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Emerging Issues in Pulmonary Infections of Cystic Fibrosis

Part of the Emerging Infectious Diseases of the 21st Century book series (EIDC)

Pulmonary infections are the leading cause of morbidity and mortality in patients with cystic fibrosis. Empiric broad-spectrum antibiotics are often used for prolonged periods and repeatedly for exacerbation of bronchiectasis. Hence, as a consequence this select group of patients has the highest incidence of multi-resistant bacteria causing respiratory colonization or infection second to none. It is estimated that 25–45% of adults with cystic fibrosis are chronically infected with multi-resistant bacteria in their airways.1

Moreover, these bacteria usually cannot be eradicated and persist in the respiratory tract despite cycles of different combination of antibiotics.

Keywords

Hypertonic Saline Pulmonary Infection Burkholderia Cepacia Nontuberculous Mycobacterium Airway Surface Liquid 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1.
    Lehtzin, N., John, M., Irizarry, R., Merlo, C., Diette, G., Boyle, M., (2006), Outcomes of adults with cystic fibrosis infected with antibiotic-resistant Pseudomonas aeruginosa. Respiration 73:27–33.Google Scholar
  2. 2.
    Boucher, R., (2005), Cystic fibrosis, in: Harrison's Principles of Internal Medicine, 16th Edition, Kasper, D.C., Braunwald, E., Fauci, A.S., Hauser, S.L., Longo, D.L., Jameson, J. L., (eds), McGraw-Hill, New York, pp. 1543–1546.Google Scholar
  3. 3.
    Brennan, A.L., Geddes, D.M., (2002), Cystic fibrosis. Curr. Opin. Infect. Dis. 15:175–182.PubMedGoogle Scholar
  4. 4.
    Fredericksen, B., Koch, C., Hoiby, N., (1997), Antibiotic treatment of initial colonization with Pseudomonas aeruginosa postpones chronic infection and prevents deterioration of pulmonary function in cystic fibrosis. Pediatr. Pulmonol. 23:330–335.Google Scholar
  5. 5.
    Starner, T.D., McCray, P.B., Jr. (2005), Pathogenesis of early lung disease in cystic fibrosis: A window of opportunity to eradicate bacteria. Ann. Intern. Med. 14:816–822.Google Scholar
  6. 6.
    Li, Z., Kosork, M.R., Farrell, P.M., Laxova, A., West, S.E.H., Green, C.G., Collins, J., Rock, M.J., Splaingord, M.L., (2005), Longitudinal development of mucoid Pseudomonas aerugi- nosa infection and lung disease progression in children with cystic fibrosis. JAMA 293: 581–588.PubMedGoogle Scholar
  7. 7.
    Goldman, M.J., Anderson, G.M., Stolzenberg, E.D., Kari, U.P., Zasloff, M., Wilson, J.M., (1997), Human beta-defensins is a salt-sensitive antibiotic in lung that is inactivated in cystic fibrosis. Cell 88:553–560.PubMedGoogle Scholar
  8. 8.
    Smith, J.J., Travis, S.M., Greenberg, E.P., Welsh, M.J., (1996), Cystic fibrosis airway epithe- lia fail to kill bacteria because of abnormal airway surface fluid. Cell 85:229–236.PubMedGoogle Scholar
  9. 9.
    Matsui, H., Grubb, B.R., Torran, R., Randell, S.H., Gatzy, J.T., Davis, C.W., Boucher, R.C., (1998), Evidence for periciliary liquid layer depletion, not abnormal ion composition, in the pathogenesis of cystic fibrosis airways disease. Cell 95:1005–1015.PubMedGoogle Scholar
  10. 10.
    Poschet, J.F., Boucher, J.C., Tatterson, L., Skidmore, J., VanDyke, R.W., Deretic, V., (2001), Molecular basis for defective glycosylation and Pseudomonas pathogenesis in cystic fibrosis lung. Proc. Natl. Acad. Sci USA 98:13972–13977.PubMedGoogle Scholar
  11. 11.
    Bryan, R., Kube, D., Perez, A., Davis, P., Prince, A., (1998), Overproduction of the CFTR, R domain leads to increased levels of asialoGMI, and increased Pseudomonas aeruginosa binding by epithelial cells. Am. J. Respir. Cell Mol. Biol. 19:269–277.PubMedGoogle Scholar
  12. 12.
    De Bentzmann, S., Roger, P., Dupuit, F., Bajolet-Laudinat, O., Fuchey, C., Plotkowski, M.C., Puchelle, E., (1996), Asialo-GMI is a receptor for Pseudomonas aeruginosa adherence to regenerating respiratory epithelial cells. Am. J. Respir. Cell Mol. Biol. 64:1582–1588.Google Scholar
  13. 13.
    Schroeder, T.H., Reiniger, N., Meluleni, G., Grout, M., Colemon, F.T., Pier, G.B., (2001), Transgenic cystic fibrosis mice exhibit reduced early clearance of Pseudomonas aeruginosa from the respiratory tract. J. Immunol. 166:7410–7418.PubMedGoogle Scholar
  14. 14.
    Meng, O., Springall, D.R., Bishop, A.E., (1998), Lack of inducible nitric oxide synthase in bronchial epithelium: a possible mechanism of susceptibility to infection in cystic fibrosis. J. Pathol. 164:323–331.Google Scholar
  15. 15.
    Sturgess, J., Imrie, J., (1982), Quantitative evaluation of the development of tracheal submu- cosal glands in infants with cystic fibrosis and control infants. Am. J. Pathol. 106:303–311.PubMedGoogle Scholar
  16. 16.
    Inglis, S.K., Wilson, S.M., (2005), Cystic fibrosis and airway submucosal glands. Pediatr. Pulmon. 40:279–284.Google Scholar
  17. 17.
    Aichele, D., Schnare, M., Saake, M., Rollinghoff, M., Gessner, A., (2006), Expression and antimicrobial function of bactericidal permeability increasing protein in cystic fibrosis patients. Infect. Immun. 74:4708–4714.PubMedGoogle Scholar
  18. 18.
    Miller, M.B., Gilligan, P.H., (2003), Laboratory aspects of management of chronic pulmonary infections in patients with cystic fibrosis. J. Clin. Microbiol. 41:4009–4015.PubMedGoogle Scholar
  19. 19.
    Cystic Fibrosis Foundation, (2002), Patient registry 2001 annual report. Cystic Fibrosis Foundation, Washington, DC.Google Scholar
  20. 20.
    Jarry, T.M., Cheung, A.L., (2006), Staphylococcus aureus escapes more efficiently from the phagosome of a cystic fibrosis bronchial epithelial cell line than from it's normal counterpart.Infect. Immun. 74:2565–2577.Google Scholar
  21. 21.
    Lyczak, J.B., Cannon, C.C., Pier, G.B., (2002), Lung infections associated with cystic fibrosis. Clin. Microbiol. Rev. 15:194–222.PubMedGoogle Scholar
  22. 22.
    Thomas, S.R., Ray, A., Hodson, M.E., Pitt, T.L., (2000), Increased sputum amino-acid concentration and auxotrophy of Pseudomonas aeruginosa in severe cystic fibrosis lung disease. Thorax 55:795–797.PubMedGoogle Scholar
  23. 23.
    Costerton, W., Veeh, R., Shirtliff, M., Paomore, M., Post, C., Ehrlich, G., (2003), The application of biofilm science to the study and control of chronic bacterial infections. J. Clin. Invest. 112:1466–1477.PubMedGoogle Scholar
  24. 24.
    Hoiby, N., (2002), Understanding bacterial biofilms in patients with cystic fibrosis: Current and innovative approaches to potential therapies. J. Cystic Fibrosis. 1:249–254.Google Scholar
  25. 25.
    Gibson, R.L., Burns, J.L., Ramsey, B.W., (2003), Pathophysiology and management of pulmonary infections in cystic fibrosis. Am. J. Respir. Crit. Care Med. 168:918–951.PubMedGoogle Scholar
  26. 26.
    Oliver, A., Canton, R., Campo, P., Baquero, F., Blazquez, J., (2000), High frequency of hypermutable Pseudomonas aeruginosa in cystic fibrosis lung infection. Science 288: 1251–1254.PubMedGoogle Scholar
  27. 27.
    Soong, G., Muir, A., Gomez, M.I., Waks, J., Reddy, B., Planet, P., Singh, P.K., Kanoko, Y., Wolfgang, M.C., Hsiao, Y.S., Tony, L., Prince, A., (2006), Bacterial neuramidases faciliatates mucosal infection by participating in biofilm production. J. Clin. Invest. 116:2297–2305.PubMedGoogle Scholar
  28. 28.
    Van Alst, N.E., Picardo, K.F., Iglewski, B.H., Haidaris, C.G., (2007) Nitrate sensing and metabolism modulate motility, biofilm formation, and virulence in Pseudomonas aeruginosa. Infect. Immun. 75:3780–3790.PubMedGoogle Scholar
  29. 29.
    MacEachran, D.P., YE, S., Bomberger, J.M., Hogan, D.A., Swiatecka-Urban, A., Stanton, B. A., O'Toole, G.A., (2007), The Pseudomonas aeruginosa secreted protein PA2934 decreases apical membrane expression of the Cystic Fibrosis Trans-membrane Conductance Regulator.Infect. Immune 75:3902–3912.Google Scholar
  30. 30.
    Isles, A., Maclusky, I., Corey, M., Gold, R., Prober, C., Flemig, P., Levison, H., (1984), Pseudomonas cepacia infection in cystic fibrosis: an emerging problem. J. Pediatr. 104: 206–210.PubMedGoogle Scholar
  31. 31.
    Heath, D.G., Hohreker, K., Carriker, C., Smith, K., Routh, J., LiPuma, J.J., Aris, R.M., Weber,, D., Gilligan, P.H., (2002), Six-year molecular analysis of Burkholderia cepacia complex isolates among cystic fibrosis patients at a referral center for lung transplantation. J. Clin. Microbiol. 40:1188–1193.PubMedGoogle Scholar
  32. 32.
    Chen, J.S., Witzmann, K.A., Spilker, T., Fink, R.J., LiPuma, J.J., (2001), Endemicity and inter-city spread of Burkholderia cepacia genomovar III in cystic fibrosis. J. Pediatr. 139: 643–641.PubMedGoogle Scholar
  33. 33.
