Tobramycin inhalation powder (TIP): An efficient treatment strategy for the management of chronic Pseudomonas aeruginosa infection in cystic fibrosis

Clinical Medicine Insights: Circulatory, Respiratory and Pulmonary Medicine

Volumn 7, Issue 1, 2013, Pages 61-77

  Lam, John ^a   Vaughan, Steven ^a   Parkins, Michael D ^a,b  

^a UNIVERSITY OF CALGARY   (Canada)

^b UNIVERSITY OF CALGARY   (Canada)

Author keywords

Aerosolized; Antibiotics; DPI; Dry powder inhaler; Nebulized; TIS; TOBI; Tobramycin inhalation solution

Indexed keywords

AZLI; AZTREONAM; COLISTIN; TOBRAMYCIN; UNCLASSIFIED DRUG;

AEROSOL; AREA UNDER THE CURVE; CHEST TIGHTNESS; COLONY FORMING UNIT; COUGHING; CYSTIC FIBROSIS; DISEASE SEVERITY; DRUG EFFICACY; DRUG FORMULATION; DRUG HALF LIFE; DRUG SAFETY; DRY POWDER INHALER; DYSGEUSIA; DYSPHONIA; DYSPNEA; FEVER; FORCED EXPIRATORY VOLUME; HUMAN; LUNG FUNCTION; MAXIMUM PLASMA CONCENTRATION; MINIMUM INHIBITORY CONCENTRATION; NEBULIZER; NEPHROTOXICITY; NEUROMUSCULAR DISEASE; OTOTOXICITY; PATIENT SATISFACTION; PORTABLE AIR COMPRESSOR; PSEUDOMONAS INFECTION; REVIEW; SCANNING ELECTRON MICROSCOPY; SORE THROAT; TIME TO MAXIMUM PLASMA CONCENTRATION;

EID: 84887779747     PISSN: 11795484     EISSN: 11795484     Source Type: Journal    
DOI: 10.4137/ccrpm.s10592     Document Type: Review

References (112)

