Applicability of Vancomycin, Meropenem and Linezolid in capillary microsamples versus dried blood spots: a validation and pilot study suitable for microsampling in critically ill children

Abstract Therapeutic drug monitoring (TDM) of antimicrobials is extremely useful in critically ill patients. However, it’s a burden for neonate or children with small circulating blood volume. In the present study, we aimed to develop and validate a microsampling TDM platform (including dried blood spots (DBS) and capillary microsamples (CMS)) for the simultaneous quantification of vancomycin, meropenem and linezolid. Paired DBS and CMS samples were obtained from ICU to evaluate its clinical application. Estimated plasma concentrations (EPC) were calculated from DBS concentrations. Agreement between methods was evaluated using Deming regression and Bland–Altman difference plots. Results for microsampling methods validation showed excellent reliability and compatible with the analysis of sample matrix and hematocrit range of the studied population. DBS and CMS results for accuracy and precision were within accepted ranges, samples were stable at room temperature for at least 2 days and 10h, respectively. Hematocrit has no impact on CMS, but sightly impact on DBS measurement. The CMS and DBS antibiotics concentrations correlated well (r > 0.98). The ratio of the drug concentration in DBS samples to that in CMS was 1.39 for vancomycin ,1.34 for meropenem and 0.94 for linezolid. EPC calculated from DBS using individual hematocrit presented comparable absolute values for vancomycin (slope:1.06) and meropenem(slope:1.04), being in mean 98%,99% of the measured CMS concentrations, respectively. Conclusion: This study provides a microsampling TDM platform validated for clinical use for a rapid quantification of three antibiotics in a small volume of blood and is suitable for real-time TDM-guided personalization of antimicrobial treatment in critically ill children.