    Chaparro, C., Maurer, J., Gutierrez, C., Krajden, M., Chan, C., Winton, T., Keshavjce, S., Scavuzzo, M., Tullis, E., Hutcheon, M., Kesten, S.E., (2001), Infection with Burkholderia cepacia complex isolates among cystic fibrosis: outcome following lung transplantation. Am. Rev. Respir. Crit. Care Med. 163:43–48.Google Scholar
  34. 34.
    Aris, R.M., Routh, J.C., LiPuma, J.J., Heath, D.G., Gilligan, P.H., (2001), Lung transplantation for cystic fibrosis patients with Burkholderia cepacia complex. Survival linked to genomovar type. Am. J. Respir. Crit. Care Med. 164:2102–2106.PubMedGoogle Scholar
  35. 35.
    Henry, D., Campbell, M., Mc Gimpsey, C., Clarke, A., Louden, L., Burns, J.L., Roe, M.H., Vandamme, P, Speert, D., (1999), Comparison of isolation media for recovery of Burkhol- deria cepacia complex from respiratory secretions of patients with cystic fibrosis. J. Clin. Microbiol. 37:1004–1007.PubMedGoogle Scholar
  36. 36.
    Sun, L., Jiang, R.Z., Stainbach, S., Holmes, A., Campanelli, C., Forstner, J., Sajjan, U., Tan, Y., Riley, M., Goldstein, R., (1995), The emergence of a highly transmissible lineage of Cbl+ Pseudomonas (Burkholderia) cepacia causing CF centre epidemics in North America and Britain. Nat. Med. 7:626–627.Google Scholar
  37. 37.
    Graff, G.R., Burns, J.L., (2002), Factor affecting the incidence of Stentotrophomonas mal- tophilia isolation in cystic fibrosis. Chest 121:1754–1760.PubMedGoogle Scholar
  38. 38.
    Saiman, L., Chen, Y., Tabibi, S., San Gibriel, R., Zhou, J., Lui, Z., Lai, L., Whittier., S., (2001), Identification and antimicrobial susceptibility of Alcaligenes xylosoxidans isolated from patients with cystic fibrosis. J. Clin. Microbiol. 39:3942–3945.PubMedGoogle Scholar
  39. 39.
    Goss, C.H., Otto, K.L., AiKen, M.L., Rubenfeld, G.D., (2002), Detecting Stentotrophomonas maltophilia does not reduce survival of patients with cystic fibrosis. Am. J. Respir. Crit Care Med. 166:356–361.PubMedGoogle Scholar
  40. 40.
    Tan, K.K., Conway, S.P., Brownlee, K.G., Etherington, C., Peckham, G., (2002), Alcaligenesinfection in cystic fibrosis. Pediatr. Pulmonol. 34:101–104.PubMedGoogle Scholar
  41. 41.
    McMenamin, J.D., Zaccone, T.M., Coenye, T., Vandamme, P., LiPuma, (2000), Misidentifi- cation of Burkholderia cepacia in US cystic fibrosis treatment centers: an analysis of 1,051 recent sputum isolates. Chest 177:1661–1665.Google Scholar
  42. 42.
    Krzewinski, J.W., Nguyen: C.D., Foster, J.M., Burns, J.L., (2001), Use of random amplified polymorphic DNA PCR to examine epidemiology of Stentotrophomonas maltophilia and Achromobactor (Alcaligenes) xylosoxidans from patients with cystic fibrosis. J. Clin. Micro- biol. 39:3597–3602.Google Scholar
  43. 43.
    Kilby, J.M., Gilligan, P.H., Yankaskas, J.R., Highsmith. W.E. Jr., Edwards, L.J., Knowles, M. R., (1992), Nontuberculous mycobacteria in adult patients with cystic fibrosis. Chest 102: 70–75.PubMedGoogle Scholar
  44. 44.
    Oliver, K.N., Weber, D.J., Wallace, R.J. Jr., Faiz, A.R., Lee, J.H., Zhang, Y., Brown-Elliot, B. A., Handler, A., Wilson, R.W., Schechter, M.S., Edwards, L.J., Chakraborti, S., Knowles, M. R., (2003), Nontuberculous mycobacteria I: multicenter prevalence study in cystic fibrosis. Am. J. Respir. Crit. Care Med. 167:828–834.Google Scholar
  45. 45.
    Sermet-Gaudelus, I., Le Bourgeois, M., Pierre-Audigier, C., Offredo, C., Guillemot, D., Halley, S., Akoua-Koffi, C., Vincent, V., Sivadon-Tardy, V., Ferroni, A., Berche, P., Schein- mann, P., Lenoir, G., Gaillard, J.-L., (2003), Mycobacterium abscessus and children with cystic fibrosis. Emerg. Infect. Dis. 9:1587–1591.PubMedGoogle Scholar
  46. 46.
    Pierre-Audigier, V., Ferroni, A., Sermet – Gaudelius, I., Le Bourgeois, M., Offredo, C., Vu- Tien, H., Fauroux, B., Mariani, P., Munck, A., Binger, E., Guillemot, D., Quesne, G., Vincent, V., Berche, P., Gaillard, J.L., (2005), Age-related prevalence and distribution of nontubercu- lous mycobacterial species among patients with cystic fibrosis. J. Clin. Microbiol. 43: 3467–3470.PubMedGoogle Scholar
  47. 47.
