Inhaled therapeutics for prevention and treatment of pneumonia

Expert Opinion on Drug Safety

Volumn 8, Issue 4, 2009, Pages 435-449

  Safdar, Amar ^a   Shelburne, Samuel A ^a   Evans, Scott E ^a   Dickey, Burton F ^a  

^a UNIVERSITY OF TEXAS   (United States)

Author keywords

Amikacin; Antifungal; Antiviral; Aspergillosis; Cancer; Colistin; Cytokine; Inhaled tobramycin; Innate immunity; Pneumonia; Pseudomonas; Transplantation; Vancomycin; Ventilator associated pneumonia; Zygomycosis

Indexed keywords

ALPHA2A INTERFERON; AMIKACIN; AMINOGLYCOSIDE ANTIBIOTIC AGENT; AMPHOTERICIN B; AMPHOTERICIN B LIPID COMPLEX; ANTIBIOTIC AGENT; ANTIFUNGAL AGENT; ANTIVIRUS AGENT; BACTERIUM LYSATE; BETA INTERFERON; CIPROFLOXACIN; COLISTIN; ERYTHROPOIETIN; GAMMA1B INTERFERON; GENTAMICIN; IMIQUIMOD; IMMUNOGLOBULIN E; IMMUNOLOGIC AGENT; INTERLEUKIN 2; INTERLEUKIN 4 RECEPTOR; MICROBIAL PRODUCTS NOT CLASSIFIED ELSEWHERE; RECOMBINANT GRANULOCYTE MACROPHAGE COLONY STIMULATING FACTOR; SOLUBLE INTERLEUKIN 4 RECEPTOR; STEROID; TOBRAMYCIN; TOLL LIKE RECEPTOR 9 AGONIST; TUBERCULOSTATIC AGENT; UNCLASSIFIED DRUG; UNINDEXED DRUG; VANCOMYCIN; VIRUS LYSATE;

ADAPTIVE IMMUNITY; AEROSOL; ANEMIA; ANTIBIOTIC RESISTANCE; ANTIMICROBIAL ACTIVITY; ANTIMICROBIAL THERAPY; ASTHMA; ATYPICAL MYCOBACTERIOSIS; BACTERIAL INFECTION; BACTERIAL PNEUMONIA; BRONCHIECTASIS; BRONCHIOLITIS OBLITERANS; BRONCHOSPASM; CHRONIC OBSTRUCTIVE LUNG DISEASE; CLINICAL TRIAL; DRUG DELIVERY SYSTEM; DRUG DOSE COMPARISON; DRUG EFFICACY; DRUG FEVER; DRUG INDUCED HEADACHE; DRUG MEGADOSE; DYSPNEA; HEART TRANSPLANTATION; HEMOPTYSIS; HEPATITIS C; HOSPITAL INFECTION; HUMAN; IMMUNOTHERAPY; INFECTION PREVENTION; INFECTIOUS PNEUMONIA; INNATE IMMUNITY; KIDNEY CARCINOMA; LOW DRUG DOSE; LUNG ASPERGILLOSIS; LUNG CANCER; LUNG FIBROSIS; LUNG METASTASIS; LUNG TRANSPLANTATION; LUNG TUBERCULOSIS; MALAISE; MEDICAL NEBULIZER; MUCOCILIARY CLEARANCE; MYCOBACTERIOSIS; MYCOSIS; NONHUMAN; PNEUMONIA; PSEUDOMONAS AERUGINOSA; PSEUDOMONAS PNEUMONIA; RESPIRATORY EPITHELIUM; RESPIRATORY TRACT ALLERGY; RESPIRATORY TRACT INFECTION; RESPIRATORY TRACT INFLAMMATION; REVIEW; SKIN LEISHMANIASIS; TRACHEOBRONCHITIS; TREATMENT OUTCOME; UNSPECIFIED SIDE EFFECT; VENTILATOR ASSOCIATED PNEUMONIA; VIRUS PNEUMONIA;

ADMINISTRATION, INHALATION; ANIMALS; ANTI-INFECTIVE AGENTS; CYTOKINES; DRUG DELIVERY SYSTEMS; HUMANS; IMMUNITY, INNATE; LUNG; MODELS, BIOLOGICAL; NEBULIZERS AND VAPORIZERS; PNEUMONIA; SALINE SOLUTION, HYPERTONIC;

EID: 67650550078     PISSN: 14740338     EISSN: None     Source Type: Journal    
DOI: 10.1517/14740330903036083     Document Type: Review

References (161)

1. The World Health Report 2004 - Changing History. Geneva: World Health Organization, 2004
2. File TM. Community-acquired pneumonia. Lancet 2003;362(9400):1991-2001
3. Joos L, Tamm M. Breakdown of pulmonary host defense in the immunocompromised host: cancer chemotherapy. Proc Am Thorac Soc 2005;2(5):445-448 (Pubitemid 43128041)
4. Knowles MR, Boucher RC. Mucus clearance as a primary innate defense mechanism for mammalian airways. J Clin Invest 2002;109(5):571-577 (Pubitemid 34204834)
5. Martin TR, Frevert CW. Innate immunity in the lungs. Proc Am Thorac Soc 2005;2(5):403-411
6. Rogan MP, Geraghty P, Greene CM, et al. Antimicrobial proteins and polypeptides in pulmonary innate defence. Respir Res 2006;7:29 (Pubitemid 43316679)
7. Travis SM, Singh PK, Welsh MJ. Antimicrobial peptides and proteins in the innate defense of the airway surface. Curr Opin Immunol 2001;13(1):89-95 (Pubitemid 32096966)
8. Flanders SACH, Saint S. Nosocomial pneumonia: state of the science. Am J Infect Control 2006;(34):84-93
9. Knowles MR, Boucher RC. Mucus clearance as a primary innate defense mechanism for mammalian airways. J Clin Invest 2002;109(5):571-577 (Pubitemid 34204834)
10. Ratjen F. Restoring airway surface liquid in cystic fibrosis. N Engl J Med 2006;354(3):291-293 (Pubitemid 43113036)
11. Tarran R, Donaldson S, Boucher RC. Rationale for hypertonic saline therapy for cystic fibrosis lung disease. Semin Respir Crit Care Med 2007;28(3):295-302 (Pubitemid 46982060)
