Inhaled antibiotic therapy for ventilator-associated tracheobronchitis and ventilator-associated pneumonia: An update

Advances in Therapy

Volumn 28, Issue 9, 2011, Pages 728-747

  Abu Salah, Tareq ^a   Dhand, Rajiv ^a  

^a University of Missouri   (United States)

Author keywords

Aerosols; Antibiotic resistance; Antibiotics; Colistin; Gram negative pneumonia; Levofloxacin; Mechanical ventilation; Nebulizer; Tracheobronchitis

Indexed keywords

AMIKACIN; AMINOGLYCOSIDE ANTIBIOTIC AGENT; AMPHOTERICIN B; ANTIBIOTIC AGENT; ARIKACE; AZTREONAM; AZTREONAM LYSINE; BETA LACTAM ANTIBIOTIC; CARBAPENEM; CEFTAZIDIME; CIPROFLOXACIN; COLISTIN; GENTAMICIN; LEVOFLOXACIN; MEROPENEM; PENTAMIDINE; PLACEBO; POLYMYXIN B; QUINOLINE DERIVED ANTIINFECTIVE AGENT; RIBAVIRIN; TOBRAMYCIN; UNCLASSIFIED DRUG; VANCOMYCIN; ZANAMIVIR;

ANTIBIOTIC THERAPY; ARTIFICIAL VENTILATION; BACTERIAL COLONIZATION; BIOFILM; CYSTIC FIBROSIS; DISEASE COURSE; DRUG BLOOD LEVEL; DRUG EFFICACY; DRUG PENETRATION; DRUG SPUTUM LEVEL; DRUG TRANSPORT; GRAM NEGATIVE BACTERIUM; GRAM NEGATIVE INFECTION; GRAM POSITIVE BACTERIUM; GRAM POSITIVE INFECTION; HUMAN; INTENSIVE CARE UNIT; LUNG CIRCULATION; MORBIDITY; MORTALITY; MULTIDRUG RESISTANCE; PATHOPHYSIOLOGY; PSEUDOMONAS AERUGINOSA; PSEUDOMONAS INFECTION; QUORUM SENSING; REVIEW; RISK FACTOR; SINGLE DRUG DOSE; TRACHEOBRONCHITIS; TREATMENT DURATION; UNSPECIFIED SIDE EFFECT; VENTILATOR ASSOCIATED PNEUMONIA; VENTILATOR ASSOCIATED TRACHEOBRONCHITIS;

ADMINISTRATION, INHALATION; AEROSOLS; ANTI-BACTERIAL AGENTS; BRONCHITIS; CROSS INFECTION; HUMANS; INTUBATION, INTRATRACHEAL; LUNG; NEBULIZERS AND VAPORIZERS; PNEUMONIA, VENTILATOR-ASSOCIATED; TRACHEITIS; VENTILATORS, MECHANICAL;

EID: 82455199209     PISSN: 0741238X     EISSN: 18658652     Source Type: Journal    
DOI: 10.1007/s12325-011-0051-z     Document Type: Review

References (130)

1. Niederman MS, Craven DE. Guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia. Am J Respir Crit Care Med. 2005;171: 388-416
2. Heyland DK, Cook DJ, Griffith L, Keenan SP, Brun-Buisson C, Canadian Critical Trials Group. The attributable morbidity and mortality of ventilatorassociated pneumonia in the critically ill patient. Am J Respir Crit Care Med. 1999;159: 1249-1256 (Pubitemid 29202563)
3. Rello J, Ollendorf DA, Oster G, et al. Epidemiology and outcomes of ventilator-associated pneumonia in a large US database. Chest. 2002;122: 2115-2121 (Pubitemid 36051151)
4. Dhand R. The role of aerosolized antimicrobials in the treatment of ventilator-associated pnemonia. Respir Care. 2007;52: 866-884
5. Luyt CE, Combes A, Nieszkowska A, Trouillet JL, Chastre J. Aerosolized antibiotics to treat ventilator-associated pneumonia. Curr Opin Infect Dis. 2009;22: 154-158
6. Craven DE, Hjalmarson KI. Ventilator-associated tracheobronchitis and pneumonia: Thinking outside the box. Clinical Infectious Diseases. 2010;51(S1): S59-S66
7. Nseir S, Di Pompeo C, Pronnier P, et al. Nosocomial tracheobronchitis in mechanically ventilated patients: Incidence, aetiology and outcome. Eur Respir J. 2002;20: 1483-1489 (Pubitemid 35460618)
8. Dallas J, Skrpky L, Abebe N, Boyle WA III, Kollef MH. Ventilator-associated tracheobronchitis (VAT) in a mixed surgical and medical ICU population. Chest. 2011;139: 513-518. Epub
9. A'Court CH, Garrard CS, Crook D, et al. Microbiologic lung surveillance in mechanically ventilated patients, using non-directed bronchial lavage and quantitative culture. Q J Med. 1993;86: 635-648 (Pubitemid 23310532)
