title: Limited sampling strategy for estimation of amikacin optimal sampling time in critically ill adults.
abstract: 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.
authors.affiliation: General Intensive Care Unit, Sina Teachning Hospital affiliated to the School of Medicine, Tehran University of Medical Sciences.
authors.forename: L
authors.initials: L
authors.lastname: Mahmoudi
authors.forename: A H
authors.initials: AH
authors.lastname: Mohammadpour
authors.forename: R
authors.initials: R
authors.lastname: Niknam
authors.forename: A
authors.initials: A
authors.lastname: Ahmadi
authors.forename: M
authors.initials: M
authors.lastname: Mojtahedzdeh
mesh_terms: D000293:Adolescent; D000328:Adult; D000583:Amikacin / Q000493:pharmacokinetics*; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics*; D019540:Area Under Curve; D003362:Cost-Benefit Analysis; D016638:Critical Illness; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D013048:Specimen Handling; D013997:Time Factors
chemical_list: D000900:Anti-Bacterial Agents; D000583:Amikacin
keywords: amikacin; area under the concentration curve; critically ill; limited sampling strategy; pharmacokinetics