Modified Augmented Renal Clearance Score Predicts Rapid Piperacillin and Tazobactam Clearance in Critically Ill Surgery and Trauma Patients
ARMY INST OF SURGICAL RESEARCH FORT SAM HOUSTON TX
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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 traumasurgical intensive care unit patients receiving piperacillintazobactam 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 KgmL 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 50at anMICof 16 KgmL. 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 mgdL 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.
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