The challenge in optimizing and adjusting the dose ofbeta-lactam antibiotics by extended infusion: an updateof the recommendations for patients with septic shock

Abstract

Beta-lactams are hydrophilic antibiotics whose pharmacokinetics are significantly altered in patients with septic shock due to pathophysiological changes, such as increased volume of distribution and renal clearance. These alterations may result in subtherapeutic plasma concentrations, increasing the risk of therapeutic failure. To counteract these effects, loading doses are recommended, which allow rapid attainment of adequate therapeutic levels. Furthermore, extended infusion of beta-lactams has been shown to be an effective strategy to
maximize drug exposure and improve clinical outcomes, reducing mortality in these critically ill patients. It is crucial to maintain full doses of beta-lactam antibiotics during the first 48 hours of treatment, regardless of renal function, to ensure therapeutic plasma concentrations and control potentially lethal infections. Evidence suggests that late dose adjustment is associated with a significant reduction in in-hospital mortality compared with early adjustments. Finally, the
implementation of these dosing strategies is essential to optimize antimicrobial management in patients with septic shock, thus improving clinical outcomes and survival.