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Aerosols and anti-infectious agents
P Diot1, P F Dequin, B Rivoire
1Groupe de Pneumologie et Imagerie de Ciblage, INSERM EMI-U 00-10, CHU Bretonneau, Tours, France. diot@med.univ_tours.fr
Abstract:
Anti-infectious agents such as pentamidine, antibiotics (mainly colistine and aminoglycosides), and amphotericin B can be administered by aerosol. Apart from pentamidine and Tobi, this route of administration is not officially approved and it constitutes an empirical approach, which has benefited from recent research summarized hereafter. The most fundamental question is related to the potentially deleterious effects of nebulization processes, especially ultrasound, on the anti-infectious properties of the drugs. Colimycin, which was chosen as a reference because its polypeptide structure makes it unstable a priori, proved to be resistant to high frequency ultrasound, which is encouraging for other molecules such as aminoglycosides or betalactamins. The nebulizer characteristics also have to be taken into account. An aerosol can be produced from an amphotericin B suspension and from colistine using both an ultrasonic nebulizer and a jet nebulizer. Differentiating between good and bad nebulizers is not dependent upon the physical process involved to nebulize the drug, but on the intrinsic characteristics of the device and its performance with a known drug. The inhaled mass of an aerosol in the respirable range must be high and dosimetric nebulizers represent significant progress. Finally, administration of anti-infectious aerosols requires a new pharmacological approach to monitor treatment, and urinary assays are promising for this purpose.
Insights
Aerosol delivery of anti-infectious drugs like colistin is effective, with ultrasound nebulization preserving drug properties. Nebulizer performance, not the nebulization method, determines efficacy for inhaled therapies.
Area of Science:
- Pharmacology
- Drug Delivery
- Infectious Diseases
Background:
- Aerosol administration of anti-infectious agents is an emerging, though often unapproved, therapeutic route.
- Key concerns involve potential drug degradation during nebulization, particularly with ultrasound technology.
Purpose of the Study:
- To evaluate the stability of anti-infectious drugs during aerosolization.
- To assess the impact of nebulizer type and characteristics on aerosol efficacy.
- To explore new methods for monitoring aerosolized anti-infectious drug therapy.
Main Methods:
- Assessed the stability of colistin, an antibiotic, under high-frequency ultrasound nebulization.
- Compared aerosol generation from amphotericin B and colistin using both ultrasonic and jet nebulizers.
- Evaluated nebulizer performance based on intrinsic device characteristics and drug compatibility.
Main Results:
- Colistin demonstrated resistance to high-frequency ultrasound, suggesting stability for other molecules like aminoglycosides.
- Both ultrasonic and jet nebulizers could produce respirable aerosols for amphotericin B and colistin.
- Nebulizer efficacy depends on device specifics and drug interaction, not solely the nebulization mechanism.
- Dosimetric nebulizers significantly improve inhaled aerosol mass in the respirable range.
Conclusions:
- Aerosolized anti-infectious agents, like colistin, are viable and potentially stable during nebulization.
- Nebulizer selection should prioritize intrinsic performance and drug compatibility for optimal aerosol delivery.
- Development of new pharmacological monitoring, such as urinary assays, is crucial for effective aerosolized anti-infectious therapy.