The relationship between vancomycin AUC/MIC and trough concentration, age, dose, renal function in Chinese critically ill pediatric patients

Abstract

To assess the pharmacokinetic parameters of vancomycin in Chinese critically ill pediatric patients, children treated with vancomycin, hospitalized in the intensive care unit were included. Samples to determine peak and trough serum concentrations were obtained on the third day of treatment. Half‐life was significantly longer in neonates and showed a decreasing trend in infants and children. In patients aged ≥1 month, AUC 24 /MIC ≥400 was achieved in 31.8% at the dose of 40 mg/kg/d, and in 48.7% at the dose of 60 mg/kg/d with an assumed MIC of 1 mg/L. Augmented renal clearance (ARC) was present in 27.3% of children, which was associated with higher vancomycin clearance and lower AUC values. A good correlation was observed between trough concentration and AUC 24 , and the trough concentration that correlated with AUC 24 of 400 were varied according to the dosage regimens, 8.42 mg/L for 6‐hintervals, and 6.63 mg/L for 8‐h intervals. To conclude, vancomycin trough concentration that related to the AUC 24 of 400 was much lower in critically ill children than that in adults. The dosage of 60 mg/kg/day did not enough for producing AUC 24 in the range of 400–600 mg h/L in critically ill children, especially in those with ARC.

Therapeutic drug monitoring of vancomycin in the case of augmented renal clearance: a case report of a paediatric patient

“…However, when it comes to defining a glomerular filtration rate cut-off value to identify an ARC state, it could be seen that there is a wide range of values in the literature. While Chen et al 7 defined ARC as a glomerular filtration rate greater than 130 mL/min/1.73 m 2 , which is accepted as a cut-off value by the vast majority of studies according to the previously done review study,1 Shimamoto et al defined ARC as an estimated glomerular filtration rate of at least 160 mL/min/1.73 m 2 8. Not only is the cut-off value of ARC important, but it is also important how it is measured.…”

Relationship between Vancomycin Trough Serum Concentrations and Clinical Outcomes in Children: a Systematic Review and Meta-Analysis

“…Therefore, the Bayesian method is difficult to perform in many hospitals in developing countries, including our hospital, which is a large tertiary teaching hospital, because of a lack of tools and required knowledge. The first-order PK equations to calculate vancomycin AUC would be the next preferred method, but of which there are certain restrictions in children on account of needing collecting 2 steady-state samples to calculate AUC ( 50 , 51 ). Second, according to a systematic review of the correlation between vancomycin trough concentrations and AUC/MIC in children, there is still a lack of research data on the target vancomycin trough concentrations in children, not to mention the target AUC/MIC.…”

Association between Augmented Renal Clearance and Inadequate Vancomycin Pharmacokinetic/Pharmacodynamic Targets in Chinese Adult Patients: A Prospective Observational Study

“…To date, few studies have focused on the association between ARC and AUC 24 /MIC indices. Chen et al [ 28 ] found that AUC 24 /MIC < 400 was more common in pediatric ARC patients from a retrospective cohort of 470 critically ill children. The present study provided evidence in adults with ARC, which is of great value for guiding vancomycin monitoring and individualized medication.…”

“…This phenomenon may be due to the fact that ARC patients tend to have relatively mild organ dysfunction and strong compensatory reserves [ 19 , 21 ]. Although evidence of the direct correlation between ARC and vancomycin treatment failure is limited, ARC has been shown to increase the likelihood of a negative outcome, owing to the clear association with subtherapeutic concentrations and lack of PK/PD target attainment [ 15 , 16 , 17 , 28 ].…”