No 68 Attainment of Therapeutic Vancomycin Trough Serum Concentrations With Empiric Dosing In Neonates Lee Choy Ee, Suhaida Shukor, Sarah Diyana Shafie, Seah Yin Kuan Hospital Kajang NMRR-17-3080-39364 INTRODUCTION Vancomycin is commonly used to treat neonatal late-onset sepsis. It is the first-line antibiotic for treatment of infections caused by coagulase-negative staphylococci (CoNS) and methicillin-resistant Staphylococcus aureus (MRSA). However, data for dosing and monitoring of vancomycin in the local neonatal population is lacking. This study aimed to assess the percentage of neonates achieving a serum trough concentration between 10 to 20 mcg/mL with empiric vancomycin dosing. MATERIALS AND METHODS RESULTS • Of the 51 patients included, only 41% achieved target trough with empiric dosing. 22% of trough concentrations were sub-therapeutic whereas 37% were supra-therapeutic. • The mean GA was 31.8 weeks whereas mean PMA was 35.3 weeks. • On average, patients were started on vancomycin at weight of 1922.5 grams for 6.7 days. • All the supra-therapeutic trough concentrations were from the preterm group when compared to term neonates (45.2% vs 0%, p <0.05). • From this preterm group, 73% were contributed by the very preterm neonates (GA<32 weeks). The percentage decreased when gestational age increased. Similar trend of distribution was also observed in PMA category. • The occurrence of nephrotoxicity is low with only one incidence reported (defined as a doubling of serum creatinine from baseline). DISCUSSION/ CONCLUSION • Our study revealed that higher percentage of trough concentrations were supra-therapeutic (37%) compared to sub-therapeutic concentrations (22%). This was in contrary to studies conducted by Ringenberg et al. and Vandendriessche et al. which reported higher proportion of sub-therapeutic trough concentrations, 71.9% and 76.2% respectively1,2. Both were using Neofax® as dosing regimen. • This could be explained by the significant reduction of clearance in premature neonates due to diminished glomerular filtration rate in early days of life. There is marked increase in renal function which occurs over the first few weeks of life3. • We found that our premature neonatal population required lower dosages than the current recommendation. A local study conducted by Lo et al showed that the clearance of vancomycin was lower than that estimated in the Caucasian patients. Hence, it is important to consider the pharmacokinetic variability among these population4. • In conclusion, our preterm neonatal population experienced much higher occurrence of supra- therapeutic trough levels. Further studies are required to evaluate the optimal dosing regimen to achieve therapeutic trough concentrations in this patient population. Figure 1: Percentage attainment of vancomycin trough concentrations and distribution according to GA and PMA. GA= gestational age; PMA= postmenstrual age; w= week REFERENCES 1. Ringenberg T, Robinson C, Meyers R, Degnan L, Shah P, Siu A, et al. Achievement of Therapeutic Vancomycin Trough Serum Concentrations with Empiric Dosing in Neonatal Intensive Care Unit Patients. Pediatr Infect Dis J. 2015 Jul;34(7):742–7. 2. Vandendriessche A, Allegaert K, Cossey V, Naulaers G, Saegeman V, Smits A. Prospective validation of neonatal vancomycin dosing regimens is urgently needed. Curr Ther Res. 2014;76:51–7. 3. Leroux S, Jacqz-Aigrain E, Biran V, Lopez E, Madeleneau D, Wallon C, et al. Clinical utility and safety of a model-based patient- tailored dose of vancomycin in neonates. Antimicrob Agents Chemother. 2016;60(4):2039–42. 4. Lo YL, Van Hasselt JGC, Heng SC, Lim CT, Lee TC, Charles BG. Population pharmacokinetics of vancomycin in premature malaysian neonates: Identification of predictors for dosing determination. Antimicrob Agents Chemother. 2010;54(6):2626–32. GA<32w GA≥32w PMA <37w PMA ≥37w <10 mcg/mL 10–20 mcg/mL >20 mcg/mL