    Olivier, K.N., Weber, D.J., Lee, J.H., Handler, A., Tuder, G, Molina, P.L., Tomashefski, J., Knowles, M.R., (2003), Nontuberculous mycobacteria: II. Nested-cohort study of impact on cystic fibrosis lung disease. Am. J. Respir. Crit. Care Med. 167:833–840.Google Scholar
  48. 48.
    Ferroni, A., Vu-Thien, H., Lanotte, P., Le Bourgeois, M., Sermet-Gaudelus, I., Fauroux, B., Marchand, S., Varaigne, F., Berche, P., Gaillard, J.L., Offredo, C., (2006), Value of Chorhex- idine decontamination method for recovery of nontuberculous mycobacteria from sputum samples of patients with cystic fibrosis. J. Clin. Microbiol. 44:2237–2239.PubMedGoogle Scholar
  49. 49.
    Bakore, N., Rickerts, V., Bargon, J., Just-Nubbling, G., (2003), Prevalance of Aspergillus fumigatus and other fungal species in the sputum of adult patients with cystic fibrosis. Mycoses 46:19–23.Google Scholar
  50. 50.
    Stevens, D.A., Moss, R.B., Kurup, V.P., Knutsen, A.P., Greenberger, P., Judson, M.A, Denning, D.W., Crameri, R., Brody, A.S., Light, M., Skove, M., Maish, W., Mastella, G., and Participants in the Cystic Fibrosis Foundation Consensus Conference, (2003), Allergic bronchopulmonary aspergillosis in cystic fibrosis state of the art: Cystic Fibrosis Foundation Consensus Conference. Clin. Infect. Dis. 37(Suppl. 3):S225–S264.PubMedGoogle Scholar
  51. 51.
    Taccetti, G., Procopio, E., Morianelti, C., Campama, S., (2000), Allergic bronchopulmonary aspergillosis in Italian cystic fibrosis patients: prevalence and percentage of positive tests in the employed diagnostic criteria. Eur. J. Epidemiol. 16:837–842.PubMedGoogle Scholar
  52. 52.
    Mastella, G., Rainisio, M., Harmes, H.K., Hodson, M., Koch, C., Navarro, J., Strandvik, B., McKenzie, S.G., (2001), Epidemiologic Registry of Cystic Fibrosis: allergic bronchopulmon- ary aspergillosis in cystic fibrosis, a European epidemiologic study. Eur. Respir. J. 16: 464–471.Google Scholar
  53. 53.
    Cimon, B., Carrere, J., Vinatier, J.F., Chazalette, J.P., Chabasse, D., Bouchara, J.P., (2001), Clinical significance of Scedosporium apiospermum in patients with cystic fibrosis. Eur. J. Clin. Microbiol Infect. Dis. 19:53–56.Google Scholar
  54. 54.
    Diemert, D., Kunimoto, D., Sard, C., Rennie, R., (2001), Sputum isolation of Wangiella dematitidis in patients with cystic fibrosis. Scand. J. Infect. Dis. 33:777–779.PubMedGoogle Scholar
  55. 55.
    Cimon, B., Carrere, J., Chazalette, J.P., Vinatier, J.F., Chabasse, D., Bouchara, J.P., (1999), Chronic airway colonization by Penicillium emesonii in a patient with cystic fibrosis. Med. Mycol. 37:291–293.PubMedGoogle Scholar
  56. 56.
    Prober, C.G., (1991), The impact of respiratory viral infections in patients with cystic fibrosis. Clin. Rev. Allergy 9:87–102.PubMedGoogle Scholar
  57. 57.
    Hiatt, P.W., Grace, S.C., Kozinetz, C.A., Raboudi, S.H., Treece, D.G., Taber, L.H., Piedra, P. A., (1999), Effects of viral lower respiratory tract infection on lung function in infants with cystic fibrosis. Pediatr. 103:619–626.Google Scholar
  58. 58.
    Thomassen, M.J., Demko, C.A., Doershuk, C., (1987), Cystic Fibrosis: a review of pulmonary infections and interventions. Pediatr. Pulmonol. 3:334–351.PubMedGoogle Scholar
  59. 59.
    Ratjen. F., Comes, G., Paul, K., Posselt, H.G., Wagner, T.O., Harmes, K., (2001), German Board of the European Registry for Cystic Fibrosis (ERCF): effect of continuous antistaphy- lococcal therapy on the rate of P. aeruginosa acquisition in patients with cystic fibrosis. Pediatr. Pulmonol. 31:13–16.PubMedGoogle Scholar
  60. 60.
    Stutman, H.R., Lieberman, J.M., Nussbaum, E., Marks, M.I., (2002), Antibiotic prophylaxis in infants and children with cystic fibrosis: a randomized controlled trial. J. Pediatr. 140: 299–305.PubMedGoogle Scholar
  61. 61.
    Valerius, N.H., Koch, C., Hoiby, N., (1991), Prevention of chronic Pseudomonas aeruginosa colonization in cystic fibrosis by early treatment. Lancet 338:725–726.PubMedGoogle Scholar
  62. 62.
    Burns, J.L., Gibson, R.L., McNamara, S., Yim, D., Emerson, J., Rosenfeld, M., Hiatt, P., McCoy, K., Castile, R., Smith, A.L., Ramsey, B.W., (2001), Longitudinal assessment of Pseudomonas aeruginosa in young children with cystic fibrosis. J. Infect. Dis. 183:444–452.PubMedGoogle Scholar
  63. 63.
