UpToDate
Official reprint from UpToDate®
www.uptodate.com ©2016 UpToDate®

Cystic fibrosis: Antibiotic therapy for lung disease

Author
Richard H Simon, MD
Section Editor
George B Mallory, MD
Deputy Editor
Alison G Hoppin, MD

INTRODUCTION

Cystic fibrosis (CF) is a multisystem disorder caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, located on chromosome 7 [1]. (See "Cystic fibrosis: Genetics and pathogenesis".)

Pulmonary disease remains the leading cause of morbidity and mortality in patients with CF [2-5]. One of the major drivers of CF lung disease is infection [6,7]. The approach to treating infection in CF is multifaceted, involving antibiotics, chest physiotherapy, inhaled medications to promote secretion clearance, and antiinflammatory agents. Undoubtedly, improved use of antibiotics is responsible for a substantial portion of the increased survival that has occurred in patients with CF (figure 1) [4,6].

The use of antibiotics to treat CF lung disease will be reviewed here. Treatments other than antibiotics for CF lung disease and the diagnosis, clinical manifestations, and investigational therapies for CF are discussed separately. (See "Cystic fibrosis: Overview of the treatment of lung disease" and "Cystic fibrosis: Clinical manifestations and diagnosis" and "Cystic fibrosis: Clinical manifestations of pulmonary disease" and "Cystic fibrosis: Investigational therapies".)

PATHOGENS

Chronic bacterial infection within the airways occurs in most patients with CF (table 1); the prevalence of each bacterial type varies with the age of the patient (figure 2).

Pseudomonas aeruginosa — For reasons that are poorly understood, the CF airway is particularly susceptible to Pseudomonas aeruginosa, with infection occurring as early as the first year of life. The prevalence of P. aeruginosa increases as patients age, such that more than 68 percent of adults are chronically infected [8]. With prolonged infection, P. aeruginosa converts to a mucoid phenotype by the production of alginate. This mucoid phenotype is seen infrequently in populations without CF, but is manifested by over 62 percent of the P. aeruginosa isolated from patients with CF. (See "Epidemiology, microbiology, and pathogenesis of Pseudomonas aeruginosa infection".)

                                               

Subscribers log in here

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information or to purchase a personal subscription, click below on the option that best describes you:
Literature review current through: Nov 2016. | This topic last updated: Wed Jun 15 00:00:00 GMT+00:00 2016.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2016 UpToDate, Inc.
References
Top
  1. Rommens JM, Iannuzzi MC, Kerem B, et al. Identification of the cystic fibrosis gene: chromosome walking and jumping. Science 1989; 245:1059.
  2. Ratjen F, Döring G. Cystic fibrosis. Lancet 2003; 361:681.
  3. Davis PB, Drumm M, Konstan MW. Cystic fibrosis. Am J Respir Crit Care Med 1996; 154:1229.
  4. Goss CH, Rosenfeld M. Update on cystic fibrosis epidemiology. Curr Opin Pulm Med 2004; 10:510.
  5. Brennan AL, Geddes DM. Cystic fibrosis. Curr Opin Infect Dis 2002; 15:175.
  6. Gibson RL, Burns JL, Ramsey BW. Pathophysiology and management of pulmonary infections in cystic fibrosis. Am J Respir Crit Care Med 2003; 168:918.
  7. Sagel SD, Gibson RL, Emerson J, et al. Impact of Pseudomonas and Staphylococcus infection on inflammation and clinical status in young children with cystic fibrosis. J Pediatr 2009; 154:183.
  8. Cystic Fibrosis Foundation Annual Patient Registry 2013. Available at: http://www.cff.org/research/ClinicalResearch/PatientRegistryReport/ (Accessed on August 07, 2015).
  9. Rosenfeld M, Gibson RL, McNamara S, et al. Early pulmonary infection, inflammation, and clinical outcomes in infants with cystic fibrosis. Pediatr Pulmonol 2001; 32:356.
  10. Emerson J, Rosenfeld M, McNamara S, et al. Pseudomonas aeruginosa and other predictors of mortality and morbidity in young children with cystic fibrosis. Pediatr Pulmonol 2002; 34:91.
  11. Aaron SD, Vandemheen KL, Ramotar K, et al. Infection with transmissible strains of Pseudomonas aeruginosa and clinical outcomes in adults with cystic fibrosis. JAMA 2010; 304:2145.
