(978) Systemic Accumulation of Tobramycin Inhalation (SATIn) Study

Introduction: The relationship between intravenous tobramycin and acute kidney injury (AKI) has been established in previous studies. However, when inhaled tobramycin is used adjunctively to treat pneumonia, drug accumulation and its impact on renal function is less understood. The package insert reports that nephrotoxicity was not seen in clinical trials, but case reports indicate that systemic accumulation may occur and induce AKI. Thus, our retrospective study evaluated the systemic accumulation of inhaled tobramycin, and its effect on kidney function.

Methods: This 3-year retrospective review of 49 non-cystic fibrosis patients with pneumonia who received inhaled tobramycin was conducted in a level 1 trauma center. All evaluated patients received at least 1 dose of inhaled tobramycin and were excluded if they had received any intravenous tobramycin during their admission. The primary objective was to evaluate serum accumulation based on trough levels. A secondary endpoint evaluated the rate of AKI as defined by a 0.3 mg/dL or greater increase in serum creatinine.

Results: 14 of the 49 patients had at least 1 tobramycin trough level with an average trough of 0.84 mcg/mL (95% confidence the mean trough >0.62 mcg/mL). This was compared to an expected average trough of 0 mcg/mL through a student’s t-test which determined the trough to be significantly higher than expected (p < 0.0001). In the same 49 patients’ logistical regression was performed to evaluate the relationship between doses of tobramycin and rate of AKI. Without any inhaled tobramycin the risk of AKI was 14%, but the risk increases by an additional 17% with each dose the patient receives, producing an odds ratio of 1.17 (95% CI 1.03-1.36).

Conclusions: Currently, the package insert does not report nephrotoxicity from inhaled tobramycin but does suggest obtaining levels if given with other nephrotoxic agents. However, our data suggests a statistically significant risk of renal injury that increases by 17% with each additional accumulating dose of inhaled tobramycin. As data is lacking for inhaled tobramycin dose adjustments, we recommend frequent monitoring with troughs and dose re-evaluation for safe and effective regimens.