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

BACKGROUND

Lung transplant recipients (LTRs) frequently receive off-label inhaled tobramycin. However, LTRs differ pharmacokinetically from cystic fibrosis (CF) patients for whom the drug is approved and may be at increased risk for toxic systemic concentrations. This study characterized the incidence and predictors of detectable serum tobramycin concentrations among LTRs without underlying CF.

METHODS

This retrospective, single-center cohort study included LTRs receiving inhaled tobramycin (without intravenous/intramuscular tobramycin) with serum concentration testing July 2015 to June 2025. Logistic regression identified predictors of elevated concentrations (tobramycin ≥ 1 µg/mL), and analysis of covariance evaluated the dose/concentration relationship controlled for timing. Acute kidney injury (AKI) was defined as ≥ 0.3 mg/dL or a 1.5× increase in serum creatinine.

RESULTS

Forty-four LTRs (median age 69 years [IQR: 63-72]) contributed 56 tobramycin concentrations; 93% were inpatients, and 9% required renal replacement therapy (RRT). Inhaled tobramycin was dosed 160 mg (59%) or 300 mg (41%) twice daily. Detectable tobramycin serum concentrations occurred in 80% of patients (median 0.4 µg/mL [IQR: 0.3-0.8]); 8 (18%) had concentrations ≥ 1 µg/mL, and 3 (7%) ≥ 2 µg/mL. The 300 mg dose was associated with elevated concentrations (OR 7.2, 95% CI: 1.1-49.2, p = 0.043), including after adjusting for concentration timing (p < 0.001). Among non-RRT patients, 55% developed new AKI a median of 3 days after concentration sampling, with tobramycin concentrations significantly higher in the AKI group (0.4 µg/mL vs. 0.2 µg/mL, p = 0.035).

CONCLUSION

LTRs without CF commonly had systemic tobramycin exposure during inhaled therapy. The 300 mg dose was linked to higher serum concentrations, supporting reduced dosing and active serum concentration monitoring to enhance safety.