  12. Dasenbrook EC, Merlo CA, Diener-West M, et al. Persistent methicillin-resistant Staphylococcus aureus and rate of FEV1 decline in cystic fibrosis. Am J Respir Crit Care Med 2008; 178:814.
  13. Sawicki GS, Rasouliyan L, Pasta DJ, et al. The impact of incident methicillin resistant Staphylococcus aureus detection on pulmonary function in cystic fibrosis. Pediatr Pulmonol 2008; 43:1117.
  14. Dasenbrook EC, Checkley W, Merlo CA, et al. Association between respiratory tract methicillin-resistant Staphylococcus aureus and survival in cystic fibrosis. JAMA 2010; 303:2386.
  15. LiPuma JJ. Burkholderia and emerging pathogens in cystic fibrosis. Semin Respir Crit Care Med 2003; 24:681.
  16. De Boeck K, Malfroot A, Van Schil L, et al. Epidemiology of Burkholderia cepacia complex colonisation in cystic fibrosis patients. Eur Respir J 2004; 23:851.
  17. Jones AM, Dodd ME, Govan JR, et al. Burkholderia cenocepacia and Burkholderia multivorans: influence on survival in cystic fibrosis. Thorax 2004; 59:948.
  18. Coenye T, Spilker T, Van Schoor A, et al. Recovery of Burkholderia cenocepacia strain PHDC from cystic fibrosis patients in Europe. Thorax 2004; 59:952.
  19. Speert DP. Advances in Burkholderia cepacia complex. Paediatr Respir Rev 2002; 3:230.
  20. Fauroux B, Hart N, Belfar S, et al. Burkholderia cepacia is associated with pulmonary hypertension and increased mortality among cystic fibrosis patients. J Clin Microbiol 2004; 42:5537.
  21. Kalish LA, Waltz DA, Dovey M, et al. Impact of Burkholderia dolosa on lung function and survival in cystic fibrosis. Am J Respir Crit Care Med 2006; 173:421.
  22. Chaparro C, Maurer J, Gutierrez C, et al. Infection with Burkholderia cepacia in cystic fibrosis: outcome following lung transplantation. Am J Respir Crit Care Med 2001; 163:43.
  23. Aris RM, Routh JC, LiPuma JJ, et al. Lung transplantation for cystic fibrosis patients with Burkholderia cepacia complex. Survival linked to genomovar type. Am J Respir Crit Care Med 2001; 164:2102.
  24. De Soyza A, Morris K, McDowell A, et al. Prevalence and clonality of Burkholderia cepacia complex genomovars in UK patients with cystic fibrosis referred for lung transplantation. Thorax 2004; 59:526.
  25. Emerson J, McNamara S, Buccat AM, et al. Changes in cystic fibrosis sputum microbiology in the United States between 1995 and 2008. Pediatr Pulmonol 2010; 45:363.
  26. Lipuma JJ. The changing microbial epidemiology in cystic fibrosis. Clin Microbiol Rev 2010; 23:299.
  27. Harris JK, De Groote MA, Sagel SD, et al. Molecular identification of bacteria in bronchoalveolar lavage fluid from children with cystic fibrosis. Proc Natl Acad Sci U S A 2007; 104:20529.
  28. 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; 177:995.
  29. Doe SJ, McSorley A, Isalska B, et al. Patient segregation and aggressive antibiotic eradication therapy can control methicillin-resistant Staphylococcus aureus at large cystic fibrosis centres. J Cyst Fibros 2010; 9:104.
  30. Sanders DB, Bittner RC, Rosenfeld M, et al. Pulmonary exacerbations are associated with subsequent FEV1 decline in both adults and children with cystic fibrosis. Pediatr Pulmonol 2011; 46:393.
  31. Waters V, Stanojevic S, Atenafu EG, et al. Effect of pulmonary exacerbations on long-term lung function decline in cystic fibrosis. Eur Respir J 2012; 40:61.
  32. Rosenfeld M, Emerson J, Williams-Warren J, et al. Defining a pulmonary exacerbation in cystic fibrosis. J Pediatr 2001; 139:359.
  33. Regelmann WE, Elliott GR, Warwick WJ, Clawson CC. Reduction of sputum Pseudomonas aeruginosa density by antibiotics improves lung function in cystic fibrosis more than do bronchodilators and chest physiotherapy alone. Am Rev Respir Dis 1990; 141:914.
