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Antibiotic Efficacy Testing in an Ex vivo Model of Pseudomonas aeruginosa and Staphylococcus aureus Biofilms in the Cystic Fibrosis Lung
Published on: January 22, 2021
Nebulized and intravenous colistin in experimental pneumonia caused by Pseudomonas aeruginosa
Qin Lu1, Cassio Girardi, Mao Zhang
1Multidisciplinary Intensive Care Unit, Department of Anesthesiology and Critical Care Medicine, La Pitié-Salpêtrière Hospital, Assistance Publique-Hôpitaux de Paris, UPMC Univ Paris 06, Paris, France.
Purpose:
Emergence of multidrug-resistant strains in intensive care units has renewed interest in colistin, which often remains the only available antimicrobial agent active against resistant Pseudomonas aeruginosa. The aim of this study is to compare lung tissue deposition and antibacterial efficiency between nebulized and intravenous administration of colistin in piglets with pneumonia caused by P. aeruginosa.
Methods:
In ventilated piglets, colistimethate was administered 24 h following bronchial inoculation of Pseudomonas aeruginosa (minimum inhibitory concentration of colistin = 2 microg ml(-1)) either by nebulization (8 mg kg(-1) every 12 h, n = 6) or by intravenous infusion (3.2 mg kg(-1) every 8 h, n = 6). All piglets were killed 49 h after inoculation. Colistin peak lung tissue concentrations and lung bacterial burden were assessed on multiple post mortem subpleural lung specimens.
Results:
Median colistin peak lung concentration following nebulization was 2.8 microg g(-1) (25-75% interquartile range = 0.8-13.7 microg g(-1)). Colistin was undetected in lung tissue following intravenous infusion. In the aerosol group, peak lung tissue concentrations were significantly greater in lung segments with mild pneumonia (median = 10.0 microg g(-1), 25-75% interquartile range = 1.8-16.1 microg g(-1)) than in lung segments with severe pneumonia (median = 1.2 microg g(-1), 25-75% interquartile range = 0.5-3.3 microg g(-1)) (p < 0.01). After 24 h of treatment, 67% of pulmonary segments had bacterial counts <10(2) cfu g(-1) following nebulization and 28% following intravenous administration (p < 0.001). In control animals, 12% of lung segments had bacterial counts <10(2) cfu g(-1) 49 h following bronchial inoculation.
Conclusion:
Nebulized colistin provides rapid and efficient bacterial killing in ventilated piglets with inoculation pneumonia caused by Pseudomonas aeruginosa.
Insights
Nebulized colistin effectively targets Pseudomonas aeruginosa lung infections in piglets, achieving better bacterial clearance than intravenous administration. This study highlights aerosolized colistin as a promising strategy for treating multidrug-resistant bacterial pneumonia.
Area of Science:
- Pharmacology
- Infectious Diseases
- Pulmonary Medicine
Background:
- Multidrug-resistant bacteria, particularly Pseudomonas aeruginosa, pose a significant threat in intensive care units.
- Colistin is often a last-resort antibiotic for infections caused by these resistant strains.
- Optimizing colistin delivery to the lungs is crucial for treating pneumonia.
Purpose of the Study:
- To compare lung tissue deposition and antibacterial efficacy of nebulized versus intravenous colistin.
- To evaluate colistin's effectiveness in piglets with Pseudomonas aeruginosa-induced pneumonia.
Main Methods:
- Ventilated piglets were inoculated with Pseudomonas aeruginosa.
- Colistin was administered via nebulization (8 mg/kg q12h) or intravenous infusion (3.2 mg/kg q8h).
- Lung tissue colistin concentrations and bacterial burden were assessed post-mortem.
Main Results:
- Nebulized colistin achieved detectable peak lung concentrations (median 2.8 µg/g), while intravenous administration did not.
- Nebulized colistin resulted in significantly greater bacterial clearance (67% of segments <10^2 cfu/g) compared to intravenous administration (28%).
- Higher colistin concentrations were observed in lung segments with milder pneumonia following nebulization.
Conclusions:
- Nebulized colistin demonstrates rapid and efficient bacterial killing in a piglet model of Pseudomonas aeruginosa pneumonia.
- Aerosolized colistin is a viable and effective method for achieving therapeutic concentrations in the lung.
- This supports nebulized colistin as a potential treatment for ventilator-associated pneumonia caused by resistant pathogens.
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