The essential role of pharmacokinetics and pharmacodynamics (PK/PD) in optimizing antimi-crobial therapy in the intensive care unit: a fundamental strategy for mitigating bacterial re-sistance

Abstract

Antimicrobial resistance (AMR) represents one of the greatest global threats to public health, worsened by the inappropriate use of antimicrobials. In the Intensive Care Unit (ICU) environment, therapeutic effectiveness is compromised by the high prevalence of pathogens and, crucially, by the pharmacokinetic (PK) instability of critically ill patients. Objective: To explore the essential roles of Pharmacokinetics and Pharmacodynamics (PK/PD) in optimizing antimicrobial therapy in the Intensive Care Unit, identifying key strategies for mitigating bacterial resistance while considering the pathophysiological variables of critically ill patients (PK), dose–response indices (PD), and the resistance characteristics of pathogens. Methods: This study is a literature review with qualitative data analysis, based on scientific articles. The Virtual Health Library (VHL) was used as the research platform, selecting health evidence from the following databases: Online System for Search and Analysis of Medical Literature (MEDLINE), Nursing Database (BDENF), Latin American and Caribbean Health Sciences Literature (LILACS), and the Capes Portal. Inclusion criteria considered: articles published within the last 10 years, written in Portuguese, English, or Spanish. Results: Dose optimization guided by PK/PD indices (such as %fT>MIC, fCmax/MIC, and fAUC/MIC) and strategies such as extended infusion of beta-lactams and Therapeutic Drug Monitoring (TDM) is essential to counteract the pathophysiological alterations typical of sepsis, such as increased volume of distribution (Vd) and augmented renal clearance (ARC). Conclusion: Optimizing antimicrobial therapy results from a balance between: (1) the host’s pathophysiological state (PK), which determines drug concentration at the infection site; (2) the drug’s mechanism of action (PD and PK/PD indices), which defines the ideal exposure required for bacterial killing; and (3) pathogen susceptibility (MIC/resistance), which determines the difficulty of achieving the therapeutic target.