(518) Evaluating the Incidence of Acute Kidney Injury and Gentamicin Synergy Dosing for Endocarditis

Introduction: Current infective endocarditis guidelines recommend two different gentamicin synergy dosing strategies for select Gram-positive organisms. The purpose of this analysis was to evaluate the incidence of acute kidney injury (AKI) with gentamicin synergy dosing, comparing divided daily and once daily dosing strategies for infective endocarditis.

Methods: This was a multi-center, retrospective analysis of adult patients who received gentamicin synergy dosing for infective endocarditis between 2015 and 2022 at two academic medical centers. Groups were split into patients who received gentamicin divided daily dosing per institutional protocol or once daily dosing (3 mg/kg). The major outcome was the incidence of AKI defined by the RIFLE (Risk, Injury, Failure, Loss of kidney function, and End-stage kidney disease) criteria after starting gentamicin. A multivariable logistic regression analysis was performed to identify possible independent predictors of developing AKI. Notable minor outcomes included hospital length of stay, need for gentamicin dose adjustments based on therapeutic drug monitoring, and assessment of each case of AKI using the Naranjo Algorithm to assess gentamicin causality.

Results: During the study period, 245 patients were evaluated, of which 147 were included: 101 in the divided dosing group and 46 in the once daily group. AKI incidence was significantly higher in the divided dosing group compared to the once daily group (52.5% vs. 13%, p< 0.001). Median hospital length of stay and need for gentamicin dose adjustments were significantly higher in the divided dosing group, 19 days [12:29] vs. 13.5 days [9:22] (p=0.007) and 31.3% vs. 11.5%, (p < 0.001), respectively. The multivariable regression analysis showed the divided dosing strategy, duration, and institution were independently associated with incidence of AKI. The average Naranjo Algorithm score in cases of AKI was 3, indicating possible gentamicin-induced AKI.

Conclusions: This analysis suggests a lower incidence of AKI in the treatment of endocarditis with gentamicin synergy dosed once daily compared to a divided daily dosing strategy. Further studies are warranted to assess if there is a difference in efficacy between dosing strategies and in gentamicin compared to no gentamicin regimens for infective endocarditis.