Impact of vancomycin pharmacokinetic/pharmacodynamic data on clinical outcomes of methicillin-resistant Staphylococcus aureus bacteremia in children
Methods: The study population consisted of hospitalized children < 18 years old with MRSA bacteremia, in whom serum Ctroughof vancomycin was determined from January 2010 to December 2013. Clinical data including demographic profiles, primary sites of infection, underlying diseases, and clinical/microbiological outcomes were retrospectively collected by reviewing medical records. AUC was calculated as daily dose/vancomycin clearance and vancomycin clearance in children was estimated by Burton revised method.
Results: A total of 42 MRSA bacteremia cases were included. The mean age of the study population was 24.6 months (range, 0-17 years) and 62% (26/42) were clinically severe cases requiring an intensive care unit stay, use of mechanical ventilation and/or death with an all-cause 30-day fatality rate of 22.5% (9/40). The vancomycin MIC50 and MIC90 were 1.0 and 2.0 μg/mL, respectively. Although Ctrough and AUC/MIC were significantly correlated (Pearson's r=0.347), the target range of AUC/MIC ≥ 400 or Ctrough ≥ 15 mcg/mL were initially achieved only in 1 (2.4%) case or 3 (7.1%) cases with the average vancomycin dosage of 37.7 mg/kg/day. Persistent bacteremia at 72 hr after initiation of vancomycin and 30-day fatality were observed more frequently in children with initial Ctrough <10 mcg/mL compared to those with Ctrough ≥10 mcg/mL [67.9% (19/28) vs 50.0% (2/4), p=0.482; 24.2% (8/33) vs 12.5% (1/8), p=0.472, respectively].
Conclusion: Although few cases with satisfactory PK/PD parameters were included in this study, it was suggested that initial Ctrough < 10mcg/mL might be associated with persistent bacteremia and higher mortality in serious MRSA bacteremia cases of children. Further study is mandatory for vancomycin dosing information to clarify optimal drug exposure and the impact on clinical outcome in the pediatric population.