ObjectiveCritically ill patients with septic shock frequently exhibit variability in antibiotic pharmacokinetics. We aimed to investigate the antibiotic concentration and time over minimum inhibitory concentration in patients with septic shock treated with prolonged and intermittent infusions.MethodsWe performed a post hoc analysis of a prospective study of patients with septic shock admitted to the intensive care unit at Helsingborg hospital from 2016 to 2018. Plasma samples were collected every 4 h for the initial 72 h following intensive care unit admission. We analyzed samples for cefotaxime (intermittent dosing), piperacillin-tazobactam (prolonged infusion), and meropenem (prolonged infusion) concentrations. Minimum inhibitory concentration values determined using epsilometer tests of bloodstream pathogens were collected, and corresponding epidemiological cut-off values were used for target attainment calculations. The primary outcome was percentage time over minimum inhibitory concentration or four times the minimum inhibitory concentration. We used linear mixed effects models for analyzing repeated measures of continuous variables.ResultsIn total, 21 patients met the criteria for septic shock, and a total of 341 samples were analyzed (average 16 per patient). All patients achieved concentrations above the minimum inhibitory concentration for 100% of the time, and 83% of the patients achieved concentrations above 4 times the minimum inhibitory concentration for 100% of the time. We found an association between continuous renal replacement therapy and levels of antibiotics exceeding the upper therapeutic target (p = 0.021, odds ratio: 15, 95% confidence interval: 1 to 974).ConclusionTarget attainment was high in this cohort study of critically ill patients with septic shock, with all patients achieving beta-lactam concentrations over the minimum inhibitory concentration 100% of the time.
Keywords: Septic shock; beta-lactam antibiotics; continuous renal replacement therapy; target attainment; therapeutic drug monitoring.