Finding the Dose for Ceftolozane-Tazobactam in Critically Ill Children with and without Acute Kidney Injury
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: Ev...
| Autores: | , , , , , , , |
|---|---|
| Tipo de recurso: | artículo |
| Fecha de publicación: | 2020 |
| País: | España |
| Institución: | Universidad de Navarra |
| Repositorio: | Dadun. Depósito Académico Digital de la Universidad de Navarra |
| Idioma: | inglés |
| OAI Identifier: | oai:dadun.unav.edu:10171/66277 |
| Acceso en línea: | https://hdl.handle.net/10171/66277 |
| Access Level: | acceso abierto |
| Palabra clave: | Ceftolozane Acute kidney injury Population pharmacokinetics Critically ill children Dose individualization Continuous renal replacement therapy |
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Finding the Dose for Ceftolozane-Tazobactam in Critically Ill Children with and without Acute Kidney InjuryButragueño-Laiseca, L. (Laura)|||/items/2b88bcfd-dbfb-45e6-a8cc-e9132bd5f565Grau, S. (Santiago)|||/items/5c8314df-cd2d-45cc-af39-e6e3c2e1ddcdCampillo, N. (Nuria)|||/items/2b5ef209-4663-4ec0-a3ab-bcc5304bad1bGarcía, X. (Xandra)|||/items/8fd45161-3e0e-45e4-81cc-4b84f4900050Padilla, B. (Belén)|||/items/4ecb466b-933a-4381-a1d5-a8671f729eb2Fernández, S.N. (Sarah N.)|||/items/dd677d3f-97fc-417e-8d96-3a72fd298fe5Santiago, M.J. (María José)|||/items/ec7caf77-3f04-4c5e-a1a5-579c093516d9Troconiz, I.F. (Iñaki F.)|||/items/e6782d1e-7a2a-42cc-95d6-55223215bf44CeftolozaneAcute kidney injuryPopulation pharmacokineticsCritically ill childrenDose individualizationContinuous renal replacement therapyBackground: 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 (CLR) was 0.88 L/h; volume of distribution (Vd) Vd1 = 3.45 L, Vd2 = 0.942 L; terminal halflife (t1/2,β) = 3.51 h, dosing interval area under the drug concentration vs. time curve at steady-state (AUCτ,SS) 397.73 mg × h × L −1 . Patient B (19 months of age, 11 kg) with eGFR of 22 mL/min/1.73 m2 received 36 mg/kg every 8 h: CLR = 0.27 L/h; Vd1 = 1.13 L; Vd2 = 1.36; t1/2,β = 6.62 h; AUCSS 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 (CLRRT) 0.39 L/h; Vd1 = 0.74 L; Vd2= 1.17; t 1/2,β = 3.51 h; AUCτ,SS 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.Dadun. Depósito Académico Digital Universidad de Navarra20232023-05-1720202020-01-0120202020-01-01journal articlehttp://purl.org/coar/resource_type/c_6501info:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/10171/66277reponame:Dadun. Depósito Académico Digital de la Universidad de Navarrainstname:Universidad de NavarraInglésengopen accesshttp://purl.org/coar/access_right/c_abf2info:eu-repo/semantics/openAccessoai:dadun.unav.edu:10171/662772026-06-21T12:47:57Z |
| dc.title.none.fl_str_mv |
Finding the Dose for Ceftolozane-Tazobactam in Critically Ill Children with and without Acute Kidney Injury |
| title |
Finding the Dose for Ceftolozane-Tazobactam in Critically Ill Children with and without Acute Kidney Injury |
| spellingShingle |
Finding the Dose for Ceftolozane-Tazobactam in Critically Ill Children with and without Acute Kidney Injury Butragueño-Laiseca, L. (Laura)|||/items/2b88bcfd-dbfb-45e6-a8cc-e9132bd5f565 Ceftolozane Acute kidney injury Population pharmacokinetics Critically ill children Dose individualization Continuous renal replacement therapy |
| title_short |
Finding the Dose for Ceftolozane-Tazobactam in Critically Ill Children with and without Acute Kidney Injury |
| title_full |
Finding the Dose for Ceftolozane-Tazobactam in Critically Ill Children with and without Acute Kidney Injury |
| title_fullStr |
Finding the Dose for Ceftolozane-Tazobactam in Critically Ill Children with and without Acute Kidney Injury |
| title_full_unstemmed |
Finding the Dose for Ceftolozane-Tazobactam in Critically Ill Children with and without Acute Kidney Injury |
| title_sort |
Finding the Dose for Ceftolozane-Tazobactam in Critically Ill Children with and without Acute Kidney Injury |
| dc.creator.none.fl_str_mv |
