Nebulized Antibiotics for Healthcare- and Ventilator-Associated Pneumonia

Abstract

Global emergence of multidrug-resistant and extensive drug-resistant gram-negative bacteria has increased the risk of treatment failure, especially for healthcare- or ventilator-associated pneumonia (HAP/VAP). Nebulization of antibiotics, by providing high intrapulmonary antibiotic concentrations, represents a promising approach to optimize the treatment of HAP/VAP due to multidrug-resistant and extensive drug-resistant gram-negative bacteria, while limiting systemic antibiotic exposure. Aminoglycosides and colistin methanesulfonate are the most common nebulized antibiotics. Although optimal nebulized drug dosing regimen is not clearly established, high antibiotic doses should be administered using vibrating-mesh nebulizer with optimized ventilator settings to ensure safe and effective intrapulmonary concentrations. When used preventively, nebulized antibiotics reduced the incidence of VAP without any effect on mortality. This approach is not yet recommended and large randomized controlled trials should be conducted to confirm its benefit and explore the impact on antibiotic selection pressure. Compared with high-dose intravenous administration, high-dose nebulized colistin methanesulfonate seems to be more effective and safer in the treatment of ventilator-associated tracheobronchitis and VAP caused by multidrug resistant and extensive-drug resistant gram-negative bacteria. Adjunctive nebulized aminoglycosides could increase the clinical cure rate and bacteriological eradication in patients suffering from HAP/VAP due to multidrug-resistant and extensive drug-resistant gram-negative bacteria. As nebulized aminoglycosides broadly diffuse in the systemic circulation of patients with extensive bronchopneumonia, monitoring of plasma trough concentrations is recommended during the period of nebulization. Large randomized controlled trials comparing high dose of nebulized colistin methanesulfonate to high dose of intravenous colistin methanesulfonate or to intravenous new β-lactams in HAP/VAP due to multidrug-resistant and extensive drug-resistant gram-negative bacteria are urgently needed.

Clinical Features and Outcomes of VAP Due to Multidrug-Resistant Klebsiella spp.: A Retrospective Study Comparing Monobacterial and Polybacterial Episodes

“…In addition, our results cannot be generalized for geographical areas with a high prevalence of carbapenemases, and further studies are required, with important implications for stewardship or preventive strategies. The implications for antimicrobial stewardship or VAP prevention are beyond the scope of this article, and we refer the readers to recent updates [ 2 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 ] addressing these important issues.…”

Efficacy of adjunctive inhaled colistin and tobramycin for ventilator-associated pneumonia: systematic review and meta-analysis

“…The rise in drug-resistant gram-negative pathogens, such as extended-spectrum beta-lactamase (ESBL)-producing and carbapenem-resistant Enterobacteriaceae, has been associated with treatment failures and increased mortality in ICU patients [ 2 ]. To address this issue, the use of adjunctive inhaled antibiotics has emerged as a viable strategy [ 3 ]. Inhaled antibiotics offer the advantage of achieving higher drug concentrations in the pulmonary epithelial cells, which is particularly beneficial for treating gram-negative infections with aminoglycosides [ 4 ].…”