  34. Hyatt AC, Chipps BE, Kumor KM, et al. A double-blind controlled trial of anti-Pseudomonas chemotherapy of acute respiratory exacerbations in patients with cystic fibrosis. J Pediatr 1981; 99:307.
  35. Saiman L, Siegel J, Cystic Fibrosis Foundation Consensus Conference on Infection Control Participants. Infection control recommendations for patients with cystic fibrosis: Microbiology, important pathogens, and infection control practices to prevent patient-to-patient transmission. Am J Infect Control 2003; 31:S1.
  36. Cystic Fibrosis Foundation, Borowitz D, Robinson KA, et al. Cystic Fibrosis Foundation evidence-based guidelines for management of infants with cystic fibrosis. J Pediatr 2009; 155:S73.
  37. Lahiri T, Hempstead SE, Brady C, et al. Clinical Practice Guidelines From the Cystic Fibrosis Foundation for Preschoolers With Cystic Fibrosis. Pediatrics 2016; 137.
  38. Hansen CR, Pressler T, Nielsen KG, et al. Inflammation in Achromobacter xylosoxidans infected cystic fibrosis patients. J Cyst Fibros 2010; 9:51.
  39. Amin R, Waters V. Antibiotic treatment for Stenotrophomonas maltophilia in people with cystic fibrosis. Cochrane Database Syst Rev 2014; :CD009249.
  40. Goss CH, Otto K, Aitken ML, Rubenfeld GD. Detecting Stenotrophomonas maltophilia does not reduce survival of patients with cystic fibrosis. Am J Respir Crit Care Med 2002; 166:356.
  41. Waters V, Yau Y, Prasad S, et al. Stenotrophomonas maltophilia in cystic fibrosis: serologic response and effect on lung disease. Am J Respir Crit Care Med 2011; 183:635.
  42. Lang BJ, Aaron SD, Ferris W, et al. Multiple combination bactericidal antibiotic testing for patients with cystic fibrosis infected with multiresistant strains of Pseudomonas aeruginosa. Am J Respir Crit Care Med 2000; 162:2241.
  43. Sanders CC, Sanders WE Jr, Goering RV. In vitro antagonism of beta-lactam antibiotics by cefoxitin. Antimicrob Agents Chemother 1982; 21:968.
  44. Aaron SD, Vandemheen KL, Ferris W, et al. Combination antibiotic susceptibility testing to treat exacerbations of cystic fibrosis associated with multiresistant bacteria: a randomised, double-blind, controlled clinical trial. Lancet 2005; 366:463.
  45. Flume PA, Mogayzel PJ Jr, Robinson KA, et al. Cystic fibrosis pulmonary guidelines: treatment of pulmonary exacerbations. Am J Respir Crit Care Med 2009; 180:802.
  46. Smith AL, Fiel SB, Mayer-Hamblett N, et al. Susceptibility testing of Pseudomonas aeruginosa isolates and clinical response to parenteral antibiotic administration: lack of association in cystic fibrosis. Chest 2003; 123:1495.
  47. Hurley MN, Ariff AH, Bertenshaw C, et al. Results of antibiotic susceptibility testing do not influence clinical outcome in children with cystic fibrosis. J Cyst Fibros 2012; 11:288.
  48. 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.
  49. Dales L, Ferris W, Vandemheen K, Aaron SD. Combination antibiotic susceptibility of biofilm-grown Burkholderia cepacia and Pseudomonas aeruginosa isolated from patients with pulmonary exacerbations of cystic fibrosis. Eur J Clin Microbiol Infect Dis 2009; 28:1275.
  50. Moskowitz SM, Emerson JC, McNamara S, et al. Randomized trial of biofilm testing to select antibiotics for cystic fibrosis airway infection. Pediatr Pulmonol 2011; 46:184.
  51. Aaron SD, Ferris W, Henry DA, et al. Multiple combination bactericidal antibiotic testing for patients with cystic fibrosis infected with Burkholderia cepacia. Am J Respir Crit Care Med 2000; 161:1206.
  52. Waters V, Ratjen F. Combination antimicrobial susceptibility testing for acute exacerbations in chronic infection of Pseudomonas aeruginosa in cystic fibrosis. Cochrane Database Syst Rev 2015; :CD006961.
  53. Smith AL, Doershuk C, Goldmann D, et al. Comparison of a beta-lactam alone versus beta-lactam and an aminoglycoside for pulmonary exacerbation in cystic fibrosis. J Pediatr 1999; 134:413.
