Pharmacokinetics-pharmacodynamics perspective to optimizing therapy with beta-lactams in critically ill patients: an update

INTRODUCTION: Several unmet clinical needs regarding the role of pharmacokinetic/pharmacodynamic (PK/PD) target attainment of beta-lactams still remains to be addressed in critically ill patients. AREAS COVERED: This review provides an updated critical reappraisal focused at optimizing the loading dose (LD) and the maintenance dose (MD) for attaining an aggressive PK/PD target. A literature search was carried out on PubMed-MEDLINE. Challenging pathophysiological conditions impacting on volume of distribution (septic shock, major burns, polytrauma) and clearance (i.e. sepsis-associated acute kidney injury [AKI], continuous renal replacement therapy [CRRT] associated or not with special hemoadsorption filters, and augmented renal clearance [ARC]) were comprehensively reviewed. EXPERT OPINION: Evidence on the PK/PD perspective to optimizing antimicrobial therapy with beta-lactams in critically ill patients is ever growing. Some unmet clinical needs still require further investigation by means of well-designed prospective studies. Specifically, defining appropriate strategies focused on aggressive PK/PD target attainment of novel beta-lactams in some challenging scenarios, namely major burns, polytrauma, ARC, sepsis-associated transient AKI, would be fundamental in helping intensivists to optimize treatment in different special critical populations. In this regard, population PK/PD studies could represent the starting point on which the TDM-guided approaches and could add further value to providing a tailored 'patient-centric' therapy.