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Prospects for the Prevention and Control of Pseudomonal Infection in Children with Cystic Fibrosis

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Abstract

Most patients with cystic fibrosis (CF) experience recurrent and chronic endobronchial Pseudomonas aeruginosa infections. It is possible to prevent or delay the onset of these chronic infections in most patients with CF by eliminating cross-infection and by early aggressive antibiotic treatment of the first positive sputum culture and of subsequent intermittent colonisation. Lung tissue damage is caused by activation of the immunologically specific inflammatory defence mechanisms of the lungs, which are initiated by the antibody response and dominated by polymorphonuclear neutrophil leucocytes and their proteolytic and oxidative products. This inflammation induces a phenotypic shift from nonmucoid to mucoid, alginate-producing phenotypes of P. aeruginosa which then grow, endobronchially, as a biofilm. Such biofilms are impossible to eradicate with antibiotics. By using chronic suppressive antibiotic maintenance therapy and anti-inflammatory drugs it is however, possible to maintain the lung function of these patients for a number of years.

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References

  1. Davidson DJ, Porteous DJ. The genetics of cystic fibrosis lung disease. Thorax 1998; 53(5): 389–97

    PubMed  CAS  Google Scholar 

  2. Høiby N, Giwercman B, Jensen ET, et al. Immune response in cystic fibrosis — helpful or harmful? In: Escobar H, Baquero CF, Suarez L, editors. Clinical ecology of cystic fibrosis. Amsterdam: Exerpta Medica, 1993: 133–41

    Google Scholar 

  3. Davis PB, Drumm M, Konstan MW. Cystic fibrosis. Am J Respir Crit Care Med 1996; 154(5): 1229–56

    PubMed  CAS  Google Scholar 

  4. Armstrong DS, Grimwood K, Carlin JB, et al. Lower airway inflammation in infants and young children with cystic fibrosis. Am J Respir Crit Care Med 1997; 156(4): 1197–204

    PubMed  CAS  Google Scholar 

  5. Alton EWFW, Geddes DM. Gene therapy for cystic fibrosis: a clinical perspective. Gene Ther 1995; 2(2): 88–95

    PubMed  CAS  Google Scholar 

  6. Frederiksen B, Laiing S, Koch C, et al. Improved survival in the Danish cystic fibrosis centre results of aggressive treatment. Pediatr Pulmonol 1996; 21: 153–8

    PubMed  CAS  Google Scholar 

  7. Pedersen SS, Jensen T, Pressler T, et al. Does centralized treatment of cystic fibrosis increase the risk of Pseudomonas aeruginosa infection? Acta Pediatr Scand 1986; 75: 840–5

    CAS  Google Scholar 

  8. Høiby N. Pseudomonas aeruginosa infection in cystic fibrosis. Diagnostic and prognostic significance of Pseudomonas aeruginosa precipitins determined by means of crossed immunoelectrophoresis: a survey. Acta Pathol Microbiol Scand 1997; Suppl. 262 (C): 3–96

    Google Scholar 

  9. Fahy JV, Keoghan MT, Crummy EJ, et al. Bacteraemia and fungaemia in adults with cystic fibrosis. J Infect 1991; 22(3): 241–5

    PubMed  CAS  Google Scholar 

  10. Barasch J, Al-Awqati Q. Defective acidification of the biosynthetic pathway in cystic fibrosis. J Cell Sci 1993; Suppl. 17: 229–33

    Google Scholar 

  11. Zliang YL, Doranz B, Yankaskas JR, et al. Genotypic analysis of respiratory mucous sulphation defects in cystic fibrosis. J Clin Invest 1995; 96(6): 2997–3004

    Google Scholar 

  12. Goldman MJ, Anderson GM, Stolzenberg ED, et al. Human beta defensin-1 is a salt-sensitive antibiotic in lung that is activated in cystic fibrosis. Cell 1997; 88: 553–60