12. Eng PA, Morton J, Douglass JA, et al. Short-term efficacy of ultrasonically nebulized hypertonic saline in cystic fibrosis. Pediatr Pulmonol 1996;21(2):77-83 (Pubitemid 26098513)
13. Robinson M, Regnis JA, Bailey DL, et al. Effect of hypertonic saline, amiloride, and cough on mucociliary clearance in patients with cystic fibrosis. Am J Respir Crit Care Med 1996;153(5):1503-1509 (Pubitemid 26141332)
14. Sood N, Bennett WD, Zeman K, et al. Increasing concentration of inhaled saline with or without amiloride: effect on mucociliary clearance in normal subjects. Am J Respir Crit Care Med 2003;167(2):158-163 (Pubitemid 36076074)
15. Wark PA, McDonald V. Nebulised hypertonic saline for cystic fibrosis. Cochrane Database Syst Rev 2003(1):CD001506
16. Donaldson SH, Bennett WD, Zeman KL, et al. Mucus clearance and lung function in cystic fibrosis with hypertonic saline. N Engl J Med 2006;354(3):241-250 (Pubitemid 43113029)
17. Elkins MR, Robinson M, Rose BR, et al. A controlled trial of long-term inhaled hypertonic saline in patients with cystic fibrosis. N Engl J Med 2006;354(3):229-240 (Pubitemid 43113028)
18. Kerem E, Bistritzer T, Hanukoglu A, et al. Pulmonary epithelial sodium-channel dysfunction and excess airway liquid in pseudohypoaldosteronism. N Engl J Med 1999;341(3):156-162 (Pubitemid 29325743)
19. Williams OW, Sharafkhaneh A, Kim V, et al. Airway mucus: from production to secretion. Am J Respir Cell Mol Biol 2006;34(5):527-536
20. Evans CM, Kim K, Tuvim MJ, et al. Mucus hypersecretion in asthma: causes and effects. Curr Opin Pulm Med 2009;15(1):4-11
21. Boucher RC. Airway surface dehydration in cystic fibrosis: pathogenesis and therapy. Annu Rev Med 2007;58:157-170 (Pubitemid 46706507)
22. Evans CM, Williams OW, Tuvim MJ, et al. Mucin is produced by clara cells in the proximal airways of antigen-challenged mice. Am J Respir Cell Mol Biol 2004;31(4):382-394 (Pubitemid 39330948)
23. Williams OW, Sharafkhaneh A, Kim V, et al. Airway mucus: from production to secretion. Am J Respir Cell Mol Biol 2006;34(5):527-536
24. Akinbi HT, Epaud R, Bhatt H, et al. Bacterial killing is enhanced by expression of lysozyme in the lungs of transgenic mice. J Immunol 2000;165(10):5760-5766 (Pubitemid 30836188)
25. Bals R, Weiner DJ, Moscioni AD, et al. Augmentation of innate host defense by expression of a cathelicidin antimicrobial peptide. Infect Immun 1999;67(11):6084-6089 (Pubitemid 29508140)
26. Cole AM, Liao HI, Stuchlik O, et al. Cationic polypeptides are required for antibacterial activity of human airway fluid. J Immunol 2002;169(12):6985- 6991 (Pubitemid 36899286)
27. Cole AM, Thapa DR, Gabayan V, et al. Decreased clearance of Pseudomonas aeruginosa from airways of mice deficient in lysozyme M. J Leukoc Biol 2005;78(5):1081-1085 (Pubitemid 41572471)
28. Moser C, Weiner DJ, Lysenko E, et al. beta-Defensin 1 contributes to pulmonary innate immunity in mice. Infect Immun 2002;70(6):3068-3072 (Pubitemid 34564168)
29. Evans SE, Hahn PY, McCann F, et al. Pneumocystis cell wall beta-glucans stimulate alveolar epithelial cell chemokine generation through nuclear factor-kappaB-dependent mechanisms. Am J Respir Cell Mol Biol 2005;32(6):490-497 (Pubitemid 40770126)
30. Agusti C, Rano A, Rovira M, et al. Inflammatory response associated with pulmonary complications in non-HIV immunocompromised patients. Thorax 2004;59(12):1081-1088 (Pubitemid 39573929)
31. Barton GM, Medzhitov R. Toll-like receptor signaling pathways. Science 2003;300(5625):1524-1525
32. Boldrick JC, Alizadeh AA, Diehn M, et al. Stereotyped and specific gene expression programs in human innate immune responses to bacteria. Proc Natl Acad Sci USA 2002;99(2):972-977 (Pubitemid 34106620)
33. Kapetanovic R, Cavaillon JM. Early events in innate immunity in the recognition of microbial pathogens. Expert Opin Biol Ther 2007;7(6):907-918 (Pubitemid 46957424)
34. Kawai T, Akira S. TLR signaling. Cell Death Differ 2006;13(5):816-825
