Continuous versus intermittent infusion of cefotaxime in critically ill patients: a randomized controlled trial comparing plasma concentrations

Heleen Aardema, Wouter Bult, Kai van Hateren, Willem Dieperink, Daan J Touw, Jan-Willem C Alffenaar, Jan G Zijlstra, Willem Dieperink

    Research output: Contribution to journalArticleAcademicpeer-review

    Abstract

    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.

    Original languageEnglish
    Pages (from-to)441-448
    Number of pages8
    JournalThe Journal of antimicrobial chemotherapy
    Volume75
    Issue number2
    DOIs
    Publication statusPublished - 1 Feb 2020

    Keywords

    • plasma drug concentration
    • intensive care units
    • renal clearance function
    • critical illness

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