    Munck, A., Bonacorsi, S., Mariani-Kurkdijian, P., Lebourgeois, M., Gérardin, M., Brahimi, N., Navarro, J., Bingen, E., (2001), Genotype characterization of Pseudomonas aeruginosa strains recovered from patients with cystic fibrosis after initial and subsequent colonization. Pediatr. Pulmonol. 32:288–292.PubMedGoogle Scholar
  64. 64.
    Gibson, R.L., Emerson, J., McNamara, S., Burns, J.L., Rosenfeld, M., Yunker, A., Hamblett, N., Accurso, F., Dovey, M., Hiatt, P., Korstan, M.W., Moss, R., Retsch-Bogert, G, Wagener, J., Waltz, D., Wilmott, R., Zeitlin, P.L., Ramsey, B,: Cystic Fibrosis Therapeutic Development Network Study Group, (2003), Significant microbiological effect of inhaled tobramycin in young children with cystic fibrosis. Am. J. Respir. Crit. Care Med. 167:841–849.PubMedGoogle Scholar
  65. 65.
    Frederiksen, H.K., Norregaard, L., Gotzche, P.C., Pressler, T., Koch, C., Hoiby, N., (1999), Changing epidemiology of Pseudomonas aeruginosa infection in Danish cystic fibrosis patients (1974–1995). Pediatr Pulmonol. 28:159–166.PubMedGoogle Scholar
  66. 66.
    Johansen, H.K., Norregaard, L., Gotzche, P.C., Presster, T., Koch, C., Hoiby, N., (2004), Antibody response to Pseudomonas aeruginosa in cystic fibrosis patients: a marker of therapeutic success? A 30year cohort study of survival in Danish CF patients after onset of chronic P. aeruginosa lung infection. Pediatr. Pumonol. 37:427–432.Google Scholar
  67. 67.
    Hoiby, N., Frederiksen, B., Pressler, T., (2005), Eradication of early Pseudomonas aeruginosa infection. J. Cyst. Fibrosis. 4 (Suppl. 2):49–54.Google Scholar
  68. 68.
    Armstrong, D.S., Grimwood, K., Carlin, J.B., Carzino, R., Gutierrez, J.P., Hull, J., Olinsky, A., Phelan, E.M., Robertson, C.F., Phelan, P.D., (1997), Lower airway inflammation in infants and young children with cystic fibrosis. Am. J. Respir. Crit. Care. 156:1197–11204.Google Scholar
  69. 69.
    Chiron-Corporation. Chiron Announces Launch of ELITE Trial. Accessed at http: 11phx. corporate-ir/phoenix:zhtml?C=105850&p=irol-news Article&ID=552967&highlight=on18October2005.
  70. 70.
    Early Pseudomonas Infection Control (EPIC) Trial. National Heart, Lung and Blood Institute (NHLBI). Accessed at www.clinicaltrials.gov./ct/gui/show/NCT00097773.
  71. 71.
    Illowite, J.S., Gorvoy, J.D., Smaldowe, G.C., (1987), Quantitative deposition of aerolized gentamicin in cystic fibrosis. Am. Rev. Respir. Dis. 136:1445–1449.Google Scholar
  72. 72.
    Geller, D.E., Pitlick, W.H., Nardella, P.A., Tracewell, W.G., Ramsey, B.W., (2002), Pharma- mcokinetics and bioavailability of aerosolized tobramycin in cystic fibrosis. Chest 122: 219–226.PubMedGoogle Scholar
  73. 73.
    Ramsey, B.W., Pepe, M.S., Quan, J.M., Otto, K.L., Montgomery, A.B., Williams-Warren, J.,Vansiljev, K.M., Borowitz, D., Bowman, C.M., Marshall, B.C., Marshall, S., Smith, A.L., (1999), Intermittent administration of inhaled tobramycin in patients with cystic fibrosis. Cystic Fibrosis Inhaled Tobramycin Study Group. N. Engl. J. Med. 340:23–30.PubMedGoogle Scholar
  74. 74.
    Moss, R.B., (2001), Administration of aerolized antibiotic in cystic fibrosis patients. Chest 120(Suppl. 3):107S–113S.PubMedGoogle Scholar
  75. 75.
    Cystic Fibrosis Foundation Patient Registry, (2002), 2001 Annual Data Report to the Center Directors. Cystic Fibrosis Foundation, Bethesda, MD.Google Scholar
  76. 76.
    Cystic Fibrosis Foundation Patient Registry, (2005), 2004 Annual Data Report to the Center Directors. Cystic Fibrosis Foundation, Bethesda, MD.Google Scholar
  77. 77.
    Littlewood, J.M., Mitter, M.G., Ghoneim, A.T., Ramsden, C.H., (1985), Nebulized colomycin for early Pseudomonas colonization in cystic fibrosis. Lancet 1:865.PubMedGoogle Scholar
  78. 78.
    Hodson, M.E., Gallagher, C.G., Govan, J.R., (2002), A randomized trial of nebulized tobra- mycin or colistin in cystic fibrosis. Eur. Respir. J. 20:658–664.PubMedGoogle Scholar
  79. 79.
    Cunningham, S., Prasad, A., Collyer, L., Carr, S., Lynn, I.B., Wallis, C., (2001), Broncho- constriction following nebulized colistin in cystic fibrosis. Arch. Dis. Child. 84:432–433.PubMedGoogle Scholar
  80. 80.
