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Published on: August 30, 2018
Continuous versus intermittent infusion of cefotaxime in critically ill patients: a randomized controlled trial
Heleen Aardema1, Wouter Bult1,2, Kai van Hateren2
1University of Groningen, University Medical Center Groningen, Department of Critical Care, Groningen, The Netherlands.
Background:
In critical care patients, reaching optimal β-lactam concentrations poses challenges, as infections are caused more often by microorganisms associated with higher MICs, and critically ill patients typically have an unpredictable pharmacokinetic/pharmacodynamic profile. Conventional intermittent dosing frequently yields inadequate drug concentrations, while continuous dosing might result in better target attainment. Few studies address cefotaxime concentrations in this population.
Objectives:
To assess total and unbound serum levels of cefotaxime and an active metabolite, desacetylcefotaxime, in critically ill patients treated with either continuously or intermittently dosed cefotaxime.
Methods:
Adult critical care patients with indication for treatment with cefotaxime were randomized to treatment with either intermittent dosing (1 g every 6 h) or continuous dosing (4 g/24 h, after a loading dose of 1 g). We defined a preset target of reaching and maintaining a total cefotaxime concentration of 4 mg/L from 1 h after start of treatment. CCMO trial registration number NL50809.042.14, Clinicaltrials.gov NCT02560207.
Results:
Twenty-nine and 30 patients, respectively, were included in the continuous dosing group and the intermittent dosing group. A total of 642 samples were available for analysis. In the continuous dosing arm, 89.3% met our preset target, compared with 50% in the intermittent dosing arm. Patients not reaching this target had a significantly higher creatinine clearance on the day of admission.
Conclusions:
These results support the application of a continuous dosing strategy of β-lactams in critical care patients and the practice of therapeutic drug monitoring in a subset of patients with higher renal clearance and need for prolonged treatment for further optimization, where using total cefotaxime concentrations should suffice.
Insights
Continuous cefotaxime dosing in critical care patients significantly improved target drug concentrations compared to intermittent dosing. This supports continuous administration and therapeutic drug monitoring for optimized treatment in this population.
Area of Science:
- Pharmacology
- Critical Care Medicine
- Infectious Diseases
Background:
- Achieving optimal beta-lactam antibiotic concentrations in critically ill patients is challenging due to resistant microorganisms and unpredictable pharmacokinetics.
- Standard intermittent dosing often fails to maintain adequate drug levels, whereas continuous infusion may improve target attainment.
- Limited research exists on cefotaxime concentrations in this vulnerable patient group.
Purpose of the Study:
- To evaluate and compare total and unbound serum concentrations of cefotaxime and its active metabolite, desacetylcefotaxime.
- To assess the efficacy of continuous versus intermittent cefotaxime dosing strategies in critically ill patients.
Main Methods:
- Randomized trial involving adult critical care patients requiring cefotaxime.
- Patients received either intermittent dosing (1g every 6 hours) or continuous dosing (4g/24 hours after a loading dose).
- Target: maintain total cefotaxime concentration of 4mg/L from 1 hour post-treatment initiation.
Main Results:
- Continuous dosing achieved the target concentration in 89.3% of patients, versus 50% in the intermittent group.
- A total of 642 samples were analyzed across 59 patients (29 continuous, 30 intermittent).
- Higher creatinine clearance on admission was associated with failure to reach target concentrations.
Conclusions:
- Continuous cefotaxime infusion is a superior strategy for achieving target concentrations in critical care settings.
- Therapeutic drug monitoring is recommended for specific patients with high renal clearance requiring extended treatment.
- Total cefotaxime concentrations are sufficient for monitoring in this context.
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