1. Ratjen F. Update in cystic fibrosis 2008. Am J Respir Crit Care Med. 2009;179:445-448.
2. Dequeker E, Stuhrmann M, Morris MA, et al. Best practice guidelines for molecular genetic diagnosis of cystic fibrosis and CFTR-related disorders-updated European recommendations. Eur J Hum Genet. 2009;17:51-65.
3. Ratjen F, Doring G. Cystic fibrosis. Lancet. 2003;361:681-689.
4. Gibson RL, Burns JL, Ramsey BW. Pathophysiology and management of pulmonary infections in cystic fibrosis. Am J Respir Crit Care Med. 2003;168:918-951.
5. Ratjen F. Recent advances in cystic fibrosis. Paediatr Respir Rev. 2008;9:144-148.
6. Razvi S, Quittell L, Sewall A, Quinton H, Marshall B, Saiman L. Respiratory microbiology of patients with cystic fibrosis in the United States, 1995-2005. Chest. 2009;136(6):1554-1560.
7. Lambiase A, Raia V, Del Pezzo M, Sepe A, Carnovale V, Rossano F. Microbiology of airway disease in a cohort of patients with cystic fibrosis. BMC Infect Dis. 2006;6:4.
8. Emerson J, Rosenfeld M, McNamara S, Ramsey B, Gibson RL. Pseudomonas aeruginosa and other predictors of mortality and morbidity in young children with cystic fibrosis. Pediatr Pulmonol. 2002;34: 91-100.
9. Kosorok MR, Zeng L, West SE, et al. Acceleration of lung disease in children with cystic fibrosis after Pseudomonas aeruginosa acquisition. Pediatr Pulmonol. 2001;32:277-287.
10. Li Z, Kosorok MR, Farrell PM, et al. Longitudinal development of mucoid Pseudomonas aeruginosa infection and lung disease progression in children with cystic fibrosis. JAMA. 2005;293:581-588.
11. Nixon GM, Armstrong DS, Carzino R, et al. Clinical outcome after early Pseudomonas aeruginosa infection in cystic fibrosis. J Pediatr. 2001;138: 699-704.
12. Poole K. Pseudomonas aeruginosa: resistance to the max. Front Microbiol. 2011;2:65.
13. Parkins MD, Elborn JS. Newer antibacterial agents and their potential role in cystic fibrosis pulmonary exacerbation management. J Antimicrob Chemother. 2010;65:1853-1861.
14. Boucher HW, Talbot GH, Bradley JS, et al. Bad bugs, no drugs: no ESKAPE! An update from the Infectious Diseases Society of America. Clin Infect Dis. 2009;48:1-12.
15. Szaff M, Hoiby N, Flensborg EW. Frequent antibiotic therapy improves survival of cystic fibrosis patients with chronic Pseudomonas aeruginosa infection. Acta Paediatr Scand. 1983;72:651-657.
16. Etherington C, Bosomworth M, Clifton I, Peckham DG, Conway SP. Measurement of urinary N-acetyl-b-D-glucosaminidase in adult patients with cystic fibrosis: before, during and after treatment with intravenous antibiotics. J Cyst Fibros. 2007;6:67-73.
17. Smyth A, Lewis S, Bertenshaw C, Choonara I, McGaw J, Watson A. Case-control study of acute renal failure in patients with cystic fibrosis in the UK. Thorax. 2008;63:532-535.
18. Al-Aloul M, Miller H, Alapati S, Stockton PA, Ledson MJ, Walshaw MJ. Renal impairment in cystic fibrosis patients due to repeated intravenous aminoglycoside use. Pediatr Pulmonol. 2005;39:15-20.
19. Elborn JS, Prescott RJ, Stack BH, et al. Elective versus symptomatic antibiotic treatment in cystic fibrosis patients with chronic Pseudomonas infection of the lungs. Thorax. 2000;55:355-358.
20. Cystic Fibrosis Trust. Antibiotic Treatment for Cystic Fibrosis. Bromley, Kent, UK: Cystic Fibrosis Trust; 2009:1-102.
21. di Sant'Agnese PaDA. Chemotherapy in infections of the respiratory tract associated with cystic fibrosis of the pancreas;observations with penicillin and drugs of the sulfonamide group, with special reference to penicllin aerosol. Am J Dis Child. 1946;72:17-61.
22. LiPuma JJ. Microbiological and immunologic considerations with aerosolized drug delivery. Chest. 2001;120:118S-123s.
23. Smith AL. Inhaled antibiotic therapy: What drug? What dose? What regimen? What formulation? J Cyst Fibros. 2002;1:189-193.
24. Kuhn RJ. Formulation of aerosolized therapeutics. Chest. 2001;120:94S-9s8.
25. Foweraker JE, Laughton CR, Brown DF, Bilton D. Phenotypic variability of Pseudomonas aeruginosa in sputa from patients with acute infective exacerbation of cystic fibrosis and its impact on the validity of antimicrobial susceptibility testing. J Antimicrob Chemother. 2005;55:921-927.
