The influence of sepsis on antimicrobials tissue penetration: The use of microdialysis technique to access free drug distribution

ABSTRACT

Abstract Sepsis is described as a life-threatening organ dysfunction caused by a host's response to infection, leading to an unbalance in body homeostasis. It is one of the leading causes of death in developed countries. Considering that in critically ill patients, such as those with sepsis, plasma concentrations do not necessarily reflect tissue concentrations, one way to assess tissue concentrations is through the microdialysis technique, which allows direct measurements of free drug at the site of action. This review was carried out after searching the Pubmed, Scielo and Web of Science databases, using the following descriptors (microdialysis AND (sepsis OR septic shock OR severe sepsis OR septicemia)) OR (microdialysis AND (sepsis OR septic shock OR severe sepsis) OR septicemia) AND (antimicrobial OR antibiotic OR antifungal)). The physiological changes generated by sepsis may imply changes in pharmacokinetic parameters, such as in clearance, which may be reduced in these patients and in volume of distribution, which presents an expansion, mainly due to edema. Both events contribute to a high inter- individual variability in tissue penetration of antimicrobials which is generally observed in patients with sepsis.