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Cystic fibrosis: Treatment of acute pulmonary exacerbations

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 [2,3]. One of the major drivers of CF lung disease is infection [4,5]. Treatment of acute pulmonary exacerbations in CF is multifaceted, involving antibiotics, chest physiotherapy, inhaled medications to promote secretion clearance, and antiinflammatory agents. Improved treatment of lung disease, in conjunction with improved nutrition, are likely responsible for the increased survival that has occurred in patients with CF (figure 1) [4,6].

The treatment of acute pulmonary exacerbations in CF will be reviewed here. Treatment of chronic pulmonary infection and other aspects of pulmonary disease in CF are discussed in separate topic reviews:

(See "Cystic fibrosis: Antibiotic therapy for chronic pulmonary infection".)

(See "Cystic fibrosis: Overview of the treatment of lung disease".)

                                       
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Literature review current through: Nov 2017. | This topic last updated: Dec 12, 2017.
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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, Bell SC, Rowe SM, et al. Cystic fibrosis. Nat Rev Dis Primers 2015; 1:15010.
  3. Elborn JS. Cystic fibrosis. Lancet 2016; 388:2519.
  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.
  5. 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.
  6. Goss CH, Rosenfeld M. Update on cystic fibrosis epidemiology. Curr Opin Pulm Med 2004; 10:510.
  7. 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.
  8. 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.
  9. Rosenfeld M, Emerson J, Williams-Warren J, et al. Defining a pulmonary exacerbation in cystic fibrosis. J Pediatr 2001; 139:359.
  10. Goss CH, Burns JL. Exacerbations in cystic fibrosis. 1: Epidemiology and pathogenesis. Thorax 2007; 62:360.
  11. Bilton D, Canny G, Conway S, et al. Pulmonary exacerbation: towards a definition for use in clinical trials. Report from the EuroCareCF Working Group on outcome parameters in clinical trials. J Cyst Fibros 2011; 10 Suppl 2:S79.
  12. Anstead M, Saiman L, Mayer-Hamblett N, et al. Pulmonary exacerbations in CF patients with early lung disease. J Cyst Fibros 2014; 13:74.
  13. Wagener JS, Rasouliyan L, VanDevanter DR, et al. Oral, inhaled, and intravenous antibiotic choice for treating pulmonary exacerbations in cystic fibrosis. Pediatr Pulmonol 2013; 48:666.
  14. Stanojevic S, McDonald A, Waters V, et al. Effect of pulmonary exacerbations treated with oral antibiotics on clinical outcomes in cystic fibrosis. Thorax 2017; 72:327.
  15. Cystic Fibrosis Foundation. Cystic Fibrosis Foundation patient registry. In: 2015 Annual Data Report, Bethesda, Maryland 2016.
  16. Heltshe SL, Goss CH, Thompson V, et al. Short-term and long-term response to pulmonary exacerbation treatment in cystic fibrosis. Thorax 2016; 71:223.
  17. Sanders DB, Bittner RC, Rosenfeld M, et al. Failure to recover to baseline pulmonary function after cystic fibrosis pulmonary exacerbation. Am J Respir Crit Care Med 2010; 182:627.
  18. Asner S, Waters V, Solomon M, et al. Role of respiratory viruses in pulmonary exacerbations in children with cystic fibrosis. J Cyst Fibros 2012; 11:433.
  19. Goffard A, Lambert V, Salleron J, et al. Virus and cystic fibrosis: rhinoviruses are associated with exacerbations in adult patients. J Clin Virol 2014; 60:147.
  20. Etherington C, Naseer R, Conway SP, et al. The role of respiratory viruses in adult patients with cystic fibrosis receiving intravenous antibiotics for a pulmonary exacerbation. J Cyst Fibros 2014; 13:49.
  21. Huang YJ, LiPuma JJ. The Microbiome in Cystic Fibrosis. Clin Chest Med 2016; 37:59.
  22. 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.
  23. Döring G, Conway SP, Heijerman HG, et al. Antibiotic therapy against Pseudomonas aeruginosa in cystic fibrosis: a European consensus. Eur Respir J 2000; 16:749.
  24. Lahiri T, Hempstead SE, Brady C, et al. Clinical Practice Guidelines From the Cystic Fibrosis Foundation for Preschoolers With Cystic Fibrosis. Pediatrics 2016; 137.
  25. Antibiotic treatment for cystic fibrosis. In: Report of the UK Cystic Fibrosis Trust Antibiotic Working Group, 3rd ed, 2009.
