Download PDF
Semin Respir Crit Care Med 2015; 36(02): 267-286
DOI: 10.1055/s-0035-1547346
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Inhaled Antibiotics in Cystic Fibrosis (CF) and Non-CF Bronchiectasis

George T.P. Tay
1   Department of Thoracic Medicine, The Prince Charles Hospital, Brisbane, Australia
,
David W. Reid
1   Department of Thoracic Medicine, The Prince Charles Hospital, Brisbane, Australia
2   Lung Inflammation and Infection Group, QIMR Berghofer Medical Research Institute, Brisbane, Australia
,
Scott C. Bell
1   Department of Thoracic Medicine, The Prince Charles Hospital, Brisbane, Australia
3   Lung Bacteria Group, QIMR Berghofer Medical Research Institute, Brisbane, Australia
› Author Affiliations
Further Information

Publication History

Publication Date:
31 March 2015 (online)

    Permissions and Reprints

Abstract

Bronchiectasis is a pathological diagnosis describing dilatation of the airways and is characterized by chronic lung sepsis. Bronchiectasis has multiple etiologies, but is usually considered in terms of whether it is due to the genetic disorder cystic fibrosis (CF) or secondary to other causes (non-CF bronchiectasis, NCFB). Inhaled antibiotics are used in bronchiectasis to suppress bacterial pathogens and reduce long-term lung function decline. The majority of the literature on inhaled antibiotics comes from studies on CF where the dominant bacterial pathogen in the airway is usually Pseudomonas aeruginosa. Thus, most aerosolized antibiotic regimens target this bacterium, but the emergence of molecular diagnostic methods has questioned this approach and more tailored strategies may need to be considered in CF based on the community composition of the lung microbiome. Similarly, the lung microbiome in NCFB has been found to be a complex polymicrobial one and the current practice of employing the same inhaled antibiotic regimes as are used in CF may no longer be appropriate in many patients. In this article, the use of inhaled antibiotics in CF and NCFB is considered in the light of improved understanding of the lung microbiome and why more tailored therapy may be needed based on molecular identification of the microbial pathogens present. The evidence for the use of currently available inhaled antibiotics and advances in inhaled drug packaging and delivery devices are discussed. Finally, the urgent need for prospective randomized clinical trials in CF and NCFB is highlighted and areas for future research identified.

Keywords

antibiotics - nebulized - inhaled - cystic fibrosis - non-CF bronchiectasis - Pseudomonas aeruginosa
 

  • References

  • 1 Cole PJ. Inflammation: a two-edged sword—the model of bronchiectasis. Eur J Respir Dis Suppl 1986; 147: 6-15
    PubMedGoogle Scholar
  • 2 Chalmers JD, Hill AT. Mechanisms of immune dysfunction and bacterial persistence in non-cystic fibrosis bronchiectasis. Mol Immunol 2013; 55 (1) 27-34
    CrossrefPubMedGoogle Scholar
  • 3 Gaga M, Bentley AM, Humbert M , et al. Increases in CD4+ T lymphocytes, macrophages, neutrophils and interleukin 8 positive cells in the airways of patients with bronchiectasis. Thorax 1998; 53 (8) 685-691
    CrossrefPubMedGoogle Scholar
  • 4 CFTR project (USA) Available at: www.cftr2.org . Accessed February 23, 2015
    PubMed
  • 5 Chang AB, Grimwood K, Mulholland EK, Torzillo PJ ; Working Group on Indigenous Paediatric Respiratory Health. Bronchiectasis in indigenous children in remote Australian communities. Med J Aust 2002; 177 (4) 200-204
    PubMedGoogle Scholar
