Datasheet for ESRD

<i>Background and Objectives: </i>Interest in the use of aminoglycosides is becoming more prevalent in clinical practice with the emergence of Gram-negative infections resistant to contemporary antibiotics. For patients undergoing chronic hemodialysis, aminoglycosides are usually administered at a low dose at the end of their hemodialysis session, but this approach remains controversial. Intradialytic infusion (IDI) of high dose of tobramycin could yield better exposure when administered early in the hemodialysis session. This study sought to characterize the pharmacokinetic profile of tobramycin IDI dosed in infected patients receiving chronic intermittent hemodialysis and to determine whether it is possible to achieve favorable pharmacokinetic targets using this approach.<i></i><br><i>Design, setting, participants, and measurements: </i>In this prospective pharmacokinetic study, a single dose (5 mg/kg) of tobramycin was administered IDI to eleven non-critically ill patients undergoing chronic intermittent hemodialysis. Blood samples were collected at selected time to determine tobramycin serum concentrations. Pharmacokinetic analysis, modelling and Monte Carlo simulations (MCS) were performed using Phoenix^TM NLME. The efficacy exposure target for non-severe Gram-negative infections and CMI≤1 were maximum concentration (C_max≥10 mg/L) and area under the curve (AUC_24h&gt;30 mg*h/L). For toxicity, the goal was to identify plasma trough concentrations &lt;2 mg/L.<i></i><br><i>Results: </i>Tobramycin disposition was best described by a zero-order input one-compartment model with two clearances. Tobramycin mean (SD) C_max, trough levels and AUC_24h were 13.1(1.3) mg/L, 1.32(0.47) mg/L and 61(23) mg*h/L, respectively. MCS run with 1000 virtual patients showed that a 5 mg/kg dose of tobramycin IDI outperformed the usual post-dialysis dosing (80% meeting all targets vs &lt; 1%, respectively).<i></i><br><i>Conclusions: </i>A single high-dose of tobramycin can achieve favorable pharmacokinetic endpoints when administered using IHI in hemodialysis patients. This dosing regimen may represent an effective and safer alternative to the usual dosing in the treatment of non-severe Gram-negative infection.