Therapeutic monitoring of vancomycin according to initial dosing regimen in pediatric patients

Abstract

PurposeThis study aimed to determine the optimal initial vancomycin dose to achieve appropriate trough levels in pediatric patients.MethodsWe analyzed clinical data for 309 children treated with intravenous vancomycin between 2004 and 2009 at 2 different hospitals in South Korea. The patients were 1-16 years old and exhibited normal renal function. Patient data, including reason for treatment and initial dosing regimen, were reviewed. Two subgroups were identified and compared according to initial vancomycin dose: 40 (35-45) mg/kg/day and 60 (55-65) mg/kg/day. Trough levels were obtained at steady state after at least 4 doses of vancomycin.ResultsPatients who received vancomycin had post-operation or wound-related infections (37.2%), localized infection (12.9%), catheter-related infections (9.4%), meningitis (8.7%), or endocarditis (6.8%). Pathogens were confirmed in 79 cases: 28 cases of methicillin-resistant Staphylococcus epidermidis (35.4%) and 25 of methicillin-resistant Staphylococcus aureus (31.6%). Out of the 309 patients, 201 (65%) received vancomycin at 40 mg/kg/day and 108 (35%) at 60 mg/kg/day. Average trough concentrations were significantly different between the groups (P<0.001). Trough levels over 10 mg/L were less likely to be achieved in the 40 mg/kg/day group (14%) than in the 60 mg/kg/day group (49%) (P<0.001). There were no differences in renal function deterioration between the groups.ConclusionA common vancomycin dosing regimen, 40 mg/kg/day, was not high enough to achieve trough levels of over 10 mg/L in pediatric patients. Careful drug monitoring must be performed, and increasing initial dose of vancomycin should be considered in pediatric patients.

Evaluation of Vancomycin Dosing and Corresponding Drug Concentrations in Pediatric Patients

“…The incidence of VIN in our study was similar to that of other trials in pediatric patients. [12][13][14] Although 7 patients met the criteria of our prespecifi ed defi nition of nephrotoxicity, only 2 patients had an increase in SCr of ≥0.5 mg/dL. Six of the 7 patients were receiving drugs with nephrotoxic potential in addition to vancomycin.…”

“…[7][8][9][10][11] However, for many practitioners, the use of increasing doses raises concern about patient tolerability and safety, especially with regard to vancomycin-induced nephrotoxicity (VIN). 7,8,[12][13][14] To begin to formulate a dosing approach to reach recommended vancomycin trough targets, more information about the infl uence of developmental factors in pediatrics would be desirable. This study was designed to gather information about dosing practices at this institution to determine the effect of patient age and vancomycin total daily dose on the ability to achieve a trough concentration in the recommended range.…”

Evaluation of Target Attainment of Vancomycin Area Under the Curve in Children With Methicillin-Resistant Staphylococcus Aureus Bacteremia

“…It has been shown that vancomycin dosing of 60 mg/kg/day divided every 6 hours typically achieves pre-dose trough concentrations of 15-20 μg/mL. [1-3] Serum vancomycin concentration troughs of 15-20 μg/mL often correlate with a 24 hour vancomycin concentration area under the curve (AUC 24h ; equivalent to vancomycin daily dose/vancomycin clearance) over the minimum inhibitory concentration of vancomycin for the isolated bacteria (MIC) ≥ 400 in S. aureus isolates with an MIC ≤ 1 μg/mL. [3-6] More recent literature suggests that serum vancomycin troughs of 8-9 μg/mL may achieve AUC ≥ 400.…”

“…[10, 11] Increasing drug exposure by increasing vancomycin concentrations can be associated with decreased renal function, especially with concomitant nephrotoxic agent use. [1, 3, 4, 11-13]…”

Validation of a Pediatric Population Pharmacokinetic Model for Vancomycin

“…In children with serious infections, it has been suggested that a vancomycin starting dose of 60 mg/kg/day divided every 6 hours should be used to achieve predose trough concentrations of 15-20 μg/mL. 1-3 This recommendation is based on the finding that children prescribed this regimen are more likely to achieve a 24 hour vancomycin concentration area under the curve (AUC) over the minimum inhibitory concentration of vancomycin for the isolated bacteria (MIC) ≥ 400 in S. aureus isolates with an MIC ≤ 1 μg/mL. 3-6 AUC/MIC is the pharmacodynamic index that best predicts efficacy of vancomycin in the treatment of MRSA in adults.…”