Risk Factors for Non-Therapeutic Initial Steady-State Vancomycin Trough Concentrations in Children and Adolescents Receiving High Empiric Doses of Intravenous Vancomycin

Whitney R. Buckel, Shahira Ghobrial, Pranita Tamma, Aaron Milstone, Yuan Zhao, Alice J. Hsu

Research output: Contribution to journalArticle

Abstract

Background: Achieving vancomycin troughs of 15–20 μg/mL remains challenging in children. Our objective was to identify risk factors associated with non-therapeutic initial vancomycin troughs in children. Methods: We conducted a retrospective cohort study of children who received intravenous vancomycin with at least one initial steady-state trough obtained. Patients who achieved therapeutic troughs (15–20 μg/mL in the 20-mg/kg/dose sub-cohort and 10–15 μg/mL in the 15-mg/kg/dose sub-cohort) were compared with those with subtherapeutic troughs (<15 and <10 μg/mL, respectively) and supratherapeutic troughs (>20 and >15 μg/mL, respectively) separately to determine risk factors associated with non-therapeutic troughs. Results: A total of 153 vancomycin courses in 140 patients met study eligibility criteria. Of 45 patients who received 20 mg/kg/dose of empiric vancomycin, 60, 16, and 24% were subtherapeutic, therapeutic, and supratherapeutic, respectively. Each 10-mL/min/1.73 m2 increase in initial creatinine clearance (CrCl) was associated with a 47% increase in the odds of an initial subtherapeutic trough (adjusted odds ratio [aOR] 1.47; 95% CI 0.98–2.22). Of 108 patients who received 15 mg/kg/dose of empiric vancomycin, 62, 19, and 19% were subtherapeutic, therapeutic, and supratherapeutic, respectively. Each 10-mL/min/1.73 m2 increase in initial CrCl was associated with an 18% increase in the odds of an initial subtherapeutic trough (aOR 1.18; 95% CI 1.02–1.37). Conclusion: Achieving vancomycin troughs of 15–20 μg/mL for severe Gram-positive infections continues to be challenging in children, even at higher empiric doses of 20 mg/kg/dose IV every 6–8 h. Children with higher initial CrCls are particularly susceptible to subtherapeutic initial steady-state vancomycin troughs.

Original languageEnglish (US)
Pages (from-to)1-9
Number of pages9
JournalPediatric Drugs
DOIs
StateAccepted/In press - Nov 21 2016

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Vancomycin
Creatinine
Odds Ratio
Cohort Studies
Therapeutics
Retrospective Studies
Infection

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Pharmacology (medical)

Cite this

@article{af19209d6af9453ba7c2840ee8e00ffe,
title = "Risk Factors for Non-Therapeutic Initial Steady-State Vancomycin Trough Concentrations in Children and Adolescents Receiving High Empiric Doses of Intravenous Vancomycin",
abstract = "Background: Achieving vancomycin troughs of 15–20 μg/mL remains challenging in children. Our objective was to identify risk factors associated with non-therapeutic initial vancomycin troughs in children. Methods: We conducted a retrospective cohort study of children who received intravenous vancomycin with at least one initial steady-state trough obtained. Patients who achieved therapeutic troughs (15–20 μg/mL in the 20-mg/kg/dose sub-cohort and 10–15 μg/mL in the 15-mg/kg/dose sub-cohort) were compared with those with subtherapeutic troughs (<15 and <10 μg/mL, respectively) and supratherapeutic troughs (>20 and >15 μg/mL, respectively) separately to determine risk factors associated with non-therapeutic troughs. Results: A total of 153 vancomycin courses in 140 patients met study eligibility criteria. Of 45 patients who received 20 mg/kg/dose of empiric vancomycin, 60, 16, and 24{\%} were subtherapeutic, therapeutic, and supratherapeutic, respectively. Each 10-mL/min/1.73 m2 increase in initial creatinine clearance (CrCl) was associated with a 47{\%} increase in the odds of an initial subtherapeutic trough (adjusted odds ratio [aOR] 1.47; 95{\%} CI 0.98–2.22). Of 108 patients who received 15 mg/kg/dose of empiric vancomycin, 62, 19, and 19{\%} were subtherapeutic, therapeutic, and supratherapeutic, respectively. Each 10-mL/min/1.73 m2 increase in initial CrCl was associated with an 18{\%} increase in the odds of an initial subtherapeutic trough (aOR 1.18; 95{\%} CI 1.02–1.37). Conclusion: Achieving vancomycin troughs of 15–20 μg/mL for severe Gram-positive infections continues to be challenging in children, even at higher empiric doses of 20 mg/kg/dose IV every 6–8 h. Children with higher initial CrCls are particularly susceptible to subtherapeutic initial steady-state vancomycin troughs.",
author = "Buckel, {Whitney R.} and Shahira Ghobrial and Pranita Tamma and Aaron Milstone and Yuan Zhao and Hsu, {Alice J.}",
year = "2016",
month = "11",
day = "21",
doi = "10.1007/s40272-016-0202-4",
language = "English (US)",
pages = "1--9",
journal = "Paediatric Drugs",
issn = "1174-5878",
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TY - JOUR