  26. Shoki AH, Mayer-Hamblett N, Wilcox PG, et al. Systematic review of blood biomarkers in cystic fibrosis pulmonary exacerbations. Chest 2013; 144:1659.
  27. Bartlett JA, Ramachandran S, Wohlford-Lenane CL, et al. Newborn Cystic Fibrosis Pigs Have a Blunted Early Response to an Inflammatory Stimulus. Am J Respir Crit Care Med 2016; 194:845.
  28. Quittner AL, Zhang J, Marynchenko M, et al. Pulmonary medication adherence and health-care use in cystic fibrosis. Chest 2014; 146:142.
  29. Cogen JD, Oron AP, Gibson RL, et al. Characterization of Inpatient Cystic Fibrosis Pulmonary Exacerbations. Pediatrics 2017; 139.
  30. Hester KL, Powell T, Downey DG, et al. Glucocorticoids as an adjuvant treatment to intravenous antibiotics for cystic fibrosis pulmonary exacerbations: a UK Survey. J Cyst Fibros 2007; 6:311.
  31. Dovey M, Aitken ML, Emerson J, et al. Oral corticosteroid therapy in cystic fibrosis patients hospitalized for pulmonary exacerbation: a pilot study. Chest 2007; 132:1212.
  32. Schechter MA, Ganapathi AM, Englum BR, et al. Spontaneously Breathing Extracorporeal Membrane Oxygenation Support Provides the Optimal Bridge to Lung Transplantation. Transplantation 2016; 100:2699.
  33. Biscotti M, Gannon WD, Agerstrand C, et al. Awake Extracorporeal Membrane Oxygenation as Bridge to Lung Transplantation: A 9-Year Experience. Ann Thorac Surg 2017; 104:412.
  34. Davis PB, di Sant'Agnese PA. Assisted ventilation for patients with cystic fibrosis. JAMA 1978; 239:1851.
  35. Jones A, Bilton D, Evans TW, Finney SJ. Predictors of outcome in patients with cystic fibrosis requiring endotracheal intubation. Respirology 2013; 18:630.
  36. 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.
  37. 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.
  38. Wientzen R, Prestidge CB, Kramer RI, et al. Acute pulmonary exacerbations in cystic fibrosis. A double-blind trial of tobramycin and placebo therapy. Am J Dis Child 1980; 134:1134.
  39. Ordoñez CL, Henig NR, Mayer-Hamblett N, et al. Inflammatory and microbiologic markers in induced sputum after intravenous antibiotics in cystic fibrosis. Am J Respir Crit Care Med 2003; 168:1471.
  40. Mayer-Hamblett N, Rosenfeld M, Emerson J, et al. Developing cystic fibrosis lung transplant referral criteria using predictors of 2-year mortality. Am J Respir Crit Care Med 2002; 166:1550.
  41. Liou TG, Adler FR, Fitzsimmons SC, et al. Predictive 5-year survivorship model of cystic fibrosis. Am J Epidemiol 2001; 153:345.
  42. Britto MT, Kotagal UR, Hornung RW, et al. Impact of recent pulmonary exacerbations on quality of life in patients with cystic fibrosis. Chest 2002; 121:64.
  43. 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.
  44. 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.
  45. 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.
  46. 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.
  47. 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.
  48. Jorth P, Staudinger BJ, Wu X, et al. Regional Isolation Drives Bacterial Diversification within Cystic Fibrosis Lungs. Cell Host Microbe 2015; 18:307.
  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. Yau YC, Ratjen F, Tullis E, et al. Randomized controlled trial of biofilm antimicrobial susceptibility testing in cystic fibrosis patients. J Cyst Fibros 2015; 14:262.
  52. Waters V, Ratjen F. Standard versus biofilm antimicrobial susceptibility testing to guide antibiotic therapy in cystic fibrosis. Cochrane Database Syst Rev 2017; 10:CD009528.
  53. 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.
  54. 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.
  55. 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.
  56. Sanders CC, Sanders WE Jr, Goering RV. In vitro antagonism of beta-lactam antibiotics by cefoxitin. Antimicrob Agents Chemother 1982; 21:968.
  57. Roehmel JF, Schwarz C, Mehl A, et al. Hypersensitivity to antibiotics in patients with cystic fibrosis. J Cyst Fibros 2014; 13:205.
  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. 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.
  61. Hansen CR, Pressler T, Nielsen KG, et al. Inflammation in Achromobacter xylosoxidans infected cystic fibrosis patients. J Cyst Fibros 2010; 9:51.
