Vancomycin Exposure Dynamics and Clinical Outcomes in Critically Ill Patients: A Retrospective Cohort Study

Objectives: Vancomycin is crucial for treating severe Gram-positive infections, but its narrow therapeutic index complicates dosing. Trough monitoring may inadequately reflect exposure, while AUC-guided dosing, although recommended, is often impractical. Alternative metrics such as the time in therapeutic range (TIR) and volatility index may reflect exposure dynamics. Augmented renal clearance (ARC) further challenges vancomycin therapy in Intensive Care Unit (ICU) settings. This study evaluated trough-based exposure metrics and their associations with ICU mortality and acute kidney injury (AKI). Methods: We retrospectively analyzed 109 ICU patients with sepsis receiving vancomycin. Exposure was assessed using mean trough concentrations, TIR (proportion of troughs within predefined ranges), and the volatility index, defined as the intra-individual standard deviation divided by the mean trough concentration (SD/mean). Outcomes were ICU mortality and AKI. Associations were evaluated using multivariable regression, bootstrap resampling, and restricted cubic splines. Results: TIR _>15 was independently associated with higher mortality (adjusted OR 3.88; p = 0.0326) and AKI stage II-III (adjusted OR 5.63; p = 0.0068). Higher mean troughs correlated with AKI stage II-III, whereas higher volatility showed an inverse association (adjusted OR 0.15; p = 0.0240). ARC (4.6%) occurred exclusively in younger patients and predicted subtherapeutic exposure (TIR _<10, p = 0.0485). Conclusions: Sustained troughs >15 mg/L were associated with mortality and nephrotoxicity, while the most favorable outcomes were descriptively observed at mean trough levels of approximately 8-12 mg/L, suggesting a possible narrow exposure range that requires prospective validation. These findings highlight the limitations of trough-based monitoring alone; the trough-derived metrics should be regarded as exploratory rather than validated decision-making tools.