10. Nseir S, Ader F, Marquette CH. Nosocomial tracheobronchitis. Curr Opin Infect Dis. 2009;22: 148-153
11. Horan TC, Andrus M, Dudeck MA. CDC/NHSN surveillance definition of health care-associated infection and criteria for specific types of infections in the acute care setting. Am J Infect Control. 2008;36: 309-332 (Pubitemid 351763841)
12. Malacarne P, Langer M, Nascimben E, et al. Building a continuous multicenter infection surveillance system in the intensive care unit: Findings from the initial data set of 9493 patients from 71 Italian intensive care units. Crit Care Med. 2008;36: 1105-1113 (Pubitemid 351482657)
13. Kampf G, Wischnewski N, Schulgen G, et al. Prevalence and risk factors for nosocomial lower respiratory tract infections in German hospitals. J Clin Epidemiol. 1998;51: 495-502 (Pubitemid 28310237)
14. Agrafiotis M, Siempos II, Falagas ME. Frequency, prevention, outcome and treatment of ventilator-associated tracheobronchitis: Systematic review and meta-analysis. Respir Med. 2010;104: 325-336
15. Chastre J, Fagon JY. Ventilator-associated pneumonia. Am J Respir Crit Care Med. 2002;165: 867-903 (Pubitemid 34774654)
16. Fridkin SK. Increasing prevalence of antimicrobial resistance in intensive care units. Crit Care Med. 2001;29(suppl. 4): N64-N68 (Pubitemid 32319753)
17. Obritsch MD, Fish DN, MacLaren R, Jung R. National surveillance of antimicrobial resistance in Pseudomonas aeruginosa isolates obtained from intensive care unit patients from 1993 to 2002. Antimicrob Agents Chemotherap. 2004;48: 4606-4610 (Pubitemid 39577660)
18. Klevens RM, Edwards JR, Tenover FC, McDonald LC, Horan T, Gaynes R. National Nosocomial Infections Surveillance System. Changes in the epidemiology of methicillin-resistant Staphylococcus aureus in intensive care units in US hospitals, 1992-2003. Clinical Infectious Diseases. 2006;42: 389-391. Epub (Pubitemid 43122317)
19. Ibrahim EH, Ward S, Sherman G, Kollef MH. A comparative analysis of patients with early-onset vs late-onset nosocomial pneumonia in the ICU setting. Chest. 2000;117: 1434-1442 (Pubitemid 30321602)
20. Carratala J, Mykietiuk A, Fernandez-Sabe N, et al. Health care-associated pneumonia requiring hospital admission: Epidemiology, antibiotic therapy, and clinical outcomes. Arch Intern Med. 2007;167: 1393-1399 (Pubitemid 47052438)
21. Michel F, Franceschini B, Berger P, et al. Early antibiotic treatment for BAL-confirmed ventilator-associated pneumonia: A role for routine endotracheal aspirate cultures. Chest. 2005;127: 589-597 (Pubitemid 40229322)
22. Depuydt P, Benoidt D, Vogelaers D, et al. Systemic surveillance cultures as a tool to predict involvement of multidrug antibiotic resistant bacteria in ventilator-associated pneumonia. Intensive Care Medicine. 2008;34: 675-682 (Pubitemid 351660083)
23. Yang KZH, Guglielmo BJ, Wiener-Kronish J. Multidrug-resistant Pseudomonas aeruginosa ventilator-associated pneumonia: The role of endotracheal aspirate surveillance cultures. Ann Pharmacother. 2009;43: 28-35
24. Hayon J, Figliolini C, Combes A, et al. Role of serial routine microbiologic culture results in the initial management of ventilator-associated pneumonia. Am J Respir Crit Care Med. 2002;165: 41-46 (Pubitemid 34053355)