  54. Elphick HE, Jahnke N. Single versus combination intravenous antibiotic therapy for people with cystic fibrosis. Cochrane Database Syst Rev 2014; :CD002007.
  55. Beringer P. The clinical use of colistin in patients with cystic fibrosis. Curr Opin Pulm Med 2001; 7:434.
  56. Conway SP, Etherington C, Munday J, et al. Safety and tolerability of bolus intravenous colistin in acute respiratory exacerbations in adults with cystic fibrosis. Ann Pharmacother 2000; 34:1238.
  57. Phaff SJ, Tiddens HA, Verbrugh HA, Ott A. Macrolide resistance of Staphylococcus aureus and Haemophilus species associated with long-term azithromycin use in cystic fibrosis. J Antimicrob Chemother 2006; 57:741.
  58. Ryan G, Jahnke N, Remmington T. Inhaled antibiotics for pulmonary exacerbations in cystic fibrosis. Cochrane Database Syst Rev 2012; 12:CD008319.
  59. Laube BL, Links JM, LaFrance ND, et al. Homogeneity of bronchopulmonary distribution of 99mTc aerosol in normal subjects and in cystic fibrosis patients. Chest 1989; 95:822.
  60. Rey E, Tréluyer JM, Pons G. Drug disposition in cystic fibrosis. Clin Pharmacokinet 1998; 35:313.
  61. Bolton CE, Ionescu AA, Evans WD, et al. Altered tissue distribution in adults with cystic fibrosis. Thorax 2003; 58:885.
  62. Touw DJ. Clinical pharmacokinetics of antimicrobial drugs in cystic fibrosis. Pharm World Sci 1998; 20:149.
  63. Massie J, Cranswick N. Pharmacokinetic profile of once daily intravenous tobramycin in children with cystic fibrosis. J Paediatr Child Health 2006; 42:601.
  64. Lindsay CA, Bosso JA. Optimisation of antibiotic therapy in cystic fibrosis patients. Pharmacokinetic considerations. Clin Pharmacokinet 1993; 24:496.
  65. Zobell JT, Young DC, Waters CD, et al. A survey of the utilization of anti-pseudomonal beta-lactam therapy in cystic fibrosis patients. Pediatr Pulmonol 2011; 46:987.
  66. Prescott WA Jr, Gentile AE, Nagel JL, Pettit RS. Continuous-infusion antipseudomonal Beta-lactam therapy in patients with cystic fibrosis. P T 2011; 36:723.
  67. Riethmueller J, Junge S, Schroeter TW, et al. Continuous vs thrice-daily ceftazidime for elective intravenous antipseudomonal therapy in cystic fibrosis. Infection 2009; 37:418.
  68. Zobell JT, Young DC, Waters CD, et al. Optimization of anti-pseudomonal antibiotics for cystic fibrosis pulmonary exacerbations: VI. Executive summary. Pediatr Pulmonol 2013; 48:525.
  69. Smyth AR, Bhatt J. Once-daily versus multiple-daily dosing with intravenous aminoglycosides for cystic fibrosis. Cochrane Database Syst Rev 2014; :CD002009.
  70. Smyth A, Tan KH, Hyman-Taylor P, et al. Once versus three-times daily regimens of tobramycin treatment for pulmonary exacerbations of cystic fibrosis--the TOPIC study: a randomised controlled trial. Lancet 2005; 365:573.
  71. Prescott WA Jr. National survey of extended-interval aminoglycoside dosing in pediatric cystic fibrosis pulmonary exacerbations. J Pediatr Pharmacol Ther 2011; 16:262.
  72. Coulthard KP, Peckham DG, Conway SP, et al. Therapeutic drug monitoring of once daily tobramycin in cystic fibrosis--caution with trough concentrations. J Cyst Fibros 2007; 6:125.
  73. Hennig S, Norris R, Kirkpatrick CM. Target concentration intervention is needed for tobramycin dosing in paediatric patients with cystic fibrosis--a population pharmacokinetic study. Br J Clin Pharmacol 2008; 65:502.
  74. Bartel K, Habash T, Lugauer S, et al. Optimal tobramycin dosage in patients with cystic fibrosis--evidence for predictability based on previous drug monitoring. Infection 1999; 27:268.
  75. Al-Aloul M, Miller H, Alapati S, et al. Renal impairment in cystic fibrosis patients due to repeated intravenous aminoglycoside use. Pediatr Pulmonol 2005; 39:15.
