Antimicrobial Stewardship in the Intensive Care Unit: The Role of Biomarkers, Pharmacokinetics, and Pharmacodynamics

The high prevalence of infectious diseases in the intensive care unit (ICU) and consequently elevated pressure for immediate and effective treatment have led to increased antimicrobial therapy consumption and misuse. Moreover, the emerging global threat of antimicrobial resistance and lack of novel antimicrobials justify the implementation of judicious antimicrobial stewardship programs (ASP) in the ICU. However, even though the importance of ASP is generally accepted, its implementation in the ICU is far from optimal and current evidence regarding strategies such as de-escalation remains controversial. The limitations of clinical guidance for antimicrobial therapy initiation and discontinuation have led to multiple studies for the evaluation of more objective tools, such as biomarkers as adjuncts for ASP. C-reactive protein and procalcitonin can be adequate for clinical use in acute infectious diseases, the latter being the most studied for ASP purposes. Although promising, current evidence highlights challenges in biomarker application and interpretation. Furthermore, the physiological alterations in the critically ill render pharmacokinetics and pharmacodynamics crucial parameters for adequate antimicrobial therapy use. Individual pharmacokinetic and pharmacodynamic targets can reduce antimicrobial therapy misuse and risk of antimicrobial resistance.