Effective sepsis treatment requires not only the timely administration of appropriate antimicrobials but also precise dosing to maximize patient survival in intensive care units (ICUs). However, the pharmacokinetics (PK) and pharmacodynamics (PD) of antibiotics in critically ill patients differ significantly from those in the general population. Understanding these pathophysiological changes is essential for optimizing antibiotic therapy. In this context, adequate dosing refers to strategies that achieve therapeutic drug concentrations at the infection site, ensuring both clinical and microbiological effectiveness while minimizing the risk of antibiotic-related toxicity.

Additionally, optimizing the mode of antibiotic administration—particularly for beta-lactams—through continuous infusion has shown benefits, including improved achievement of PK/PD targets, higher clinical cure rates, and better microbiological eradication.

To ensure proper antimicrobial dosing, therapeutic drug monitoring (TDM) is the preferred approach. However, TDM is not universally available in all ICUs or for all antimicrobial agents. In its absence, clinicians must rely on factors such as the patient's clinical condition, the identified pathogen, the impact of organ dysfunction requiring extracorporeal therapies, and the physicochemical properties of antimicrobials to guide dosing decisions. The pharmacokinetics of antimicrobials can vary widely between critically ill patients and even within the same patient throughout their ICU stay, emphasizing the need for individualized dosing strategies and dynamic reassessments.

This review aims to outline the key pathophysiological changes observed in critically ill patients and their influence on antimicrobial dosing decisions, while also providing practical considerations to help clinicians optimize antimicrobial therapy in this patient population. Finally, the outstanding challenges in delivering optimal antimicrobial therapy to critically ill patients will be explored, highlighting areas for future research.