Finding the Dose for Ceftolozane-Tazobactam in Critically Ill Children with and without Acute Kidney Injury
Butragueño-Laiseca, Laura (Instituto de Salud Carlos III)
Troconiz, Iñaki (Instituto de Investigación Sanitaria de Navarra)
Grau, Santiago (Universitat Autònoma de Barcelona. Departament de Farmacologia, de Terapèutica i de Toxicologia)
Campillo, Núria (Hospital del Mar (Barcelona, Catalunya))
García-González, Xandra (Hospital General Universitario Gregorio Marañón)
Padilla, Belén (Hospital General Universitario Gregorio Marañón)
Fernández, Sarah N. (Instituto de Salud Carlos III)
Santiago, María José (Instituto de Salud Carlos III)

Date:	2020
Abstract:	Background: Ceftolozane-tazobactam is a new antibiotic against multidrug-resistant pathogens such as Pseudomonas aeruginosas. Ceftolozane-tazobactam dosage is still uncertain in children, especially in those with renal impairment or undergoing continuous renal replacement therapy (CRRT). Methods: Evaluation of different ceftolozane-tazobactam dosing regimens in three critically ill children. Ceftolozane pharmacokinetics (PK) were characterized by obtaining the patient's specific parameters by Bayesian estimation based on a population PK model. The clearance (CL) in patient C undergoing CRRT was estimated using the prefilter, postfilter, and ultrafiltrate concentrations simultaneously. Variables such as blood, dialysate, replacement, and ultrafiltrate flow rates, and hematocrit were integrated in the model. All PK analyses were performed using NONMEM v. 7. 4. Results: Patient A (8 months of age, 8. 7 kg) with normal renal function received 40 mg/kg every 6 h: renal clearance (CL) was 0. 88 L/h; volume of distribution (Vd) Vd = 3. 45 L, Vd = 0. 942 L; terminal halflife (t) = 3. 51 h, dosing interval area under the drug concentration vs. time curve at steady-state (AUC) 397. 73 mg × h × L −1. Patient B (19 months of age, 11 kg) with eGFR of 22 mL/min/1. 73 m 2 received 36 mg/kg every 8 h: CL = 0. 27 L/h; Vd = 1. 13 L; Vd = 1. 36; t = 6. 62 h; AUC 1481. 48 mg × h × L −1. Patient C (9 months of age, 5. 8 kg), with severe renal impairment undergoing CRRT received 30 mg/kg every 8 h: renal replacement therapy clearance (CL) 0. 39 L/h; Vd 0. 74 L; Vd 1. 17; t 3. 51 h; AUC 448. 72 mg × h × L −1. No adverse effects attributable to antibiotic treatment were observed. Conclusions: Our results suggest that a dose of 35 mg/kg every 8 h can be appropriate in critically ill septic children with multi-drug resistance Pseudomonas aeruginosa infections. A lower dose of 10 mg/kg every 8 h could be considered for children with severe AKI. For patients with CRRT and a high effluent rate, a dose of 30 mg/kg every 8 h can be considered.
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Ceftolozane ; Acute kidney injury ; Population pharmacokinetics ; Critically ill children ; Dose individualization ; Continuous renal replacement therapy
Published in:	Antibiotics, Vol. 9 (december 2020) , ISSN 2079-6382

DOI: 10.3390/antibiotics9120887
PMID: 33321721

14 p, 543.2 KB

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