25. Rouby JJ, Martin De Lassale E, Poete P, et al. Nosocomial bronchopneumonia in the critically ill. Histologic and bacteriologic aspects. Am Rev Respir Dis. 1992;146: 1059-1066
26. Honeybourne D, Baldwin DR. The site concentrations of antimicrobial agents in the lung. J Antimicrobial Chemotherap. 1992;30: 249-260
27. Wilkinson TM, Patel IS, Wilks M, Donaldson GC, Wedzicha JA. Airway bacterial load and FEV1 decline in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2003;167: 1090-1095 (Pubitemid 36459654)
28. Palmer LB, Smaldone GC, Chen JJ, et al. Aerosolized antibiotics and ventilator-associated tracheobronchitis in the intensive care unit. Crit Care Med. 2008;36: 2008-2013
29. Miller DD, Amin MM, Palmer LB, et al. Aerosol delivery and modern mechanical ventilation: In vitro/in vivo evaluation. Am J Respir Crit Care Med. 2003;168: 1205-1209 (Pubitemid 37421837)
30. Weibel ER, Gil J. Structure-function relationships at the alveolar level. In West JB, ed. Bioengineering aspects of the lung. New York: Marcel Dekker, 1977
31. Niederman MS. Principles of antibiotic use and the selection of empiric therapy for pneumonia. In Fishman's Pulmonary Diseases and Disorders. Fishman AP, Elias JA, Fishman JA, Grippi MA, Kaiser LR, Senior RM, eds. McGraw Hill, New York, 3rd ed; 1998. Chap 122; pp 1939-1949
32. Stachelin LA. Structure and function of intercellular junctions. Int Rev Cytol. 1974;39: 191-283
33. Baldwin DR, Honeybourne D, Wise R. Pulmonary disposition of antimicrobial agents: Methodological considerations. Antimicrob Agents Chemotherap. 1992;36: 1171-1175
34. Levy J, Smith AL, Kenny MA, Ramsey B, Schoenknecht FD. Bioactivity of gentamicin in purulent sputum from patients with cystic fibrosis or bronchiectasis: Comparison with activity in serum. J Infectious Diseases. 1983;148: 1069-1076 (Pubitemid 14206311)
35. Mendelman PM, Smith AL, Levy J, et al. Aminoglycoside penetration, inactivation, and efficacy in cystic fibrosis sputum. Am Rev Respir Dis. 1985;132: 761-765 (Pubitemid 16247735)
36. Valcke Y, Pauwels R, Van der Straeten M. Pharmacokinetics of antibiotics in the lungs. Eur Respir J. 1990;3: 715-722 (Pubitemid 20228711)
37. McCullagh A, Rosenthal M, Wanner A, Hurtado A, Padley S, Bush A. The bronchial circulation -worth a closer look. Pediatr Pulmonol. 2010;45: 1-13
38. Ilowite JS, Gorvoy JD, Smaldone GC. Quantitative deposition of aerosolized gentamicin in cystic fibrosis. Am Rev Respir Dis. 1987;136: 1445-1449 (Pubitemid 18030280)
39. Bergogne-Bérézin E. Pharmacokinetics of antibiotics in cystic fibrosis patients with particular reference to the bronchopulmonary tree. Infection. 1987;15: 288-294
40. LeConte P, Potel G, Peltier P, et al. Lung distribution and pharmacokinetics of aerosolized tobramycin. Am Rev Respir Dis. 1993;147: 1279-1282 (Pubitemid 23149891)
41. Dhand R. Aerosol delivery during mechanical ventilation: From basic techniques to new devices. J Aerosol Med Pulm Drug Deliv. 2008;21: 45-60
42. Dhand R, Guntur VP. How best to deliver aerosol medications to mechanically-ventilated patients. Clin Chest Med. 2008;29: 277-296 (Pubitemid 351601908)
43. O'Doherty MJ, Thomas SH, Page CJ, et al. Delivery of a nebulized aerosol to a lung model during mechanical ventilation. Effect of ventilator settings and nebulizer type, position, and volume of fill. Am Rev Respir Dis. 1992;146: 383-388
