

4. Division of Pathology and Laboratory Medicine, Cincinnati Children’s Hospital Medical Center , Cincinnati, OH , USA

5. Department of Pediatrics, University of Cincinnati College of Medicine , Cincinnati, OH , USA

6. University Medical Center Groningen, Department of Clinical Pharmacy and Pharmacology, University of Groningen , Groningen , The Netherlands

7. Medimatics , Maastricht , The Netherlands

8. Division of Hospital Medicine, Cincinnati Children’s Hospital Medical Center , Cincinnati, OH , USA

Abstract

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.

Funder

National Institutes of Health

Publisher

Oxford University Press (OUP)

Subject

Infectious Diseases,Pharmacology (medical),Pharmacology,Microbiology (medical)

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