    Fernandez, J.D., Santiago, R.T., Matacon, M.P., Mayo, R.C., Sańchez, G.T., (1994), Inhaled aztreonam therapy in patients with cystic fibrosis colonized with Pseudomonas aeruginosa. An. Esp. Pediatr. 40:185–188.Google Scholar
  81. 81.
    Cystic Fibrosis Foundation Clinical Trials & Studies, (2006), Anti-Infection therapies. Cystic Fibrosis Foundation, Besthesda, MD, http:/www.cff.org/research/clinical-trials/ongoing- trials/anti-infection/#IV_VS/Inhaled-Antibiotics.
  82. 82.
    Reed, M.D., Stern, R.C., Myers, C.M., Yamashita, T.S., Blumer, J.L., (1988), Lack of unique ciprofloxacin pharmacokinetic characteristics in patients with cystic fibrosis. J. Clin. Pharmacol. 28:691–699.PubMedGoogle Scholar
  83. 83.
    Ball, P., (1990), Emergent resistance to ciprofloxacin amongst Pseudomonas aeruginosa and Staphylococcus aureus: clinical significance and therapeutic approaches. J. Antimicrob. Che- mother 26(Suppl. F):165–179.Google Scholar
  84. 84.
    Chysky, V., Kapila, K., Hullman, R., Arcieri, G., Schacht, P., Echols, R., (1991), Safety of ciprofloxacin in children: worldwide clinical experience based on compassionate use: emphasis on joint evaluation. Infections 19:289–296.Google Scholar
  85. 85.
    Jaffe, A., Bush, A., (2001), Antiinflammatory effects of macrolides in lung disease. Pediatr. Pulmonol. 31:464–473.PubMedGoogle Scholar
  86. 86.
    Tateda, K., Ishii, Y., Matsumoto, T., Furuya, N., Nagasluma, M., Matsunaga, T., Ohno, A., Miyazaki, S., Yomaguchi, K., (1996), Direct evidence for antipseudomonal activity of macrolides: exposure-dependent bactericidal activity and inhibition of protein synthesis by erythromycin, clarithromycin, and azithromycin. Antimicrob. Agents Chemother. 40: 2271–2275.PubMedGoogle Scholar
  87. 87.
    Wozniak, D.J., Keyser, R., (2004), Effects of subinhibitory concentration of macrolide antibiotics on Pseudomonas aeruginosa. Chest 125(Suppl. 2):62S–69S.PubMedGoogle Scholar
  88. 88.
    Labro, M.T., (1998), Antiinflammatory effects of macrolides: a new therapeutic potential? J. Antimicrob. Chemother. 41:37–46.PubMedGoogle Scholar
  89. 89.
    Equi, A., Balfour-Lynn, I.M., Bush, A., Rosenthal, M., (2002), Long term azithromycin in children with cystic fibrosis: a randomized, placebo-controlled crossover trial. Lancet 360:978–984.PubMedGoogle Scholar
  90. 90.
    Wolter, J., Seeney, S, Bell, S., Bowler, S., Masel, P., McCormach, J., (2002), Effect of long nterm treatment with azithromycin on disease parameters in cystic fibrosis: a randomized trial. Thorax 57:212–216.PubMedGoogle Scholar
  91. 91.
    Saiman, L., Marshall, B.C., Mayer-Hamblatt, N., Burns, J.L., Quittner, A.L., Cibene, D.A., Coquillette, S., Fieberg, A.Y., Accurso, F.J., Campbell, P.W.3rd, (2003), The Macrolide Study Group: a multicenter, randomized, placebo controlled, double-blind trial of azithro- mycin in patients with cystic fibrosis chronically infected with Pseudomonas aeruginosa. JAMA 290:1749–1756.PubMedGoogle Scholar
  92. 92.
    Elphick, H.E., Tan, A., (2006), Single versus combination therapy for people with cystic fibrosis. Cochrane Database of Systematic Reviews; accessed at: 00075320–100000000– 01458.Google Scholar
  93. 93.
    Aaron, S.D., Vandemheen, K.L., Ferris, W., Fergusson, D., Tullis, E., Haase, D., Berthiaume, Y., Brown, N., Wilcox, P., Yizghatlion, V., Bye, P., Bell, S., Chan, F., Rose, B., Jeanneret, A., Stephenson, A., Noseworthy, M., Freitag, A., Paterson, N., Doucette, S., Harbour, C., Ruel, M., MacDonald, N., (2005), Combination antibiotic susceptibility testing to treat exacerbation of cystic fibrosis associated with multiresistant bacteria: a randomized, double-blind controlled trial. Lancet 366:463–471.PubMedGoogle Scholar
  94. 94.
    Etherington, C., Hall, M., Conway, S., Peckham, D., Denton, M., (2008), Clinical impact of reducing routine susceptibility testing in chronic Pseudomonas aeruginosa infections in cystic fibrosis. J. Antimicrob. Chemother. 61:425–427.PubMedGoogle Scholar
  95. 95.
    Lechtzin, N., John, M., Irizarry, R., Merlo, C., Diette, G.B., Boyle, M.P., (2006), Outcomes of adults with cystic fibrosis infected with antibiotic-resistant Pseudomonas aeruginosa. Respiration 73:27–33.PubMedGoogle Scholar
  96. 96.