44. O'Riordan TG, Greco MJ, Perry RJ, et al. Nebulizer function during mechanical ventilation. Am Rev Respir Dis. 1992;145: 1117-1122
45. O'Riordan TG, Palmer LB, Smaldone GC. Aerosol deposition in mechanically ventilated patients. Optimizing nebulizer delivery. Am J Respir Crit Care Med. 1994;149: 214-219 (Pubitemid 24066122)
46. Palmer LB. Aerosolized antibiotics in critically ill ventilated patients. Curr Opin Crit Care. 2009;15: 413-418
47. 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 (Pubitemid 28028437)
48. Dhand R. Nebulizers that use a vibrating mesh or plate with multiple apertures to generate aerosol. Respir Care. 2002;47: 1406-1416; discussion 1416-1418
49. Pedersen KM, Handlos VN, Heslet L, Kristensen HG. Factors influencing the in vitro deposition of tobramycin aerosol: A comparison of an ultrasonic nebulizer and a high-frequency vibrating mesh nebulizer. J Aerosol Med. 2006;19: 175-183 (Pubitemid 43993384)
50. Ehrmann S, Mercier E, Vecellio L, et al. Pharmacokinetics of high-dose nebulized amikacin in mechanically-ventilated healthy subjects. Intensive Care Medicine. 2008;34: 755-762 (Pubitemid 351660079)
51. Dhand R, Sohal H. Pulmonary Drug Delivery System for inhalation therapy in mechanically-ventilated subjects. Expert Rev Med Devices. 2008;5: 9-18
52. Luyt CE, Clavel M, Guntupalli K, et al. Pharmacokinetics and lung delivery of PDDS-aerosolized amikacin (NKTR-061) in intubated and mechanically ventilated patients with nosocomial pneumonia. Critical Care. 2009;13;R200. Epub
53. Zarilli GM, Monteforte M, Baram D, et al. Systemic versus aerosolized delivery of vancomycin for MRSA: Concentrations in lungs and serum [abstract]. Am J Respir Crit Care Med. 2008;177: A286
54. Geller DE, Flume P, Griffith DC. Pharmacokinetics and safety of MP-376 (levofloxacin inhalation solution) in cystic fibrosis subjects. Antimicrob Agents Chemotherap. 2011;55: 2636-2640
55. King P, Lomovskaya O, Griffith DC, et al. In vitro pharmacodynamics of levofloxacin and other aerosolized antibiotics under multiple conditions relevant to chronic pulmonary infection in cystic fibrosis. Antimicrob Agents Chemotherap. 2010;54: 143-148
56. King P, Citron DM, Griffith DC, Lomovskaya O, Dudley MN. Effect of oxygen limitation on the in vitro activity of levofloxacin and other antibiotics administered by the aerosol route against Pseudomonas aeruginosa from cystic fibrosis patients. Diagn Microbiol Infect Dis. 2010;66: 181-186
57. Inglis TJ, Millar MR, Jones JG, Robinson DA. Tracheal tube biofilm as a source of bacterial colonization of the lung. J Clin Microbiol. 1989;27: 2014-2018 (Pubitemid 19208985)
58. Prince AS. Biofilms, antimicrobial resistance, and airway infection. N Engl J Med. 2002;347: 1110-1111
59. Shah C, Kollef MH. Endotracheal tube intraluminal volume loss among mechanically ventilated patients. Crit Care Med. 2004;32: 120-125 (Pubitemid 38125572)
60. Adair CG, Gorman SP, Feron BM, et al. Implications of endotracheal tube biofilm for ventilator-associated pneumonia. Intensive Care Medicine. 1999;25: 1072-1076 (Pubitemid 29525061)
61. Gorman SP, McGovern JG, Woolfson AD, Adair CG, Jones DS. The concomitant development of poly(vinyl chloride)-related biofilm and antimicrobial resistance in relation to ventilator-associated pneumonia. Biomaterials 2001;22: 2741-2747 (Pubitemid 32727990)
