Pharmacokinetics and pharmacodynamics of meropenem by extended or continuous infusion in low body weight critically ill patients

Background: Pathophysiological changes such as extreme body weights in critically ill patients with severe infections may alter the pharmacokinetics (PK) of antimicrobials, leading to treatment failure or toxicity. There are almost no PK data on meropenem in critically ill patients with low body wei...

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Autores: Luque Pardos, Sònia, Benítez-Cano, Adela, Larrañaga, Leire, Sorli Redó, M. Luisa, Navarrete Rouco, Maria Eugenia, Campillo Ambrós, Núria, Carazo Cordobés, Jesús, Ramos, Isabel, Adalia Bartolomé, Ramón, Grau Cerrato, Santiago
Tipo de documento: artigo
Estado:Versão publicada
Data de publicação:2021
País:España
Recursos:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositório:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:10230/51901
Acesso em linha:http://hdl.handle.net/10230/51901
http://dx.doi.org/10.3390/antibiotics10060666
Access Level:Acceso aberto
Palavra-chave:Antibiotics
Low body weight
Meropenem
Pharmacodynamics
Pharmacokinetics
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spelling Pharmacokinetics and pharmacodynamics of meropenem by extended or continuous infusion in low body weight critically ill patientsLuque Pardos, SòniaBenítez-Cano, AdelaLarrañaga, LeireSorli Redó, M. LuisaNavarrete Rouco, Maria EugeniaCampillo Ambrós, NúriaCarazo Cordobés, JesúsRamos, IsabelAdalia Bartolomé, RamónGrau Cerrato, SantiagoAntibioticsLow body weightMeropenemPharmacodynamicsPharmacokineticsBackground: Pathophysiological changes such as extreme body weights in critically ill patients with severe infections may alter the pharmacokinetics (PK) of antimicrobials, leading to treatment failure or toxicity. There are almost no PK data on meropenem in critically ill patients with low body weight (LwBW) and therefore information is lacking on the most appropriate dosing regimens, especially when administered by extended infusion. Objectives: To assess if the current administered doses of meropenem could lead to supratherapeutic concentrations in LwBW patients and to identify the factors independently associated with overexposure. Methods: A matched case-control 1:1 study of surgical critically ill patients treated with meropenem administered by extended or continuous infusion and undergoing therapeutic drug monitoring was conducted. Cases (patients with LwBW (body mass index (BMI) < 18.5 kg/m2)) were matched with normal body weight controls (NBW) (patients with BMI ≥ 18.5 kg/m2 and ≤30 kg/m2)) by age, gender, baseline renal function and severity status (APACHE II score). A 100% fT > MIC was considered an optimal pharmacokinetic/pharmacodynamic (PK/PD) target and 100% fT > 10 × MIC as supratherapeutic exposure. Results: Thirty-six patients (18 cases and 18 controls) were included (median (range) age, 57.5 (26-75) years; 20 (55.6% male)). Meropenem was administered by 6 h (extended) or 8 h (continuous) infusion at a median (range) daily dose of 5 (1-6) g/day. Similar median meropenem trough plasma concentrations (Cmin,ss), measured pre-dose on day three to four of treatment) were observed in the two groups (19.9 (22.2) mg/L vs 22.4 (25.8) mg/L, p > 0.999). No differences in the proportion of patients with an optimal or a supratherapeutic PKPD target between cases and controls were observed. A baseline estimated glomerular filtration rate (eGFR) < 90 mL/min was the only factor independently associated with a supratherapeutic PK/PD target. Conclusions: LwBW seems not to be a risk factor for achieving a supratherapeutic PK/PD target in critically ill patients receiving meropenem at standard doses by extended or continuous infusion.MDPI202120212021info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttp://hdl.handle.net/10230/51901http://dx.doi.org/10.3390/antibiotics10060666reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésAntibiotics (Basel). 2021;10(6):666© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).http://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:recercat.cat:10230/519012026-05-29T05:05:01Z
dc.title.none.fl_str_mv Pharmacokinetics and pharmacodynamics of meropenem by extended or continuous infusion in low body weight critically ill patients
title Pharmacokinetics and pharmacodynamics of meropenem by extended or continuous infusion in low body weight critically ill patients
spellingShingle Pharmacokinetics and pharmacodynamics of meropenem by extended or continuous infusion in low body weight critically ill patients