  • 6 Singleton R, Morris A, Redding G , et al. Bronchiectasis in Alaska Native children: causes and clinical courses. Pediatr Pulmonol 2000; 29 (3) 182-187
    CrossrefPubMedGoogle Scholar
  • 7 Amitani R, Wilson R, Rutman A , et al. Effects of human neutrophil elastase and Pseudomonas aeruginosa proteinases on human respiratory epithelium. Am J Respir Cell Mol Biol 1991; 4 (1) 26-32
    CrossrefPubMedGoogle Scholar
  • 8 Fuschillo S, De Felice A, Balzano G. Mucosal inflammation in idiopathic bronchiectasis: cellular and molecular mechanisms. Eur Respir J 2008; 31 (2) 396-406
    CrossrefPubMedGoogle Scholar
  • 9 Wojnarowski C, Studnicka M, Kühr J , et al. Determinants of eosinophil cationic protein in nasal lavages in children. Clin Exp Allergy 1998; 28 (3) 300-305
    CrossrefPubMedGoogle Scholar
  • 10 Hirota N, Martin JG. Mechanisms of airway remodeling. Chest 2013; 144 (3) 1026-1032
    CrossrefPubMedGoogle Scholar
  • 11 Ward C, Rydell-Törmänen K, Westergren-Thorsson G, Eriksson LT, Walters H. Infection and remodelling: a 21st century model of bronchiectasis?. Eur Respir J 2011; 38 (4) 758-760
    CrossrefPubMedGoogle Scholar
  • 12 Colin AA, Ali-Dinar T. Endobronchial biopsy in childhood. Chest 2007; 131 (6) 1626-1627
    CrossrefPubMedGoogle Scholar
  • 13 Bedrossian CW, Greenberg SD, Singer DB, Hansen JJ, Rosenberg HS. The lung in cystic fibrosis. A quantitative study including prevalence of pathologic findings among different age groups. Hum Pathol 1976; 7 (2) 195-204
    CrossrefPubMedGoogle Scholar
  • 14 Morrissey BM, Evans SJ. Severe bronchiectasis. Clin Rev Allergy Immunol 2003; 25 (3) 233-247
    CrossrefPubMedGoogle Scholar
  • 15 Bienvenu T, Sermet-Gaudelus I, Burgel PR , et al. Cystic fibrosis transmembrane conductance regulator channel dysfunction in non-cystic fibrosis bronchiectasis. Am J Respir Crit Care Med 2010; 181 (10) 1078-1084
    CrossrefPubMedGoogle Scholar
  • 16 Gonska T, Choi P, Stephenson A , et al. Role of cystic fibrosis transmembrane conductance regulator in patients with chronic sinopulmonary disease. Chest 2012; 142 (4) 996-1004
    CrossrefPubMedGoogle Scholar
  • 17 King PT, Holdsworth SR, Freezer NJ, Villanueva E, Holmes PW. Characterisation of the onset and presenting clinical features of adult bronchiectasis. Respir Med 2006; 100 (12) 2183-2189
    CrossrefPubMedGoogle Scholar
  • 18 Ooi CY, Dupuis A, Ellis L , et al. Does extensive genotyping and nasal potential difference testing clarify the diagnosis of cystic fibrosis among patients with single-organ manifestations of cystic fibrosis?. Thorax 2014; 69 (3) 254-260
    CrossrefPubMedGoogle Scholar
  • 19 Pasteur MC, Helliwell SM, Houghton SJ , et al. An investigation into causative factors in patients with bronchiectasis. Am J Respir Crit Care Med 2000; 162 (4, Pt 1) 1277-1284
    CrossrefPubMedGoogle Scholar
  • 20 Pignatti PF, Bombieri C, Marigo C, Benetazzo M, Luisetti M. Increased incidence of cystic fibrosis gene mutations in adults with disseminated bronchiectasis. Hum Mol Genet 1995; 4 (4) 635-639
    CrossrefPubMedGoogle Scholar
  • 21 Pasteur MC, Bilton D, Hill AT ; British Thoracic Society Bronchiectasis non-CF Guideline Group. British Thoracic Society guideline for non-CF bronchiectasis. Thorax 2010; 65 (Suppl. 01) i1-i58
    CrossrefPubMedGoogle Scholar
  • 22 UK CF Registry Annual Data Report 2011. London, UK: © Cystic Fibrosis Trust 2013; 2013
    Google Scholar
  • 23 Australia CF. 2012 15th Annual Report from the Cystic Fibrosis Data Registry. Sydney, Australia: Cystic Fibrosis Australia; 2013
    Google Scholar