35. Kopp E, Medzhitov R. Recognition of microbial infection by Toll-like receptors. Curr Opin Immunol 2003;15(4):396-401 (Pubitemid 36930075)
36. Zhang G, Ghosh S. Toll-like receptor-mediated NF-kappaB activation: a phylogenetically conserved paradigm in innate immunity. J Clin Invest 2001;107(1):13-19 (Pubitemid 32047406)
37. Ulevitch RJ. Therapeutics targeting the innate immune system. Nat Rev Immunol 2004;4(7):512-520 (Pubitemid 38931766)
38. Arevalo I, Tulliano G, Quispe A, et al. Role of imiquimod and parenteral meglumine antimoniate in the initial treatment of cutaneous leishmaniasis. Clin Infect Dis 2007;44(12):1549-1554 (Pubitemid 46871500)
39. Kanistanon D, Hajjar AM, Pelletier MR, et al. A Francisella mutant in lipid A carbohydrate modification elicits protective immunity. PLoS Pathog 2008;4(2):e24 (Pubitemid 351340714)
40. Lembo A, Pelletier M, Iyer R, et al. Administration of a synthetic TLR4 agonist protects mice from pneumonic tularemia. J Immunol 2008;180(11):7574-7581
41. Luhrmann A, Deiters U, Skokowa J, et al. In vivo effects of a synthetic 2-kilodalton macrophage-activating lipopeptide of Mycoplasma fermentans after pulmonary application. Infect Immun 2002;70(7):3785-3792
42. McHutchison JG, Bacon BR, Gordon SC, et al. Phase 1B, randomized, double-blind, dose-escalation trial of CPG 10101 in patients with chronic hepatitis C virus. Hepatology 2007;46(5):1341-1349 (Pubitemid 350155515)
43. Raberg L, Sim D, Read AF. Disentangling genetic variation for resistance and tolerance to infectious diseases in animals. Science 2007;318(5851):812-814
44. Williams TN, Mwangi TW, Wambua S, et al. Negative epistasis between the malaria-protective effects of alpha + -thalassemia and the sickle cell trait. Nat Genet 2005;37(11):1253-1257 (Pubitemid 41568709)
45. Evans SE, Scott BL, Clement CG, et al. Stimulated innate resistance of lung epithelium protects mice broadly against bacteria and fungi. Am J Respir Cell Mol Biol 2009 Mar 27 [Epub ahead of print] PMID: 19329554
46. Dennis DT, Inglesby TV, Henderson DA, et al. Tularemia as a biological weapon: medical and public health management. JAMA 2001;285(21):2763-2773 (Pubitemid 32525374)
47. Hilleman MR. Overview: cause and prevention in biowarfare and bioterrorism. Vaccine 2002;20(25-26):3055-3067 (Pubitemid 34887951)
48. Wayne Conlan J, Shen H, Kuolee R, et al. Aerosol-, but not intradermal-immunization with the live vaccine strain of Francisella tularensis protects mice against subsequent aerosol challenge with highly virulent type A strain of the pathogen by an alphabeta T cell- and interferon gamma- dependent mechanism. Vaccine 2005;23(19):2477-2485 (Pubitemid 40332519)
49. Wilkening DA. Sverdlovsk revisited: modeling human inhalation anthrax. Proc Natl Acad Sci USA 2006;103(20):7589-7594 (Pubitemid 43752825)
50. Tuvim MJ, Evans SE, Clement CG, et al. Augmented lung inflammation protects against influenza A pneumonia. PLoS ONE 2009;4(1):e4176
51. Clement CG, Evans SE, Evans CM, et al. Stimulation of lung innate immunity protects against lethal pneumococcal pneumonia in mice. Am J Respir Crit Care Med 2008;177(12):1322-1330 (Pubitemid 351860909)
52. Moghaddam SJ, Clement CG, De la Garza MM, et al. Haemophilus influenzae lysate induces aspects of the chronic obstructive pulmonary disease phenotype. Am J Respir Cell Mol Biol 2008;38(6):629-638 (Pubitemid 351841563)
53. Brandl K, Plitas G, Mihu CN, et al. Vancomycin-resistant enterococci exploit antibiotic-induced innate immune deficits. Nature 2008;455(7214):804-807
54. Hoogerwerf JJ, de Vos AF, Bresser P, et al. Lung inflammation induced by lipoteichoic acid or lipopolysaccharide in humans. Am J Respir Crit Care Med 2008;178(1):34-41 (Pubitemid 351919191)
55. Reppe K, Tschernig T, Luhrmann A, et al. Immunostimulation with macrophage-activating lipopeptide-2 increased survival in murine pneumonia. Am J Respir Cell Mol Biol 2009;40(4):474-481
56. Bagchi A, Herrup EA, Warren HS, et al. MyD88-dependent and MyD88-independent pathways in synergy, priming, and tolerance between TLR agonists. J Immunol 2007;178(2):1164-1171 (Pubitemid 46095190)