26. Foweraker JE, Laughton CR, Brown DF, Bilton D. Comparison of methods to test antibiotic combinations against heterogeneous populations of multiresistant Pseudomonas aeruginosa from patients with acute infective exacerbations in cystic fibrosis. Antimicrob Agents Chemother. 2009;53: 4809-4815.
27. Workentine ML, Sibley CD, Glezerson B, et al. Phenotypic heterogeneity of Pseudomonas aeruginosa populations in a cystic fibrosis patient. PLoS One. 2013;8:e60225.
28. Morosini MI, García-Castillo M, Loza E, Pérez-Vázquez M, Baquero F, Cantón R. Breakpoints for predicting Pseudomonas aeruginosa susceptibility to inhaled tobramycin in cystic fibrosis patients: use of high-range Etest strips. J Clin Microbiol. 2005;43:4480-4485.
29. Skindersoe ME, Alhede M, Phipps R, et al. Effects of antibiotics on quorum sensing in Pseudomonas aeruginosa. Antimicrob Agents Chemother. 2008;52:3648-3663.
30. Hybenova D, Majtan V. The infuence of postantibiotic effects and postantibi-otic effects of sub-inhibitory concentrations of quinolones and aminoglycosides on phospholipase C of Pseudomonas aeruginosa. Pharmazie. 1997;52:157-159.
31. Jensen T, Pedersen SS, Garne S, et al. Colistin inhalation therapy in cystic fibrosis patients with chronic Pseudomonas aeruginosa lung infection. J Antimicrob Chemother. 1987;19:831-838.
32. Schuster A, Haliburn C, Döring G, Goldman MH; Freedom Study Group. Safety, effcacy and convenience of colistimethate sodium dry powder for inhalation (Colobreathe DPI) in patients with cystic fibrosis: a randomised study. Thorax. 2013;68:344-350.
33. McCoy KS, Quittner AL, Oermann CM, Gibson RL, Retsch-Bogart GZ, Montgomery AB. Inhaled aztreonam lysine for chronic airway Pseudomonas aeruginosa in cystic fibrosis. Am J Respir Crit Care Med. 2008;178:921-928.
34. Retsch-Bogart GZ, Burns JL, Otto KL, et al; AZLI Phase II Study Group. A phase 2 study of aztreonam lysine for inhalation to treat patients with cystic fibrosis and Pseudomonas aeruginosa infection. Pediatr Pulmonol. 2008;43:47-58.
35. Retsch-Bogart GZ, Quittner AL, Gibson RL, et al. Effcacy and safety of inhaled aztreonam lysine for airway pseudomonas in cystic fibrosis. Chest. 2009;135:1223-1232.
36. Oermann CM, Retsch-Bogart GZ, Quittner AL, et al. An 18-month study of the safety and effcacy of repeated courses of inhaled aztreonam lysine in cystic fibrosis. Pediatr Pulmonol. 2010.
37. Assael BM, Pressler T, Bilton D, et al; For the AZLI Active Comparator Study Group. Inhaled aztreonam lysine vs. inhaled tobramycin in cystic fibrosis: A comparative effcacy trial. J Cyst Fibros. In press.
38. Parkins MD, Elborn JS. Aztreonam lysine: a novel inhalational antibiotic for cystic fibrosis. Expert Rev Respir Med. 2010;4:435-444.
39. Moskowitz SM, Silva SJ, Mayer-Hamblett N, et al; Investigators and Coordinators of the Epidemiologic Study of Cystic Fibrosis (ESCF). Shifting patterns of inhaled antibiotic use in cystic fibrosis. Pediatr Pulmonol. 2008;43:874-881.
40. 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;340:23-30.
41. Konstan MW, Geller DE, Minić P, Brockhaus F, Zhang J, Angyalosi G. Tobramycin inhalation powder for P. aeruginosa infection in cystic fibrosis: The EVOLVE trial. Pediatr Pulmonol. 2010.
42. Sawicki GS, Signorovitch JE, Zhang J, et al. Reduced mortality in cystic fibrosis patients treated with tobramycin inhalation solution. Pediatr Pulmonol. 2012;47:44-52.
43. Stephens D, Garey N, Isles A, Levison H, Gold R. Effcacy of inhaled tobramycin in the treatment of pulmonary exacerbations in children with cystic fibrosis. Pediatr Infect Dis. 1983;2:209-211.
44. Pechere JC, Roy B, Dugal R. Distribution and elimination kinetics of intravenously and intramusculary administered tobramycin in man. Int J Clin Pharmacol Biopharm. 1976;14:313-318.
45. Pechere JC, Dugal R. Pharmacokinetics of intravenously administered tobramycin in normal volunteers and in renal-impaired and hemodialyzed patients. J Infect Dis. 1976;134 Suppl:S118-S124.
