Effect of nebulizer system on tobramycin concentration using functional respiratory imaging (FRI)

Abstract

Introduction: Inhaled tobramycin is important in the treatment of Pseudomonas aeruginosa (Pa) infections in cystic fibrosis (CF). The bactericidal efficacy of tobramycin is concentration-dependent. In this study, the differences between different nebulizers devices are assessed on tobramycin (Bramitob®) concentrations calculated using Functional Respiratory Imaging (FRI). Methods: FRI particle simulations were performed on CT-reconstructed airway models of CF subjects. Two jet nebulizer systems were simulated: AKITA® JET and PARI LC Plus®. For the AKITA® JET, the controlled breathing and aerosol pulse timing was determined based on the FEV1. For the PARI LC Plus®, respiratory rates and tidal volumes were generated for the specific age and height, based on Wallis (2005) and Zapletal (1987). Results: 12 CT-scans (8 female) were selected, median [range] age 15 [11-17] years, CF-CT bronchiectasis subscore 8.33 [0-12.85] % of max., FEV1 92.6 [81.7-123] %pred. For the same labeled dose, the concentration of Bramitob® in the peripheral lung regions was much higher for AKITA® JET compared to PARI LC Plus® (Figure 1). Concentrations were at least a magnitude higher than the minimal inhibitory concentration for Pa. Conclusions: High concentrations of inhaled tobramycin are delivered to the lung with the AKITA® JET being twice as efficient as the PARI LC Plus®. Supported by unrestricted grant by Chiesi Farmaceutici S.p.A.