A retrospective cohort analysis of factors influencing continuous antibiotic therapy with ampicillin.

Aims: There are limited data on ampicillin/sulbactam, both for continuous infusion and for use in critically ill patients. We aimed to identify factors that help predict ampicillin plasma levels during continuous antibiotic therapy in intensive care patients.

Main Methods: We retrospectively reviewed and retrieved a large dataset of patients who received continuous ampicillin infusion with therapeutic drug monitoring between 2015 and 2022. Patients initially received standard dosing (single shot of 2/1 g followed by continuous infusion of 6/3 g ampicillin/sulbactam per day), which was then adjusted based on the results of regular therapeutic drug monitoring and according to a target range of 30-60 mg/l (equivalent to four to eight times the minimum inhibitory concentration of ampicillin for Enterobacterales).

Main Results: 466 measurements from 225 patients (152 male, mean age 61 years) were analyzed. Initial measurements of ampicillin plasma levels were below the predefined optimal therapeutic range in 50 %, within the range in 30 % and above the range in 20 %. Target attainment increased to 70 % by the 4th measurement. There was a significant negative correlation between ampicillin plasma levels and estimated glomerular filtration rate (eGFR) (r = -0.74; p < 0.001) and, to a lesser extent, with height (r = -0.31; p < 0.001). Based on multiple linear regression, eGFR and body weight or height were the factors accounting for 63 % of the variability in the data.

Significance: To optimise target achievement, ampicillin dosing in critically ill patients requires a personalized approach based on renal function. Importantly, patients with normal or augmented eGFR require higher standard doses of ampicillin/sulbactam.