57. Trinchieri G, Sher A. Cooperation of Toll-like receptor signals in innate immune defence. Nat Rev Immunol 2007;7(3):179-190 (Pubitemid 46310482)
58. Medzhitov R. Recognition of microorganisms and activation of the immune response. Nature 2007;449(7164):819-826 (Pubitemid 47598622)
59. Foster SL, Hargreaves DC, Medzhitov R. Gene-specific control of inflammation by TLR-induced chromatin modifications. Nature 2007;447(7147):972- 978 (Pubitemid 46975746)
60. Tazawa R, Hamano E, Arai T, et al. Granulocyte-macrophage colony-stimulating factor and lung immunity in pulmonary alveolar proteinosis. Am J Respir Crit Care Med 2005;171(10):1142-1149 (Pubitemid 40663727)
61. Anderson PM, Markovic SN, Sloan JA, et al. Aerosol granulocyte macrophage-colony stimulating factor: a low toxicity, lung-specific biological therapy in patients with lung metastases. Clin Cancer Res 1999;5(9):2316-2323 (Pubitemid 29437308)
62. Trapnell BC, Whitsett JA, Nakata K. Pulmonary alveolar proteinosis. N Engl J Med 2003;349(26):2527-2539
63. Kinnula V, Mattson K, Cantell K. Pharmacokinetics and toxicity of inhaled human interferon-alpha in patients with lung cancer. J Interferon Res 1989;9(4):419-423 (Pubitemid 19194199)
64. Maasilta P, Halme M, Mattson K, et al. Pharmacokinetics of inhaled recombinant and natural alpha interferon. Lancet 1991;337(8737):371
65. Kinnula V, Cantell K, Mattson K. Effect of inhaled natural interferon-alpha on diffuse bronchioalveolar carcinoma. Eur J Cancer 1990;26(6):740-741 (Pubitemid 20275115)
66. Maasilta P, Holsti LR, Halme M, et al. Natural alpha-interferon in combination with hyperfractionated radiotherapy in the treatment of non-small cell lung cancer. Int J Radiat Oncol Biol Phys 1992;23(4):863-868
67. Giosue S, Casarini M, Alemanno L, et al. Effects of aerosolized interferon-alpha in patients with pulmonary tuberculosis. Am J Respir Crit Care Med 1998;158(4):1156-1162 (Pubitemid 28489016)
68. Giosue S, Casarini M, Ameglio F, et al. Aerosolized interferon-alpha treatment in patients with multi-drug-resistant pulmonary tuberculosis. Eur Cytokine Netw 2000;11(1):99-104 (Pubitemid 30145409)
69. Martin RJ, Boguniewicz M, Henson JE, et al. The effects of inhaled interferon gamma in normal human airways. Am Rev Respir Dis 1993;148(6 Pt 1):1677-1682 (Pubitemid 2024141)
70. Boguniewicz M, Martin RJ, Martin D, et al. The effects of nebulized recombinant interferon-gamma in asthmatic airways. J Allergy Clin Immunol 1995;95(1 Pt 1):133-135
71. Condos R, Raju B, Canova A, et al. Recombinant gamma interferon stimulates signal transduction and gene expression in alveolar macrophages in vitro and in tuberculosis patients. Infect Immun 2003;71(4):2058-2064 (Pubitemid 36368740)
72. Raju B, Hoshino Y, Kuwabara K, et al. Aerosolized gamma interferon (IFN-gamma) induces expression of the genes encoding the IFN-gamma-inducible 10-kilodalton protein but not inducible nitric oxide synthase in the lung during tuberculosis. Infect Immun 2004;72(3):1275-1283 (Pubitemid 38263745)
73. Condos R, Rom WN, Schluger NW. Treatment of multidrug-resistant pulmonary tuberculosis with interferon-gamma via aerosol. Lancet 1997;349(9064):1513-1515 (Pubitemid 27216363)
74. Condos R, Hull FP, Schluger NW, et al. Regional deposition of aerosolized interferon-gamma in pulmonary tuberculosis. Chest 2004;125(6):2146-2155 (Pubitemid 38788183)
75. Moss RB, Mayer-Hamblett N, Wagener J, et al. Randomized, double-blind, placebo-controlled, dose-escalating study of aerosolized interferon gamma-1b in patients with mild to moderate cystic fibrosis lung disease. Pediatr Pulmonol 2005;39(3):209-218 (Pubitemid 40460688)
76. Nakos G, Malamou-Mitsi VD, Lachana A, et al. Immunoparalysis in patients with severe trauma and the effect of inhaled interferon-gamma. Crit Care Med 2002;30(7):1488-1494 (Pubitemid 34756229)
77. Virgolini I, Kurtaran A, Leimer M, et al. Inhalation scintigraphy with iodine-123-labeled interferon gamma-1b: pulmonary deposition and dose escalation study in healthy volunteers. J Nucl Med 1997;38(9):1475-1481 (Pubitemid 27386215)
