Impact of beta-lactam antibiotic renal dose adjustment on clinical outcomes in patients with septic shock and acute kidney injury from gram-negative bloodstream infections: a multicenter observational study

Objective: 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, in the absence of beta-lactam therapeutic drug monitoring, may result in suboptimal drug exposure and subject patients to inadequate treatment.We hypothesized that patients without renal dose adjustment in the first 48 hours would have improved vasopressor free days compared to those who underwent renal dose adjustment in critically ill patients with acute kidney injury and septic shock secondary to gram-negative bloodstream infection.Design: Multi-center, retrospective, observational cohort study 6 Setting: Intensive care unit Participants: Adult patients with septic shock secondary to gram-negative bloodstream infections and acute kidney injury who received empiric, in vitro active cefepime, piperacillintazobactam, or meropenem across 10 centers from 2013-2019. Interventions: noneMeasurements and Main Results: Inverse probability of treatment weighting with regression adjustment was utilized to analyze the primary outcome ofvasopressor-free days at 28 days, and secondary outcomes of in-hospital mortality and ventilator free days at 28 days.The final analysis included 173 patients (74 in the dose-adjusted group, 99 in the unadjusted group).Following regression adjustment, median vasopressor-free days was not different between the dose-adjusted and unadjusted group: 27.15 days versus 27.55 days, respectively; mean difference 0.79 [95% CI-3.62, 5.21].In-hospital mortality was similar between the dose-adjusted and unadjusted groups, respectively: 28% versus 32%; OR. -0.98 [95% CI 0.84, 1.15], and no difference were seen in ventilator-free days at 28 days. Conclusions:In patients with shock and gram-negative bacteremia, renal dose adjustment was not associated with significantly fewer days alive and free from vasopressor agents.Prospective, randomized controlled trials are needed to demonstrate that renal dose adjustment is safe and not required in the first 48 hours in patients with septic shock and acute kidney injury. Key words: