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

• Main Authors: Anna Kyriakoudi (Author), Konstantinos Pontikis (Author), Georgia Valsami (Author), Stavrina Avgeropoulou (Author), Efthymios Neroutsos (Author), Eirini Christodoulou (Author), Eleni Moraitou (Author), Sophia L. Markantonis (Author), Aristides Dokoumetzidis (Author), Jordi Rello (Author), Antonia Koutsoukou (Author)
• Format: Book
• Published: MDPI AG, 2022-11-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.
• Notes: 10.3390/antibiotics11111528; 2079-6382
• Keywords: inhaled colistin; colistin pharmacokinetics; ELF colistin concentration; vibrating mesh nebulizer; jet nebulizer; critically ill; Therapeutics. Pharmacology; RM1-950
• Source: Antibiotics, Vol 11, Iss 11, p 1528 (2022)

<i>Background:</i> 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. <i>Methods:</i> 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. <i>Results:</i> Surprisingly, VMN and JN led to comparable formed colistin exposures in the epithelial lining fluid (ELF) (median (IQR) AUC_0-24: 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. <i>Conclusions:</i> 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.