(531) Rethinking Aminoglycoside Dosing in CRRT: A Retrospective Evaluation of Dosing Strategies

Introduction: Critically-ill patients in the ICU experience physiologic changes that impact antibiotic pharmacokinetics (PK) and pharmacodynamics (PD). Aminoglycosides are renally eliminated and the unpredictable renal function of ICU patients can make it difficult to achieve and maintain therapeutic targets. In addition, initiating continuous renal replacement therapy (CRRT) can further impact PK and PD. This study evaluated the target attainment of traditional vs. extended interval aminoglycoside dosing techniques in patients on CRRT.

Methods: This was a single-center, retrospective study of adult patients receiving aminoglycosides and PK monitoring while receiving CRRT from January 2018 to June 2023. Patients were excluded if they had suspected or confirmed meningitis/ventriculitis or CRRT interruptions of four or more hours. The primary outcome was the percentage of patients who met target peaks and/or troughs with traditional and extended-interval dosing and monitoring strategies. Secondary outcomes included analysis of the type of dosing strategies utilized, median aminoglycoside dose and dosing interval based on CRRT flow rate, and the proportion of time during aminoglycoside course of therapy with therapeutic peaks/troughs based on indication.

Results: A total of 32 patients met criteria, with 77 levels analyzed. Overall, 45% of patients used traditional dosing, and 55% used extended interval dosing. The most commonly used aminoglycoside was tobramycin (n=20), followed by amikacin (n=17), and gentamicin (n=10). The median dose and interval was amikacin 15 mg/kg (IQR 7.5-21 mg/kg) and tobramycin 7 mg/kg (IQR 5-7 mg/kg) every 36 hours (IQR 24-48 hr), with a median 2.5 L/hr (IQR 1.5-3.5 L/hr) CRRT flow rate. A total of 27% of patients met target levels with traditional dosing, and 62% met target levels with extended interval dosing (P= 0.0206).

Conclusions: In this analysis, extended interval dosing aminoglycoside in CRRT patients led to more consistent therapeutic levels as compared to traditional dosing. These findings unveil the potential need for a prospective interventional study with a larger sample size evaluating appropriate dosing strategies for aminoglycosides in CRRT.