Intra-Individual Variability of Vancomycin Trough Concentrations Before and After Implementation of a Standardized...

Area of Science:

• Pharmacology
• Clinical Pharmacy
• Health Informatics

Background:

• Standardized operating procedures (SOPs) for intravenous vancomycin therapy enhance population-level trough target attainment and reduce nephrotoxicity in orthopedic patients.
• However, population-level metrics do not fully represent individual patient therapeutic stability, as intra-individual variability in vancomycin trough concentrations impacts both efficacy and safety.

Purpose of the Study:

• To assess the impact of implementing a vancomycin SOP on patient-level variability metrics in orthopedic inpatients.
• To evaluate changes in intra-individual vancomycin trough concentration variability and zone transitions post-SOP implementation.

Main Methods:

• Secondary analysis of prospectively and retrospectively collected data from the Halle Vancomycin SOP cohort, comparing pre-SOP (n=58) and post-SOP (n=23) patient groups.
• Analysis included patient-level variability metrics (CV%, swing index, MSSD, range) and Markov transition matrices to assess trough concentration stability and zone movements.
• Primary analysis focused on patients with at least three trough measurements.

Main Results:

• Median CV% decreased from 43.5% to 32.5% (p=0.011), and the swing index decreased from 1.09 to 0.75 (p=0.002) post-SOP.
• Individual trough concentration range also reduced significantly, and target-zone persistence increased from 37.8% to 57.6%.
• Subtherapeutic vancomycin levels decreased from 38.5% to 26.6%, while target-zone levels increased from 28.5% to 44.7% post-SOP.

Conclusions:

• Implementation of the vancomycin SOP led to stabilization of individual exposure profiles in orthopedic inpatients, beyond just improved population-level attainment.
• The SOP was associated with reduced intra-individual variability and a greater proportion of trough concentrations trending towards the therapeutic target range.
• Patient-level variability metrics serve as valuable complementary quality indicators for protocolized vancomycin management, warranting further multicenter validation.