  76. Tan KH, Mulheran M, Knox AJ, Smyth AR. Aminoglycoside prescribing and surveillance in cystic fibrosis. Am J Respir Crit Care Med 2003; 167:819.
  77. Bertenshaw C, Watson AR, Lewis S, Smyth A. Survey of acute renal failure in patients with cystic fibrosis in the UK. Thorax 2007; 62:541.
  78. Soulsby N, Greville H, Coulthard K, Doecke C. Renal dysfunction in cystic fibrosis: is there cause for concern? Pediatr Pulmonol 2009; 44:947.
  79. O'Donnell EP, Scarsi KK, Scheetz MH, et al. Risk factors for aminoglycoside ototoxicity in adult cystic fibrosis patients. Int J Antimicrob Agents 2010; 36:94.
  80. Green CG, Doershuk CF, Stern RC. Symptomatic hypomagnesemia in cystic fibrosis. J Pediatr 1985; 107:425.
  81. Geller DE, Pitlick WH, Nardella PA, et al. Pharmacokinetics and bioavailability of aerosolized tobramycin in cystic fibrosis. Chest 2002; 122:219.
  82. Li J, Nation RL, Turnidge JD. Defining the dosage units for colistin methanesulfonate: urgent need for international harmonization. Antimicrob Agents Chemother 2006; 50:4231; author reply 4231.
  83. Lim LM, Ly N, Anderson D, et al. Resurgence of colistin: a review of resistance, toxicity, pharmacodynamics, and dosing. Pharmacotherapy 2010; 30:1279.
  84. Pleasants RA, Michalets EL, Williams DM, et al. Pharmacokinetics of vancomycin in adult cystic fibrosis patients. Antimicrob Agents Chemother 1996; 40:186.
  85. Payen S, Serreau R, Munck A, et al. Population pharmacokinetics of ciprofloxacin in pediatric and adolescent patients with acute infections. Antimicrob Agents Chemother 2003; 47:3170.
  86. Montgomery MJ, Beringer PM, Aminimanizani A, et al. Population pharmacokinetics and use of Monte Carlo simulation to evaluate currently recommended dosing regimens of ciprofloxacin in adult patients with cystic fibrosis. Antimicrob Agents Chemother 2001; 45:3468.
  87. Schaefer HG, Stass H, Wedgwood J, et al. Pharmacokinetics of ciprofloxacin in pediatric cystic fibrosis patients. Antimicrob Agents Chemother 1996; 40:29.
  88. Treggiari MM, Rosenfeld M, Mayer-Hamblett N, et al. Early anti-pseudomonal acquisition in young patients with cystic fibrosis: rationale and design of the EPIC clinical trial and observational study'. Contemp Clin Trials 2009; 30:256.
  89. Christensson BA, Nilsson-Ehle I, Ljungberg B, et al. Increased oral bioavailability of ciprofloxacin in cystic fibrosis patients. Antimicrob Agents Chemother 1992; 36:2512.
  90. Steen HJ, Scott EM, Stevenson MI, et al. Clinical and pharmacokinetic aspects of ciprofloxacin in the treatment of acute exacerbations of pseudomonas infection in cystic fibrosis patients. J Antimicrob Chemother 1989; 24:787.
  91. Reed MD, Stern RC, Bertino JS Jr, et al. Dosing implications of rapid elimination of trimethoprim-sulfamethoxazole in patients with cystic fibrosis. J Pediatr 1984; 104:303.
  92. VanDevanter DR, O'Riordan MA, Blumer JL, Konstan MW. Assessing time to pulmonary function benefit following antibiotic treatment of acute cystic fibrosis exacerbations. Respir Res 2010; 11:137.
  93. Collaco JM, Green DM, Cutting GR, et al. Location and duration of treatment of cystic fibrosis respiratory exacerbations do not affect outcomes. Am J Respir Crit Care Med 2010; 182:1137.
  94. Sequeiros IM, Jarad NA. Extending the course of intravenous antibiotics in adult patients with cystic fibrosis with acute pulmonary exacerbations. Chron Respir Dis 2012; 9:213.
  95. Donati MA, Guenette G, Auerbach H. Prospective controlled study of home and hospital therapy of cystic fibrosis pulmonary disease. J Pediatr 1987; 111:28.
  96. Wolter JM, Bowler SD, Nolan PJ, McCormack JG. Home intravenous therapy in cystic fibrosis: a prospective randomized trial examining clinical, quality of life and cost aspects. Eur Respir J 1997; 10:896.
