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Updated: Jul 15, 2026

Multiplex Therapeutic Drug Monitoring by Isotope-dilution HPLC-MS/MS of Antibiotics in Critical Illnesses
Published on: August 30, 2018
Time over minimum inhibitory concentration and variations in beta-lactam concentrations during prolonged and
Ylva Mattisson1,2, Jonas Tverring1,2
1Division of Infection Medicine, Department of Clinical Sciences, Lund University, Sweden.
Abstract:
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.
Insights
Critically ill patients with septic shock achieved high antibiotic target attainment. All patients reached concentrations above the minimum inhibitory concentration (MIC), with 83% exceeding four times the MIC.
Area of Science:
- Pharmacology
- Critical Care Medicine
- Infectious Diseases
Background:
- Antibiotic pharmacokinetics are highly variable in critically ill patients with septic shock.
- Optimizing antibiotic dosing is crucial for effective treatment of severe infections.
Purpose of the Study:
- To investigate antibiotic concentrations and time over minimum inhibitory concentration (MIC) in septic shock patients.
- To compare prolonged versus intermittent infusion strategies for cefotaxime, piperacillin-tazobactam, and meropenem.
Main Methods:
- Post hoc analysis of a prospective study involving 21 septic shock patients.
- Plasma antibiotic concentrations analyzed over 72 hours post-ICU admission.
- Target attainment calculated using MIC and epidemiological cut-off values.
Main Results:
- All patients achieved 100% time over MIC for cefotaxime, piperacillin-tazobactam, and meropenem.
- 83% of patients achieved 100% time over 4x MIC.
- Continuous renal replacement therapy was associated with exceeding upper therapeutic antibiotic targets (OR 15).
Conclusions:
- High target attainment for beta-lactam antibiotics was observed in critically ill septic shock patients.
- Prolonged infusions appear effective in achieving therapeutic antibiotic levels.
- Further research on RRT impact on antibiotic levels is warranted.
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