Vancomycin Pharmacologic Modeling in Critically-Ill Children Following Modified IDSA Guidelines

Purpose: This study evaluated the success rates of current pediatric vancomycin dosing regimens in achieving initial serum trough concentrations ≥ 10 mg/L and the projected initial dosing requirements to achieve serum trough concentration 10-20 mg/L in the critically-ill child as recommended by the IDSA.

Methods: A retrospective chart review of 40 pediatric patients in the PICU receiving vancomycin between May 1, 2009 thru May 1, 2010 was performed. Patient medical history, hospital course, antimicrobial therapy including resultant vancomycin serum concentrations, microbiologic results, renal function and patient outcomes were documented. Pharmacokinetic parameters were calculated using a one-compartment model.

Results: The currently published initial dosing regimens achieved trough concentrations ≥ 10mg/L in 52% of critically-ill patients. The 20 mg/kg every 8 hour regimen was mostly likely to obtain initial target trough concentrations as compared to other dosing regimens (p<0.05). A total of 83 vancomycin sample pair were evaluated to determine pharmacokinetic characteristics. Mean vancomycin clearance (0.134 L/kg/hr) was similar to that seen in other pediatric patient populations. Based upon microbiologic data, a projected dose of 75-90 mg/kg/day would be needed initially to achieve an AUC/MIC ratio >400 in MRSA patients with a MIC=2.

Conclusion: The current dosing recommendations of vancomycin in pediatric dosing references do not consistently achieve serum trough concentrations ≥ 10 mg/L in the critically-ill child. Based upon increasing MIC's associated with Staphylococcus aureus, current regimens do not achieve optimal pharmacodynamic eradication of these organisms and could possible promote resistance. A prospective study evaluating initial vancomycin doses of 75-90 mg/kg/day is warranted to assess the safety and efficacy of this higher dosing regimen in this patient population.