  62. Somayaji R, Stanojevic S, Tullis DE, et al. Clinical Outcomes Associated with Achromobacter Species Infection in Patients with Cystic Fibrosis. Ann Am Thorac Soc 2017; 14:1412.
  63. Amin R, Waters V. Antibiotic treatment for Stenotrophomonas maltophilia in people with cystic fibrosis. Cochrane Database Syst Rev 2014; :CD009249.
  64. 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.
  65. 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.
  66. Rey E, Tréluyer JM, Pons G. Drug disposition in cystic fibrosis. Clin Pharmacokinet 1998; 35:313.
  67. Bolton CE, Ionescu AA, Evans WD, et al. Altered tissue distribution in adults with cystic fibrosis. Thorax 2003; 58:885.
  68. Touw DJ. Clinical pharmacokinetics of antimicrobial drugs in cystic fibrosis. Pharm World Sci 1998; 20:149.
  69. Massie J, Cranswick N. Pharmacokinetic profile of once daily intravenous tobramycin in children with cystic fibrosis. J Paediatr Child Health 2006; 42:601.
  70. Lindsay CA, Bosso JA. Optimisation of antibiotic therapy in cystic fibrosis patients. Pharmacokinetic considerations. Clin Pharmacokinet 1993; 24:496.
  71. 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.
  72. 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.
  73. 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.
  74. 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.
  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. Smyth AR, Bhatt J, Nevitt SJ. Once-daily versus multiple-daily dosing with intravenous aminoglycosides for cystic fibrosis. Cochrane Database Syst Rev 2017; 3:CD002009.
  82. Prescott WA Jr. National survey of extended-interval aminoglycoside dosing in pediatric cystic fibrosis pulmonary exacerbations. J Pediatr Pharmacol Ther 2011; 16:262.
  83. 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.
  84. 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.
  85. 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.
  86. Aminimanizani A, Beringer PM, Kang J, et al. Distribution and elimination of tobramycin administered in single or multiple daily doses in adult patients with cystic fibrosis. J Antimicrob Chemother 2002; 50:553.
  87. Geller DE, Pitlick WH, Nardella PA, et al. Pharmacokinetics and bioavailability of aerosolized tobramycin in cystic fibrosis. Chest 2002; 122:219.
  88. 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.
  89. 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.
  90. Lim LM, Ly N, Anderson D, et al. Resurgence of colistin: a review of resistance, toxicity, pharmacodynamics, and dosing. Pharmacotherapy 2010; 30:1279.
  91. Pleasants RA, Michalets EL, Williams DM, et al. Pharmacokinetics of vancomycin in adult cystic fibrosis patients. Antimicrob Agents Chemother 1996; 40:186.
  92. 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.
  93. 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.
  94. Schaefer HG, Stass H, Wedgwood J, et al. Pharmacokinetics of ciprofloxacin in pediatric cystic fibrosis patients. Antimicrob Agents Chemother 1996; 40:29.
  95. 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.
  96. Christensson BA, Nilsson-Ehle I, Ljungberg B, et al. Increased oral bioavailability of ciprofloxacin in cystic fibrosis patients. Antimicrob Agents Chemother 1992; 36:2512.
  97. 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.
  98. 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.
  99. 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.
  100. 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.
  101. 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.
  102. Donati MA, Guenette G, Auerbach H. Prospective controlled study of home and hospital therapy of cystic fibrosis pulmonary disease. J Pediatr 1987; 111:28.
  103. 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.
  104. Balaguer A, González de Dios J. Home versus hospital intravenous antibiotic therapy for cystic fibrosis. Cochrane Database Syst Rev 2015; :CD001917.
  105. Bosworth DG, Nielson DW. Effectiveness of home versus hospital care in the routine treatment of cystic fibrosis. Pediatr Pulmonol 1997; 24:42.
  106. 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.
  107. 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.