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.