Role of fluid status markers as risk factors for suboptimal vancomycin concentration during continuous infusion in...

Vancomycin is widely used in neonatal sepsis but proportion of newborn reaching recommended concentration is variable. Fluid status impact on vancomycin level remains understudied. We aimed to study fluid factors impacting vancomycin concentration at 24 h of treatment. We performed a prospective and retrospective observational monocentric study of NICU patients requiring a vancomycin treatment. We used a continuous infusion protocol, with age-appropriate loading and maintenance doses. Vancomycin target serum concentration after 24 h (C_24h) was above 20 mg/L. Demographic, infections, and organ failure variables were analyzed as potential predictors of C_24h. Over the study period, 70 infective episodes in 52 patients were included. At treatment initiation, the median post-natal age was 12.5 days (IQR 7-23), post menstrual age 30 weeks (IQR 28-35), and median weight 1140 g (IQR 835-1722). Germs isolated were mainly gram-positive with 73.5% being coagulase-negative Staphylococci. Median C_24h was 18.7 mg/L (IQR 15.4-22.4). Overall, 41 (58.6%) treatments had a C_24h < 20 mg/L. After multivariate analysis, higher creatinine level (OR 1.03 (95% CI 1.002-1.06)) was associated with C_24h ≥ 20 mg/L; weight gain the day before infection (OR 0.21 (95% CI 0.05-0.79)) and positive biomarkers of inflammation (OR 0.22 (0.05-0.94)) were associated with C_24h < 20 mg/L.

Vancomycin C_24h was underdosed in 60% of patients and factors linked to changes in vancomycin pharmacokinetic such as volume of distribution and clearance, linked to creatinine level, inflammation, or weight gain, were identified.

• Adjustment of vancomycin regimen remains difficult due to inter- and intra-individual variability of vancomycin pharmacokinetics. • Impact of fluid status on vancomycin concentration in critically ill neonates is incompletely studied.

• Proportion of patients with adequate vancomycin concentration using a target adapted to nosocomial gram-positive bacteria MIC is low. • We confirmed the role of creatinine level and report two new factors associated with low vancomycin concentration: presence of systemic inflammation and weight gain.