T1 - Risk Factors for Non-Therapeutic Initial Steady-State Vancomycin Trough Concentrations in Children and Adolescents Receiving High Empiric Doses of Intravenous Vancomycin

AU - Buckel, Whitney R.

AU - Ghobrial, Shahira

AU - Tamma, Pranita

AU - Milstone, Aaron

AU - Zhao, Yuan

AU - Hsu, Alice J.

PY - 2016/11/21

Y1 - 2016/11/21

N2 - Background: Achieving vancomycin troughs of 15–20 μg/mL remains challenging in children. Our objective was to identify risk factors associated with non-therapeutic initial vancomycin troughs in children. Methods: We conducted a retrospective cohort study of children who received intravenous vancomycin with at least one initial steady-state trough obtained. Patients who achieved therapeutic troughs (15–20 μg/mL in the 20-mg/kg/dose sub-cohort and 10–15 μg/mL in the 15-mg/kg/dose sub-cohort) were compared with those with subtherapeutic troughs (<15 and <10 μg/mL, respectively) and supratherapeutic troughs (>20 and >15 μg/mL, respectively) separately to determine risk factors associated with non-therapeutic troughs. Results: A total of 153 vancomycin courses in 140 patients met study eligibility criteria. Of 45 patients who received 20 mg/kg/dose of empiric vancomycin, 60, 16, and 24% were subtherapeutic, therapeutic, and supratherapeutic, respectively. Each 10-mL/min/1.73 m2 increase in initial creatinine clearance (CrCl) was associated with a 47% increase in the odds of an initial subtherapeutic trough (adjusted odds ratio [aOR] 1.47; 95% CI 0.98–2.22). Of 108 patients who received 15 mg/kg/dose of empiric vancomycin, 62, 19, and 19% were subtherapeutic, therapeutic, and supratherapeutic, respectively. Each 10-mL/min/1.73 m2 increase in initial CrCl was associated with an 18% increase in the odds of an initial subtherapeutic trough (aOR 1.18; 95% CI 1.02–1.37). Conclusion: Achieving vancomycin troughs of 15–20 μg/mL for severe Gram-positive infections continues to be challenging in children, even at higher empiric doses of 20 mg/kg/dose IV every 6–8 h. Children with higher initial CrCls are particularly susceptible to subtherapeutic initial steady-state vancomycin troughs.

AB - Background: Achieving vancomycin troughs of 15–20 μg/mL remains challenging in children. Our objective was to identify risk factors associated with non-therapeutic initial vancomycin troughs in children. Methods: We conducted a retrospective cohort study of children who received intravenous vancomycin with at least one initial steady-state trough obtained. Patients who achieved therapeutic troughs (15–20 μg/mL in the 20-mg/kg/dose sub-cohort and 10–15 μg/mL in the 15-mg/kg/dose sub-cohort) were compared with those with subtherapeutic troughs (<15 and <10 μg/mL, respectively) and supratherapeutic troughs (>20 and >15 μg/mL, respectively) separately to determine risk factors associated with non-therapeutic troughs. Results: A total of 153 vancomycin courses in 140 patients met study eligibility criteria. Of 45 patients who received 20 mg/kg/dose of empiric vancomycin, 60, 16, and 24% were subtherapeutic, therapeutic, and supratherapeutic, respectively. Each 10-mL/min/1.73 m2 increase in initial creatinine clearance (CrCl) was associated with a 47% increase in the odds of an initial subtherapeutic trough (adjusted odds ratio [aOR] 1.47; 95% CI 0.98–2.22). Of 108 patients who received 15 mg/kg/dose of empiric vancomycin, 62, 19, and 19% were subtherapeutic, therapeutic, and supratherapeutic, respectively. Each 10-mL/min/1.73 m2 increase in initial CrCl was associated with an 18% increase in the odds of an initial subtherapeutic trough (aOR 1.18; 95% CI 1.02–1.37). Conclusion: Achieving vancomycin troughs of 15–20 μg/mL for severe Gram-positive infections continues to be challenging in children, even at higher empiric doses of 20 mg/kg/dose IV every 6–8 h. Children with higher initial CrCls are particularly susceptible to subtherapeutic initial steady-state vancomycin troughs.

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