Optimizing β-lactams treatment in critically-ill patients using pharmacokinetics/pharmacodynamics targets: are first conventional doses effective?. Issue 7 (3rd July 2017)

• Record Type: Journal Article
• Authors: Delattre, Isabelle K.; Taccone, Fabio S.; Jacobs, Frédérique; Hites, Maya; Dugernier, Thierry; Spapen, Herbert; Laterre, Pierre-François; Wallemacq, Pierre E.; Van Bambeke, Françoise; Tulkens, Paul M.
• Is Part Of: Expert review of anti-infective therapy. Volume 15:Issue 7(2017)
• Page Start: 677
• Page End: 688
• Publication Date: 2017-07-03
• Subjects: Β-lactams -- critically-ill patients -- PK/PD targets -- first dose -- maximal efficacy; Anti-infective agents -- Research -- Periodicals; 616.90461
• DOI: 10.1080/14787210.2017.1338139
• Languages: English
• ISSNs: 1478-7210

Abstract

ABSTRACT: 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.