  • 24 Cystic Fibrosis Foundation Patient Registry 2012 Annual Data Report. Bethesda, Maryland: © 2013 Cystic Fibrosis Foundation; 2013
    Google Scholar
  • 25 Zemanick ET, Sagel SD, Harris JK. The airway microbiome in cystic fibrosis and implications for treatment. Curr Opin Pediatr 2011; 23 (3) 319-324
    CrossrefPubMedGoogle Scholar
  • 26 Hare KM, Grimwood K, Leach AJ , et al. Respiratory bacterial pathogens in the nasopharynx and lower airways of Australian indigenous children with bronchiectasis. J Pediatr 2010; 157 (6) 1001-1005
    CrossrefPubMedGoogle Scholar
  • 27 Kapur N, Grimwood K, Masters IB, Morris PS, Chang AB. Lower airway microbiology and cellularity in children with newly diagnosed non-CF bronchiectasis. Pediatr Pulmonol 2012; 47 (3) 300-307
    CrossrefPubMedGoogle Scholar
  • 28 Angrill J, Agustí C, de Celis R , et al. Bacterial colonisation in patients with bronchiectasis: microbiological pattern and risk factors. Thorax 2002; 57 (1) 15-19
    CrossrefPubMedGoogle Scholar
  • 29 Chan SL, Chan-Yeung MM, Ooi GC , et al. Validation of the Hong Kong Chinese version of the St. George Respiratory Questionnaire in patients with bronchiectasis. Chest 2002; 122 (6) 2030-2037
    CrossrefPubMedGoogle Scholar
  • 30 Palwatwichai A, Chaoprasong C, Vattanathum A, Wongsa A, Jatakanon A. Clinical, laboratory findings and microbiologic characterization of bronchiectasis in Thai patients. Respirology 2002; 7 (1) 63-66
    CrossrefPubMedGoogle Scholar
  • 31 Rogers GB, van der Gast CJ, Cuthbertson L , et al. Clinical measures of disease in adult non-CF bronchiectasis correlate with airway microbiota composition. Thorax 2013; 68 (8) 731-737
    CrossrefPubMedGoogle Scholar
  • 32 Tunney MM, Einarsson GG, Wei L , et al. Lung microbiota and bacterial abundance in patients with bronchiectasis when clinically stable and during exacerbation. Am J Respir Crit Care Med 2013; 187 (10) 1118-1126
    CrossrefPubMedGoogle Scholar
  • 33 Rogers GB, Zain NM, Bruce KD , et al. A novel microbiota stratification system predicts future exacerbations in bronchiectasis. Ann Am Thorac Soc 2014; 11 (4) 496-503
    PubMedGoogle Scholar
  • 34 Evans SA, Turner SM, Bosch BJ, Hardy CC, Woodhead MA. Lung function in bronchiectasis: the influence of Pseudomonas aeruginosa. Eur Respir J 1996; 9 (8) 1601-1604
    CrossrefPubMedGoogle Scholar
  • 35 Ho PL, Chan KN, Ip MS , et al. The effect of Pseudomonas aeruginosa infection on clinical parameters in steady-state bronchiectasis. Chest 1998; 114 (6) 1594-1598
    CrossrefPubMedGoogle Scholar
  • 36 Martínez-García MA, Soler-Cataluña JJ, Perpiñá-Tordera M, Román-Sánchez P, Soriano J. Factors associated with lung function decline in adult patients with stable non-cystic fibrosis bronchiectasis. Chest 2007; 132 (5) 1565-1572
    CrossrefPubMedGoogle Scholar
  • 37 Miszkiel KA, Wells AU, Rubens MB, Cole PJ, Hansell DM. Effects of airway infection by Pseudomonas aeruginosa: a computed tomographic study. Thorax 1997; 52 (3) 260-264
    CrossrefPubMedGoogle Scholar
  • 38 Wilson CB, Jones PW, O'Leary CJ, Hansell DM, Cole PJ, Wilson R. Effect of sputum bacteriology on the quality of life of patients with bronchiectasis. Eur Respir J 1997; 10 (8) 1754-1760
    CrossrefPubMedGoogle Scholar
  • 39 Brodt AM, Stovold E, Zhang L. Inhaled antibiotics for stable non-cystic fibrosis bronchiectasis: a systematic review. Eur Respir J 2014; 44 (2) 382-393
    CrossrefPubMedGoogle Scholar
  • 40 Ryan G, Singh M, Dwan K. Inhaled antibiotics for long-term therapy in cystic fibrosis. Cochrane Database Syst Rev 2011; (3) CD001021
