Int J Antimicrob Agents. 2020 Jul 30:106124. doi: 10.1016/j.ijantimicag.2020.106124. Online ahead of print.
BACKGROUND: Modifications of antibiotics pharmacokinetics parameters have been reported in critically ill patients, resulting in a risk of treatment failure. We aimed to determine optimized amikacin (AMK), gentamicin (GEN) and tobramycin (TOB) intravenous dosing regimens in this population.
METHODS: Patients admitted to medical ICU and treated with AMK, GEN or TOB were included. Analyses were realized using a parametric population approach. Monte-Carlo simulations were performed and the probability of target attainment (PTA) was calculated using Cmax/MIC≥8 and through concentrations as targets.
RESULTS: 117 critically ill patients hospitalized, were studied. Median values of clearance (interidividual variability, ɷ2) were 3.51 L/h (0.539), 3.53 L/h (0.297), 2.70 L/h (0.339) and 5.07 L/h (0.339) for AMK, GEN, TOB and TOB with cystic fibrosis (CF), respectively. Median values of central volume of distribution were 30.2 L (0.215), 20.0 L (0.109) and 25.6 L (0.177) for AMK, GEN and TOB, respectively. Simulations showed that doses should be adjusted to the actual body weight and creatinine clearance for AMK and GEN, and according to creatinine clearance and presence of CF for TOB.
CONCLUSION: Our recommendations for treating P. aeruginosa infections in this population include using initial doses of 35mg/kg for AMK or 10mg/kg for TOB (CF and non CF patients). GEN demonstrated the best rates of target attainment against S. aureus infections with a dose of 5mg/kg. High aminoglycosides doses are required in this population, efficacy and safety targets are then conflicting andTDM remain an important tool to deal with this issue.