1. Expert Rev Anti Infect Ther. 2017 Jul;15(7):677-688. doi: 10.1080/14787210.2017.1338139. Epub 2017 Jun 19. Optimizing β-lactams treatment in critically-ill patients using pharmacokinetics/pharmacodynamics targets: are first conventional doses effective? Delattre IK(1)(2), Taccone FS(3), Jacobs F(4), Hites M(4), Dugernier T(5), Spapen H(6), Laterre PF(7), Wallemacq PE(2), Van Bambeke F(1), Tulkens PM(1). Author information: (1)a Louvain Drug Research Institute , Université catholique de Louvain , Brussels , Belgium. (2)b Department of Clinical Chemistry , Cliniques Universitaires St-Luc , Brussels , Belgium. (3)c Department of Intensive Care , Hôpital Erasme , Brussels , Belgium. (4)d Department of Infectious Diseases , Hôpital Erasme , Brussels , Belgium. (5)e Department of Intensive Care , Clinique St-Pierre , Ottignies , Belgium. (6)f Department of Intensive Care , Universitair Ziekenhuis Brussel , Brussels , Belgium. (7)g Department of Intensive Care , Cliniques Universitaires St-Luc , Brussels , Belgium. INTRODUCTION: The pharmacokinetic/pharmacodynamic index determining β-lactam activity is the percentage of the dosing interval (%T) during which their free serum concentration remains above a critical threshold over the minimum inhibitory concentration (MIC). Regrettably, neither the value of %T nor that of the threshold are clearly defined for critically-ill patients. Areas covered: We review and assess the targets proposed for β-lactams in critical illness by screening the literature since 1997. Depending on the study intention (clinical cure vs. suppression of resistance), targets proposed range from 20%T > 1xMIC to 100%T > 5xMIC. Assessment and comparative analysis of their respective clinical efficacy suggest that a value of 100%T > 4xMIC may be needed. Simulation studies, however, show that this target will not be reached at first dose for the majority of critically-ill patients if using the most commonly recommended doses. Expert commentary: Considering that critically-ill patients are highly vulnerable and likely to experience antibiotic underexposure, and because effective initial treatment is a key determinant of clinical outcome, we support the use of a target of 100%T > 4xMIC, which could not only maximize efficacy but also minimize emergence of resistance. Clinical and microbiological studies are needed to test for the feasibility and effectiveness of reaching such a demanding target. DOI: 10.1080/14787210.2017.1338139 PMID: 28571493