Limited sampling strategy for estimation of amikacin optimal sampling time in critically ill adults

Aminoglycosides are a class of antibiotics that are commonly used in the treatment of gram-negative pathogens in the critically ill population. Unfortunately, dosing of these aminoglycosides in critically ill patients is difficult due to their altered pharmacokinetics in the critically ill and narrow therapeutic index. In this study, we evaluated whether a limited sampling strategy can be used to predict the area under the concentration (AUC) curve of amikacin concentrations over a 24-hour period after a single dose of intravenous amikacin (25 mg/kg). This open-labelled, non-comparative prospective study recruited 20 adult critically ill trauma patients with a diagnosis of hospital-acquired infection. We assessed the best estimate of plasma amikacin concentrations over a 24-hour period by multiple stepwise regression, using nine blood samples during this study period as the gold standard. Using a jackknife procedure, the AUC of amikacin over a 24-hour period was estimated by choosing a combination of the amikacin concentrations measured at different time-points. Overall, the mean prediction error of all models was not statistically different from zero (P >0.05). Based on bias and imprecision, all models gave good estimate of AUC of amikacin over a 24-hour period, but a two-point sampling strategy at 1.5 and 6 hours post-dose appeared to offer the best compromise between accuracy and cost-effectiveness in optimising the dosing of amikacin in critically ill patients.