How to Use Aminoglycosides in the Intensive Care Unit

Abstract

The aminoglycosides (AG) schedule of administration in patients with septic shock consists in a high dose once daily (7-9 mg/kg of gentamicin/tobramycin; 2530 mg/kg of amikacine) in a 30 minutes infusion and for a maximum of 5 days. The total body weight must be used except for obese patients. AG administration in critically ill septic patients is complicated by an extreme inter-and intraindividual variability in drug pharmacokinetic characteristics: the volume of distribution is frequently increased, while the elimination constant can be either increased or decreased. The case for patients needing continuous or discontinuous renal replacement therapy is addressed in this review. The Cmax objective is 8-10 fold the MIC then taper the dose as soon as the MIC has been provided, which unfortunately often takes longer than the AG-treatment duration. Several therapeutic drug monitoring (TDM) options have been proposed in critically ill patients: simple linear dose adjustment according to AG serum concentration to nomograms, other pharmacological method based on the determination of intermediate AG assay before Cmin, and Bayesian methods. The translation of these complex TDM methods into better clinical outcomes remains uncertain but these programs could reduce AG-associated NT in patients with septic shock. Therefore, the questions of the possible application of TDM to ICU setting remain unanswered. Indeed, high workload, often in situation of emergency, is a substantial obstacle to a sophisticated optimized AG administration. A simple linear adjustment of AG doses is recommended so far. All these recommendations have led to a global decrease of AG nephrotoxicity for the last decades.