62. Bauer TT, Torres A, Ferrer R, Heyer CM, Schultze-Werninghaus G, Rasche K. Biofilm formation in endotracheal tubes. Association between pneumonia and the persistence of pathogens. Monaldi Arch Chest Dis. 2002;57: 84-87 (Pubitemid 34873746)
63. Mah TF, Pitts B, Pellock B, Walker GC, Stewart PS, O'Toole GA. A genetic basis for Pseudomonas aeruginosa biofilm antibiotic resistance. Nature. 2003;426: 306-310 (Pubitemid 37463151)
64. Favre-Bonte S, Chamot E, Kohler T, Romand JA, van Delden C. Autoinducer production and quorum-sensing dependent phenotypes of Pseudomonas aeruginosa vary according to isolation site during colonization of intubated patients. BMC Microbiol. 2007;7: 33
65. Greenberg EP. Bacterial communication: Tiny teamwork. Nature. 2003;424: 134
66. Le Berre R, Nguyen S, Nowak E, et al. Quorum-sensing activity and related virulence factor expression in clinically pathogenic isolates of Pseudomonas aeruginosa. Clin Microbiol Infect. 2008;14: 337-43. Epub (Pubitemid 351356524)
67. Sadikot RT, Blackwell TS, Christman JW, Prince AS. Pathogen-host interactions in Pseudomonas aeruginosa pneumonia. Am J Respir Crit Care Med. 2005;171: 1209-1223. Epub (Pubitemid 40740727)
68. Latifi A, Foglino M, Tanaka K, Williams P, Lazdunski A. A hierarchical quorum-sensing cascade in Pseudomonas aeruginosa links the transcriptional activators LasR and RhIR (VsmR) to expression of the stationary-phase sigma factor RpoS. Mol Microbiol. 1996;21: 1137-1146 (Pubitemid 26313241)
69. Dénervaud V, TuQuoc P, Blanc D, et al. Characterization of cell-to-cell signaling-deficient Pseudomonas aeruginosa strains colonizing intubated patients. J Clin Microbiol. 2004;42: 554-562 (Pubitemid 38222628)
70. Kohler T, Guanella R, Carlet J, van Delden C. Quorum sensing dependent virulence during Pseudomonas aeruginosa colonization and pneumonia in mechanically ventilated patients. Thorax. 2010;65: 703-710
71. Njoroge J, Sperandio V. Jamming bacterial communication: New approaches for the treatment of infectious diseases. EMBO Mol Med. 2009;1: 201-210
72. Zhuo H, Yang K, Lynch SV, et al. Increased mortality of ventilated patients with endotracheal Pseudomonas aeruginosa without clinical signs of infection. Crit Care Med. 2008;36: 2495-2503
73. Matsushima A, Tasaki O, Shimizu K, et al. Preemptive antibiotic treatment based on Gram staining reduced the incidence of ARDS in mechanically ventilated patients. J Trauma. 2008;65: 309-315
74. Marr AK, Overhage J, Bains M. The Lon protease of Pseudomonas aeruginosa is induced by aminoglycosides and is involved in biofilm formation and motility. Microbiology. 2007;153: 474-482
75. Adair CG, Gorman SP, Byers LM, et al. Eradication of endotracheal biofilm by nebulized gentamicin. Intensive Care Medicine. 2002;28: 426-431
76. Kollef MH, Afessa B, Anzueto A et al. Silver-coated endotracheal tubes and incidence of ventilator-associated pneumonia: The NASCENT randomized trial. JAMA. 2008;300;805-813
77. Raad II, Mohamed JA, Reitzel RA, et al. The prevention of biofilm colonization by multidrug-resistant pathogens that cause ventilator-associated pneumonia with antimicrobial-coated endotracheal tubes. Biomaterials. 2011;32: 2689-2694
78. Le J, Ashley ED, Neuhauser MM, et al. Consensus summary of aerosolized antimicrobial agents: Application of guideline criteria. Pharmacotherapy. 2010;30: 562-584
79. Geller DE, Flume PA, Staab D, et al. Levofloxacin Inhalation Solution (MP-376) in patients with cystic fibrosis with Pseudomonas aeruginosa. Am J Respir Crit Care Med. 2011;183: 1510-1516. Epub