    PubMedGoogle Scholar
  • 41 Rogers GB, van der Gast CJ, Serisier DJ. Predominant pathogen competition and core microbiota divergence in chronic airway infection. ISME J 2015; 9 (1) 217-225
    CrossrefPubMedGoogle Scholar
  • 42 Fodor AA, Klem ER, Gilpin DF , et al. The adult cystic fibrosis airway microbiota is stable over time and infection type, and highly resilient to antibiotic treatment of exacerbations. PLoS ONE 2012; 7 (9) e45001
    CrossrefPubMedGoogle Scholar
  • 43 Smith DJ, Badrick AC, Zakrzewski M , et al. Pyrosequencing reveals transient cystic fibrosis lung microbiome changes with intravenous antibiotics. Eur Respir J 2014; 44 (4) 922-930
    CrossrefPubMedGoogle Scholar
  • 44 Mahenthiralingam E. Emerging cystic fibrosis pathogens and the microbiome. Paediatr Respir Rev 2014; 15 (Suppl. 01) 13-15
    PubMedGoogle Scholar
  • 45 Tunney MM, Field TR, Moriarty TF , et al. Detection of anaerobic bacteria in high numbers in sputum from patients with cystic fibrosis. Am J Respir Crit Care Med 2008; 177 (9) 995-1001
    CrossrefPubMedGoogle Scholar
  • 46 Tunney MM, Klem ER, Fodor AA , et al. Use of culture and molecular analysis to determine the effect of antibiotic treatment on microbial community diversity and abundance during exacerbation in patients with cystic fibrosis. Thorax 2011; 66 (7) 579-584
    CrossrefPubMedGoogle Scholar
  • 47 Jones AM. Anaerobic bacteria in cystic fibrosis: pathogens or harmless commensals?. Thorax 2011; 66 (7) 558-559
    CrossrefPubMedGoogle Scholar
  • 48 van der Gast CJ, Cuthbertson L, Rogers GB , et al. Three clinically distinct chronic pediatric airway infections share a common core microbiota. Ann Am Thorac Soc 2014; 11 (7) 1039-1048
    CrossrefPubMedGoogle Scholar
  • 49 Høiby N, Bjarnsholt T, Givskov M, Molin S, Ciofu O. Antibiotic resistance of bacterial biofilms. Int J Antimicrob Agents 2010; 35 (4) 322-332
    CrossrefPubMedGoogle Scholar
  • 50 Høiby N, Ciofu O, Bjarnsholt T. Pseudomonas aeruginosa biofilms in cystic fibrosis. Future Microbiol 2010; 5 (11) 1663-1674
    CrossrefPubMedGoogle Scholar
  • 51 Oggioni MR, Trappetti C, Kadioglu A , et al. Switch from planktonic to sessile life: a major event in pneumococcal pathogenesis. Mol Microbiol 2006; 61 (5) 1196-1210
    CrossrefPubMedGoogle Scholar
  • 52 Starner TD, Zhang N, Kim G, Apicella MA, McCray Jr PB. Haemophilus influenzae forms biofilms on airway epithelia: implications in cystic fibrosis. Am J Respir Crit Care Med 2006; 174 (2) 213-220
    CrossrefPubMedGoogle Scholar
  • 53 Coakley RJ, Taggart C, Canny G, Greally P, O'Neill SJ, McElvaney NG. Altered intracellular pH regulation in neutrophils from patients with cystic fibrosis. Am J Physiol Lung Cell Mol Physiol 2000; 279 (1) L66-L74
    PubMedGoogle Scholar
  • 54 Poulsen JH, Fischer H, Illek B, Machen TE. Bicarbonate conductance and pH regulatory capability of cystic fibrosis transmembrane conductance regulator. Proc Natl Acad Sci U S A 1994; 91 (12) 5340-5344
    CrossrefPubMedGoogle Scholar
  • 55 Moriarty TF, Elborn JS, Tunney MM. Effect of pH on the antimicrobial susceptibility of planktonic and biofilm-grown clinical Pseudomonas aeruginosa isolates. Br J Biomed Sci 2007; 64 (3) 101-104
    PubMedGoogle Scholar
  • 56 Worlitzsch D, Tarran R, Ulrich M , et al. Effects of reduced mucus oxygen concentration in airway Pseudomonas infections of cystic fibrosis patients. J Clin Invest 2002; 109 (3) 317-325
    CrossrefPubMedGoogle Scholar