46. Thompson RQ, Presti EA. Nebramycin, a new broad-spectrum antibiotic complex. III. Isolation and chemical-physical properties. Antimicrob Agents Chemother (Bethesda). 1967;7:332-340.
47. Stark WM, Hoehn MM, Knox NG. Nebramycin, a new broad-spectrum antibiotic complex. I. Detection and biosynthesis. Antimicrob Agents Chemother (Bethesda). 1967;7:314-323.
48. Lynch SR, Puglisi JD. Structural origins of aminoglycoside specifcity for prokaryotic ribosomes. J Mol Biol. 2001;306:1037-1058.
49. Peterson AA, Hancock RE, McGroarty EJ. Binding of polycationic antibiotics and polyamines to lipopolysaccharides of Pseudomonas aeruginosa. J Bacteriol. 1985;164:1256-1261.
50. Taber HW, Mueller JP, Miller PF, et al. Bacterial uptake of aminoglycoside antibiotics. Microbiol Rev. 1987;51:439-4357.
51. Craig WA, Redington J, Ebert SC. Pharmacodynamics of amikacin in vitro and in mouse thigh and lung infections. J Antimicrob Chemother. 1991;27 Suppl C:29-40.
52. Burns JL, Van Dalfsen JM, Shawar RM, et al. Effect of chronic intermittent administration of inhaled tobramycin on respiratory microbial fora in patients with cystic fibrosis. J Infect Dis. 1999;179:1190-1196.
53. Islam S, Oh H, Jalal S, et al. Chromosomal mechanisms of aminoglycoside resistance in Pseudomonas aeruginosa isolates from cystic fibrosis patients. Clin Microbiol Infect. 2009;15:60-66.
54. Westbrock-Wadman S, Sherman DR, Hickey MJ, et al. Characterization of a Pseudomonas aeruginosa effux pump contributing to aminoglycoside impermeability. Antimicrob Agents Chemother. 1999;43:2975-2983.
55. Fraud S, Poole K. Oxidative stress induction of the MexXY multi-drug effux genes and promotion of aminoglycoside resistance development in Pseudomonas aeruginosa. Antimicrob Agents Chemother. 2011;55:1068-1074.
56. Poole K. Aminoglycoside resistance in Pseudomonas aeruginosa. Antimicrob Agents Chemother. 2005;49:479-487.
57. Konstan M, Parkins M, Angyalosi G, Higgins M. Tobramycin inhalation powder is as effective as tobramycin inhalation solution in patients with cystic fibrosis: a subgroup analysis of the EAGER trial. Am J Respir Crit Care Med. 2013;187(meeting abstracts):Abstract 39401
58. Mendelman PM, Smith AL, Levy J, Weber A, Ramsey B, Davis RL. Aminoglycoside penetration, inactivation, and effcacy in cystic fibrosis sputum. Am Rev Respir Dis. 1985;132:761-765.
59. Hunt BE, Weber A, Berger A, Ramsey B, Smith AL. Macromolecular mechanisms of sputum inhibition of tobramycin activity. Antimicrob Agents Chemother. 1995;39:34-39.
60. Vaudaux P, Waldvogel FA. Gentamicin inactivation in purulent exudates: role of cell lysis. J Infect Dis. 1980;142:586-593.
61. Smith AL, Ramsey BW, Hedges DL, et al. Safety of aerosol tobramycin administration for 3 months to patients with cystic fibrosis. Pediatr Pulmonol. 1989;7:265-271.
62. Ramsey BW, Dorkin HL, Eisenberg JD, et al. Effcacy of aerosolized tobramy-cin in patients with cystic fibrosis. N Engl J Med. 1993;328:1740-1746.
63. Le Brun PP, de Boer AH, Gjaltema D, et al. Inhalation of tobramycin in cystic fibrosis. Part 2: optimization of the tobramycin solution for a jet and an ultrasonic nebulizer. Int J Pharm. 1999;189:215-225.
64. Le Brun PP, de Boer AH, Gjaltema D, et al. Inhalation of tobramycin in cystic fibrosis. Part 1: the choice of a nebulizer. Int J Pharm. 1999;189:205-214.
65. Mogayzel PJ, Naureckas ET, Robinson KA, et al; Pulmonary Clinical Practice Guidelines Committee. Cystic fibrosis pulmonary guidelines. Chronic medications for maintenance of lung health. Am J Respir Crit Care Med. 2013;187:680-689.
66. Murphy TD, Anbar RD, Lester LA, et al. Treatment with tobramycin solution for inhalation reduces hospitalizations in young CF subjects with mild lung disease. Pediatr Pulmonol. 2004;38:314-320.
67. Iles R, Legh-Smith J, Drummond M, Prevost A, Vowler S. Economic evaluation of Tobramycin nebuliser solution in cystic fibrosis. J Cyst Fibros. 2003;2:120-128.
