Serum Concentration at 24 h With Intensive Beta-Lactam Therapy in Sepsis and Septic Shock: A Prospective Study: Beta-Lactam Blood Levels in Sepsis.

Abstract

Introduction: Early administration of appropriate antibiotics has been shown to be among the most effective interventions to reduce mortality in septic patients. We evaluated the attainment of efficacy and safety targets at 24 h associated with the use of intensive beta-lactam therapy in patients admitted to the intensive care unit for sepsis. Methods: This was a prospective study with patients who received beta-lactams for sepsis or septic shock between February 2023 and September 2023. The antibiotic dose was unadjusted for renal function and administered by a loading dose followed by extended infusions, according to local practices. Blood samples were taken at the trough 24 h after the start of the beta-lactam to obtain serum levels. These levels were compared to efficacy and innocuity thresholds found in the literature. Results: Among 36 included patients, all of them achieved serum concentrations above the minimum inhibitory concentration (MIC) for 100% of the therapeutic interval and 75% of them achieved serum concentrations above four times the MIC for 100% of the therapeutic interval. The predefined toxicity thresholds were reached by 8.3% of patients. Renal impairment was the factor most associated with the achievement of higher serum levels. Conclusion: Nonrenally adjusted doses of beta-lactams administered by extended infusion showed good attainment of effective concentrations and few toxic concentrations in critically ill patients with sepsis or septic shock. Further studies are needed to better define the association between toxic concentrations and toxicity manifestations.