80. Torres A, Valencia M. Does ventilator-associated tracheobronchitis need antibiotic treatment? Critical Care. 2005;9: 255-256. Epub (Pubitemid 40796801)
81. 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: 328-330 (Pubitemid 30469842)
82. Ahmed QA, Niederman MS. Respiratory infection in the chronically critically ill patient. Ventilator-associated pneumonia and tracheobronchitis. Clin Chest Med. 2001;22: 71-85 (Pubitemid 32290596)
83. Pereira GH, Muller PR, Levin AS. Salvage treatment of pneumonia and initial treatment of tracheobronchitis caused by multidrug-resistant Gram-negative bacilli with inhaled polymyxin B. Diagn Microbiol Infect Dis. 2007;58: 235-240 (Pubitemid 46856815)
84. Nseir S, DiPompeo C, Soubrier S, et al. Outcomes of ventilated COPD patients with nosocomial tracheobronchitis: A case control study. Infection. 2004;32: 210-216 (Pubitemid 39070600)
85. Nseir S, DiPompeo C, Soubrier S, et al. Effect of ventilator-associated tracheobronchitis on outcome in patients without chronic respiratory failure: A case control study. Critical Care. 2005;9: R238-R245
86. Nsier S, Favory R, Josefowicz E, et al. Antimicrobial treatment for ventilator-associated tracheobronchitis: A randomized, controlled, multicenter study. Critical Care. 2008;12: R62
87. Cunha BA. Aerosolized antibiotics are not a good idea-don't go with the flow: Premum Non Nocere! Crit Care Med. 2009;37: 799-800; author reply 800-801
88. Rello J. Bench-to-bedside review: Therapeutic options and issues in the management of ventilator-associated bacterial pneumonia. Critical Care. 2005;9: 259-265 (Pubitemid 40796803)
89. Kollef MH. Inadequate antimicrobial treatment: An important determinant of outcome of hospitalized patients. Clinical Infectious Diseases. 2000;31;S131-S138 (Pubitemid 32291120)
90. Ibrahim EH, Sherman G, Ward S, Fraser VJ, Kollef MH. The influence of inadequate antimicrobial treatment of bloodstream infections on patient outcomes in the ICU setting. Chest. 2000;118: 146-155 (Pubitemid 30485502)
91. Cosgrove SE, Kaye KS, Elipoulous GM, Carmeli Y. Health and economic outcomes of the emergence of third-generation cephalosporin resistance in Enterobacter species. Arch Intern Med. 2002;162: 185-190 (Pubitemid 34098188)
92. Kollef MH, Morrow LE, Niederman MS, et al. Clinical characteristics and treatment patterns among patients with ventilator-associated pneumonia. Chest. 2006;129: 1210-1218
93. Soo Hoo GW, Wen YE, Nguyen TV, Goetz MB. Impact of clinical guidelines in the management of severe hospital-acquired pneumonia. Chest. 2005;128: 2778-2787 (Pubitemid 41507640)
94. Schlueter M, James C, Dominguez A, et al. Practice patterns for antibiotic de-escalation in culture-negative healthcare-associated pneumonia. Infection. 2010;38: 357-362
95. Masterton RG. Antibiotic de-escalation. Crit Care Clin. 2011;27: 149-162
96. Klepser ME. Role of nebulized antibiotics for the treatment of respiratory infections. Curr Opin Infect Dis. 2004;17: 109-112 (Pubitemid 38453389)
97. Lesho E. Role of inhaled antibacterials in hospital acquired and ventilator-associated pneumonia. Expert Rev Anti Infect Ther. 2005;3: 445-451 (Pubitemid 40872538)
98. Hagerman JK, Hancock KE, Klepser ME. Aerosolised antibiotics: A critical appraisal of their use. Expert Opin Drug Delivery. 2006;3: 71-86 (Pubitemid 43056392)