  • 57 Field TR, White A, Elborn JS, Tunney MM. Effect of oxygen limitation on the in vitro antimicrobial susceptibility of clinical isolates of Pseudomonas aeruginosa grown planktonically and as biofilms. Eur J Clin Microbiol Infect Dis 2005; 24 (10) 677-687
    CrossrefPubMedGoogle Scholar
  • 58 Hill D, Rose B, Pajkos A , et al. Antibiotic susceptabilities of Pseudomonas aeruginosa isolates derived from patients with cystic fibrosis under aerobic, anaerobic, and biofilm conditions. J Clin Microbiol 2005; 43 (10) 5085-5090
    CrossrefPubMedGoogle Scholar
  • 59 Döring G, Flume P, Heijerman H, Elborn JS ; Consensus Study Group. Treatment of lung infection in patients with cystic fibrosis: current and future strategies. J Cyst Fibros 2012; 11 (6) 461-479
    CrossrefPubMedGoogle Scholar
  • 60 Amin R, Ratjen F. Emerging drugs for cystic fibrosis. Expert Opin Emerg Drugs 2014; 19 (1) 143-155
    CrossrefPubMedGoogle Scholar
  • 61 Tullis DE, Burns JL, Retsch-Bogart GZ , et al. Inhaled aztreonam for chronic Burkholderia infection in cystic fibrosis: a placebo-controlled trial. J Cyst Fibros 2014; 13 (3) 296-305
    CrossrefPubMedGoogle Scholar
  • 62 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
    CrossrefPubMedGoogle Scholar
  • 63 Ramsey BW, Pepe MS, Quan JM , et al; Cystic Fibrosis Inhaled Tobramycin Study Group. Intermittent administration of inhaled tobramycin in patients with cystic fibrosis. N Engl J Med 1999; 340 (1) 23-30
    CrossrefPubMedGoogle Scholar
  • 64 Moss RB. Long-term benefits of inhaled tobramycin in adolescent patients with cystic fibrosis. Chest 2002; 121 (1) 55-63
    CrossrefPubMedGoogle Scholar
  • 65 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 (4) 314-320
    CrossrefPubMedGoogle Scholar
  • 66 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 2011; 46 (3) 230-238
    CrossrefPubMedGoogle Scholar
  • 67 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 (9) 921-928
    CrossrefPubMedGoogle Scholar
  • 68 Oermann CM, Retsch-Bogart GZ, Quittner AL , et al. An 18-month study of the safety and efficacy of repeated courses of inhaled aztreonam lysine in cystic fibrosis. Pediatr Pulmonol 2010; 45 (11) 1121-1134
    CrossrefPubMedGoogle Scholar
  • 69 Retsch-Bogart GZ, Quittner AL, Gibson RL , et al. Efficacy and safety of inhaled aztreonam lysine for airway pseudomonas in cystic fibrosis. Chest 2009; 135 (5) 1223-1232
    CrossrefPubMedGoogle Scholar
  • 70 Wainwright CE, Quittner AL, Geller DE , et al. Aztreonam for inhalation solution (AZLI) in patients with cystic fibrosis, mild lung impairment, and P. aeruginosa. J Cyst Fibros 2011; 10 (4) 234-242
    CrossrefPubMedGoogle Scholar
  • 71 Jensen T, Pedersen SS, Garne S, Heilmann C, Høiby N, Koch C. Colistin inhalation therapy in cystic fibrosis patients with chronic Pseudomonas aeruginosa lung infection. J Antimicrob Chemother 1987; 19 (6) 831-838
    CrossrefPubMedGoogle Scholar
  • 72 Hodson ME, Gallagher CG, Govan JR. A randomised clinical trial of nebulised tobramycin or colistin in cystic fibrosis. Eur Respir J 2002; 20 (3) 658-664
    CrossrefPubMedGoogle Scholar
  • 73 Schuster A, Haliburn C, Döring G, Goldman MH ; Freedom Study Group. Safety, efficacy and convenience of colistimethate sodium dry powder for inhalation (Colobreathe DPI) in patients with cystic fibrosis: a randomised study. Thorax 2013; 68 (4) 344-350
    CrossrefPubMedGoogle Scholar
  • 74 Assael BM, Pressler T, Bilton D , et al; AZLI Active Comparator Study Group. Inhaled aztreonam lysine vs. inhaled tobramycin in cystic fibrosis: a comparative efficacy trial. J Cyst Fibros 2013; 12 (2) 130-140
