An In Vitro Calibration Model for Vancomycin Quantification in Brain Extracellular Fluid: Toward Improved Dosing in Postoperative Infections.

Postoperative central nervous system (CNS) infections are associated with high mortality and present a therapeutic challenge due to limited antibiotic penetration into the brain extracellular fluid (ECF). Vancomycin, frequently used in this setting, requires therapeutic drug monitoring; however, its quantification in brain ECF via microdialysis is limited by the need for accurate calibration of relative recovery (RR). This study aimed to determine the in vitro RR of vancomycin under conditions simulating clinical neuromonitoring to support application in clinical practice. Vancomycin RR was assessed using forward dialysis and retrodialysis techniques at a fixed perfusion rate of 0.3 μL/min, consistent with standard neuromonitoring protocols. Vancomycin concentrations were measured using a homogeneous enzyme immunoassay across subtherapeutic, therapeutic, and supratherapeutic levels. RR was calculated as the ratio of microdialysate to reference solution concentrations. Mean RR was 86.5% (SD 3.6%) for forward dialysis and 86.4% (SD 2.1%) for retrodialysis, with no significant difference between techniques (p = 0.957). RR remained consistent across all tested concentration levels (p = 0.051). A strong correlation was observed between vancomycin concentrations in the microdialysate and the study solution (r = 0.997, p < 0.001). The high and stable RR achieved under clinically relevant conditions supports the use of this in vitro microdialysis model as a reliable calibration tool. This model may aid in estimating vancomycin concentrations in brain fluid, facilitating dose optimization in patients undergoing microdialysis-based monitoring for postoperative CNS infections.