99. Czosnowski QA, Wood GC, Magnotti LJ, et al. Adjunctive aerosolized antibiotics for treatment of ventilator-associated pneumonia. Pharmacotherapy. 2009;29: 1054-1060
100. Ghannam DE, Rodriguez DH, Raad II, Safdar A. 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: 253-259
101. Niederman MS, Chastre J, Corkery K, et al. Inhaled amikacin reduces IV antibiotic use in intubated mechanically ventilated patients (abstract). Am J Respir Crit Care Med. 2007;175: A326
102. Ioannidou E, Siempos II, Falagas ME. Administration of antimicrobials via the respiratory tract for the treatment of patients with nosocomial pneumonia. J Antimicrob Chemotherap. 2007;60: 1216-1226 (Pubitemid 350168316)
103. Lu Q, Yang J, Liu Z, et al. Nebulized ceftazidime and amikacin in ventilator-associated pneumonia caused by Pseudomonas aeruginosa. Am J Respir Crit Care Med. 2011;184: 106-115. Epub 2011
104. Mohr AM, Sifri ZC, Horng HS, et al. Use of aerosolized aminoglycosides in the treatment of Gram-negative ventilator-associated pneumonia. Surg Infect (Larchmt). 2007;8: 349-357 (Pubitemid 47186305)
105. Fagon JY, Chastre J, Hance AJ, Montravers P, Novara A, Gibert C. Nosocomial pneumonia in ventilated patients: A cohort study evaluating attributable mortality and hospital stay. Am J Med. 1993;94: 281-288 (Pubitemid 23074802)
106. Falagas ME, Kasiakou SK, Tsiordas S, Michalopoulos A. The use of intravenous and aerosolized polymyxins for the treatment of infections in critically ill patients: A review of the recent literature. CM &R. 2006;4: 138-146 (Pubitemid 44047368)
107. Levin AS, Barone AA, Penco J, et al. Intravenous colistin as therapy for nosocomial infections caused by multidrug-resistant Pseudomonas aeruginosa and Acinetobacter baumannii. Clinical Infectious Diseases. 1999;28: 1008-1011 (Pubitemid 29203530)
108. Garnacho-Montero J, Ortiz-Leyba C, Jimenez-Jimenez FJ, et al. Treatment of multidrug-resistant Acinetobacter baumannii ventilator-associated pneumonia (VAP) with intravenous colistin: A comparison with imipenem-susceptible VAP. Clinical Infectious Diseases. 2003;36: 1111-1118 (Pubitemid 36549630)
109. Linden PK, Kusne S, Coley K, et al. Use of parenteral colistin for the treatment of sepsis from multi resistant gram-negative bacilli in critically ill patients. Critical Care. 2003;37: E154-e160
110. Markou N, Apostolakos H, Koumoudiou C, et al. Intravenous colistin in the treatment of sepsis from multiresistant gram-negative bacilli in critically ill patients. Critical Care. 2003;7: R78-R83
111. Kasiakou SK, Michalopoulos A, Soteriades ES, et al. Combination therapy with intravenous colistin for management of infections due to multidrug-resistant Gram-negative bacteria in patients without cystic fibrosis. Antimicrob Agents Chemotherap. 2005;49: 3136-3146 (Pubitemid 41060551)
112. Montero M, Horcajada JP, Sorli L, et al. Effectiveness and safety of colistin for the treatment of multidrug-resistant Pseudomonas aeruginosa infections. Infection. 2009;37: 461-465
113. Gounden R, Bamford C, van Zyl-Smit R, Cohen K, Maartens G. Safety and effectiveness of colistin compared with tobramycin for multi-drug resistant Acinetobacter baumannii infections. BMC Infectious Diseases. 2009;9: 26
114. Reina R, Estenssoro E, Saenz G, et al. Safety and efficacy of colistin in Acinetobacter and Pseudomonas infections. Intensive Care Medicine. 2005;31: 1058-1065 (Pubitemid 41125336)
