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Nebulized Amikacin and Fosfomycin for Severe Pseudomonas aeruginosa Pneumonia: An Experimental Study
Gianluigi Li Bassi, Ana Motos1,2,3, Laia Fernandez-Barat
1Department of Pulmonary and Critical Care Medicine, Hospital Clinic, Barcelona, Spain.
Objectives:
Latest trials failed to confirm merits of nebulized amikacin for critically ill patients with nosocomial pneumonia. We studied various nebulized and IV antibiotic regimens in a porcine model of severe Pseudomonas aeruginosa pneumonia, resistant to amikacin, fosfomycin, and susceptible to meropenem.
Design:
Prospective randomized animal study.
Setting:
Animal Research, University of Barcelona, Spain.
Subjects:
Thirty female pigs.
Interventions:
The animals were randomized to receive nebulized saline solution (CONTROL); nebulized amikacin every 6 hours; nebulized fosfomycin every 6 hours; IV meropenem alone every 8 hours; nebulized amikacin and fosfomycin every 6 hours; amikacin and fosfomycin every 6 hours, with IV meropenem every 8 hours. Nebulization was performed through a vibrating mesh nebulizer. The primary outcome was lung tissue bacterial concentration. Secondary outcomes were tracheal secretions P. aeruginosa concentration, clinical variables, lung histology, and development of meropenem resistance.
Measurements And Main Results:
We included five animals into each group. Lung P. aeruginosa burden varied among groups (p < 0.001). In particular, IV meropenem and amikacin and fosfomycin + IV meropenem groups presented lower P. aeruginosa concentrations versus amikacin and fosfomycin, amikacin, CONTROL, and fosfomycin groups (p < 0.05), without significant difference between these two groups undergoing IV meropenem treatment. The sole use of nebulized antibiotics resulted in dense P. aeruginosa accumulation at the edges of the interlobular septa. Amikacin, amikacin and fosfomycin, and amikacin and fosfomycin + IV meropenem effectively reduced P. aeruginosa in tracheal secretions (p < 0.001). Pathognomonic clinical variables of respiratory infection did not differ among groups. Resistance to meropenem increased in IV meropenem group versus amikacin and fosfomycin + meropenem (p = 0.004).
Conclusions:
Our findings corroborate that amikacin and fosfomycin alone efficiently reduced P. aeruginosa in tracheal secretions, with negligible effects in pulmonary tissue. Combination of amikacin and fosfomycin with IV meropenem does not increase antipseudomonal pulmonary tissue activity, but it does reduce development of meropenem-resistant P. aeruginosa, in comparison with the sole use of IV meropenem. Our findings imply potential merits for preemptive use of nebulized antibiotics in order to reduce resistance to IV meropenem.
Insights
Nebulized antibiotics like amikacin and fosfomycin reduced Pseudomonas aeruginosa in secretions but not lung tissue. Combining them with IV meropenem curbed resistance development compared to IV meropenem alone.
Area of Science:
- Infectious Diseases
- Pulmonology
- Pharmacology
Background:
- Nosocomial pneumonia treatment requires effective antibiotic strategies.
- Previous trials showed limited success with nebulized amikacin in critically ill patients.
- Pseudomonas aeruginosa is a common pathogen in hospital-acquired pneumonia.
Purpose of the Study:
- To evaluate nebulized and intravenous antibiotic regimens in a porcine model of Pseudomonas aeruginosa pneumonia.
- To compare the efficacy of amikacin, fosfomycin, and meropenem, alone and in combination, on bacterial load and resistance.
- To assess the impact of nebulized antibiotics on lung tissue and tracheal secretions.
Main Methods:
- A prospective randomized animal study using a porcine model of severe Pseudomonas aeruginosa pneumonia.
- Animals received saline (control), nebulized amikacin, nebulized fosfomycin, intravenous meropenem, or combinations thereof.
- Outcomes included lung and tracheal bacterial concentrations, clinical variables, lung histology, and meropenem resistance development.
Main Results:
- Intravenous meropenem and combination therapy with nebulized amikacin/fosfomycin + IV meropenem significantly reduced lung P. aeruginosa burden.
- Nebulized antibiotics alone effectively reduced P. aeruginosa in tracheal secretions but had minimal impact on lung tissue.
- The combination therapy reduced the development of meropenem resistance compared to IV meropenem alone.
Conclusions:
- Nebulized amikacin and fosfomycin are effective in reducing P. aeruginosa in tracheal secretions but not in lung tissue.
- Combination therapy with nebulized amikacin/fosfomycin and IV meropenem may mitigate the development of meropenem resistance.
- Preemptive use of nebulized antibiotics could be a strategy to preserve the efficacy of intravenous meropenem.
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