78. Rao RD, Anderson PM, Arndt CA, et al. Aerosolized granulocyte macrophage colony-stimulating factor (GM-CSF) therapy in metastatic cancer. Am J Clin Oncol 2003;26(5):493-498 (Pubitemid 37248269)
79. Niven RW, Whitcomb KL, Shaner L, et al. The pulmonary absorption of aerosolized and intratracheally instilled rhG-CSF and monoPEGylated rhG-CSF. Pharm Res 1995;12(9):1343-1349
80. Machida M, Hayashi M, Awazu S. Pulmonary absorption of recombinant human granulocyte colony-stimulating factor (rhG-CSF) after intratracheal administration to rats. Biol Pharm Bull 1996;19(2):259-262 (Pubitemid 26088358)
81. Gatmaitan BG, Carruthers MM, Lerner AM. Gentamicin in treatment of primary Gram-negative pneumonias. Am J Med Sci 1970;260(2):90-94
82. Pines A, Raafat H, Plucinski K. Gentamicin and colistin in chronic purulent bronchial infections. Br Med J 1967;2(5551):543-545
83. Klastersky J, Geuning C, Mouawad E, et al. Endotracheal gentamicin in bronchial infections in patients with tracheostomy. Chest 1972;61(2):117-120
84. Pines A, Raafat H, Siddiqui GM, et al. Treatment of severe pseudomonas infections of the bronchi. Br Med J 1970;1(5697):663-665
85. Odio W, Van Laer E, Klastersky J. Concentrations of gentamicin in bronchial secretions after intramuscular and endotracheal administration. J Clin Pharmacol 1975;15(7):518-524
86. Panidis D, Markantonis SL, Boutzouka E, et al. Penetration of gentamicin into the alveolar lining fluid of critically ill patients with ventilator-associated pneumonia. Chest 2005;128(2):545-552 (Pubitemid 41140478)
87. Carcas AJ, Garcia-Satue JL, Zapater P, et al. Tobramycin penetration into epithelial lining fluid of patients with pneumonia. Clin Pharmacol Ther 1999;65(3):245-250 (Pubitemid 29142930)
88. Valcke YJ, Vogelaers DP, Colardyn FA, et al. Penetration of netilmicin in the lower respiratory tract after once-daily dosing. Chest 1992;101(4):1028- 1032
89. Braude AC, Hornstein A, Klein M, et al. Pulmonary disposition of tobramycin. Am Rev Respir Dis 1983;127(5):563-565
90. Kuhn RJ. Pharmaceutical considerations in aerosol drug delivery. Pharmacotherapy 2002;22(3 Pt 2):80S-5S (Pubitemid 34203075)
91. Goldstein I, Wallet F, Nicolas-Robin A, et al. Lung deposition and efficiency of nebulized amikacin during Escherichia coli pneumonia in ventilated piglets. Am J Respir Crit Care Med 2002;166(10):1375-1381 (Pubitemid 35292705)
92. Goldstein I, Wallet F, Robert J, et al. Lung tissue concentrations of nebulized amikacin during mechanical ventilation in piglets with healthy lungs. Am J Respir Crit Care Med 2002;165(2):171-175 (Pubitemid 34084452)
93. Klastersky J, Carpentier-Meunier F, Kahan-Coppens L, et al. Endotracheally administered antibiotics for gram-negative bronchopneumonia. Chest 1979;75(5):586-591 (Pubitemid 9178586)
94. Flume P, Klepser ME. The rationale for aerosolized antibiotics. Pharmacotherapy 2002;22(3 Pt 2):71S-9S
95. Moore RD, Lietman PS, Smith CR. Clinical response to aminoglycoside therapy: importance of the ratio of peak concentration to minimal inhibitory concentration. J Infect Dis 1987;155(1):93-99 (Pubitemid 17225088)
96. Moore RD, Smith CR, Lietman PS. The association of aminoglycoside plasma levels with mortality in patients with gram-negative bacteremia. J Infect Dis 1984;149(3):443-448 (Pubitemid 14138249)
97. Schentag JJ. Correlation of pharmacokinetic parameters to efficacy of antibiotics: relationships between serum concentrations, MIC values, and bacterial eradication in patients with gram-negative pneumonia. Scand J Infect Dis Suppl 1990;74:218-234
98. Deziel-Evans LM, Murphy JE, Job ML. Correlation of pharmacokinetic indices with therapeutic outcome in patients receiving aminoglycosides. Clin Pharm 1986;5(4):319-324 (Pubitemid 16060926)
99. Collins T, Gerding DN. Aminoglycosides versus beta-lactams in gram-negative pneumonia. Semin Respir Infect 1991;6(3):136-146
100. Burns JL, Van Dalfsen JM, Shawar RM, et al. Effect of chronic intermittent administration of inhaled tobramycin on respiratory microbial flora in patients with cystic fibrosis. J Infect Dis 1999;179(5):1190-1196 (Pubitemid 29196500)
