An Assessment of Vancomycin Pharmacokinetic Variability in Pediatric Cardiology Patients

Abstract

Objectives To establish the steady-state pharmacokinetic profile of vancomycin in pediatric cardiology patients; determine an empiric vancomycin dose; and evaluate the correlation between fluid balance and volume of distribution (Vd), serum creatinine and clearance (CL), and daily dose of furosemide and Vd. Methods Retrospective pharmacokinetic evaluation in 36 pediatric cardiology, cardiac surgery, or cardiac transplant patients treated with vancomycin. The pharmacokinetic profile for vancomycin including elimination half-life (t1/2), elimination rate constant (ke), volume of distribution (Vd), and clearance (CL) was calculated for each patient. The relationship between fluid balance and Vd, serum creatinine and CL, and the total daily dose of furosemide and Vd was evaluated. Results The patient population had an average half-life of 5.9±1.2 hr and a Vd of 0.4±0.12 L/kg. A statistically significant correlation was noted between serum creatinine and CL (r2=0.19, P<0.01). Additionally, a statistically significant correlation exists between the total daily furosemide dose and the Vd (r2=0.31, P<0.01). A dose of 10 mg/kg/dose every 12 hrs was predicted to result in the greatest number of serum vancomycin concentrations within the reference range. Conclusions Routine monitoring of serum vancomycin concentrations is prudent for this population, and special consideration should be given to those with elevated serum creatinine and to those receiving large doses of furosemide.

Improved Vancomycin Dosing in Children Using Area Under the Curve Exposure

“…Some studies focused exclusively on pediatric patients with cancer, cardiac disease, critically-ill status or obesity. 11–13, 16, 18–20 In contrast, we included children of varying ages (except for neonates and infants < 3 months) and weights (i.e., obese), different concomitant disease states (e.g., cancer), concurrent use of nephrotoxic drugs, and stay in the intensive care unit. This diversity may have contributed to the intersubject variability in our estimate of CL.…”

Empirical Vancomycin Dosing in Pediatric Patients with Congenital Heart Disease and the Impact of Cardiopulmonary Bypass on Trough Concentrations

“…In addition to these two investigations, the only other existing reports specifically targeting the use of vancomycin in the pediatric congenital or acquired heart disease population consist entirely of expert opinion . The AHA released an updated scientific statement in 2015 on the management of infective endocarditis in childhood, advocating for vancomycin doses of 60 mg/kg/day divided every 6 hours .…”

“…Whereas the earlier cited study aimed for a goal vancomycin trough concentration of 5–10 μg/dl, it is standard practice at our institution to aim for concentrations of 8–15 μg/dl obtained ahead of bacterial identification and antimicrobial susceptibility information availability. Vancomycin concentrations within this goal range are typically not met with clinical intervention in the form of dose adjustments, as long as there is concomitant clinical improvement and the absence of the development of AKI.…”

“…Indications ranging from perioperative prophylaxis after congenital heart surgery to treatment for endocarditis, in addition to the consideration of minimum inhibitory concentration (MIC) of identified organisms, may necessitate significantly different doses to reach disparate goal vancomycin trough concentrations and thus achieve maximum safety and efficacy. One study supports the use of 20 mg/kg/day divided every 12 hours to achieve a goal vancomycin trough of 5–10 μg/ml in pediatric cardiology patients . Although the American Heart Association (AHA) has released dosing guidelines for patients with endocarditis, evidence‐based dosing guidelines specifically for pediatric patients with CHD are lacking …”

Optimizing Guideline-Recommended Antibiotic Doses for Pediatric Infective Endocarditis

“…PK modeling suggests that in children with congenital heart disease, doses between 30 and 40 mg/kg/d, rather than 60 mg/kg/d recommended by the 2015 IE Update, predict trough vancomycin concentrations of approximately 12 to 16 mg/L. 9 Because of the underlying disease state, greater PK variability is also observed in these patients. 10 The 2015 IE Update recommends a maximum daily vancomycin dose of 2 g without supporting evidence, and we posit that using the recommended maximum may result in suboptimal AUC:MIC exposures for many patients.…”