Cargando…

Dosage Regimens for Meropenem in Children with Pseudomonas Infections Do Not Meet Serum Concentration Targets

There have been literature reports that some recommended meropenem dosage regimens may fail to meet therapeutic targets in some high‐risk children and adults. We evaluated this observation in children using literature studies conducted in infants and children. Observed and, as necessary, simulated d...

Descripción completa

Detalles Bibliográficos
Autores principales: Hassan, Hazem E., Ivaturi, Vijay, Gobburu, Jogarao, Green, Thomas P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7070814/
https://www.ncbi.nlm.nih.gov/pubmed/31692264
http://dx.doi.org/10.1111/cts.12710
_version_ 1783506061535215616
author Hassan, Hazem E.
Ivaturi, Vijay
Gobburu, Jogarao
Green, Thomas P.
author_facet Hassan, Hazem E.
Ivaturi, Vijay
Gobburu, Jogarao
Green, Thomas P.
author_sort Hassan, Hazem E.
collection PubMed
description There have been literature reports that some recommended meropenem dosage regimens may fail to meet therapeutic targets in some high‐risk children and adults. We evaluated this observation in children using literature studies conducted in infants and children. Observed and, as necessary, simulated data from the literature were combined, yielding a data set of 288 subjects (1 day to ~ 17 years). A population pharmacokinetic model was fit to the data and then used to simulate the recommended dosing regimens and estimate the proportion of subjects achieving recommended target exposures. A two‐compartment model best fit the data with weight, postnatal age, gestational age, and serum creatinine as covariates. The US Food and Drug Administration (FDA)‐approved dosing regimens achieved targets in ~ 90% or more of subjects less than 3 months of age for organisms with minimum inhibitory concentration (MIC)'s of 2 and 4 mg/L; however, only 68.4% and 41.7% of subjects older than 3 months and weighing < 50 kg achieved target exposures for organisms with MIC's of 2 and 4 mg/L, respectively [Correction added on January 23, 2020, after first online publication: "> 3 months" corrected to "less than 3 months".]. Moreover, for subjects weighing more than 50 kg, only 41.3% and 17% achieved these respective targets. Simulation studies were used to explore the impact of changing dose, dosing interval, and infusion duration on the likelihood of achieving therapeutic targets in these groups. Our findings illustrate that current dosing recommendations for children over 3 months of age fail to meet therapeutic targets in an unacceptable fraction of patients. Further investigation is needed to develop new dosing strategies in these patients.
format Online
Article
Text
id pubmed-7070814
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher John Wiley and Sons Inc.
record_format MEDLINE/PubMed
spelling pubmed-70708142020-03-17 Dosage Regimens for Meropenem in Children with Pseudomonas Infections Do Not Meet Serum Concentration Targets Hassan, Hazem E. Ivaturi, Vijay Gobburu, Jogarao Green, Thomas P. Clin Transl Sci Research There have been literature reports that some recommended meropenem dosage regimens may fail to meet therapeutic targets in some high‐risk children and adults. We evaluated this observation in children using literature studies conducted in infants and children. Observed and, as necessary, simulated data from the literature were combined, yielding a data set of 288 subjects (1 day to ~ 17 years). A population pharmacokinetic model was fit to the data and then used to simulate the recommended dosing regimens and estimate the proportion of subjects achieving recommended target exposures. A two‐compartment model best fit the data with weight, postnatal age, gestational age, and serum creatinine as covariates. The US Food and Drug Administration (FDA)‐approved dosing regimens achieved targets in ~ 90% or more of subjects less than 3 months of age for organisms with minimum inhibitory concentration (MIC)'s of 2 and 4 mg/L; however, only 68.4% and 41.7% of subjects older than 3 months and weighing < 50 kg achieved target exposures for organisms with MIC's of 2 and 4 mg/L, respectively [Correction added on January 23, 2020, after first online publication: "> 3 months" corrected to "less than 3 months".]. Moreover, for subjects weighing more than 50 kg, only 41.3% and 17% achieved these respective targets. Simulation studies were used to explore the impact of changing dose, dosing interval, and infusion duration on the likelihood of achieving therapeutic targets in these groups. Our findings illustrate that current dosing recommendations for children over 3 months of age fail to meet therapeutic targets in an unacceptable fraction of patients. Further investigation is needed to develop new dosing strategies in these patients. John Wiley and Sons Inc. 2019-11-20 2020-03 /pmc/articles/PMC7070814/ /pubmed/31692264 http://dx.doi.org/10.1111/cts.12710 Text en © 2019 The Authors. Clinical and Translational Science published by Wiley Periodicals, Inc. on behalf of the American Society for Clinical Pharmacology and Therapeutics. This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Research
Hassan, Hazem E.
Ivaturi, Vijay
Gobburu, Jogarao
Green, Thomas P.
Dosage Regimens for Meropenem in Children with Pseudomonas Infections Do Not Meet Serum Concentration Targets
title Dosage Regimens for Meropenem in Children with Pseudomonas Infections Do Not Meet Serum Concentration Targets
title_full Dosage Regimens for Meropenem in Children with Pseudomonas Infections Do Not Meet Serum Concentration Targets
title_fullStr Dosage Regimens for Meropenem in Children with Pseudomonas Infections Do Not Meet Serum Concentration Targets
title_full_unstemmed Dosage Regimens for Meropenem in Children with Pseudomonas Infections Do Not Meet Serum Concentration Targets
title_short Dosage Regimens for Meropenem in Children with Pseudomonas Infections Do Not Meet Serum Concentration Targets
title_sort dosage regimens for meropenem in children with pseudomonas infections do not meet serum concentration targets
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7070814/
https://www.ncbi.nlm.nih.gov/pubmed/31692264
http://dx.doi.org/10.1111/cts.12710
work_keys_str_mv AT hassanhazeme dosageregimensformeropeneminchildrenwithpseudomonasinfectionsdonotmeetserumconcentrationtargets
AT ivaturivijay dosageregimensformeropeneminchildrenwithpseudomonasinfectionsdonotmeetserumconcentrationtargets
AT gobburujogarao dosageregimensformeropeneminchildrenwithpseudomonasinfectionsdonotmeetserumconcentrationtargets
AT greenthomasp dosageregimensformeropeneminchildrenwithpseudomonasinfectionsdonotmeetserumconcentrationtargets