AUC-Guided Vancomycin Dosing in Adolescent Patients With Suspected Sepsis.
Vancomycin is a first-line treatment for β-lactam-resistant Gram-positive bacterial infections. Understanding the pharmacokinetic (PK) and pharmacodynamic (PD) characteristics of vancomycin in an adolescent population is of clinical importance in this often overlooked pediatric population. This retrospective study investigated vancomycin PK-PD in an adolescent cohort (12 to 18 years of age) of 463 patients (57% male, 81% white) admitted to the Intermountain Healthcare System between January 2006 and December 2013. Population PK modeling was performed in NONMEM 7.3. Vancomycin PK was well described with a 1-compartment model that identified both body weight (WT) and creatinine clearance (CRCL) as covariates significantly impacting vancomycin disposition. The model was then utilized to determine dosing strategies that achieved the targeted area under the 24-hour time curve vs minimum inhibitory concentration (AUC0-24/MIC) ratio of ≥400. Additionally, these data were correlated with minimum steady-state concentrations (Css,min) to find an acceptable target trough concentration range in adolescents. This analysis demonstrated that Css,minranging from 10 to 12.5 mg/L were highly predictive of achieving an AUC0-24/MIC ≥400 when the MIC was ≤1 mg/L. These results suggest that the target trough concentration for adolescents may be lower than that for adults.
Department of Pharmaceutical Sciences, University of Findlay, Findlay, OH, USA.
Shankar
S
Lanke
Division of Clinical Pharmacology, Department of Pediatrics, University of Utah, Salt Lake City, UT, USA.
Tian
T
Yu
Division of Clinical Pharmacology, Department of Pediatrics, University of Utah, Salt Lake City, UT, USA.
Joseph E
JE
Rower
Division of Clinical Pharmacology, Department of Pediatrics, University of Utah, Salt Lake City, UT, USA.
Alfred H
AH
Balch
Intermountain Healthcare, Pediatric Clinical Program, Salt Lake City, UT, USA.
E Kent
EK
Korgenski
Division of Clinical Pharmacology, Department of Pediatrics, University of Utah, Salt Lake City, UT, USA.|Department of Pharmacology and Toxicology, College of Pharmacy, University of Utah College of Pharmacy, Salt Lake City, UT, USA.
Catherine M
CM
Sherwin
D000293:Adolescent; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000097:blood*; D019540:Area Under Curve; D002648:Child; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests; D012189:Retrospective Studies; D018805:Sepsis / Q000097:blood* / Q000175:diagnosis / Q000188:drug therapy; D014640:Vancomycin / Q000008:administration & dosage* / Q000097:blood*
D000900:Anti-Bacterial Agents; D014640:Vancomycin
adolescents; pediatrics; pharmacodynamics; population pharmacokinetics; vancomycin