Beta-lactam dosing in patients with sepsis and aki: a multicenter observational study

Introduction: Beta-lactam antibiotics are the backbone of therapy for critically ill patients with sepsis; however, these patients experience pharmacokinetic changes that alter beta-lactam exposure. Adjusting doses for acute kidney injury during the first 48 hours of admission to the ICU may result in suboptimal drug exposure and subject patients to inadequate therapy. We evaluated the association of beta-lactam antibiotic dose adjustment within the first 48 hours of therapy, on shock-free days in critically ill patients with acute kidney injury and septic shock secondary to gram-negative bloodstream infections. Methods: Multi-center, retrospective, observational cohort study of adult ICU patients with septic shock secondary to gram-negative bloodstream infections who received empiric, in vitro active cefepime, piperacillin-tazobactam, or meropenem. Primary outcome was shock-free days at 28 days which was modeled with linear regression. Secondary outcomes were ventilator-free days at 28 days, ICU mortality, and analysis of outcomes in patients with CrCL < 50ml/min at the time of beta-lactam initiation. Results: A total of 179 patients were included in the final analysis (103 in the adjusted group, 76 in the unadjusted group). Dose adjusting the beta-lactam was not associated with a difference in shock-free days at 28 days (β 2.25, [95% CI -2.04, 6.54], p=0.30. There was no difference in ventilator-free days at 28 days, or overall mortality. Conclusions: In patients with gram negative bacteremia and shock, there was no difference in clinical outcomes in patients who had their beta-lactams renally dose adjusted verses those who did not. Prospective, randomized interventional studies are needed to test if renal dose adjustments impact outcomes in patients with septic shock.