Introduction: High-dose aminoglycosides can be used as part of empiric dual gram-negative antibiotic therapy in critically ill patients with septic shock. Previous literature demonstrates that a single dose of amikacin at 25-30 mg/kg can achieve target pharmacokinetic/pharmacodynamic (PK/PD) parameters in critically ill patients. However, there is a lack of data evaluating clinical outcomes and nephrotoxicity associated with this dosing regimen. This study will evaluate clinical outcomes associated with a single administration of high-dose amikacin in critically ill patients with septic shock. Methods: This was a retrospective, single-center cohort study of critically ill patients with septic shock admitted to the intensive care unit (ICU) at an academic medical center from August 2023 to August 2024. Patients who received a single dose of amikacin ≥25 mg/kg for dual-gram negative coverage were compared to patients who received no aminoglycosides as part of empiric antibiotic therapy for septic shock. The primary outcome was shock resolution by day 14. Secondary outcomes included in-hospital mortality, hospital length of stay, ICU length of stay, and new renal failure. Results: Of 222 patients screened, 155 met inclusion criteria. 75 patients received high-dose amikacin (48%), while 80 patients were included in the control group (52%). There was no difference in shock resolution by day 14 in patients receiving high-dose amikacin compared to control (55% vs 56%, p=0.72). There were no differences in in-hospital mortality (44% vs 44%, p=0.98), or new renal failure (30% vs 19%, p=0.42). Among patients that received amikacin, patients that survived had a shorter median time to receiving amikacin compared to patients that did not survive (0 days vs 1 days, p=0.04). Conclusions: In critically ill patients with septic shock, a single administration of high-dose amikacin was not associated with greater shock resolution by day 14. There was no difference in the incidence of new renal failure between groups. Among patients that received amikacin, patients that survived to hospital discharge had a shorter time to receive amikacin compared to non-survivors.
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