    CrossrefPubMedGoogle Scholar
  • 75 Hodson ME, Penketh AR, Batten JC. Aerosol carbenicillin and gentamicin treatment of Pseudomonas aeruginosa infection in patients with cystic fibrosis. Lancet 1981; 2 (8256) 1137-1139
    PubMedGoogle Scholar
  • 76 MacLusky IB, Gold R, Corey M, Levison H. Long-term effects of inhaled tobramycin in patients with cystic fibrosis colonized with Pseudomonas aeruginosa. Pediatr Pulmonol 1989; 7 (1) 42-48
    CrossrefPubMedGoogle Scholar
  • 77 Nolan G, Moivor P, Levison H, Fleming PC, Corey M, Gold R. Antibiotic prophylaxis in cystic fibrosis: inhaled cephaloridine as an adjunct to oral cloxacillin. J Pediatr 1982; 101 (4) 626-630
    CrossrefPubMedGoogle Scholar
  • 78 Wiesemann HG, Steinkamp G, Ratjen F , et al. Placebo-controlled, double-blind, randomized study of aerosolized tobramycin for early treatment of Pseudomonas aeruginosa colonization in cystic fibrosis. Pediatr Pulmonol 1998; 25 (2) 88-92
    CrossrefPubMedGoogle Scholar
  • 79 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
    CrossrefPubMedGoogle Scholar
  • 80 Nikolaizik WH, Trociewicz K, Ratjen F. Bronchial reactions to the inhalation of high-dose tobramycin in cystic fibrosis. Eur Respir J 2002; 20 (1) 122-126
    CrossrefPubMedGoogle Scholar
  • 81 Alothman GA, Alsaadi MM, Ho BL , et al. Evaluation of bronchial constriction in children with cystic fibrosis after inhaling two different preparations of tobramycin. Chest 2002; 122 (3) 930-934
    CrossrefPubMedGoogle Scholar
  • 82 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
    CrossrefPubMedGoogle Scholar
  • 83 Konstan MW, Flume PA, Kappler M , et al. Safety, efficacy and convenience of tobramycin inhalation powder in cystic fibrosis patients: The EAGER trial. J Cyst Fibros 2011; 10 (1) 54-61
    CrossrefPubMedGoogle Scholar
  • 84 Dietzsch HJ, Gottschalk B, Heyne K, Leupoid W, Wunderlich P. Cystic fibrosis: comparison of two mucolytic drugs for inhalation treatment (acetylcysteine and arginine hydrochloride). Pediatrics 1975; 55 (1) 96-100
    PubMedGoogle Scholar
  • 85 Gibson RL, Retsch-Bogart GZ, Oermann C , et al. Microbiology, safety, and pharmacokinetics of aztreonam lysinate for inhalation in patients with cystic fibrosis. Pediatr Pulmonol 2006; 41 (7) 656-665
    CrossrefPubMedGoogle Scholar
  • 86 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 (1) 47-58
    CrossrefPubMedGoogle Scholar
  • 87 Jensen T, Koch C, Pedersen SS, Høiby N. Aztreonam for cystic fibrosis patients who are hypersensitive to other beta-lactams. Lancet 1987; 1 (8545) 1319-1320
    PubMedGoogle Scholar
  • 88 Day AJ, Williams J, McKeown C, Bruton A, Weller PH Evaluation of inhaled colomycin in children with cystic fibrosis. 10th International Cystic Fibrosis Congress; 1988: 106
    PubMed
  • 89 Goss CH, Bell SC. Aztreonam for inhalation solution, challenges to drug approval and integration into CF care. J Cyst Fibros 2013; 12 (2) 99-101
    CrossrefPubMedGoogle Scholar
  • 90 Mogayzel Jr 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 (7) 680-689
    CrossrefPubMedGoogle Scholar
  • 91 Smyth AR, Bell SC, Bojcin S , et al. European Cystic Fibrosis Society Standards of Care: Best Practice guidelines. J Cyst Fibros 2014; 13 (Suppl. 01) S23-S42
    PubMedGoogle Scholar
  • 92 Valerius NH, Koch C, Høiby N. Prevention of chronic Pseudomonas aeruginosa colonisation in cystic fibrosis by early treatment. Lancet 1991; 338 (8769) 725-726
    CrossrefPubMedGoogle Scholar
  • 93 Langton Hewer SC, Smyth AR. Antibiotic strategies for eradicating Pseudomonas aeruginosa in people with cystic fibrosis. Cochrane Database Syst Rev 2014; 11: CD004197
