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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...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2018
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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. |
format | Online Article Text |
id | pubmed-6282491 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
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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