68. LeLorier J, Perreault S, Birnbaum H, Greenberg P, Sheehy O. Savings in direct medical costs from the use of tobramycin solution for inhalation in patients with cystic fibrosis. Clin Ther. 2000;22:140-151.
69. Foundation CF. Cystic Fibrosis Foundation Patient Registry: Annual report to the center directors. Bethesda, MD, 2010.
70. Foundation CCF. Canadian Cystic Fibrosis Foundation Patient Data Registry Report. Toronto, CANADA, 2011.
71. Ashlock MA, Beall RJ, Hamblett NM, et al. A pipeline of therapies for cystic fibrosis. Semin Respir Crit Care Med. 2009;30:611-626.
72. Marshall BC, Penland CM, Hazle L, et al. Cystic fibrosis foundation: achieving the mission. Respir Care. 2009;54:788-795; discussion 795.
73. Sawicki GS, Sellers DE, Robinson WM. High treatment burden in adults with cystic fibrosis: challenges to disease self-management. J Cyst Fibros. 2009;8:91-96.
74. Foundation CF. Cystic Fibrosis Foundation Patient Registry: Annual report to the centre directors. Bethesda, Maryland: Cystic Fibrosis Foundation, 2008.
75. Sawicki GS, Ren CL, Konstan MW, et al. Treatment complexity in cystic fibrosis: Trends over time and associations with site-specific outcomes. J Cyst Fibros. 2013.
76. Modi AC, Lim CS, Yu N, Geller D, Wagner MH, Quittner AL. A multi-method assessment of treatment adherence for children with cystic fibrosis. J Cyst Fibros. 2006;5:177-185.
77. Modi AC, Quittner AL. Barriers to treatment adherence for children with cystic fibrosis and asthma: what gets in the way? J Pediatr Psychol. 2006;31:846-858.
78. Briesacher BA, Quittner AL, Saiman L, Sacco P, Fouayzi H, Quittell LM. Adherence with tobramycin inhaled solution and health care utilization. BMC Pulm Med. 2011;11:5.
79. Briesacher BA, Quittner A, Saiman L, Fouayzi H, Sacco P, Quiettel L. Adherence to tobramycin inhaled solution and health care utilization. Am J Respir Crit Care Med. 2009;179(meeting abstracts):Absract A1184.
80. Arias Llorente RP, Bousono Garcia C, Diaz Martin JJ. Treatment compliance in children and adults with cystic fibrosis. J Cyst Fibros. 2008;7: 359-367.
81. Dziuban EJ, Saab-Abazeed L, Chaudhry SR, Streetman DS, Nasr SZ. Identifying barriers to treatment adherence and related attitudinal patterns in adolescents with cystic fibrosis. Pediatr Pulmonol. 2010;45:450-458.
82. Hubert D, Leroy S, Nove-Josserand R, et al. Pharmacokinetics and safety of tobramycin administered by the PARI eFlow rapid nebulizer in cystic fibrosis. J Cyst Fibros. 2009;8:332-337.
83. Govoni M, Poli G, Acerbi D, et al. Pharmacokinetic and tolerability pro-fles of tobramycin nebuliser solution 300 mg/4 ml administered by PARI eFlow((R)) rapid and PARI LC Plus((R)) nebulisers in cystic fibrosis patients. Pulm Pharmacol Ther. 2013;26:249-255.
84. Li Z, Zhang Y, Wurtz W, et al. Characterization of nebulized liposomal ami-kacin (Arikace) as a function of droplet size. J Aerosol Med Pulm Drug Deliv. 2008;21:245-254.
85. Sweeney LG, Wang Z, Loebenberg R, Wong JP, Lange CF, Finlay WH. Spray-freeze-dried liposomal ciprofoxacin powder for inhaled aerosol drug delivery. Int J Pharm. 2005;305:180-185.
86. Geller DE, Konstan MW, Smith J, Noonberg SB, Conrad C. Novel tobramy-cin inhalation powder in cystic fibrosis subjects: pharmacokinetics and safety. Pediatr Pulmonol. 2007;42:307-313.
87. Duddu SP, Sisk SA, Walter YH, et al. Improved lung delivery from a passive dry powder inhaler using an Engineered PulmoSphere powder. Pharm Res. 2002;19:689-695.
88. Shah SP, Misra A. Liposomal amikacin dry powder inhaler: effect of fnes on in vitro performance. AAPS Pharm Sci Tech. 2004;5:e65.
89. Yang Y, Tsifansky MD, Wu CJ, Yang HI, Schmidt G, Yeo Y. Inhalable antibiotic delivery using a dry powder co-delivering recombinant deoxy-ribonuclease and ciprofoxacin for treatment of cystic fibrosis. Pharm Res. 2010;27:151-160.
90. Burdock GA. Safety assessment of hydroxypropyl methylcellulose as a food ingredient. Food Chem Toxicol. 2007;45:2341-2351.
