Exploring real-world vancomycin target attainment in neonatal intensive care in the context of Staphylococcal infections: a retrospective observational cohort study

Abstract Background: Vancomycin is commonly prescribed in late onset sepsis (LOS) in neonatal intensive care (NICU). Despite variation in vancomycin population pharmacokinetics, a paucity of evidence exists to support dose optimisation. This study explored the relationship between trough vancomycin concentrations and estimated area-under-the-concentration-time-curve (AUC) to minimum inhibitory concentration (MIC) ratios in real-world practice. Methods: Patients treated with vancomycin for LOS in two tertiary NICUs between October 2022 and February 2023 were included. Electronic patient record data on demographics, microbiology, dosing, therapeutic drug monitoring (TDM), and outcomes were extracted; these were used to estimate individual patient AUC and AUC:MIC ratios using Bayesian forecasting. Trough and AUC estimates were compared. Target attainment was estimated using an AUC:MIC>400, and toxicity using AUC>600 mg·h/L. Estimates for target attainment were evaluated at different MICs. Results: 32 patients, with 41 discrete treatment episodes, were analysed. Median gestational age at birth was 26.5 (IQR 25-30) weeks. Ten patients (31%) were female and median weight was 0.87 (IQR 0.7-1.4) kg. Trough concentrations correlated poorly with AUC estimates (r2=0.38). Dose adjustment using troughs did not improve AUC/MIC target attainment. Acute kidney injury (AKI) occurred in 4/41 (10%) treatment episodes; peak median AUC was 1170.4 (IQR 839.1-1493.7) mg·h/L compared to 582.1 (IQR 485.4-699.3) mg·h/L in those without AKI. For individual episodes, AUC/MIC targets at day 2 would be met for vancomycin in 30/41 (73%) for organisms with an MIC of 1 mg/L, 1/41 (2%) for MIC 2 mg/L, and 0/41 (0%) for MIC 4 mg/L. Conclusion: Using trough based TDM correlated poorly with AUC-based estimates for target attainment. Dose adjustment using trough-based TDM fails to improve drug-exposure, especially with MIC >1mg/L.