4.1. Study Population

The study population consisted of 24 critically ill adult patients, admitted to the intensive care unit of the First Department of Pulmonology of the National and Kapodistrian University of Athens between June 2014 and November 2017. All patients were intubated and mechanically ventilated, and received inhaled CMS as part of their treatment for VAP or VAT caused by Gram-negative pathogens. Subjects were studied around the first dose of nebulized treatment, which always preceded intravenous treatment, to avoid confounding by colistin (or CMS) reaching the ELF via the systemic circulation. We excluded patients that received a dose different to the institution’s standard of 2 million international units (mIU) (~160 mg) of CMS and patients who were planned to receive intravenous colistin within 8 h of nebulization initiation. We also excluded patients with: (i) a creatinine clearance (CR_CL) of less than 30 mL/min, (ii) severe hypoxemia defined as PaO₂/FiO₂ of less than 150, (iii) pneumothorax, (iv) severe bronchospasm, (v) intra-alveolar hemorrhage, (vi) refractory septic shock, (vii) prior colistin treatment, either intravenously or by inhalation, within 7 days prior to index nebulization and, (viii) previous hypersensitivity reaction to colistin (Figure 1).

Demographic, clinical, and microbiological characteristics of the study population were recorded on the first day of nebulized CMS administration.