Whitney R Buckel1, Shahira Ghobrial2, Pranita D Tamma3, Aaron M Milstone3, Yuan Zhao3, Alice J Hsu4. 1. Department of Pharmacy, Intermountain Medical Center, Murray, UT, USA. 2. Division of Pediatric Pharmacy, Department of Pharmacy, The Johns Hopkins Hospital, 600 N. Wolfe Street, Carnegie 180, Baltimore, MD, 21287, USA. 3. Division of Pediatric Infectious Diseases, Department of Pediatrics, The Johns Hopkins University School of Medicine, Baltimore, MD, USA. 4. Division of Pediatric Pharmacy, Department of Pharmacy, The Johns Hopkins Hospital, 600 N. Wolfe Street, Carnegie 180, Baltimore, MD, 21287, USA. ajenh1@jhmi.edu.
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.
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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