Appropriate antimicrobial therapy in critically ill patients

Appropriate antibiotic therapy in the critically ill requires more specialised considerations than just selecting the most suitable antibiotic and adhering to traditional dosing guidelines. Unfortunately, most of the guideline recommendations are based on research that either underrepresent or exclude critically ill patients. The pathophysiology of critical illness, as in the case of intraabdominal sepsis, has many unique features unseen in noncritically ill patients. These include inconsistent changes in important physiological phenomena that govern drug disposition. It follows that the disposition of several antimicrobials is markedly different and variable in the critically ill relative to that described by the drug development clinical trials often conducted on healthy volunteers or noncritically ill patients. Drug disposition determines how much of a dose to administer; thus altered disposition simply means that the dose required for critically ill patients to ensure optimal effects is likely to be different. Indeed several clinical studies have illustrated that standard doses of antimicrobials such as beta-lactam antibiotics, vancomycin, aminoglycosides, fluoroquinolones and fluconazole are largely inadequate in critically ill patients due to high variability of changes in disposition. Therefore, dosing regimens should be tailored to the unique dosing requirements of individual patients. This chapter presents a discussion on the current understandings of special dosing considerations for appropriate antimicrobials therapy of critically ill patients with intraabdominal sepsis