Pharmacokinetic Characteristics of Nebulized Colistimethate Sodium Using Two Different Types of Nebulizers in Critically Ill Patients with Ventilator-Associated Respiratory Infections

Abstract

Colistin pharmacokinetics; Critically ill; Inhaled colistin

Farmacocinética de la colistina; Enfermo crítico; Colistina inhalada

Farmacocinètica de la colistina; Malalt crític; Colistina inhalada

Background: Rising antimicrobial resistance has led to a revived interest in inhaled colistin treatment in the critically ill patient with ventilator-associated respiratory infection (VARI). Nebulization via vibrating mesh nebulizers (VMNs) is considered the current standard-of-care, yet the use of generic jet nebulizers (JNs) is more widespread. Few data exist on the intrapulmonary pharmacokinetics of colistin when administered through VMNs, while there is a complete paucity regarding the use of JNs. Methods: In this study, 18 VARI patients who received 2 million international units of inhaled colistimethate sodium (CMS) through a VMN were pharmacokinetically compared with six VARI patients who received the same drug dose through a JN, in the absence of systemic CMS administration. Results: Surprisingly, VMN and JN led to comparable formed colistin exposures in the epithelial lining fluid (ELF) (median (IQR) AUC0–24: 86.2 (46.0–185.9) mg/L∙h with VMN and 91.5 (78.1–110.3) mg/L∙h with JN). The maximum ELF concentration was 10.4 (4.7–22.6) mg/L and 7.4 (6.2–10.3) mg/L, respectively. Conclusions: Based on our results, JN might be considered a viable alternative to the theoretically superior VMN. Therapeutic drug monitoring in the ELF can be advised due to the observed low exposure, high variability, and appreciable systemic absorption.

This research was funded by Norma Hellas S.A., grant number 06797/2017, managed by the Special Research Account of the National and Kapodistrian University of Athens (ELKE).