Antibiotics aerosol delivery

The potential benefit of aerosolized antibiotic therapy is dependent on three factors characteristics of the disease, aerosol delivery system, and properties of the antimicrobial agent [5]. Diseases that are likely to respond better cause infection in the airway without significant parenchymal or systemic involvement (e.g., cystic fibrosis). There is a significant need for research and scientific advances in the area of aerosol delivery of these therapies. Delivery systems that produce reliable, consistent, and reproducible aerosols are essential. Formulation of drug products requires attention to integrity, stability, tolerability, and overall suitability for aerosolization. 

Antimicrobial and antiendotoxin cationic peptide, CM3, incorporated into liposomes was suggested for the aerosol delivery, and corresponding models describing its potential distribution in lungs of patients with different breathing patterns have been developed.Liposomes with calcitonin have been developed for intranasal delivery. Liposomal forms of the peptide antibiotic, polymyxin B, showed certain promise in different models.355-357... 

Eiel SB. Aerosol delivery of antibiotics to the lower airways of patients with cystic fibrosis. Chest 1995 107 615-645. 

The use of the aerosol route for delivery of antibiotics for pulmonary infections remains controversial. The majority of pediatric studies have been conducted in children with cystic fibrosis. In these patients distribution of the antibiotic to the desired tissue site is impeded because of the viscosity of the sputum in patients with acute exacerbations of their pulmonary infections [91,92], Long-term studies have demonstrated preventive benefits of aerosolized antibiotics in children with cystic fibrosis who are colonizing Pseudomonas aeruginosa in their lungs but are not acutely ill [93,94], Cyclic administration of tobramycin administered by nebulizer has received FDA approval [95],... 

Patients suffering from cystic fibrosis often use various aerosolized drugs. To reduce the viscosity of the mucus in the airways, recombinant human deoxyribonuclease is used. This enzyme is the first recombinant protein that has been developed for specific delivery to the lungs via the airways. It has a local action on the mucus in the airways and its absorption is minimal. Another drug that decreases the viscosity of the mucus is acetylcysteine. Aerosolized antibiotics are a further group of therapeutics that is widely used by cystic fibrosis patients. Solutions of antibiotics like tobramycin or colistin are used in nebulizers to prevent exacerbation of the disease. Pentamidine has been used for the prophylaxis of Pneumocystis pneumonia in patients infected with HIV virus, while chronic rejection of lung transplants provided a reason to develop an aerosol formulation of cyclosporine A. 

The delivery of antibiotics to the lower airway through aerosolization offers several theoretical advantages over systemically administered therapy [3,4], It allows for direct deposition at the site of infection, resulting in high concentrations that may be beneficial in eradicating bacteria. The risk of adverse or toxic effects may be lower as a result of this method of administration. 

Much of the interest in aerosol therapy has focused on the management of patients with cystic fibrosis and has extended beyond the use of aerosolized antibiotics to various proteins and biotechnological therapies. The use of these therapies is discussed elsewhere in this publication (see Chs. 16, 17). Recent advances in the use of antibiotics directed against bacterial infections and technologic improvements of delivery systems has spurred additional research into the use of antifungal and antiviral therapies as well [5],... 

It is important to note that although aerosolization of antibiotic therapy has resulted in significantly higher sputum concentrations, systemic treatment is clearly more effective than this topical route of delivery. This suggests that factors other than sputum concentrations are important in the overall efficacy of therapy. 

For many drugs, the optimum site of action remains unknown, and the dose of many therapeutic agents may be less pertinent than their delivery profile down the tracheobronchial tree. Whereas it is likely that steroid therapy for asthma is best delivered to the larger airways, antibiotics for cystic fibrosis may need to be delivered to the more distal airways and alveoli. However, further improvements in aerosol and nebulizer technologies may be required before antiinflammatory agents can be effectively delivered to the periphery of the lung. 

Palmer LB, Smaldone GC, Simon SR, O Riordan TG, Cuccia A. Aerosolized antibiotics in mechanically ventilated patients delivery and response. Crit Care Med 1998 26 31-39. 

Antibiotic concentrations in respiratory secretions following systemic administration (oral or parenteral) may be inadequate for rapid treatment of airway disease such as tracheitis or bronchitis (71). Administration of antibiotics by aerosol has been used successfully and safely in children with cystic fibrosis and in infants and children who have endotracheal or tracheostomy tubes (72-74). Nebulization of antibiotic solutions allows delivery of high concentrations of antibiotics (10-40 times greater than following parenteral... 

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