Inline nebulized aerosol delivery of colistin methanesulfonate via high-flow nasal cannula system

Nebulized colistin methanesulfonate (CMS) is an essential adjunct therapy for pneumonia caused by multidrug-resistant Gram-negative bacteria, offering higher colistin concentrations in the lungs while minimizing systemic toxicity. However, the delivery efficiency of CMS via high-flow nasal cannula (HFNC) remains uncertain due to factors such as flow rate and humidification, which can affect aerosol delivery and lung deposition. This study evaluated the feasibility of delivering 160 mg CMS using a vibrating mesh nebulizer (VMN) integrated into an HFNC system. The physicochemical properties of CMS solutions with varying concentrations (26.7–160 mg/mL) were assessed using either injectable water or normal saline. Saline was selected to produce final CMS concentrations of 26.7–53.3 mg/mL, based on osmolarity, permeant anion content, and viscosity. An in vitro model incorporating a realistic nasal airway replica and two breathing patterns was used to evaluate aerosol performance across HFNC flow rates from 10 to 60 L/min and diluent volumes of 3 and 6 mL (corresponding to CMS concentrations to 53.3 and 26.7 mg/mL, respectively). Lower HFNC flow rates were associated with higher inhaled doses (87.4 ± 14.3 mg at 10 L/min vs. 8.5 ± 2.0 mg at 60 L/min, p < 0.01), particularly under distressed breathing conditions (107.4 ± 8.8 mg at 10 L/min vs. 3.7 ± 0.4 mg at 60 L/min, p < 0.01). Additionally, larger diluent volumes significantly increased total lung deposition (36.0 ± 2.0 mg with a 3 mL diluent vs. 71.1 ± 3.1 mg with a 6 mL diluent at 10 L/min under distressed breathing, p < 0.05). Fugitive emissions peaked between 10 and 20 L/min, particularly during quiet breathing. A predictive model for inhaled dose demonstrated strong linear correlation with experimental data (R² > 0.85). These findings support the clinical application of inline nebulized CMS and offer insights into optimizing dosing strategies while highlighting the need to manage fugitive emissions.