TY - JOUR
T1 - Cefepime pharmacokinetics in critically ill children and young adults undergoing continuous kidney replacement therapy
AU - Pavia, Kathryn
AU - Hambrick, H. Rhodes
AU - Paice, Kelli
AU - Tang, Peter
AU - Punt, Nieko
AU - Kaplan, Jennifer
AU - Goldstein, Stuart L.
AU - Vinks, Alexander A.
AU - Mizuno, Tomoyuki
AU - Tang Girdwood, Sonya
N1 - Publisher Copyright:
© The Author(s) 2023. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please e-mail: [email protected].
PY - 2023/9
Y1 - 2023/9
N2 - 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.
AB - 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.
U2 - 10.1093/jac/dkad192
DO - 10.1093/jac/dkad192
M3 - Article
C2 - 37466170
AN - SCOPUS:85169847900
SN - 0305-7453
VL - 78
SP - 2140
EP - 2147
JO - The Journal of antimicrobial chemotherapy
JF - The Journal of antimicrobial chemotherapy
IS - 9
ER -