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1507. Pharmacodynamic Target Attainment of Daptomycin Against Staphylococcus aureus for Treatment of Pediatric Osteomyelitis

BACKGROUND: Daptomycin (DAP) is lipopeptide that frequently is used to treat infections caused by Staphylococcus aureus in adult patients. There are limited data using daptomycin in pediatric patients for the treatment of osteomyelitis caused by S. aureus. This study’s objective is to describe pharm...

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Autores principales: Stimes, Grant, Girotto, Jennifer E, Courter, Joshua D
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6809531/
http://dx.doi.org/10.1093/ofid/ofz360.1371
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author Stimes, Grant
Girotto, Jennifer E
Courter, Joshua D
author_facet Stimes, Grant
Girotto, Jennifer E
Courter, Joshua D
author_sort Stimes, Grant
collection PubMed
description BACKGROUND: Daptomycin (DAP) is lipopeptide that frequently is used to treat infections caused by Staphylococcus aureus in adult patients. There are limited data using daptomycin in pediatric patients for the treatment of osteomyelitis caused by S. aureus. This study’s objective is to describe pharmacodynamic (PD) target attainment of daptomycin in pediatric patients with osteomyelitis. METHODS: Medline was queried to obtain PD targets, pediatric pharmacokinetic models, and bone penetration information to build a model for DAP. A 10,000 subject Monte Carlo simulation was performed to estimate steady-state concentrations in the bone. Simulations modeled 30-minute infusions with using 12 mg/kg/dose IV q24h for patients less than 7 years and 10 mg/kg/dose IV q24h for patients 7 years and older. Goal PD targets were: AUC(24): MIC of 666 μg hours/mL for log1 killing and AUC(24): MIC of 1,061 for log2 killing. The CLSI breakpoint of 1 mg/L was used as a starting point and MIC’s were analyzed below that level. RESULTS: PD target attainment in percentages is listed for DAP below in Tables 1 and 2 and are separated by age groups of patients. CONCLUSION: The studied DAP doses did not reach any PD target attainment at the CLSI breakpoint of 1 mg/L. Based on these data, DAP should not be empirically used to treat SA osteomyelitis unless the exact MIC is known. Furthermore, modern pediatric pharmacokinetic studies of DAP for pediatric osteomyelitis are warranted. [Image: see text] DISCLOSURES: All authors: No reported disclosures.
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spelling pubmed-68095312019-10-28 1507. Pharmacodynamic Target Attainment of Daptomycin Against Staphylococcus aureus for Treatment of Pediatric Osteomyelitis Stimes, Grant Girotto, Jennifer E Courter, Joshua D Open Forum Infect Dis Abstracts BACKGROUND: Daptomycin (DAP) is lipopeptide that frequently is used to treat infections caused by Staphylococcus aureus in adult patients. There are limited data using daptomycin in pediatric patients for the treatment of osteomyelitis caused by S. aureus. This study’s objective is to describe pharmacodynamic (PD) target attainment of daptomycin in pediatric patients with osteomyelitis. METHODS: Medline was queried to obtain PD targets, pediatric pharmacokinetic models, and bone penetration information to build a model for DAP. A 10,000 subject Monte Carlo simulation was performed to estimate steady-state concentrations in the bone. Simulations modeled 30-minute infusions with using 12 mg/kg/dose IV q24h for patients less than 7 years and 10 mg/kg/dose IV q24h for patients 7 years and older. Goal PD targets were: AUC(24): MIC of 666 μg hours/mL for log1 killing and AUC(24): MIC of 1,061 for log2 killing. The CLSI breakpoint of 1 mg/L was used as a starting point and MIC’s were analyzed below that level. RESULTS: PD target attainment in percentages is listed for DAP below in Tables 1 and 2 and are separated by age groups of patients. CONCLUSION: The studied DAP doses did not reach any PD target attainment at the CLSI breakpoint of 1 mg/L. Based on these data, DAP should not be empirically used to treat SA osteomyelitis unless the exact MIC is known. Furthermore, modern pediatric pharmacokinetic studies of DAP for pediatric osteomyelitis are warranted. [Image: see text] DISCLOSURES: All authors: No reported disclosures. Oxford University Press 2019-10-23 /pmc/articles/PMC6809531/ http://dx.doi.org/10.1093/ofid/ofz360.1371 Text en © The Author(s) 2019. Published by Oxford University Press on behalf of Infectious Diseases Society of America. http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Abstracts
Stimes, Grant
Girotto, Jennifer E
Courter, Joshua D
1507. Pharmacodynamic Target Attainment of Daptomycin Against Staphylococcus aureus for Treatment of Pediatric Osteomyelitis
title 1507. Pharmacodynamic Target Attainment of Daptomycin Against Staphylococcus aureus for Treatment of Pediatric Osteomyelitis
title_full 1507. Pharmacodynamic Target Attainment of Daptomycin Against Staphylococcus aureus for Treatment of Pediatric Osteomyelitis
title_fullStr 1507. Pharmacodynamic Target Attainment of Daptomycin Against Staphylococcus aureus for Treatment of Pediatric Osteomyelitis
title_full_unstemmed 1507. Pharmacodynamic Target Attainment of Daptomycin Against Staphylococcus aureus for Treatment of Pediatric Osteomyelitis
title_short 1507. Pharmacodynamic Target Attainment of Daptomycin Against Staphylococcus aureus for Treatment of Pediatric Osteomyelitis
title_sort 1507. pharmacodynamic target attainment of daptomycin against staphylococcus aureus for treatment of pediatric osteomyelitis
topic Abstracts
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6809531/
http://dx.doi.org/10.1093/ofid/ofz360.1371
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