Evaluating the Relationship between Vancomycin Trough Concentration and 24-Hour Area under the Concentration-Time Curve in Neonates

Abstract

Bacterial sepsis is a major cause of morbidity and mortality in neonates, especially those involving methicillin-resistant (MRSA). Guidelines by the Infectious Diseases Society of America recommend the vancomycin 24-h area under the concentration-time curve to MIC ratio (AUC/MIC) of >400 as the best predictor of successful treatment against MRSA infections when the MIC is ≤1 mg/liter. The relationship between steady-state vancomycin trough concentrations and AUC values (mg·h/liter) has not been studied in an Asian neonatal population. We conducted a retrospective chart review in Singapore hospitals and collected patient characteristics and therapeutic drug monitoring data from neonates on vancomycin therapy over a 5-year period. A one-compartment population pharmacokinetic model was built from the collected data, internally validated, and then used to assess the relationship between steady-state trough concentrations and AUC A Monte Carlo simulation sensitivity analysis was also conducted. A total of 76 neonates with 429 vancomycin concentrations were included for analysis. Median (interquartile range) was 30 weeks (28 to 36 weeks) for postmenstrual age (PMA) and 1,043 g (811 to 1,919 g) for weight at the initiation of treatment. Vancomycin clearance was predicted by weight, PMA, and serum creatinine. For MRSA isolates with a vancomycin MIC of ≤1, our major finding was that the minimum steady-state trough concentration range predictive of achieving an AUC/MIC of >400 was 8 to 8.9 mg/liter. Steady-state troughs within 15 to 20 mg/liter are unlikely to be necessary to achieve an AUC/MIC of >400, whereas troughs within 10 to 14.9 mg/liter may be more appropriate.

The Effectiveness of a Vancomycin Dosing Guideline in the Neonatal Intensive Care Unit for Achieving Goal Therapeutic Trough Concentrations

“…The clearance and volume estimates determined in our study are similar to those previously published in neonatal populations, suggesting that these findings have the potential to be extended to other institutions. 11,20,22 There are few studies that have published the effects of implementing a new vancomycin dosing guideline in a NICU. 23,24 A study by Grimsley and colleagues sought to evaluate population pharmacokinetics of vancomycin in neonates due to the high percentage, approximately 30% of vancomycin troughs being <5 mg/L and only 33% of first troughs in their target range of 5 to 12 mg/L.…”

“…7 Current data from NICU studies suggest a minimum vancomycin total daily dose of 40 to 60 mg/kg/day [8][9][10] to achieve desired pharmacodynamic endpoints when the MIC is ࣙ1 in some age groups, but there are still very limited data correlating vancomycin efficacy with trough concentrations or AUC-to-MIC ratios in pediatric or neonatal patients. 7,11 Over the past decade, research conducted to study vancomycin PK patterns in neonates has demonstrated that size, renal function, and age are predictors of vancomycin clearance. [7][8][9][10][11][12][13][14][15][16] Current clinical practice extrapolates neonatal vancomycin dosing and target trough concentrations from adult data.…”

“…7,11 Over the past decade, research conducted to study vancomycin PK patterns in neonates has demonstrated that size, renal function, and age are predictors of vancomycin clearance. [7][8][9][10][11][12][13][14][15][16] Current clinical practice extrapolates neonatal vancomycin dosing and target trough concentrations from adult data. Current recommendations for the dosing of vancomycin in neonates for the treatment of bacteremia are 10 mg/kg/dose, 4 though recent research has used vancomycin dosing of 15 mg/kg/dose to achieve therapeutic trough concentrations, 12,14 with one study recommending more aggressive dosing regimens up to 20 mg/kg/dose.…”

Pharmacokinetics, Tissue Distribution and Excretion of a Novel Diuretic (PU-48) in Rats

“…Because the kidneys play an important role in drug metabolism and excretory, and it is the target organ by PU-48 diuretic role. Therefore, understanding the pharmacokinetic and pharmacodynamic (PK-PD) relationship of PU-48, and its underlining mechanism, is critical [ 49 , 50 , 51 , 52 ]. In the present research, low recoveries of PU-48 parent drug indicated that PU-48 had an almost complete metabolism in rats.…”

<p>Vancomycin Dosage and Its Association with Clinical Outcomes in Pediatric Patients with Gram-Positive Bacterial Infections</p>

“…Accumulating evidence supports the efficacy of TDM based on the area under the concentration-time curve for 24 hours (AUC 24 ). [19][20][21] However, a more practical way of vancomycin TDM especially in pediatric care is still using trough levels because multiple blood samples per patient are required for monitoring AUC 24 . 22 Therefore, this study was designed to evaluate the therapeutic outcomes and resistance development risks along with potential renal toxicities of vancomycin therapy depending on initial steady-state trough levels among pediatric patients with GPB infections.…”