    Burkhardt, O., Lehmann, C., Madabushi, R., Kumar, V., Derendorf, H., Welte, T., (2006), Once-daily tobramycin in cystic fibrosis: better for clinical outcome than thrice daily but more resistance development. J. Antimicrob. Chemother. 58:822–829.PubMedGoogle Scholar
  97. 97.
    Lewin, C., Doherty, C., Gowan, J., (1993), Invitro activities of meropenem, PD127391, PD131628, ceftazidime, chloramphenical, co-trimoxazole, and ciprofloxacin against Pseu- domonas cepacia. Antimicrob. Agents. Chemother. 37:123–125.PubMedGoogle Scholar
  98. 98.
    Burns, J., Saiman, L., (1999), Burkholderia cepacia infection in cystic fibrosis. Pediatr. Infect. Dis. J. 18:123–125.Google Scholar
  99. 99.
    Vartivarian, S., Anaissie, E., Bodey, G., Spingg, H., Rolston, K., (1994), A changing pattern of susceptibility of Xanthomonas maltophilia to antimicrobial agents; implications for therapy. Antimicrob. Agents Chemother. 38:624–627.PubMedGoogle Scholar
  100. 100.
    Saiman, L., Chen, Y., Tabibi, S., San Gabriel, P., Zhou, J., Liu, Z., Lai, L., Whittier, S., (2001), Identification and antimicrobial susceptibility of Alcaligenes xylosoxidans isolated from patients with cystic fibrosis. J. Clin. Microbiol 39:3942–3945.PubMedGoogle Scholar
  101. 101.
    Maiz-Carro, L., Navas-Elorza, E., (2002), Nontubercilous mycobacterial pulmonary infection in patients with cystic fibrosis. Am. J. Resp. Med. 1:107–117.Google Scholar
  102. 102.
    Petrini, B, (2006), Mycobacterium abscessus: an emerging-rapid-growing potential pathogen. APMIS 114:319–328.PubMedGoogle Scholar
  103. 103.
    Langford, D.T., Hiller, J., (1984), Prospective, controlled study of a polyvalent Pseudomonas vaccine in cystic fibrosis: three year results. Arch. Dis. Child 59:1131–1134.PubMedGoogle Scholar
  104. 104.
    Lang, A.B., Schaad, U.B., Rudeberg, A., Wedgwood, J., Que J.U., Furer, E., Cryz, S.J., Jr., (1995), Effect of high-affinity anti-Pseudomonas aeruginosa lypopolysaccharide antibodies induced by immunization on the rate of Pseudomonas aeruginosa infection in patients with cystic fibrosis. J. Pediatr. 127:711–717.PubMedGoogle Scholar
  105. 105.
    Doring G, Dorner, F., (1997), A multicenter vaccine trial using the Pseudomonas aeruginosa flagella vaccine immunization in patients with cystic fibrosis. Behring Inst. Mitteilungen 98:338–344.Google Scholar
  106. 106.
    Wark, P.A.B., McDonald, V., Jones, A.P., (2006), Nebulized hypertonic saline for cystic fibrosis. Cochrane Database of Systematic Review. Access: 00075320–100000000–00452.Google Scholar
  107. 107.
    Donaldson, S.H., Bennett, W.D., Zeman, K.L., Knowles, M.R., Tarran, R., Boucher, R.C., (2006), Mucus clearance and lung function in cystic fibrosis with hypertonic saline. N. Engl. J. Med. 354:241–250.PubMedGoogle Scholar
  108. 108.
    Elkins, M.R., Robinson, M., Rose, B.R., Harbour, C., Moriarty, C.P., Marks, G.B., Belou- sova, E.G., Xuan, W., Bye, P.T.P, for the National Hypertonic Saline in Cystic Fibrosis (NHSCF) Study Group, (2006), A controlled trial of long-term inhaled hypertonic saline in patients with cystic fibrosis N. Engl. J. Med. 354:229–240.PubMedGoogle Scholar
  109. 109.
    Ratjen, F., (2006), Restoring airway surface liquid in cystic fibrosis. (Editorial), N. Engl. J. Med. 354:291–293.PubMedGoogle Scholar
  110. 110.
    Fuchs H.J., Borowitz, D.S., Christiansen, D.H., Morris, E.M., Nash, M.L., Ramsey, B.W.,m Rosenstein, B.J., Smith, A.L., Wohl, M.E., (1994), The Pulmozyme Study Group: Effect of aerolized recombinant human DNASE on exacerbations of respiratory symptoms and pulmonary function in patients with cystic fibrosis. N. Engl. J. Med. 331:637–642.PubMedGoogle Scholar
  111. 111.
    Quan, J.M., Tiddens, H.A., Sy, J.P., McKenzie, S.G., Montgomery, M.D., Robinson, P.J., Wohl, M.E., Konstan, M.-W., (2001), The Pulmozyme Early Intervention Trial Study Group: a two year randomized, placebo-controlled trail of dornase alfa in young patients with cystic fibrosis with mild lung function abnormalities. J. Pediatr. 139:813–820.PubMedGoogle Scholar
  112. 112.
