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Advisor(s)
Abstract(s)
A fundamental step in the successful management of sepsis and septic shock is early
empiric antimicrobial therapy. However, for this to be effective, several decisions must be addressed
simultaneously: (1) antimicrobial choices should be adequate, covering the most probable pathogens;
(2) they should be administered in the appropriate dose, (3) by the correct route, and (4) using the
correct mode of administration to achieve successful concentration at the infection site. In critically
ill patients, antimicrobial dosing is a common challenge and a frequent source of errors, since these
patients present deranged pharmacokinetics, namely increased volume of distribution and altered
drug clearance, which either increased or decreased. Moreover, the clinical condition of these patients
changes markedly over time, either improving or deteriorating. The consequent impact on drug
pharmacokinetics further complicates the selection of correct drug schedules and dosing during
the course of therapy. In recent years, the knowledge of pharmacokinetics and pharmacodynamics,
drug dosing, therapeutic drug monitoring, and antimicrobial resistance in the critically ill patients
has greatly improved, fostering strategies to optimize therapeutic efficacy and to reduce toxicity
and adverse events. Nonetheless, delivering adequate and appropriate antimicrobial therapy is
still a challenge, since pathogen resistance continues to rise, and new therapeutic agents remain
scarce. We aim to review the available literature to assess the challenges, impact, and tools to optimize individualization of antimicrobial dosing to maximize exposure and effectiveness in critically
ill patients.
Description
Keywords
pharmacokinetics antibiotics sepsis