• Sean N Avedissian, Erin Bradley, Diana Zhang, John S Bradley, Lama H Nazer, Tri M Tran, Austin Nguyen, and Jennifer Le.
• 1University of California San Diego, Skaggs School of Pharmacy and Pharmaceutical Sciences and School of Medicine, La Jolla, CA. 2Miller Children's Hospital, Long Beach, CA. 3Department of Pharmacy Practice, Midwestern University, Chicago College of Pharmacy, Downers Grove, IL. 4Division of Critical Care Medicine in the Department of Pediatrics at Northwestern University Feinberg School of Medicine, Ann & Robert H. Lurie Children's Hospital, Chicago, IL. 5The Division of Infectious Diseases, University of San Diego, School of Medicine and Rady Children's Hospital of San Diego, La Jolla, CA. 6Department of Pharmacy, King Hussein Cancer Center, Amman, Jordan.
• Pediatr Crit Care Me. 2017 Sep 1; 18 (9): e388-e394.

ObjectivesThe objectives of this study were to: 1) evaluate the prevalence of augmented renal clearance in critically ill pediatric patients using vancomycin clearance; 2) derive the pharmacokinetic model that best describes vancomycin clearance in critically ill pediatric patients; and 3) correlate vancomycin clearance with creatinine clearance estimated by modified Schwartz or Cockcroft-Gault.DesignRetrospective, two-center, cohort study from 2003 to 2016.SettingClinical drug monitoring services in the PICUs at two tertiary care, teaching hospitals.PatientsChildren from 1 to 21 years old.InterventionsNone.Measurements And Main ResultsIdentify patients with augmented renal clearance (vancomycin clearance ≥ 130 mL/min/1.73 m used as definition of augmented renal clearance). Derive final population-based pharmacokinetic model and estimate individual patient pharmacokinetic parameters. Compare estimated glomerular filtration rate (modified Schwartz or Cockcroft-Gault depending on age < or ≥ 17 yr) with vancomycin clearance. Augmented renal clearance was identified in 12% of 250 total subjects. The final population-based pharmacokinetic model for vancomycin clearance (L/hr) was 0.118 × weight (e). Median vancomycin clearance in those with versus without augmented renal clearance were 141.3 and 91.7 mL/min/1.73 m, respectively (p < 0.001). By classification and regression tree analysis, patients who were more than 7.9 years old were significantly more likely to experience augmented renal clearance (17% vs 4.6% in those ≤ 7.9 yr old; p = 0.002). In patients with augmented renal clearance, 79% of 29 had vancomycin trough concentrations less than 10 µg/mL, compared with 52% of 221 in those without augmented renal clearance (p < 0.001). Vancomycin clearance was weakly correlated to the glomerular filtration rate estimated by the modified Schwartz or Cockcroft-Gault method (Spearman R = 0.083).ConclusionsAugmented renal clearance was identified in one of 10 critically ill pediatric patients using vancomycin clearance, with an increase of approximately 50 mL/min/1.73 m in those with augmented renal clearance. As augmented renal clearance results in subtherapeutic antibiotic concentrations, optimal dosing is essential in those exhibiting augmented renal clearance.

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