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Children's Continuous Infusion of Vancomycin
Vancomycin is a glycopeptide antibiotic used to treat a wide variety of systemic Gram-positive infections, including methicillin resistantStaphylococcus aureus(MRSA) and methicillin resistant coagulase-negativeStaphylococcus(MRCNS) in adult and pediatric populations. Vancomycin exhibits time-dependent bactericidal activity, meaning that the time in which the concentration of the drug in the body is above the minimum inhibitory concentration (MIC) affects antimicrobial efficacy.
In adults, the vancomycin area under the plasma concentration-time curve (AUC) to MIC ratio (AUC/MIC) > 400 has long been the best predictor of clinical and bacteriological efficacy for patients with severe infections caused by MRSA . Recently, a revised consensus guideline developed by different scientific associations has been published, recommending a target of an AUC/MIC ratio of 400 to 600 (assuming a MIC of 1 mg/L) for empiric dosing in both adult and pediatric patients to maximize clinical efficacy and minimize nephrotoxicity . However, there is a lack of evidence for this parameter in children due to the complexity of vancomycin clearance in the various pediatric age groups, and the differences in tissue site-of-infection drug exposure as a consequence of higher pharmacokinetic variability . Due to the impracticalities of calculating the AUC, target trough concentrations of 15 to 20 mg/L are used as a surrogate marker in adults with normal renal function when MIC is ≤1 mg/mL . For the pediatric population, there is more controversy in establishing a target trough concentration. The majority of studies suggest a trough concentration between 6–11 mg/L to achieve AUC/MIC > 400, however no consensus has been reached .
In adults, continuous infusion of vancomycin (CIV) has been evaluated as an alternative to intermittent infusion of vancomycin (IIV) with potential advantages including: earlier concentration target attainment, less variability in serum concentrations, ease of drug level monitoring, and lower risk of nephrotoxicity . When compared to adults, achieving therapeutic serum vancomycin concentrations (SVCs) with IIV in children requires higher doses and shorter intervals given their increased renal clearance . However, higher doses have also been associated with increased nephrotoxicity in pediatrics .
This systematic review aims to provide efficacy and safety evidence for CIV within the pediatric population
2. Clinical Efficacy
The entry is from 10.3390/antibiotics10080912
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