Inhaled therapeutics for prevention and treatment of pneumonia.
The lungs are the most common site of serious infection owing to their large surface area exposed to the external environment and minimum barrier defense. However, this architecture makes the lungs readily available for topical therapy. Therapeutic aerosols include those directed towards improving mucociliary clearance of pathogens, stimulation of innate resistance to microbial infection, cytokine stimulation of immune function and delivery of antibiotics. In our opinion inhaled antimicrobials are underused, especially in patients with difficult-to-treat lung infections. The use of inhaled antimicrobial therapy has become an important part of the treatment of airway infection with Pseudomonas aeruginosa in cystic fibrosis and the prevention of invasive fungal infection in patients undergoing heart and lung transplantation. Cytokine inhaled therapy has also been explored in the treatment of neoplastic and infectious disease. The choice of pulmonary drug delivery systems remains critical as air-jet and ultrasonic nebulizer may deliver sub-optimum drug concentration if not used properly. In future development of this field, we recommend an emphasis on the study of the use of aerosolized hypertonic saline solution to reduce pathogen burden in the airways of subjects infected with microbes of low virulence, stimulation of innate resistance to prevent pneumonia in immunocompromised subjects using cytokines or synthetic pathogen-associated molecular pattern analogues and more opportunities for the use of inhaled antimicrobials. These therapeutics are still in their infancy but show great promise.
Safdar
Amar
A
The University of Texas, Department of Infectious Diseases, M. D. Anderson Cancer Center, Infection Control and Employee Health, 402, 1515 Holcombe Boulevard, Texas 77030, Houston, USA. asafdar@mdanderson.org
Shelburne
Samuel A
SA
Evans
Scott E
SE
Dickey
Burton F
BF
D000280:Administration, Inhalation; D000818:Animals; D000890:Anti-Infective Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D016207:Cytokines / Q000008:administration & dosage* / Q000627:therapeutic use; D016503:Drug Delivery Systems / Q000295:instrumentation / Q000379:methods*; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects; D008168:Lung / Q000187:drug effects / Q000276:immunology; D008954:Models, Biological; D009330:Nebulizers and Vaporizers / Q000639:trends; D011014:Pneumonia / Q000188:drug therapy* / Q000517:prevention & control*; D012462:Saline Solution, Hypertonic / Q000008:administration & dosage* / Q000627:therapeutic use
D000890:Anti-Infective Agents; D016207:Cytokines; D012462:Saline Solution, Hypertonic