101. Valcke Y, Pauwels R, Van der Straeten M. The penetration of aminoglycosides into the alveolar lining fluid of rats. The effect of airway inflammation. Am Rev Respir Dis 1990;142(5):1099-1103
102. Meers P, Neville M, Malinin V, et al. Biofilm penetration, triggered release and in vivo activity of inhaled liposomal amikacin in chronic Pseudomonas aeruginosa lung infections. J Antimicrob Chemother 2008;61(4):859-868
103. Davis KK, Kao PN, Jacobs SS, et al. Aerosolized amikacin for treatment of pulmonary Mycobacterium avium infections: an observational case series. BMC Pulm Med 2007;7:2 (Pubitemid 46359485)
104. McCall CY, Spruill WJ, Wade WE. The use of aerosolized tobramycin in the treatment of a resistant pseudomonal pneumonitis. Ther Drug Monit 1989;11(6):692-695 (Pubitemid 19267403)
105. Dopfer R, Brand P, Mullinger B, et al. Inhalation of tobramycin in patients with cystic fibrosis: comparison of two methods. J Physiol Pharmacol 2007;58(Suppl 5)(Pt 1):141-154 (Pubitemid 351346663)
106. Lenoir G, Antypkin YG, Miano A, et al. Efficacy, safety, and local pharmacokinetics of highly concentrated nebulized tobramycin in patients with cystic fibrosis colonized with Pseudomonas aeruginosa. Paediatr Drugs 2007;9(Suppl 1):11-20 (Pubitemid 46879110)
107. Ramsey BW, Dorkin HL, Eisenberg JD, et al. Efficacy of aerosolized tobramycin in patients with cystic fibrosis. N Engl J Med 1993;328(24):1740-1746 (Pubitemid 23170123)
108. Ratjen F, Doring G. Cystic fibrosis. Lancet 2003;361(9358):681-689
109. Canton R, Cobos N, de Gracia J, et al. Antimicrobial therapy for pulmonary pathogenic colonisation and infection by Pseudomonas aeruginosa in cystic fibrosis patients. Clin Microbiol Infect 2005;11(9):690-703 (Pubitemid 41167334)
110. Sexauer WP, Fiel SB. Aerosolized antibiotics in cystic fibrosis. Semin Respir Crit Care Med 2003;24(6):717-726
111. Kun P, Landau LI, Phelan PD. Nebulized gentamicin in children and adolescents with cystic fibrosis. Aust Paediatr J 1984;20(1):43-45 (Pubitemid 14123235)
112. Wall MA, Terry AB, Eisenberg J, et al. Inhaled antibiotics in cystic fibrosis. Lancet 1983;1(8337):1325
113. Steinkamp G, Tummler B, Gappa M, et al. Long-term tobramycin aerosol therapy in cystic fibrosis. Pediatr Pulmonol 1989;6(2):91-98
114. Smith AL, Ramsey BW, Hedges DL, et al. Safety of aerosol tobramycin administration for 3 months to patients with cystic fibrosis. Pediatr Pulmonol 1989;7(4):265-271
115. Ramsey BW, Pepe MS, Quan JM, et al. Intermittent administration of inhaled tobramycin in patients with cystic fibrosis. Cystic Fibrosis Inhaled Tobramycin Study Group. N Engl J Med 1999;340(1):23-30
116. Moss RB. Long-term benefits of inhaled tobramycin in adolescent patients with cystic fibrosis. Chest 2002;121(1):55-63 (Pubitemid 34114228)
117. Stephens D, Garey N, Isles A, et al. Efficacy of inhaled tobramycin in the treatment of pulmonary exacerbations in children with cystic fibrosis. Pediatr Infect Dis 1983;2(3):209-211
118. Schaad UB, Wedgwood-Krucko J, Suter S, et al. Efficacy of inhaled amikacin as adjunct to intravenous combination therapy (ceftazidime and amikacin) in cystic fibrosis. J Pediatr 1987;111(4):599-605 (Pubitemid 17140544)
119. Bilton D, Henig N, Morrissey B, et al. Addition of inhaled tobramycin to ciprofloxacin for acute exacerbations of Pseudomonas aeruginosa infection in adult bronchiectasis. Chest 2006;130(5):1503-1510 (Pubitemid 44786746)
120. Barker AF. Bronchiectasis. N Engl J Med 2002;346(18):1383-1393
121. Rubin BK. Aerosolized antibiotics for non-cystic fibrosis bronchiectasis. J Aerosol Med Pulm Drug Deliv 2008;21(1):71-76
122. Drobnic ME, Sune P, Montoro JB, et al. Inhaled tobramycin in non-cystic fibrosis patients with bronchiectasis and chronic bronchial infection with Pseudomonas aeruginosa. Ann Pharmacother 2005;39(1):39-44 (Pubitemid 40052376)
