High-Dose Nebulized Colistin Methanesulfonate and the Role in Hospital-Acquired Pneumonia Caused by Gram-Negative Bacteria with Difficult-to-Treat Resistance: A Review

Hospital-acquired pneumonia, including ventilator-associated pneumonia (VAP) due to difficult-to-treat-resistant (DTR) Gram-negative bacteria, contributes significantly to morbidity and mortality in ICUs. In the era of COVID-19, the incidences of secondary nosocomial pneumonia and the demand for invasive mechanical ventilation have increased dramatically with extremely high attributable mortality. Treatment options for DTR pathogens are limited. Therefore, an increased interest in high-dose nebulized colistin methanesulfonate (CMS), defined as a nebulized dose above 6 million IU (MIU), has come into sight. Herein, the authors present the available modern knowledge regarding high-dose nebulized CMS and current information on pharmacokinetics, clinical studies, and toxicity issues. A brief report on types of nebulizers is also analyzed. High-dose nebulized CMS was administrated as an adjunctive and substitutive strategy. High-dose nebulized CMS up to 15 MIU was attributed with a clinical outcome of 63%. High-dose nebulized CMS administration offers advantages in terms of efficacy against DTR Gram-negative bacteria, a favorable safety profile, and improved pharmacokinetics in the treatment of VAP. However, due to the heterogeneity of studies and small sample population, the apparent benefit in clinical outcomes must be proven in large-scale trials to lead to the optimal use of high-dose nebulized CMS.

Automated summary

Hospital-acquired pneumonia, including ventilator-associated pneumonia (VAP), is a significant cause of morbidity and mortality in ICUs, particularly due to difficult-to-treat-resistant (DTR) Gram-negative bacteria. The COVID-19 pandemic has led to an increase in cases of secondary nosocomial pneumonia and the need for invasive mechanical ventilation, resulting in high mortality rates. High-dose nebulized colistin methanesulfonate (CMS) has gained interest as a treatment option for DTR pathogens. This review provides an overview of the current knowledge on high-dose nebulized CMS, including pharmacokinetics, clinical studies, toxicity issues, and types of nebulizers. While high-dose nebulized CMS has shown promising efficacy, safety, and improved pharmacokinetics in the treatment of VAP, large-scale trials are needed to confirm its clinical benefits.