How much vancomycin dose is enough for the MRSA infection in pediatric patients with various degrees of renal function?

Document Type: Research article

Authors

1 Department of Clinical Pharmacology, Wuhan Medical & Healthcare Center for Women and Children, Hubei, China

2 Department of Clinical Pharmacology, Wuhan Medical & Healthcare Center for Women and Children, Hubei, China.

Abstract

Today, an increase in vancomycin dose has been proposed to ensure efficacy. However, the risk of nephrotoxicity will increase with the dose. This study was aimed at evaluating the dosage regimens of vancomycin in pediatric patients based on pharmacokinetics/pharmacodynamics (PK/PD) and to optimize dosage individualization. Population pharmacokinetics analysis was performed on 155 Chinese children (aged 1 month to 16 years), which were divided into various renal function subpopulations. Monte Carlo simulation was carried to evaluate the efficacy and safety of vancomycin dosage regimens on each subpopulation. Compared with children with normal renal function as glomerular filtration rate (GFR)≥90 mL/min•1.73m2, the clearance of vancomycin decreased by 39.4% and the half life increased 1.74 fold respectively in children with moderate renal inadequacy (30≤GFR<60 mL/min•1.73m2). When vancomycin was administered as conventional dosage (40-60mg•kg-1•d-1) to against methicillin-resistant staphylococcus aureus (MRSA) with higher MICs of 1-2 mg•L-1 for children with normal renal function, the probability of efficacy target attainment( PTA) at AUC0-24h/MIC≥400 (where AUC is the area under curve and MIC is the minimum inhibitory concentration) achieved≤63.64%. While vancomycin dosage exceeded 70mg•kg-1•d-1 for children with normal renal function, 50mg•kg-1•d-1 for mild renal inadequacy (60≤GFR<90 mL/min•1.73m2), 30mg•kg-1•d-1 for moderate renal inadequacy respectively, the PTA at trough concentration above 20 mg•L-1 achieved >20%, that not to be suggested for high risk of nephrotoxicity. Considering both efficacy and safety, the conventional vancomycin dosage is not enough and adjustable interval is narrow for againsting MRSA with MICs of 1-2 mg•L-1.

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