123. Barker AF, Couch L, Fiel SB, et al. Tobramycin solution for inhalation reduces sputum Pseudomonas aeruginosa density in bronchiectasis. Am J Respir Crit Care Med 2000;162(2 Pt 1):481-485 (Pubitemid 30647187)
124. Scheinberg P, Shore E. A pilot study of the safety and efficacy of tobramycin solution for inhalation in patients with severe bronchiectasis. Chest 2005;127(4):1420-1426 (Pubitemid 46224309)
125. Dodek P, Keenan S, Cook D, et al. Evidence-based clinical practice guideline for the prevention of ventilator-associated pneumonia. Ann Intern Med 2004;141(4):305-313 (Pubitemid 39079293)
126. Falagas ME, Siempos II, Bliziotis IA, et al. Administration of antibiotics via the respiratory tract for the prevention of ICU-acquired pneumonia: a meta-analysis of comparative trials. Crit Care 2006;10(4):R123 (Pubitemid 47086878)
127. Rathgeber J, Zielmann S, Panzer C, et al. Prevention of pneumonia by endotracheal micronebulization of tobramycin. Anasthesiol Intensivmed Notfallmed Schmerzther 1993;28(1):23-29 (Pubitemid 23115185)
128. Klastersky J, Huysmans E, Weerts D, et al. Endotracheally administered gentamicin for the prevention of infections of the respiratory tract in patients with tracheostomy: a double-blind study. Chest 1974;65(6):650-654
129. Tablan OC, Anderson LJ, Besser R, et al. Guidelines for preventing health-care-associated pneumonia, 2003: recommendations of CDC and the Healthcare Infection Control Practices Advisory Committee. MMWR Recomm Rep 2004;53(RR-3):1-36
130. Falagas ME, Agrafiotis M, Athanassa Z, et al. Administration of antibiotics via the respiratory tract as monotherapy for pneumonia. Expert Rev Anti Infect Ther 2008;6(4):447-452
131. Ghannam DE, Rodriguez GH, Raad II, et al. Inhaled aminoglycosides in cancer patients with ventilator-associated gram-negative bacterial pneumonia: safety and feasibility in the era of escalating drug resistance. Eur J Clin Microbiol Infect Dis 2009;28(3):253-259
132. Palmer LB, Smaldone GC, Chen JJ, et al. Aerosolized antibiotics and ventilatorassociated tracheobronchitis in the intensive care unit. Crit Care Med 2008;36(7):2008-2013
133. Morosini MI, Garcia-Castillo M, Loza E, et al. Breakpoints for predicting Pseudomonas aeruginosa susceptibility to inhaled tobramycin in cystic fibrosis patients: use of high-range Etest strips. J Clin Microbiol 2005;43(9):4480-4485 (Pubitemid 41298231)
134. Linden PK, Paterson DL. Parenteral and inhaled colistin for treatment of ventilator-associated pneumonia. Clin Infect Dis 2006;43(Suppl 2):S89-S4 (Pubitemid 44267146)
135. Michalopoulos A, Fotakis D, Virtzili S, et al. Aerosolized colistin as adjunctive treatment of ventilator-associated pneumonia due to multidrug-resistant gram-negative bacteria: a prospective study. Respir Med 2008;102(3):407-412 (Pubitemid 351179979)
136. Kwa AL, Loh C, Low JG, et al. Nebulized colistin in the treatment of pneumonia due to multidrug-resistant Acinetobacter baumannii and Pseudomonas aeruginosa. Clin Infect Dis 2005;41(5):754-757 (Pubitemid 41170367)
137. Berlana D, Llop JM, Fort E, et al. Use of colistin in the treatment of multiple-drug-resistant gram-negative infections. Am J Health Syst Pharm 2005;62(1):39-47 (Pubitemid 40394633)
138. Hamer DH. Treatment of nosocomial pneumonia and tracheobronchitis caused by multidrug-resistant Pseudomonas aeruginosa with aerosolized colistin. Am J Respir Crit Care Med 2000;162(1):328-330 (Pubitemid 30469842)
139. McCoy KS, Quittner AL, Oermann CM, et al. Inhaled aztreonam lysine for chronic airway Pseudomonas aeruginosa in cystic fibrosis. Am J Respir Crit Care Med. 2008;178(9):921-928
140. Safdar A. Strategies to enhance immune function in hematopoietic transplantation recipients who have fungal infections. Bone Marrow Transplant 2006;38(5):327-337 (Pubitemid 44241541)
141. Safdar A. Difficulties with fungal infections in acute myelogenous leukemia patients: immune enhancement strategies. Oncologist 2007;12(Suppl 2):2-6
142. Safdar ARG, Lichtiger B, Dickey BF, et al. Recombinant interferon gamma 1 b immune enhancement in 20 patients with hematologic malignancies and systemic opportunistic infections treated with donor granulocyte transfusions. Cancer 2006;106(12):2664-2671 (Pubitemid 43911836)