    PubMedGoogle Scholar
  • 94 Tiddens HA, De Boeck K, Clancy JP , et al; ALPINE study investigators. Open label study of inhaled aztreonam for Pseudomonas eradication in children with cystic fibrosis: The ALPINE study. J Cyst Fibros 2015; 14 (1) 111-119
    CrossrefPubMedGoogle Scholar
  • 95 Ryan G, Jahnke N, Remmington T. Inhaled antibiotics for pulmonary exacerbations in cystic fibrosis. Cochrane Database Syst Rev 2012; 12: CD008319
    PubMedGoogle Scholar
  • 96 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
    CrossrefPubMedGoogle Scholar
  • 97 Clancy JP, Dupont L, Konstan MW , et al; Arikace Study Group. Phase II studies of nebulised Arikace in CF patients with Pseudomonas aeruginosa infection. Thorax 2013; 68 (9) 818-825
    CrossrefPubMedGoogle Scholar
  • 98 Geller DE, Flume PA, Griffith DC , et al. Pharmacokinetics and safety of MP-376 (levofloxacin inhalation solution) in cystic fibrosis subjects. Antimicrob Agents Chemother 2011; 55 (6) 2636-2640
    CrossrefPubMedGoogle Scholar
  • 99 Geller DE, Flume PA, Staab D, Fischer R, Loutit JS, Conrad DJ ; Mpex 204 Study Group. Levofloxacin inhalation solution (MP-376) in patients with cystic fibrosis with Pseudomonas aeruginosa. Am J Respir Crit Care Med 2011; 183 (11) 1510-1516
    CrossrefPubMedGoogle Scholar
  • 100 Trapnell BC, McColley SA, Kissner DG , et al; Phase 2 FTI Study Group. Fosfomycin/tobramycin for inhalation in patients with cystic fibrosis with pseudomonas airway infection. Am J Respir Crit Care Med 2012; 185 (2) 171-178
    CrossrefPubMedGoogle Scholar
  • 101 Grimwood K, Bell SC, Chang AB. Antimicrobial treatment of non-cystic fibrosis bronchiectasis. Expert Rev Anti Infect Ther 2014; 12 (10) 1277-1296
    CrossrefPubMedGoogle Scholar
  • 102 Insmed, Inc TR02-107 trial report. Available from: www.insmed.com/pdf/Pub9%209_13_09.pdf
    PubMed
  • 103 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
    CrossrefPubMedGoogle Scholar
  • 104 Drobnic ME, Suñé P, Montoro JB, Ferrer A, Orriols R. Inhaled tobramycin in non-cystic fibrosis patients with bronchiectasis and chronic bronchial infection with Pseudomonas aeruginosa. Ann Pharmacother 2005; 39 (1) 39-44
    CrossrefPubMedGoogle Scholar
  • 105 Murray MP, Govan JR, Doherty CJ , et al. A randomized controlled trial of nebulized gentamicin in non-cystic fibrosis bronchiectasis. Am J Respir Crit Care Med 2011; 183 (4) 491-499
    CrossrefPubMedGoogle Scholar
  • 106 Wilson R, Welte T, Polverino E , et al. Ciprofloxacin dry powder for inhalation in non-cystic fibrosis bronchiectasis: a phase II randomised study. Eur Respir J 2013; 41 (5) 1107-1115
    CrossrefPubMedGoogle Scholar
  • 107 Serisier DJ, Bilton D, De Soyza A , et al; ORBIT-2 investigators. Inhaled, dual release liposomal ciprofloxacin in non-cystic fibrosis bronchiectasis (ORBIT-2): a randomised, double-blind, placebo-controlled trial. Thorax 2013; 68 (9) 812-817
    CrossrefPubMedGoogle Scholar
  • 108 Haworth CS, Foweraker JE, Wilkinson P, Kenyon RF, Bilton D. Inhaled colistin in patients with bronchiectasis and chronic Pseudomonas aeruginosa infection. Am J Respir Crit Care Med 2014; 189 (8) 975-982
    CrossrefPubMedGoogle Scholar
  • 109 Barker AF, O'Donnell AE, Flume P , et al. Aztreonam for inhalation solution in patients with non-cystic fibrosis bronchiectasis (AIR-BX1 and AIR-BX2): two randomised double-blind, placebo-controlled phase 3 trials. Lancet Respir Med 2014; 2 (9) 738-749
    CrossrefPubMedGoogle Scholar
