Target attainment with continuously administered cefotaxime in critically ill patients - a retrospective cohort study

Cefotaxime is a beta-lactam-antibiotic commonly used in the treatment of severe pneumonia, sepsis, and meningitis. However, there is little scientific literature regarding continuously administered cefotaxime in critically ill patients. We aimed at evaluating cefotaxime dosing performance and at characterizing factors with relevance for cefotaxime plasma levels.

We retrospectively screened electronic medical records of critically ill patients who had received cefotaxime continuously - starting with an initial 2 g loading dose followed by continuous infusion of 6 g per day - along with regular cefotaxime-plasma-level measurements and dose adjustments according to a predefined target concentration window. Additionally, we extracted a broad range of related clinical and laboratory parameters and conducted correlation and regression analyses.

Cefotaxime plasma levels of >8 mg/l (>4xMIC breakpoint for Enterobacterales) initially were reached in all (96/96) patients and remained above 8 mg/l (236/237) in nearly all follow-up measurements based on 338 single cefotaxime measurements of 105 patients. Additionally, 90 % (85/96) of first plasma level measurements surpassed the eightfold MIC breakpoint for Enterobacterales (16 mg/l). In accordance with a highly significant negative correlation (-0.69 [-0.79 - -0.56]) between the estimated glomerular filtration rate (eGFR) and cefotaxime plasma levels, multiple linear regression attributed nearly 50 % of plasma level variance to the eGFR.

Our real-world analysis demonstrates that continuous administration of a standard dose of 6 g cefotaxime per day invariably ensures bactericidal plasma concentrations regarding Enterobacterales even with augmented renal function. We propose specific adjustments of daily doses for normal and reduced renal function.