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Background We previously documented that 2 published vancomycin dosing regimens resulted in subtherapeutic exposure in 66.3 and 76.2% of neonates.1 A new dosing regimen derived from a population pharmacokinetic (PK) analysis and using a loading dose, was implemented in our unit.2 We aimed to investigate if the new regimen results in improved vancomycin exposure (target trough 10–15 mg/L). Methods Clinical data and early (24 h after start) vancomycin therapeutic drug monitoring (TDM) in neonates receiving vancomycin for medical reasons, were retrospectively collected and pooled with 2 historical cohorts [cohort 1 (2011, n=193 observations), dosing based on postmenstrual age (PMA) and creatininemia and cohort 2 (2012, n=101 observations), dosing based on PMA and postnatal age (PNA)]. The new regimen [cohort 3 (2018, n=71 observations)] consists of a loading dose, followed by dosing based on birthweight, PNA and ibuprofen co-treatment [2]. Clinical characteristics and early TDM were compared across the cohorts using the Kruskal-Wallis Test. Results were significant if p< 0.05. Results Clinical characteristics (cohort 1, 2 and 3 respectively) did not differ significantly across the cohorts. Median (IQ range) GA was 32.8 (28.4–37.6), 32.1 (28.5–37.5), 28 (26–38) weeks with p=0.097; PNA 13 (6–26), 12 (7–23), 14 (10–25) days with p=0.15 and creatininemia 0.43 (0.33–0.55), 0.49 (0.33–0.65), 0.45 (0.32–0.57) mg/dL with p=0.15. Median vancomycin trough level was 7.8 (5.1–11.3), 5.8 (4.1–8.7), 13.3 (9.9–17.3) mg/L with p< 0.0001. With the new regimen, 25.4% of trough levels was < 10 mg/L, 40.8% >15 mg/L, and 33.8% was on target, versus 23.3 and 19.8% on target in cohort 1 and 2 respectively. Conclusion A population PK model-based vancomycin dosing regimen using a loading dose, resulted in improved neonatal vancomycin exposure. Although only 25% of trough levels was subtherapeutic, dosing optimalisation for cases with supratherapeutic exposure is also needed, as well as further prospective validation. References Vandendriessche, et al. Curr Ther Res Clin Exp 2014. Janssen, et al. AAC 2015. Disclosure(s) Nothing to disclose