  97. Balaguer A, González de Dios J. Home versus hospital intravenous antibiotic therapy for cystic fibrosis. Cochrane Database Syst Rev 2015; :CD001917.
  98. Bosworth DG, Nielson DW. Effectiveness of home versus hospital care in the routine treatment of cystic fibrosis. Pediatr Pulmonol 1997; 24:42.
  99. Thornton J, Elliott R, Tully MP, et al. Long term clinical outcome of home and hospital intravenous antibiotic treatment in adults with cystic fibrosis. Thorax 2004; 59:242.
  100. Nazer D, Abdulhamid I, Thomas R, Pendleton S. Home versus hospital intravenous antibiotic therapy for acute pulmonary exacerbations in children with cystic fibrosis. Pediatr Pulmonol 2006; 41:744.
  101. Diver JM, Schollaardt T, Rabin HR, et al. Persistence mechanisms in Pseudomonas aeruginosa from cystic fibrosis patients undergoing ciprofloxacin therapy. Antimicrob Agents Chemother 1991; 35:1538.
  102. Sheldon CD, Assoufi BK, Hodson ME. Regular three monthly oral ciprofloxacin in adult cystic fibrosis patients infected with Pseudomonas aeruginosa. Respir Med 1993; 87:587.
  103. Breen L, Aswani N. Elective versus symptomatic intravenous antibiotic therapy for cystic fibrosis. Cochrane Database Syst Rev 2012; :CD002767.
  104. 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.
  105. Brett MM, Simmonds EJ, Ghoneim AT, Littlewood JM. The value of serum IgG titres against Pseudomonas aeruginosa in the management of early pseudomonal infection in cystic fibrosis. Arch Dis Child 1992; 67:1086.
  106. Szaff M, Høiby N, Flensborg EW. Frequent antibiotic therapy improves survival of cystic fibrosis patients with chronic Pseudomonas aeruginosa infection. Acta Paediatr Scand 1983; 72:651.
  107. Høiby N, Koch C. Maintenance treatment of chronic pseudomonas aeruginosa infection in cystic fibrosis. Thorax 2000; 55:349.
  108. Ryan G, Singh M, Dwan K. Inhaled antibiotics for long-term therapy in cystic fibrosis. Cochrane Database Syst Rev 2011; :CD001021.
  109. Langton Hewer SC, Smyth AR. Antibiotic strategies for eradicating Pseudomonas aeruginosa in people with cystic fibrosis. Cochrane Database Syst Rev 2014; :CD004197.
  110. 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.
  111. Moss RB. Long-term benefits of inhaled tobramycin in adolescent patients with cystic fibrosis. Chest 2002; 121:55.
  112. 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; 179:1190.
  113. Bowman CM. The long-term use of inhaled tobramycin in patients with cystic fibrosis. J Cyst Fibros 2002; 1:194.
  114. Parkins MD, Elborn JS. Tobramycin Inhalation Powder™: a novel drug delivery system for treating chronic Pseudomonas aeruginosa infection in cystic fibrosis. Expert Rev Respir Med 2011; 5:609.
  115. 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; 10:54.
  116. Konstan MW, Flume PA, Galeva I, et al. One-year safety and efficacy of tobramycin powder for inhalation in patients with cystic fibrosis. Pediatr Pulmonol 2016; 51:372.
  117. 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; 178:921.
  118. Retsch-Bogart GZ, Quittner AL, Gibson RL, et al. Efficacy and safety of inhaled aztreonam lysine for airway pseudomonas in cystic fibrosis. Chest 2009; 135:1223.
  119. 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; 45:1121.
  120. 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; 10:234.
  121. Conway SP, Pond MN, Watson A, et al. Intravenous colistin sulphomethate in acute respiratory exacerbations in adult patients with cystic fibrosis. Thorax 1997; 52:987.
  122. Alothman GA, Ho B, Alsaadi MM, et al. Bronchial constriction and inhaled colistin in cystic fibrosis. Chest 2005; 127:522.
  123. 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.
  124. Hodson ME, Gallagher CG, Govan JR. A randomised clinical trial of nebulised tobramycin or colistin in cystic fibrosis. Eur Respir J 2002; 20:658.
  125. Adeboyeku D, Scott S, Hodson ME. Open follow-up study of tobramycin nebuliser solution and colistin in patients with cystic fibrosis. J Cyst Fibros 2006; 5:261.
