Inhaled Tobramycin Dose and Systemic Absorption in Lung Transplant Recipients Without Cystic Fibrosis.

Area of Science:

• Pharmacology
• Nephrology
• Pulmonology

Background:

• Lung transplant recipients (LTRs) commonly receive off-label inhaled tobramycin.
• Pharmacokinetics in LTRs differ from cystic fibrosis (CF) patients, potentially increasing toxicity risk.
• This study investigates tobramycin concentrations in LTRs without CF.

Purpose of the Study:

• To determine the incidence of detectable serum tobramycin concentrations in LTRs without CF.
• To identify predictors of elevated serum tobramycin concentrations.
• To assess the relationship between inhaled tobramycin dosing and serum concentrations.

Main Methods:

• Retrospective, single-center cohort study of LTRs receiving inhaled tobramycin.
• Serum tobramycin concentrations were measured, with logistic regression identifying predictors of elevated levels (≥1 µg/mL).
• Analysis of covariance assessed the dose-concentration relationship; acute kidney injury (AKI) was defined by serum creatinine changes.

Main Results:

• 80% of LTRs had detectable serum tobramycin; 18% had concentrations ≥1 µg/mL.
• The 300 mg inhaled tobramycin dose was associated with elevated concentrations (OR 7.2, p=0.043).
• 55% of non-renal replacement therapy patients developed AKI, with higher tobramycin concentrations in this group (p=0.035).

Conclusions:

• LTRs without CF frequently experience systemic tobramycin exposure from inhaled therapy.
• The 300 mg dose is linked to higher serum concentrations, indicating a need for dose reduction.
• Active serum concentration monitoring is recommended to improve safety in LTRs receiving inhaled tobramycin.