Butragueño-Laiseca, L. (Laura)|||/items/2b88bcfd-dbfb-45e6-a8cc-e9132bd5f565 Grau, S. (Santiago)|||/items/5c8314df-cd2d-45cc-af39-e6e3c2e1ddcd Campillo, N. (Nuria)|||/items/2b5ef209-4663-4ec0-a3ab-bcc5304bad1b García, X. (Xandra)|||/items/8fd45161-3e0e-45e4-81cc-4b84f4900050 Padilla, B. (Belén)|||/items/4ecb466b-933a-4381-a1d5-a8671f729eb2 Fernández, S.N. (Sarah N.)|||/items/dd677d3f-97fc-417e-8d96-3a72fd298fe5 Santiago, M.J. (María José)|||/items/ec7caf77-3f04-4c5e-a1a5-579c093516d9 Troconiz, I.F. (Iñaki F.)|||/items/e6782d1e-7a2a-42cc-95d6-55223215bf44 |
| author |
Butragueño-Laiseca, L. (Laura)|||/items/2b88bcfd-dbfb-45e6-a8cc-e9132bd5f565 |
| author_facet |
Butragueño-Laiseca, L. (Laura)|||/items/2b88bcfd-dbfb-45e6-a8cc-e9132bd5f565 Grau, S. (Santiago)|||/items/5c8314df-cd2d-45cc-af39-e6e3c2e1ddcd Campillo, N. (Nuria)|||/items/2b5ef209-4663-4ec0-a3ab-bcc5304bad1b García, X. (Xandra)|||/items/8fd45161-3e0e-45e4-81cc-4b84f4900050 Padilla, B. (Belén)|||/items/4ecb466b-933a-4381-a1d5-a8671f729eb2 Fernández, S.N. (Sarah N.)|||/items/dd677d3f-97fc-417e-8d96-3a72fd298fe5 Santiago, M.J. (María José)|||/items/ec7caf77-3f04-4c5e-a1a5-579c093516d9 Troconiz, I.F. (Iñaki F.)|||/items/e6782d1e-7a2a-42cc-95d6-55223215bf44 |
| author_role |
author |
| author2 |
Grau, S. (Santiago)|||/items/5c8314df-cd2d-45cc-af39-e6e3c2e1ddcd Campillo, N. (Nuria)|||/items/2b5ef209-4663-4ec0-a3ab-bcc5304bad1b García, X. (Xandra)|||/items/8fd45161-3e0e-45e4-81cc-4b84f4900050 Padilla, B. (Belén)|||/items/4ecb466b-933a-4381-a1d5-a8671f729eb2 Fernández, S.N. (Sarah N.)|||/items/dd677d3f-97fc-417e-8d96-3a72fd298fe5 Santiago, M.J. (María José)|||/items/ec7caf77-3f04-4c5e-a1a5-579c093516d9 Troconiz, I.F. (Iñaki F.)|||/items/e6782d1e-7a2a-42cc-95d6-55223215bf44 |
| author2_role |
author author author author author author author |
| dc.contributor.none.fl_str_mv |
Dadun. Depósito Académico Digital Universidad de Navarra |
| dc.subject.none.fl_str_mv |
Ceftolozane Acute kidney injury Population pharmacokinetics Critically ill children Dose individualization Continuous renal replacement therapy |
| topic |
Ceftolozane Acute kidney injury Population pharmacokinetics Critically ill children Dose individualization Continuous renal replacement therapy |
| description |
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 (CLR) was 0.88 L/h; volume of distribution (Vd) Vd1 = 3.45 L, Vd2 = 0.942 L; terminal halflife (t1/2,β) = 3.51 h, dosing interval area under the drug concentration vs. time curve at steady-state (AUCτ,SS) 397.73 mg × h × L −1 . Patient B (19 months of age, 11 kg) with eGFR of 22 mL/min/1.73 m2 received 36 mg/kg every 8 h: CLR = 0.27 L/h; Vd1 = 1.13 L; Vd2 = 1.36; t1/2,β = 6.62 h; AUCSS 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 (CLRRT) 0.39 L/h; Vd1 = 0.74 L; Vd2= 1.17; t 1/2,β = 3.51 h; AUCτ,SS 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. |
| publishDate |
2020 |
| dc.date.none.fl_str_mv |
2020 2020-01-01 2020 2020-01-01 2023 2023-05-17 |
| dc.type.none.fl_str_mv |
journal article http://purl.org/coar/resource_type/c_6501 |
| dc.type.openaire.fl_str_mv |
info:eu-repo/semantics/article |
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article |
| dc.identifier.none.fl_str_mv |
https://hdl.handle.net/10171/66277 |
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https://hdl.handle.net/10171/66277 |
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Inglés eng |
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Inglés |
| language |
eng |
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open access http://purl.org/coar/access_right/c_abf2 |
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info:eu-repo/semantics/openAccess |
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open access http://purl.org/coar/access_right/c_abf2 |
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openAccess |
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application/pdf |
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reponame:Dadun. Depósito Académico Digital de la Universidad de Navarra instname:Universidad de Navarra |
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