  126. Schuster A, Haliburn C, Döring G, et al. Safety, efficacy and convenience of colistimethate sodium dry powder for inhalation (Colobreathe DPI) in patients with cystic fibrosis: a randomised study. Thorax 2013; 68:344.
  127. Assael BM, Pressler T, Bilton D, et al. Inhaled aztreonam lysine vs. inhaled tobramycin in cystic fibrosis: a comparative efficacy trial. J Cyst Fibros 2013; 12:130.
  128. Flume PA, O'Sullivan BP, Robinson KA, et al. Cystic fibrosis pulmonary guidelines: chronic medications for maintenance of lung health. Am J Respir Crit Care Med 2007; 176:957.
  129. Smyth AR, Bell SC, Bojcin S, et al. European Cystic Fibrosis Society Standards of Care: Best Practice guidelines. J Cyst Fibros 2014; 13 Suppl 1:S23.
  130. Saiman L, Mehar F, Niu WW, et al. Antibiotic susceptibility of multiply resistant Pseudomonas aeruginosa isolated from patients with cystic fibrosis, including candidates for transplantation. Clin Infect Dis 1996; 23:532.
  131. McCoy KS, Retsch-Bogart GZ, Gibson R, et al. Relevance of established susceptibility breakpoints to clinical efficacy of inhaled antibiotic therapies in cystic fibrosis. Pediatr Pulmonol 2008; 31 Suppl:351.
  132. Smyth AR, Walters S. Prophylactic anti-staphylococcal antibiotics for cystic fibrosis. Cochrane Database Syst Rev 2014; :CD001912.
  133. Stutman HR, Lieberman JM, Nussbaum E, Marks MI. Antibiotic prophylaxis in infants and young children with cystic fibrosis: a randomized controlled trial. J Pediatr 2002; 140:299.
  134. Tramper-Stranders GA, Wolfs TF, van Haren Noman S, et al. Controlled trial of cycled antibiotic prophylaxis to prevent initial Pseudomonas aeruginosa infection in children with cystic fibrosis. Thorax 2010; 65:915.
  135. Frederiksen B, Koch C, Høiby N. Antibiotic treatment of initial colonization with Pseudomonas aeruginosa postpones chronic infection and prevents deterioration of pulmonary function in cystic fibrosis. Pediatr Pulmonol 1997; 23:330.
  136. Johansen HK, Nørregaard L, Gøtzsche PC, et al. Antibody response to Pseudomonas aeruginosa in cystic fibrosis patients: a marker of therapeutic success?--A 30-year cohort study of survival in Danish CF patients after onset of chronic P. aeruginosa lung infection. Pediatr Pulmonol 2004; 37:427.
  137. Treggiari MM, Rosenfeld M, Retsch-Bogart G, et al. Approach to eradication of initial Pseudomonas aeruginosa infection in children with cystic fibrosis. Pediatr Pulmonol 2007; 42:751.
  138. Douglas TA, Brennan S, Gard S, et al. Acquisition and eradication of P. aeruginosa in young children with cystic fibrosis. Eur Respir J 2009; 33:305.
  139. Mayer-Hamblett N, Kloster M, Rosenfeld M, et al. Impact of Sustained Eradication of New Pseudomonas aeruginosa Infection on Long-term Outcomes in Cystic Fibrosis. Clin Infect Dis 2015; 61:707.
  140. Zemanick ET, Emerson J, Thompson V, et al. Clinical outcomes after initial pseudomonas acquisition in cystic fibrosis. Pediatr Pulmonol 2015; 50:42.
  141. Ratjen F, Munck A, Kho P, et al. Treatment of early Pseudomonas aeruginosa infection in patients with cystic fibrosis: the ELITE trial. Thorax 2010; 65:286.
  142. Ratjen F, Döring G, Nikolaizik WH. Effect of inhaled tobramycin on early Pseudomonas aeruginosa colonisation in patients with cystic fibrosis. Lancet 2001; 358:983.
  143. Treggiari MM, Retsch-Bogart G, Mayer-Hamblett N, et al. Comparative efficacy and safety of 4 randomized regimens to treat early Pseudomonas aeruginosa infection in children with cystic fibrosis. Arch Pediatr Adolesc Med 2011; 165:847.
