649: APPLICATION OF THE HARTFORD NOMOGRAM IN CRITICALLY ILL PATIENTS A PHARMACOKINETIC STUDY

Abstract

Learning Objectives: Early attainment and maintenance of therapeutic antimicrobial drug levels are necessary to avoid treatment failure and persistence of infection. The Hartford nomogram has been utilized for extended interval dosing of aminoglycosides; however, the limited data available assessing the nomogram in the critically ill has shown accuracy in 62% of critically ill patients. The purpose of this study was to identify the appropriateness of use of the Hartford nomogram in a critically ill patient population. Methods: This was a prospective, pharmacokinetic study including patients who received an extended interval aminoglycoside dose and two serum samples collected. Patients were excluded if they were on intermittent hemodialysis, had cystic fibrosis, or appropriate serum samples were not drawn. The primary outcome was to compare the percentage of appropriately predicted dosing intervals between the Hartford nomogram and calculated two-level kinetics. Secondary outcomes included microbiological cure, average dose required to obtain target concentrations following dose adjustments, and rate of target achievement of peak goals using Hartford nomogram dosing Results: Thirty five patients were included [20 (57%) received amikacin and 15 (43%) received tobramycin]. Overall, 12 (34%) patients had an appropriately predicted dosing interval when comparing the nomogram to calculated two-level kinetics. The nomogram most accurately predicted the 24 hour dosing interval (60%); however, accuracy declined as the interval extended to 36 (26%) and 48 hours (17%). Four patients (80%) demonstrated microbiological cure, while one patient included from the tobramycin group did not achieve microbiological cure. Hartford extended interval dosing for amikacin and tobramycin resulted in attainment of target peaks in four patients (20%) and zero patients, respectively. When using two-level pharmacokinetics to calculate maintenance dosing, weight-based dosing increased for both amikacin (17 mg/kg) and tobramycin (10.5 mg/kg). Conclusions: Aminoglycoside dosing in critically ill patients should be individualized with two-level kinetics rather than a dosing nomogram to ensure pharmacokinetic optimization.