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

Aardema, H., Bult, W., van Hateren, K., Dieperink, W., Touw, D. J., Alffenaar, J-W. C. & Zijlstra, J. G., Feb-2020, In : Journal of Antimicrobial Chemotherapy. 75, 2, p. 441-448 8 p.

Research output: Contribution to journalArticleAcademicpeer-review

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
JournalJournal of Antimicrobial Chemotherapy
Volume75
Issue number2
Early online date7-Nov-2019
Publication statusPublished - Feb-2020

    Keywords

  • INTENSIVE-CARE-UNIT, DEFINING ANTIBIOTIC LEVELS, PROLONGED INFUSION, SEVERE SEPSIS, ANTIMICROBIAL THERAPY, DOSE OPTIMIZATION, PIPERACILLIN, OUTCOMES, MEROPENEM, MORTALITY

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