Understanding antimicrobial pharmacokinetics in critically ill patients to optimize antimicrobial therapy: A narrative review

Effective treatment of sepsis not only demands prompt administration of appropriate antimicrobials but also requires precise dosing to enhance the likelihood of patient survival. Adequate dosing refers to the administration of doses that yield therapeutic drug concentrations at the infection site. This ensures a favorable clinical and microbiological response while avoiding antibiotic-related toxicity. Therapeutic drug monitoring (TDM) is the recommended approach for attaining these goals. However, TDM is not universally available in all intensive care units (ICUs) and for all antimicrobial agents. In the absence of TDM, healthcare practitioners need to rely on several factors to make informed dosing decisions. These include the patient's clinical condition, causative pathogen, impact of organ dysfunction (requiring extracorporeal therapies), and physicochemical properties of the antimicrobials. In this context, the pharmacokinetics of antimicrobials vary considerably between different critically ill patients and within the same patient over the course of ICU stay. This variability underscores the need for individualized dosing. This review aimed to describe the main pathophysiological changes observed in critically ill patients and their impact on antimicrobial drug dosing decisions. It also aimed to provide essential practical recommendations that may aid clinicians in optimizing antimicrobial therapy among critically ill patients.