191: Assessing Pediatric Vancomycin Exposures & the Influences of Body Composition

Statement of Purpose: Vancomycin is commonly prescribed for empiric and targeted treatment of serious gram-positive infections, but optimal dosing in neonates and infants is informed by sparse data. Accurate dosing among pediatric patients is further hampered by rapid changes in body weight and composition along with limited pharmacokinetic data. We aimed to quantify relationships between vancomycin exposure in neonates and infants to patient characteristics, and to identify any dose adjustments to accommodate changes in body composition and weight with patient age.

Description of Methods & Materials: We collected data on neonates and infants who received vancomycin for empiric therapy or targeted therapy of a known gram-positive infection at a level III NICU between January 2018 and August 2020. The data collected included patient dose of vancomycin, vancomycin dosing interval, initial vancomycin trough level, concomitant antimicrobials administered, serum creatinine, BUN levels, weight, height, sex and race. Vancomycin concentrations were collected as part of routine care. Trough concentrations in clinical settings have been targeted to 10 to 20 mg/L to achieve an AUC_0-24:MIC >400 when the MIC is 1 mg/L. Dose-normalized AUC values were plotted as a function of body weight, and nonlinear regression was implemented to quantify the relationship.

Data & Results: Data encompassed 48 neonates and infants, with a median postmenstrual age of 31 weeks and a median weight of 1.23 kg at the time of vancomycin dosing. Among the pediatric patients, only 29% (14 neonates) achieved the targeted trough levels initially. However, after implementing adjustments to attain therapeutic levels, the percentage increased to 31% (15 neonates). Specifically, out of 25 trough levels that were adjusted, 15 successfully met the target trough levels, while the remaining 10 fell below the targeted trough levels. The median initial trough was 8.70 mg/L, and the median AUC was 534.9 mg*h/L. The median dose of vancomycin administered was 15.9 mg, with doses ranging from 6.80 mg to 63 mg. The study found a direct linear relationship between trough and AUC. Table 1: The dosing varied per patient according to their weight, while the dosing interval was determined using postmenstrual age (PMA) and postnatal age. Figure 1: The dose-normalized AUC decreased as body weight increased. Our findings suggest that vancomycin clearance can be correlated to PMA, weight, and serum creatinine levels. Nonlinear regression of dose-normalized AUC versus body weight showed an exponential decrease in total exposure as body weight increased.

Interpretation, Conclusion or Significance: This study's results improve understanding of pharmacokinetics of vancomycin in neonates and infants and its impact on clinical decision-making. The majority of initial vancomycin troughs observed in this study were outside the desired range of 10-20 mg/L and required adjustments to reach therapeutic levels. The findings from this study can inform clinical practice and help ensure that neonates and infants receive the most effective and safe treatment possible.

Disclosures: