STRAtified Dosing based on Augmented renal clearance for CEFtriaxone in patients with severe community-acquired pneumonia: STRADA-CEF trial.

This project aims to increase the clinical outcome and cost-effectiveness of ceftriaxone therapy in patients admitted to the intensive care unit (ICU) with severe community-acquired pneumonia (sCAP).
This will be accomplished by using a simple dose optimization strategy, being dose stratification from the standard-of-care 2g once daily (i.e., q24h) to 2g q12h in patients with increased renal function
(i.e., augmented renal clearance [ARC]). ARC has been shown to be the single largest driver for underexposure to ceftriaxone in critically ill patients. We expect this intervention to result in better clinical outcomes, such as reduced ICU length of stay (LOS). In contrast to therapeutic drug monitoring, which is the currently recommended dose optimization strategy for ceftriaxone in critically ill patients, our intervention is less resource and time consuming and the dose
recommendation is straightforward. The only tool needed for this approach is the publicly available ARC predictor that uses six universally available predictors (sex, age, serum creatinine, day from ICU admission, and trauma or cardiac surgery related ICU admission). Hence, if proven to be successful, we expect that the studied dose stratification strategy could be easily implemented not only in Flanders, but worldwide, including low-resource countries where ceftriaxone is a popular antibiotic (due to its low cost and general availability). Furthermore, the knowledge gathered in this study might serve as proof of concept for follow-up studies examining the clinical outcomes of (ARC-based) dose
optimization strategies with other antimicrobials in critically ill patients, as ARC has been shown to be a major risk factor for underexposure to many antimicrobials in a broad ICU setting