  • 110 Couch LA. Treatment With tobramycin solution for inhalation in bronchiectasis patients with Pseudomonas aeruginosa. Chest 2001; 120 (3, Suppl): 114S-117S
    CrossrefPubMedGoogle Scholar
  • 111 Chang AB, Bell SC, Torzillo PJ , et al. Chronic suppurative lung disease and bronchiectasis in children and adults in Australia and New Zealand: TSANZ guidelines. Med J Aust 2015; 202 (1) 21-23
    CrossrefPubMedGoogle Scholar
  • 112 Woodhead M. New guidelines for the management of adult lower respiratory tract infections. Eur Respir J 2011; 38 (6) 1250-1251
    CrossrefPubMedGoogle Scholar
  • 113 Bilton D, Henig N, Morrissey B, Gotfried M. Addition of inhaled tobramycin to ciprofloxacin for acute exacerbations of Pseudomonas aeruginosa infection in adult bronchiectasis. Chest 2006; 130 (5) 1503-1510
    CrossrefPubMedGoogle Scholar
  • 114 Daniels T, Mills N, Whitaker P. Nebuliser systems for drug delivery in cystic fibrosis. Paediatr Respir Rev 2013; 14 (2) 98-99
    CrossrefPubMedGoogle Scholar
  • 115 Dubus JC, Bassinet L, Chedevergne F , et al; GRAM (Groupe aérosols et mucoviscidose de la Société française de mucoviscidose). [Inhaled treatments in cystic fibrosis: what's new in 2013?]. Rev Mal Respir 2014; 31 (4) 336-346
    CrossrefPubMedGoogle Scholar
  • 116 Zhou QT, Tang P, Leung SS, Chan JG, Chan HK. Emerging inhalation aerosol devices and strategies: where are we headed?. Adv Drug Deliv Rev 2014; 75: 3-17
    CrossrefPubMedGoogle Scholar
  • 117 Tiddens HA, Bos AC, Mouton JW, Devadason S, Janssens HM. Inhaled antibiotics: dry or wet?. Eur Respir J 2014; 44 (5) 1308-1318
    CrossrefPubMedGoogle Scholar
  • 118 Uttley L, Tappenden P. Dry powder inhalers in cystic fibrosis: same old drugs but different benefits?. Curr Opin Pulm Med 2014; 20 (6) 607-612
    PubMedGoogle Scholar
  • 119 Tappenden P, Harnan S, Uttley L , et al. The cost effectiveness of dry powder antibiotics for the treatment of Pseudomonas aeruginosa in patients with cystic fibrosis. Pharmacoeconomics 2014; 32 (2) 159-172
    CrossrefPubMedGoogle Scholar
  • 120 Manca ML, Cassano R, Valenti D , et al. Isoniazid-gelatin conjugate microparticles containing rifampicin for the treatment of tuberculosis. J Pharm Pharmacol 2013; 65 (9) 1302-1311
    CrossrefPubMedGoogle Scholar
  • 121 Dames P, Gleich B, Flemmer A , et al. Targeted delivery of magnetic aerosol droplets to the lung. Nat Nanotechnol 2007; 2 (8) 495-499
    CrossrefPubMedGoogle Scholar
  • 122 Plank C. Nanomagnetosols: magnetism opens up new perspectives for targeted aerosol delivery to the lung. Trends Biotechnol 2008; 26 (2) 59-63
    CrossrefPubMedGoogle Scholar
  • 123 Stokell JR, Gharaibeh RZ, Hamp TJ, Zapata MJ, Fodor AA, Steck TR. Analysis of Changes in Diversity and Abundance of the Microbial Community in a Cystic Fibrosis Patient over a Multiyear Period. J Clin Microbiol 2015; 53 (1) 237-247
    CrossrefPubMedGoogle Scholar
  • 124 Sherrard LJ, Tunney MM, Elborn JS. Antimicrobial resistance in the respiratory microbiota of people with cystic fibrosis. Lancet 2014; 384 (9944) 703-713
    CrossrefPubMedGoogle Scholar
  • 125 Quittner AL, Marciel KK, Salathe MA , et al. A preliminary quality of life questionnaire-bronchiectasis: a patient-reported outcome measure for bronchiectasis. Chest 2014; 146 (2) 437-448
    CrossrefPubMedGoogle Scholar
  • 126 Quittner AL, O'Donnell AE, Salathe MA , et al. Quality of Life Questionnaire-Bronchiectasis: final psychometric analyses and determination of minimal important difference scores. Thorax 2015; 70 (1) 12-20
    CrossrefPubMedGoogle Scholar