Modified Augmented Renal Clearance Score Predicts Rapid Piperacillin and Tazobactam Clearance in Critically Ill Surgery and Trauma Patients.

摘要

BACKGROUND: Recent evidence suggests that current antimicrobial dosing may be inadequate for some critically ill patients. A major contributor in patients with unimpaired renal function may be Augmented Renal Clearance (ARC), wherein urinary creatinine clearance exceeds that predicted by serum creatinine concentration. We used pharmacokinetic data to evaluate the diagnostic accuracy of a recently proposed ARC score. METHODS: Pharmacokinetic data from trauma/surgical intensive care unit patients receiving piperacillin/tazobactam were evaluated. We combined intermediate scores (4Y6 points) into a single low score (e6) group and compared pharmacokinetic parameters against the high (Q7) ARC score group. Diagnostic performance was evaluated using median clearance and volume of distribution, area under the antibiotic time-concentration curve (AUC), and achievement of free concentrations greater than a minimum inhibitory concentration (MIC) of 16 Kg/mL for at least 50% of the dose interval ( f T 9 MIC Q 50%). Alternative dosing strategies were explored in silico. RESULTS: The ARC score was 100% sensitive and 71.4% specific for detecting increased clearance, increased volume of distribution, decreased AUC, and f T 9 MIC G 50%at anMICof 16 Kg/mL. The area under the receiver operating characteristic curve was 0.86 for each, reflecting a high degree of diagnostic accuracy for the ARC score. Serum creatinine less than 0.6 mg/dL had comparable specificity (71.4%) but was less sensitive (66.7%) and accurate (area under the receiver operating characteristic curve, 0.69) for detecting higher clearance rates. Monte Carlo pharmacokinetic simulations demonstrated increased time at therapeutic drug levels with extended infusion dosing at a drug cost savings of up to 66.7% over multiple intermittent dosing regimens.