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

IntroductionSeveral 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 coveredThis 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 opinionEvidence 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.