91. Geller DE, Weers J, Heuerding S. Development of an inhaled dry-powder formulation of tobramycin using pulmosphere technology. J Aerosol Med Pulm Drug Deliv. 2011.
92. Pavkov RG, Geller DE, Ament B, Heuerding S, Gupta A. Dynamic inspira-tory fow characteristics through the T-326 dry powder inhaler in cystic fibrosis patients. RDD Europe. 2013;2:325-328.
93. Geller DE, Ament B, Heuerding S, Maykut R, Pavkov R. Inspiratory fow characteristics of the T-326 dry powder inhaler (DPI) in CF patients. J Cyst Fibros. 2013;12(Suppl 1):S66.
94. Tiddens HA, Geller DE, Challoner P, et al. Effect of dry powder inhaler resistance on the inspiratory fow rates and volumes of cystic fibrosis patients of six years and older. J Aerosol Med. 2006;19:456-465.
95. Standeardt T, Speirs RJ, Raon N, et al. Young cystic fibrosis patients can effectively use a novel high-payload capsule based dry powder inhaler with tobramycin powder for inhalation (TPI). Pediatr Pulmonol. 2004;38:Abstract 279.
96. Novartis Pharmaceuticals Canada Inc. TOBI Podhaler. Product Mongraph. Dorval, Quebec: Novartis Pharmaceuticals Canada Inc; 2011.
97. Galeva I, Konstan MW, Higgins M, et al. Tobramycin inhalation powder manufactured by improved process in cystic fibrosis: the randomized EDIT trial. Curr Med Res Opin. 2013.
98. Konstan MW, Flume PA, Kappler M, et al. Safety, effcacy and convenience of tobramycin inhalation powder in cystic fibrosis patients: The EAGER trial. J Cyst Fibros. 2011;10:54-61.
99. Atkinson MJ, Sinha A, Hass SL, et al. Validation of a general measure of treatment satisfaction, the Treatment Satisfaction Questionnaire for Medication (TSQM), using a national panel study of chronic disease. Health Qual Life Outcomes. 2004;2:12.
100. Regnault A, Balp MM, Kulich K, Viala-Danten M. Validation of the Treatment Satisfaction Questionnaire for Medication in patients with cystic fibrosis. J Cyst Fibros. 2012;11:494-501.
101. Bertino JS, Booker LA, Franck PA, Jenkins PL, Franck KR, Nafziger AN. Incidence of and signifcant risk factors for aminoglycoside-associated nephrotoxicity in patients dosed by using individualized pharmacokinetic monitoring. J Infect Dis. 1993;167:173-179.
102. Kahlmeter G, Dahlager JI. Aminoglycoside toxicity-a review of clinical studies published between 1975 and 1982. J Antimicrob Chemother. 1984;13 Suppl A:9-22.
103. Brummett RE, Fox KE. Aminoglycoside-induced hearing loss in humans. Antimicrob Agents Chemother. 1989;33:797-800.
104. Brummett RE, Morrison RB. The incidence of aminoglycoside antibiotic-induced hearing loss. Arch Otolaryngol Head Neck Surg. 1990;116:406-410.
105. Pittinger CB. Convergence of interests in antibiotic-induced neuromuscu-lar blockade. Acta Physiol Pharmacol Latinoam. 1989;39:393-396.
106. Hoffmann IM, Rubin BK, Iskandar SS, Schechter MS, Nagaraj SK, Bitzan MM. Acute renal failure in cystic fibrosis: association with inhaled tobramycin therapy. Pediatr Pulmonol. 2002;34:375-377.
107. Mulrennan SA, Helm J, Thomas RB, Dodd M, Jones A, Webb K. Aminoglycoside ototoxicity susceptibility in cystic fibrosis. Thorax. 2009;64:271-272.
108. Patatanian L. Inhaled tobramycin-associated hearing loss in an adolescent with renal failure. Pediatr Infect Dis J. 2006;25:276-278.
109. Nikolaizik WH, Vietzke D, Ratjen F. A pilot study to compare tobramycin 80 mg injectable preparation with 300 mg solution for inhalation in cystic fibrosis patients. Can Respir J. 2008;15:259-262.
110. Ratjen F, Rietschel E, Kasel D, et al. Pharmacokinetics of inhaled colistin in patients with cystic fibrosis. J Antimicrob Chemother. 2006;57:306-311.
111. Brown C, Nash EF, Camerson, S, Rashid, R and JL Whitehouse. Clinical outcomes and patient satisfaction following initation of the TOBI podhaler in CF adults. Journal of cystic fibrosis. 2013;12 Suppl 1:s65.
112. Nash E, Ahitan B, Brown C, Rashid R, Whitehouse JL. Comparison of phara-macy presecription refll frequency in CF adults before and after switching from tobramycin inhalation solution (TIS) to TOBI podhaler - 'real world' evidence of improved adherence. Journal of cystic fibrosis. 2013.