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

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 , 
(7)g Department of Intensive Care , Cliniques Universitaires St-Luc , Brussels , 

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