Impact of cumulative glucocorticoid exposure on vancomycin clearance in hospitalized children: A retrospective cohort study

Abstract Introduction Augmented renal clearance (ARC) can lead to subtherapeutic vancomycin exposure in children. The impact of prior glucocorticoid (GC) exposure on vancomycin pharmacokinetics remains poorly understood. We evaluated the association between GC exposure and vancomycin clearance in paediatric patients. Methods We conducted a retrospective cohort study of paediatric patients undergoing vancomycin therapeutic drug monitoring. GC exposure within 2 years was quantified as prednisolone‐equivalent dose. Vancomycin clearance was estimated using the allometrically normalized dose‐to‐level ( D / L ) ratio. Associations were assessed using correlation and multivariable regression adjusted for age, sex, eGFR and inflammatory markers. Results Among 245 hospitalized children receiving vancomycin, 157 (64.1%) had prior GC exposure. GC‐exposed children had higher vancomycin D / L ratios ( p = .018). Cumulative GC exposure showed weak positive associations with higher vancomycin clearance (2‐year window: Spearman ρ = .16, p = .013). However, in the fully adjusted model, the association between cumulative GC exposure and D / L ratio was not significant ( β = −.0077 per 10 mg kg −1 , 95% CI −0.026 to 0.010, p = .40). GC exposure was associated with higher odds of subtherapeutic trough concentrations (<10 mg/L) (odds ratio 1.45, 95% CI 1.04–2.01). Conclusions Children with prior GC exposure had lower early vancomycin trough concentrations and higher unadjusted D / L ratios. However, the association between GC exposure and vancomycin clearance was attenuated after adjustment, suggesting that GC exposure may reflect underlying physiologic or disease‐related factors rather than an independent determinant of clearance. Closer therapeutic drug monitoring may be warranted at treatment initiation.

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Journal
British Journal of Clinical Pharmacology
Published
2026-07-01
DOI
https://doi.org/10.1002/bcp.70672
Primary Topic
Antimicrobial Resistance in Staphylococcus
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article
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article

Impact of cumulative glucocorticoid exposure on vancomycin clearance in hospitalized children: A retrospective cohort study

Tamorah Lewis, Erin Chung, Shinya Ito, Ruud H J Verstegen et al.
British Journal of Clinical Pharmacology
Antimicrobial Resistance in Staphylococcus
article

Impact of cumulative glucocorticoid exposure on vancomycin clearance in hospitalized children: A retrospective cohort study

Tamorah Lewis, Erin Chung, Shinya Ito, Ruud H J Verstegen, Kouki Tomari, Cintia Cruz, Aleena Azim
article en

Abstract

Abstract Introduction Augmented renal clearance (ARC) can lead to subtherapeutic vancomycin exposure in children. The impact of prior glucocorticoid (GC) exposure on vancomycin pharmacokinetics remains poorly understood. We evaluated the association between GC exposure and vancomycin clearance in paediatric patients. Methods We conducted a retrospective cohort study of paediatric patients undergoing vancomycin therapeutic drug monitoring. GC exposure within 2 years was quantified as prednisolone‐equivalent dose. Vancomycin clearance was estimated using the allometrically normalized dose‐to‐level ( D / L ) ratio. Associations were assessed using correlation and multivariable regression adjusted for age, sex, eGFR and inflammatory markers. Results Among 245 hospitalized children receiving vancomycin, 157 (64.1%) had prior GC exposure. GC‐exposed children had higher vancomycin D / L ratios ( p = .018). Cumulative GC exposure showed weak positive associations with higher vancomycin clearance (2‐year window: Spearman ρ = .16, p = .013). However, in the fully adjusted model, the association between cumulative GC exposure and D / L ratio was not significant ( β = −.0077 per 10 mg kg −1 , 95% CI −0.026 to 0.010, p = .40). GC exposure was associated with higher odds of subtherapeutic trough concentrations (<10 mg/L) (odds ratio 1.45, 95% CI 1.04–2.01). Conclusions Children with prior GC exposure had lower early vancomycin trough concentrations and higher unadjusted D / L ratios. However, the association between GC exposure and vancomycin clearance was attenuated after adjustment, suggesting that GC exposure may reflect underlying physiologic or disease‐related factors rather than an independent determinant of clearance. Closer therapeutic drug monitoring may be warranted at treatment initiation.

British Journal of Clinical Pharmacology
University of Toronto (CA), Hospital for Sick Children (CA), Institute for Clinical Evaluative Sciences (CA)
Good health and well-being
Openalex Percentile: Top 8%
Antimicrobial Resistance in Staphylococcus
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