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

Background: Standardized operating procedures (SOPs) for intravenous vancomycin therapy have been shown to improve population-level trough target attainment and to reduce nephrotoxicity in orthopedic inpatients. However, mean target attainment on a population level does not capture how stably an individual patient remains within the therapeutic window. Intra-individual variability of vancomycin trough concentrations has remained underreported as a patient-level quality indicator in the orthopedic stewardship literature, despite its direct clinical relevance, as alternating sub- and supratherapeutic phases compromise both efficacy and safety independently of the mean exposure. Methods: We conducted a secondary analysis of the prospectively and retrospectively collected data of the Halle Vancomycin SOP cohort. Pre-SOP (n = 58) and post-SOP (n = 23) patient cohorts were compared with respect to patient-level variability metrics, including the coefficient of variation (CV%), swing index, mean absolute successive difference (MSSD), range of trough values, zone-transition frequencies, and the proportion of "stable" patients defined as CV% below 20%. First-order Markov transition matrices were computed to characterize the directionality of trough movements between subtherapeutic, target, and supratherapeutic zones. The primary analysis was restricted to patients with at least three documented trough measurements. Results: The median CV% decreased from 43.5% (IQR 33.5-51.5) pre-SOP to 32.5% (IQR 21.9-38.6) post-SOP (Mann-Whitney U, p = 0.011). The swing index decreased from 1.09 to 0.75 (p = 0.002), and the median range of individual trough concentrations shrank from 19.1 mg/L to 13.2 mg/L (p = 0.029). The absolute number of zone transitions per patient did not differ significantly between cohorts, but their directionality differed substantially: target-zone persistence increased from 37.8% to 57.6%. Across all 403 measurements, subtherapeutic values declined from 38.5% to 26.6%, while target-zone measurements rose from 28.5% to 44.7%. In the post-SOP cohort, longer therapy duration was associated with lower CV% (Spearman ρ = -0.52, p = 0.032). Conclusions: In addition to improvements in population-level target attainment, implementation of the SOP was associated with stabilization of the individual exposure profile of orthopedic inpatients receiving intravenous vancomycin. Intra-individual variability was lower in the post-SOP cohort, and transitions between zones were more often oriented toward the target range. These findings, derived from a single-centre secondary analysis with a small post-SOP cohort, support patient-level variability metrics as a complementary quality indicator in protocolized vancomycin management and warrant prospective multicentre validation.