Abstract
Optimal vancomycin exposure is important to minimize treatment failure of methicillin-resistant Staphylococcus aureus (MRSA) bacteremia. We aimed to analyze the impact of initial vancomycin pharmacokinetic/pharmacodynamic (PK/PD) parameters, including the initial vancomycin C trough and the area under the curve (AUC)/minimal inhibitory concentration (MIC) on the outcomes of pediatric MRSA bacteremia. The study population consisted of hospitalized children aged between 2 months and 18 years with MRSA bacteremia, in whom C trough was measured at least one time within the time period of January 2010 to March 2018. Demographic profiles, underlying diseases, and clinical/microbiological outcomes were abstracted retrospectively. During the study period, 73 cases of MRSA bacteremia occurred in children with a median age of 12.4 months. Severe clinical outcomes leading to intensive care unit stay and/or use of mechanical ventilation occurred in 47.5% (35/73); all-cause 30-day mortality was 9.7% (7/72). The median dosage of vancomycin was 40.0 mg/kg/day. There was a weak linear relationship between C trough and the corresponding AUC/MIC (r = 0.235). ROC curves for achieving an AUC/MIC of 300 suggested that the initial C trough at 10 μg/mL could be used as a cut-off value with a sensitivity of 90.5% and a specificity of 44%. Although persistent bacteremia at 48-72 hours after vancomycin administration was observed more frequently when the initial C trough was < 10 μg/mL and initial AUC/MIC was < 300, initial AUC/MIC < 300 was the only risk factor associated with persistent bacteremia at 48-72 hours (adjusted OR 3.05; 95% CI, 1.07-8.68). Initial C trough and AUC/MIC were not associated with 30-day mortality. Although there was a weak relationship between C trough and AUC/MIC, initial AUC/MIC < 300 could be used as a predictor of persistent MRSA bacteremia at 48-72 hours. Further prospective data on optimal vancomycin dosing are necessary to improve clinical and microbiological outcomes in pediatric MRSA bacteremia.
Highlights
Methicillin-resistant Staphylococcus aureus (MRSA) is one of the major health concerns in both healthcare-associated and community-acquired infections in children, and clinical outcomes of MRSA bacteremia are considered to be worse than cases caused by methicillin-susceptible S. aureus (MSSA) [1, 2]
Recent studies have suggested that high concentrations of vancomycin may not be necessary for pediatric populations; vancomycin C trough 7–10 μg/mL could predict the achievement of area under the curve (AUC)/minimal inhibitory concentration (MIC) > 400 at a dose of 15 mg/kg/dose every 6 hours in the case of patients with normal renal function, if the MIC 1 μg/mL [6], and the risk of vancomycin nephrotoxicity may increase if C trough exceeds the predetermined range [7,8,9]
We analyzed the relationship between initial vancomycin C trough and AUC/MIC, and the impact of these PK/PD parameters on clinical/microbiological outcomes of MRSA bacteremia in a pediatric population
Summary
Methicillin-resistant Staphylococcus aureus (MRSA) is one of the major health concerns in both healthcare-associated and community-acquired infections in children, and clinical outcomes of MRSA bacteremia are considered to be worse than cases caused by methicillin-susceptible S. aureus (MSSA) [1, 2]. To achieve favorable clinical outcomes while avoiding vancomycin toxicity associated with an overdose, the methods of monitoring of vancomycin administration have been studied. The results of these studies suggested that a ratio of the area under the curve to the minimum inhibitory concentration (AUC/MIC) has been correlated with efficacy in experiments conducted in vitro [3]. C trough is not highly correlated with AUC/MIC and is insufficient as a surrogate marker for clinical outcomes, in pediatric populations and in adults [10, 11]
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