  144. Adjemian J, Olivier KN, Prevots DR. Nontuberculous mycobacteria among patients with cystic fibrosis in the United States: screening practices and environmental risk. Am J Respir Crit Care Med 2014; 190:581.
  145. Floto RA, Olivier KN, Saiman L, et al. US Cystic Fibrosis Foundation and European Cystic Fibrosis Society consensus recommendations for the management of non-tuberculous mycobacteria in individuals with cystic fibrosis. Thorax 2016; 71 Suppl 1:i1.
  146. Olivier KN, Weber DJ, Wallace RJ Jr, et al. Nontuberculous mycobacteria. I: multicenter prevalence study in cystic fibrosis. Am J Respir Crit Care Med 2003; 167:828.
  147. Mussaffi H, Rivlin J, Shalit I, et al. Nontuberculous mycobacteria in cystic fibrosis associated with allergic bronchopulmonary aspergillosis and steroid therapy. Eur Respir J 2005; 25:324.
  148. Esther CR Jr, Esserman DA, Gilligan P, et al. Chronic Mycobacterium abscessus infection and lung function decline in cystic fibrosis. J Cyst Fibros 2010; 9:117.
  149. Griffith DE, Aksamit T, Brown-Elliott BA, et al. An official ATS/IDSA statement: diagnosis, treatment, and prevention of nontuberculous mycobacterial diseases. Am J Respir Crit Care Med 2007; 175:367.
  150. Albrecht C, Ringshausen F, Ott S, et al. Should all adult cystic fibrosis patients with repeated nontuberculous mycobacteria cultures receive specific treatment? A 10-year case-control study. Eur Respir J 2016; 47:1575.
  151. Chalermskulrat W, Sood N, Neuringer IP, et al. Non-tuberculous mycobacteria in end stage cystic fibrosis: implications for lung transplantation. Thorax 2006; 61:507.
  152. Chernenko SM, Humar A, Hutcheon M, et al. Mycobacterium abscessus infections in lung transplant recipients: the international experience. J Heart Lung Transplant 2006; 25:1447.
  153. Mroueh S, Spock A. Allergic bronchopulmonary aspergillosis in patients with cystic fibrosis. Chest 1994; 105:32.
  154. Kraemer R, Deloséa N, Ballinari P, et al. Effect of allergic bronchopulmonary aspergillosis on lung function in children with cystic fibrosis. Am J Respir Crit Care Med 2006; 174:1211.
  155. Amin R, Dupuis A, Aaron SD, Ratjen F. The effect of chronic infection with Aspergillus fumigatus on lung function and hospitalization in patients with cystic fibrosis. Chest 2010; 137:171.
  156. Aaron SD, Vandemheen KL, Freitag A, et al. Treatment of Aspergillus fumigatus in patients with cystic fibrosis: a randomized, placebo-controlled pilot study. PLoS One 2012; 7:e36077.
  157. Skov M, Koch C, Reimert CM, Poulsen LK. Diagnosis of allergic bronchopulmonary aspergillosis (ABPA) in cystic fibrosis. Allergy 2000; 55:50.
  158. Nikolaizik WH, Weichel M, Blaser K, Crameri R. Intracutaneous tests with recombinant allergens in cystic fibrosis patients with allergic bronchopulmonary aspergillosis and Aspergillus allergy. Am J Respir Crit Care Med 2002; 165:916.
  159. Stevens DA, Moss RB, Kurup VP, et al. Allergic bronchopulmonary aspergillosis in cystic fibrosis--state of the art: Cystic Fibrosis Foundation Consensus Conference. Clin Infect Dis 2003; 37 Suppl 3:S225.
  160. Scott FW, Pitt TL. Identification and characterization of transmissible Pseudomonas aeruginosa strains in cystic fibrosis patients in England and Wales. J Med Microbiol 2004; 53:609.
  161. Parkins MD, Glezerson BA, Sibley CD, et al. Twenty-five-year outbreak of Pseudomonas aeruginosa infecting individuals with cystic fibrosis: identification of the prairie epidemic strain. J Clin Microbiol 2014; 52:1127.
  162. Jones AM, Dodd ME, Morris J, et al. Clinical outcome for cystic fibrosis patients infected with transmissible pseudomonas aeruginosa: an 8-year prospective study. Chest 2010; 137:1405.
  163. Saiman L, Siegel JD, LiPuma JJ, et al. Infection prevention and control guideline for cystic fibrosis: 2013 update. Infect Control Hosp Epidemiol 2014; 35 Suppl 1:S1.