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Dosing of Ceftriaxone and Metronidazole for Children With Severe Acute Malnutrition

Infants and young children with severe acute malnutrition (SAM) are treated with empiric broad‐spectrum antimicrobials. Parenteral ceftriaxone is currently a second‐line agent for invasive infection. Oral metronidazole principally targets small intestinal bacterial overgrowth. Children with SAM may...

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Autores principales: Standing, Joseph F., Ongas, Martin O., Ogwang, Caroline, Kagwanja, Nancy, Murunga, Sheila, Mwaringa, Shalton, Ali, Rehema, Mturi, Neema, Timbwa, Moline, Manyasi, Christine, Mwalekwa, Laura, Bandika, Victor L., Ogutu, Bernhards, Waichungo, Joseph, Kipper, Karin, Berkley, James A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6282491/
https://www.ncbi.nlm.nih.gov/pubmed/29574688
http://dx.doi.org/10.1002/cpt.1078
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author Standing, Joseph F.
Ongas, Martin O.
Ogwang, Caroline
Kagwanja, Nancy
Murunga, Sheila
Mwaringa, Shalton
Ali, Rehema
Mturi, Neema
Timbwa, Moline
Manyasi, Christine
Mwalekwa, Laura
Bandika, Victor L.
Ogutu, Bernhards
Waichungo, Joseph
Kipper, Karin
Berkley, James A.
author_facet Standing, Joseph F.
Ongas, Martin O.
Ogwang, Caroline
Kagwanja, Nancy
Murunga, Sheila
Mwaringa, Shalton
Ali, Rehema
Mturi, Neema
Timbwa, Moline
Manyasi, Christine
Mwalekwa, Laura
Bandika, Victor L.
Ogutu, Bernhards
Waichungo, Joseph
Kipper, Karin
Berkley, James A.
author_sort Standing, Joseph F.
collection PubMed
description Infants and young children with severe acute malnutrition (SAM) are treated with empiric broad‐spectrum antimicrobials. Parenteral ceftriaxone is currently a second‐line agent for invasive infection. Oral metronidazole principally targets small intestinal bacterial overgrowth. Children with SAM may have altered drug absorption, distribution, metabolism, and elimination. Population pharmacokinetics of ceftriaxone and metronidazole were studied, with the aim of recommending optimal dosing. Eighty‐one patients with SAM (aged 2–45 months) provided 234 postdose pharmacokinetic samples for total ceftriaxone, metronidazole, and hydroxymetronidazole. Ceftriaxone protein binding was also measured in 190 of these samples. A three‐compartment model adequately described free ceftriaxone, with a Michaelis–Menten model for concentration and albumin‐dependent protein binding. A one‐compartment model was used for both metronidazole and hydroxymetronidazole, with only 1% of hydroxymetronidazole predicted to be formed during first‐pass. Simulations showed 80 mg/kg once daily of ceftriaxone and 12.5 mg/kg twice daily of metronidazole were sufficient to reach therapeutic targets.
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spelling pubmed-62824912018-12-10 Dosing of Ceftriaxone and Metronidazole for Children With Severe Acute Malnutrition Standing, Joseph F. Ongas, Martin O. Ogwang, Caroline Kagwanja, Nancy Murunga, Sheila Mwaringa, Shalton Ali, Rehema Mturi, Neema Timbwa, Moline Manyasi, Christine Mwalekwa, Laura Bandika, Victor L. Ogutu, Bernhards Waichungo, Joseph Kipper, Karin Berkley, James A. Clin Pharmacol Ther Research Infants and young children with severe acute malnutrition (SAM) are treated with empiric broad‐spectrum antimicrobials. Parenteral ceftriaxone is currently a second‐line agent for invasive infection. Oral metronidazole principally targets small intestinal bacterial overgrowth. Children with SAM may have altered drug absorption, distribution, metabolism, and elimination. Population pharmacokinetics of ceftriaxone and metronidazole were studied, with the aim of recommending optimal dosing. Eighty‐one patients with SAM (aged 2–45 months) provided 234 postdose pharmacokinetic samples for total ceftriaxone, metronidazole, and hydroxymetronidazole. Ceftriaxone protein binding was also measured in 190 of these samples. A three‐compartment model adequately described free ceftriaxone, with a Michaelis–Menten model for concentration and albumin‐dependent protein binding. A one‐compartment model was used for both metronidazole and hydroxymetronidazole, with only 1% of hydroxymetronidazole predicted to be formed during first‐pass. Simulations showed 80 mg/kg once daily of ceftriaxone and 12.5 mg/kg twice daily of metronidazole were sufficient to reach therapeutic targets. John Wiley and Sons Inc. 2018-04-19 2018-12 /pmc/articles/PMC6282491/ /pubmed/29574688 http://dx.doi.org/10.1002/cpt.1078 Text en © 2018 The Authors Clinical Pharmacology & Therapeutics published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research
Standing, Joseph F.
Ongas, Martin O.
Ogwang, Caroline
Kagwanja, Nancy
Murunga, Sheila
Mwaringa, Shalton
Ali, Rehema
Mturi, Neema
Timbwa, Moline
Manyasi, Christine
Mwalekwa, Laura
Bandika, Victor L.
Ogutu, Bernhards
Waichungo, Joseph
Kipper, Karin
Berkley, James A.
Dosing of Ceftriaxone and Metronidazole for Children With Severe Acute Malnutrition
title Dosing of Ceftriaxone and Metronidazole for Children With Severe Acute Malnutrition
title_full Dosing of Ceftriaxone and Metronidazole for Children With Severe Acute Malnutrition
title_fullStr Dosing of Ceftriaxone and Metronidazole for Children With Severe Acute Malnutrition
title_full_unstemmed Dosing of Ceftriaxone and Metronidazole for Children With Severe Acute Malnutrition
title_short Dosing of Ceftriaxone and Metronidazole for Children With Severe Acute Malnutrition
title_sort dosing of ceftriaxone and metronidazole for children with severe acute malnutrition
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6282491/
https://www.ncbi.nlm.nih.gov/pubmed/29574688
http://dx.doi.org/10.1002/cpt.1078
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