Luque Pardos, Sònia
Antibiotics
Low body weight
Meropenem
Pharmacodynamics
Pharmacokinetics
title_short Pharmacokinetics and pharmacodynamics of meropenem by extended or continuous infusion in low body weight critically ill patients
title_full Pharmacokinetics and pharmacodynamics of meropenem by extended or continuous infusion in low body weight critically ill patients
title_fullStr Pharmacokinetics and pharmacodynamics of meropenem by extended or continuous infusion in low body weight critically ill patients
title_full_unstemmed Pharmacokinetics and pharmacodynamics of meropenem by extended or continuous infusion in low body weight critically ill patients
title_sort Pharmacokinetics and pharmacodynamics of meropenem by extended or continuous infusion in low body weight critically ill patients
dc.creator.none.fl_str_mv Luque Pardos, Sònia
Benítez-Cano, Adela
Larrañaga, Leire
Sorli Redó, M. Luisa
Navarrete Rouco, Maria Eugenia
Campillo Ambrós, Núria
Carazo Cordobés, Jesús
Ramos, Isabel
Adalia Bartolomé, Ramón
Grau Cerrato, Santiago
author Luque Pardos, Sònia
author_facet Luque Pardos, Sònia
Benítez-Cano, Adela
Larrañaga, Leire
Sorli Redó, M. Luisa
Navarrete Rouco, Maria Eugenia
Campillo Ambrós, Núria
Carazo Cordobés, Jesús
Ramos, Isabel
Adalia Bartolomé, Ramón
Grau Cerrato, Santiago
author_role author
author2 Benítez-Cano, Adela
Larrañaga, Leire
Sorli Redó, M. Luisa
Navarrete Rouco, Maria Eugenia
Campillo Ambrós, Núria
Carazo Cordobés, Jesús
Ramos, Isabel
Adalia Bartolomé, Ramón
Grau Cerrato, Santiago
author2_role author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Antibiotics
Low body weight
Meropenem
Pharmacodynamics
Pharmacokinetics
topic Antibiotics
Low body weight
Meropenem
Pharmacodynamics
Pharmacokinetics
description Background: Pathophysiological changes such as extreme body weights in critically ill patients with severe infections may alter the pharmacokinetics (PK) of antimicrobials, leading to treatment failure or toxicity. There are almost no PK data on meropenem in critically ill patients with low body weight (LwBW) and therefore information is lacking on the most appropriate dosing regimens, especially when administered by extended infusion. Objectives: To assess if the current administered doses of meropenem could lead to supratherapeutic concentrations in LwBW patients and to identify the factors independently associated with overexposure. Methods: A matched case-control 1:1 study of surgical critically ill patients treated with meropenem administered by extended or continuous infusion and undergoing therapeutic drug monitoring was conducted. Cases (patients with LwBW (body mass index (BMI) < 18.5 kg/m2)) were matched with normal body weight controls (NBW) (patients with BMI ≥ 18.5 kg/m2 and ≤30 kg/m2)) by age, gender, baseline renal function and severity status (APACHE II score). A 100% fT > MIC was considered an optimal pharmacokinetic/pharmacodynamic (PK/PD) target and 100% fT > 10 × MIC as supratherapeutic exposure. Results: Thirty-six patients (18 cases and 18 controls) were included (median (range) age, 57.5 (26-75) years; 20 (55.6% male)). Meropenem was administered by 6 h (extended) or 8 h (continuous) infusion at a median (range) daily dose of 5 (1-6) g/day. Similar median meropenem trough plasma concentrations (Cmin,ss), measured pre-dose on day three to four of treatment) were observed in the two groups (19.9 (22.2) mg/L vs 22.4 (25.8) mg/L, p > 0.999). No differences in the proportion of patients with an optimal or a supratherapeutic PKPD target between cases and controls were observed. A baseline estimated glomerular filtration rate (eGFR) < 90 mL/min was the only factor independently associated with a supratherapeutic PK/PD target. Conclusions: LwBW seems not to be a risk factor for achieving a supratherapeutic PK/PD target in critically ill patients receiving meropenem at standard doses by extended or continuous infusion.
publishDate 2021
dc.date.none.fl_str_mv 2021
2021
2021
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10230/51901
http://dx.doi.org/10.3390/antibiotics10060666
url http://hdl.handle.net/10230/51901
http://dx.doi.org/10.3390/antibiotics10060666
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Antibiotics (Basel). 2021;10(6):666
dc.rights.none.fl_str_mv http://creativecommons.org/licenses/by/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
dc.source.none.fl_str_mv reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,812429

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