143. Montoya JG, Chaparro SV, Celis D, et al. Invasive aspergillosis in the setting of cardiac transplantation. Clin Infect Dis 2003;37(Suppl 3):S281-92 (Pubitemid 37260465)
144. Garcia-Vidal CUA, Kirby KA, Marr KA. Epidemiology of invasive mold infections in allogeneic stem cell transplant recipients: biological risk factors for infection according to time after transplantation. Clin Infect Dis 2008;47(8):1041-1050
145. Mattiuzzi GN, Kantarjian H, Faderl S, et al. Amphotericin B lipid complex as prophylaxis of invasive fungal infections in patients with acute myelogenous leukemia and myelodysplastic syndrome undergoing induction chemotherapy. Cancer 2004;100(3):581-589 (Pubitemid 38124777)
146. Singh N, Limaye AP, Forrest G, et al. Late-onset invasive aspergillosis in organ transplant recipients in the current era. Med Mycol 2006;44(5):445-449 (Pubitemid 44173328)
147. Schmitt HJ, Bernard EM, Hauser M, et al. Aerosol amphotericin B is effective for prophylaxis and therapy in a rat model of pulmonary aspergillosis. Antimicrob Agents Chemother 1988;32(11):1676-1679 (Pubitemid 18267614)
148. Cicogna CE, White MH, Bernard EM, et al. Efficacy of prophylactic aerosol amphotericin B lipid complex in a rat model of pulmonary aspergillosis. Antimicrob Agents Chemother 1997;41(2):259-261 (Pubitemid 27111015)
149. Koizumi T, Kubo K, Kaneki T, et al. Pharmacokinetic evaluation of amphotericin B in lung tissue: lung lymph distribution after intravenous injection and airspace distribution after aerosolization and inhalation of amphotericin B. Antimicrob Agents Chemother 1998;42(7):1597-1600 (Pubitemid 28311548)
150. Corcoran TE, Venkataramanan R, Mihelc KM, et al. Aerosol deposition of lipid complex amphotericin-B (Abelcet) in lung transplant recipients. Am J Transplant 2006;6(11):2765-2773 (Pubitemid 44571699)
151. Drew RH, Dodds Ashley E, Benjamin DK Jr, et al. Comparative safety of amphotericin B lipid complex and amphotericin B deoxycholate as aerosolized antifungal prophylaxis in lung-transplant recipients. Transplantation 2004;77(2):232-237 (Pubitemid 38155752)
152. Montoya JG, Giraldo LF, Efron B, et al. Infectious complications among 620 consecutive heart transplant patients at stanford university medical center. Clin Infect Dis 2001;33(5):629-640 (Pubitemid 32762936)
153. Palmer SM, Drew RH, Whitehouse JD, et al. Safety of aerosolized amphotericin B lipid complex in lung transplant recipients. Transplantation 2001;72(3):545-548 (Pubitemid 32769650)
154. Boots RJ, Paterson DL, Allworth AM, et al. Successful treatment of post-influenza pseudomembranous necrotising bronchial aspergillosis with liposomal amphotericin, inhaled amphotericin B, gamma interferon and GM-CSF. Thorax 1999;54(11):1047-1049 (Pubitemid 29495403)
155. Safdar A, O'Brien S, Kouri IF. Efficacy and feasibility of aerosolized amphotericin B lipid complex therapy in caspofungin breakthrough pulmonary zygomycosis. Bone Marrow Transplant 2004;34(5):467-468 (Pubitemid 39232379)
156. Dhand R, Guntur VP. How best to deliver aerosol medications to mechanically ventilated patients. Clin Chest Med 2008;29(2):277-96, vi (Pubitemid 351601908)
157. MacIntyre NR, Silver RM, Miller CV, et al. Aerosol delivery in intubated, mechanically ventilated patients. Crit Care Med 1985;13(2):81-84 (Pubitemid 15174131)
158. Aerosol consensus statement-1991. American Association for Respiratory Care. Respir Care 1991;36(9):916-921
159. Dhand R, Sohal H. Pulmonary drug delivery system for inhalation therapy in mechanically ventilated patients. Expert Rev Med Devices 2008;5(1):9-18
160. Blanchard JDCD, et al. Lung deposition of interferon gamma - 1b following inhalation via AERx System vs. Respirgard II™ nebulizer. Am J Respir Crit Care Med 2003;167:A373 [Meeting Abstract]
161. Watts AB, McConville JT, Williams RO. Current therapies and technological advances in aqueous aerosol drug delivery. Drug Dev Ind Pharm 2008;34(9):913-922