115. Kallel H, Bahloul M, Hergafi L, et al. Colistin as salvage therapy for nosocomial infections caused by multidrug-resistant bacteria in the ICU. International Journal of Antimicrobial Agents. 2006;28: 366-369 (Pubitemid 44403003)
116. Koomanachai P, Tiengrim S, Kiratisin P, Thamlikitkul V. Efficacy and safety of colistin (colistimethate sodium) for therapy of infections caused by multidrug-resistant Pseudomonas aeruginosa and Acinetobacter baumannii in Sriraj Hospital, Bangkok, Thailand. Int Journal of Infectious Diseases. 2007;11: 402-406 (Pubitemid 47239447)
117. Michalapoulos A, Kastakou SK, Mastora Z, et al. Aerosolized colistin for the treatment of nosocomial pneumonia due to multidrug-resistant Gram-negative bacteria in patients without cystic fibrosis. Critical Care. 2005;9: R53-R59
118. Kwa AL, Loh C, Low JG, Kurup A, Tam VH. Nebulized colistin in the treatment of pneumonia due to multidrug-resistant Acinetobacter baumannii and Pseudomonas aeruginosa. Clinical Infectious Diseases. 2005;41: 754-757 (Pubitemid 41170367)
119. Berlana D, Llop JM, Fort E, Badia MB, Jodar R. Use of colistin in the treatment of multiple-drug-resistant gram-negative infections. Am J Health Syst Pharm. 2005;62: 39-47 (Pubitemid 40394633)
120. Mataouakkil S, Charra B, Hachimi A, et al. Colistin and rifampicin in the treatment of nosocomial infections from multiresistant Acinetobacter baumannii. J Infect. 2006;53: 274-278 (Pubitemid 44391062)
121. 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: 407-412 (Pubitemid 351179979)
122. Falagas ME, Siempos II, Rafailidis PI, et al. Inhaled colistin as monotherapy for multidrug-resistant gram (-) nosocomial pneumonia: A case series. Respir Med. 2009;103: 707-713
123. Michalopoulos A, Metaxas E, Falagas M. Aerosol delivery of antimicrobial Agents during mechanical ventilation: Current practice and perspectives. Current Drug Delivery. 2011;8: 208-212
124. Singh N, Rogers P, Atwood CW, et al. Short course empiric antibiotic therapy for patients with pulmonary infiltrates in the intensive care unit. A proposed solution for indiscriminate antibiotic prescription. Am J Respir Crit Care Med. 2000;162: 505-511 (Pubitemid 30647191)
125. Chastre J, Wolff M, Fagon JY, et al. Comparison of 8 vs 15 days of antibiotic therapy for ventilatorassociated pneumonia in adults: A randomized trial. JAMA. 2003;290: 2588-2598 (Pubitemid 37443289)
126. Luyt CE, Eldon MA, Stass H, Gribben D, Corkery K, Chastre J. Pharmacokinetics and tolerability of amikacin administered as BAY41-6551 aerosol in mechanically ventilated patients with Gramnegative pneumonia and acute renal failure. J Aerosol Med Pulm Drug Deliv. 2011;24
127. Stass H, Corkery K, Gribben D, Eldon MA. Pharmacokinetics and tolerability of BAY41-6551 in subjects with chronic kidney disease. J Aerosol Med Pulm Drug Deliv. 2011;24
128. Linden PK, Paterson DL. Parenteral and inhaled colistin for treatment of ventilator-associated pneumonia. Clinical Infectious Diseases. 2006;43: S89-S94 (Pubitemid 44267146)
129. McCoy KS. Compounded colistimethate as possible cause of fatal acute respiratory distress syndrome. N Engl J Med. 2007;357: 2310-2311 (Pubitemid 350190777)
130. Feeley TW, Du Moulin GC, Hedley-Whyte J et al. Aerosol polymyxin and pneumonia in seriously ill patients. N Engl J Med. 1975,293: 471-475.