    Jones, A.P., Wallis, C.E., Kearney, C.E., Kearney, C.E., (2006), Recombinant human deoxyribonuclease for cystic fibrosis. Cochrane Database of Systematic Reviews. Access no: 00075320–100000000–00909.Google Scholar
  113. 113.
    Suri, R., Metcalf, C., Lees, B., Grieve, R., Flather, M., Normand, C., Thompson, S., Bush, A., Wallis, C., (2001), Comparison of hypertonic saline and alternate-day or daily recombinant human deoxy-ribonuclease in children with cystic fibrosis: a randomized trial. Lancet 358:1316–1321.PubMedGoogle Scholar
  114. 114.
    Korstan, M.W., Davis, P.B., (2002), Pharmacological approaches for discovery and development of new anti-inflammatory agents for the treatment of cystic fibrosis. Adv. Drug Deliv. Rev. 54:1409–1423.Google Scholar
  115. 115.
    Lands, L.C., Desateux, C., Crighton, A., (2006), Oral non-steroidal anti-inflammatory drug therapy for cystic fibrosis. Cochrane Database Systematic Reviews. Access no: 00075320– 100000000–003494.Google Scholar
  116. 116.
    Rich, D.P., Anderson, M.P., Gregory, R.J., Chery, S.H., Paul, S., Jefferson, D.M., McCann, J. D., Klirger, K.W., Smith, A.E., Welsh, M.J., (1990), Expression of cystic fibrosis transmem- brane conductance regulator corrects defective chloride channel regulation in cystic fibrosis airway epithelial cells. Nature 347:358–363.PubMedGoogle Scholar
  117. 117.
    Cystic Fibrisis Foundation, (2004), Annual Report: Research. Cystic Fibrosis Foundation, Bethesda, MD access: no:http://www.cff.org/uploadedfiles/publications/files/2004Annual- ReportFinal.pdf.
  118. 118.
    Borghouthi, S., Guerdoud, L.M., Speert, D.P., (1996), Inhibition by dextran of Pseudomonas aeruginosa adherence to epithelial cells: Am. J. Respir. Crit. Care Med. 154:1788–1793.Google Scholar
  119. 119.
    Chiu, C.H., Wong, S., Hancock, R.E., Speert, D.P., (2001), Adherence of Burkholderia cepacia to respiratory tract epithelial cells and inhibition with dextrans. Microbiol. 147:2651–2658.Google Scholar
  120. 120.
    Bryan, R., Feldman, M., Jawetz, S.C., Rajan, S., DiMargo Tang, H.B., Scheffler, L., Speert, D.P., Prince, A., (1999), The effects of aerolized dextran in a mouse model of Pseudomonas aeruginosa pulmonary infection. J. Infect. Dis. 179:1449–1458.PubMedGoogle Scholar
  121. 121.
    Feng, W., Garrett, H., Speert, D.P., King, M., (1998), Improved clearability of cystic fibrosis sputum with dextran treatment in vitro. Am. J. Respir. Care Med. 184:29–32.Google Scholar
  122. 122.
    Cole, A.M., Liao, H., Stuchlik, O., Tilan, J., Pohl, J., Ganz, T., (2002), Cationic polypeptide are required for antibacterial activity of human airway fluid. J. Immunol. 169:6985–6991.PubMedGoogle Scholar
  123. 123.
    Goldman, M.J., Anderson, G.M., Stolzenberg, E.D., Kari, U.P., Zasloff, M., Wilson, J.M., (1997), Human beta-defensin-1 is a salt-sensitive antibiotic that is inactivated in cystic fibrosis. Cell 88:553–560.PubMedGoogle Scholar
  124. 124.
    Ramsey, B, Rodman, D., Redman, R., Haeslsen, M., Johnson, C., Hamblett, N., Fugii, C., Loury, D., (2001), Phase I safety and tolerability study of ascending multiple doses of aerolized isegaran HCL solution (1B-367) in adults with cystic fibrosis. Pediatr. Pulmonol. 32:A263.Google Scholar
  125. 125.
    Ganz, T., (2001), Fatal attraction evaded: how pathogenic bacteria resist cationic polypep- tides. J. Exp. Med. 193:F31–F34.PubMedGoogle Scholar
  126. 126.
    Hoffman, N., Lee, B., Rasmussen, T.B., Song, Z., Johansen, H.K., Givskow, M., Hoiby, N., (2007), Azithromycin block quorum sensing and alginate polymer formation and increases sensitivity to serum and stationary-growth-phase killing of Pseudomonas aeruginosa and attenuates chronic P. aeruginosa lung infection in CFTR(−/−) mice. Antimicrob. Agents Chemother. 51:3677–3687.Google Scholar
  127. 127.
    Overhage, J., Campisano, A., Bains, M., Torfs, ECW, Rehm, BHA, Hancock, REW, (2008), Human host defense peptide LL-37 prevents bacterial biofilm formation. Infect. Immun. 76:4176–4182.PubMedGoogle Scholar
  128. 128.
    van der Plas, M.J., Jukema, G.N., Wai, S.W., Dogterom-Ballering, H.C., Lagendijk, E.L., van Gulpen, C., van Dissel, J.T., Bloemberg, G.V., Nibbesring, P.H., (2008), Maggot excretions/secretions are differentially effective against biofilms of Staphylococcus aureus and Pseudomonas aeruginosa. J. Antimicrob. Chemother. 61:117–122.PubMedGoogle Scholar

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