Evaluation of early achievement of an AUC/MIC of >400 for Vancomycin in children with methicillin-resistant Staphylococcus aureus bacteremia

Abstract Background Methicillin-resistant Staphylococcus aureus (MRSA) bacteremia causes morbidity and mortality in children. The standard treatment for MRSA bacteremia is vancomycin, which should achieve a 24 hour area under the curve over the minimum inhibitory concentration ratio (AUC/ MIC) of >400. Whether or not attaining AUC/ MIC >400 early in the disease course improves outcomes in children is controversial. The aim of our study was to determine whether early achievement of AUC/ MIC >400 improved outcomes in children with MRSA bacteremia. Methods Children whose blood culture grew MRSA between March 2010 and April 2017 at Tokyo Metropolitan Children’s Medical Center were enrolled. The exclusion criteria were no vancomycin administration, use of extracorporeal membrane oxygenation, no data on dosage and vancomycin MIC, and cases of contamination. Susceptibility testing was performed by a microdilution method. The outcomes of patients who achieved an AUC/MIC >400 at the first assessment prior to the Fourth or Fifth vancomycin dose were compared with those of patients who did not. The clinical outcomes were persistent bacteremia on Days 3 and 7, mortality at 30 days, and the recurrence of MRSA bacteremia. Results In total 175 MRSA isolates from 50 children were identified. Of these 56 episodes were eligible for enrollment. Forty-one subjects (73.2%) were boys. The median age was 9 months (interquartile range: 1.8–120.5 months). The median initial dose of vancomycin was 40 mg/kg (interquartile range: 30–44.3 mg/kg). Among MRSA isolates, vancomycin MIC of < 0.5 mcg/mL, 1 mcg/mL and 2 mcg/mL were 1 (1.8%), 53 (94.6%) and 2 (3.6%), respectively. Fifteen patients (26.8%) achieved AUC/MIC >400 early. The two groups did not differ significantly in terms of persistent bacteremia on Days 3 (P = 0.96) or 7 (P = 0.82), mortality at 30 days (P = 0.47), or the recurrence of MRSA bacteremia (P = 1.0). Conclusion Children with bacteremia who achieved AUC/ MIC>400 early did not differ significantly from children who did not in terms of their clinical outcomes. Disclosures All authors: No reported disclosures.