    PubMed  CAS  Google Scholar 

  13. Pier GB, Grout M, Zaidi TS. Cystic fibrosis transmembrane conductance regulator is an epithelial cell receptor for clearance of Pseudomonas aeruginosa from the lung. Proc Natl Acad Sci U S A 1997; 94(22): 12088–93

    PubMed  CAS  Google Scholar 

  14. Khan TZ, Wagener JS, Bost T, et al. Early pulmonary inflammation in infants with cystic fibrosis. Am J Respir Crit Care Med 1995; 151(4): 1075–82

    PubMed  CAS  Google Scholar 

  15. Petersen NT, Høiby N, Mordhorst C-H, et al. Respiratory infections in cystic fibrosis cause by virus, chlamydia and mycoplasma: possible synergism with Pseudomonas aeruginosa. Acta Pediatr Scand 1981; 70: 623–8

    CAS  Google Scholar 

  16. Knowles MR, Olivier K, Noone P, et al. Pharmacologic modulation of salt and water in the airway epithelium in cystic fibrosis. Am J Respir Crit Care Med 1995; 151Suppl. 3: S65–9

    PubMed  CAS  Google Scholar 

  17. Rosenstein BJ, Zeitlin PL. Cystic fibrosis. Lancet 1998; 351(9098): 277–82

    PubMed  CAS  Google Scholar 

  18. Knowles MR, Noone PG, Holineker K, et al. A double-blind, placebo controlled, dose ranging study to evaluate the safety and biological efficacy of the lipid-DNA complex GR213487B in the nasal epithelium of adult patients with cystic fibrosis. Hum Gene Ther 1998; 9(2): 249–69

    PubMed  CAS  Google Scholar 

  19. Hodson ME. Clinical studies of rhDNase in moderately and severely affected patients with cystic fibrosis — an overview. Respiration 1995; 62Suppl. 1: 29–32

    PubMed  Google Scholar 

  20. Cantin AM. DNase 1 acutely increases cystic fibrosis sputum elastase activity and its potential to induce lung haemorrhage in mice. Am J Respir Crit Care Med 1998; 157(2): 464–9

    PubMed  CAS  Google Scholar 

  21. Abman SH, Ogle JW, Harbeck RJ, et al. Early bacteriologic, immunologic, and clinical courses of young infants with cystic fibrosis identified by neonatal screening. J Pediatr 1991; 119(2) 211–7

    PubMed  CAS  Google Scholar 

  22. Høiby N. Microbiology of lung infections in cystic fibrosis patients. Acta Pediatr Scand 1982; Suppl. 301: 33–54

    Google Scholar 

  23. Ramsey BW, Wentz KR, Smith AL, et al. Predictive value of oropharyngeal cultures for identifying lower airway bacteria in cystic fibrosis patients. Am Rev Respir Dis 1991; 144(2): 331–7

    PubMed  CAS  Google Scholar 

  24. Armstrong DS, Grimwood K, Carlin JB, et al. Bronchoalveolar lavage or oropharyngeal cultures to identify lower respiratory pathogens in infants with cystic fibrosis. Pediatr Pulmonol 1996; 21: 267–75

    PubMed  CAS  Google Scholar 

  25. Rosenfeld M, Emerson J, Accurso F, et al. Diagnostic accuracy of oropharyngeal cultures in infants and young children with cystic fibrosis. Pediatr Pulmonol 1999; 28: 321–8

    PubMed  CAS  Google Scholar 

  26. Høiby N, Frederiksen B. Microbiology of cystic fibrosis. In: Hodson ME, Geddes DM, editor. Cystic fibrosis. 2nd ed. London: Athola, 2000: 83–107

    Google Scholar 

  27. Høiby N. Epidemiological investigations of the respiratory tract bacteriology in patients with cystic fibrosis. Acta Pathol Microbiol Scand Sect B 1974; 82: 541–50

    Google Scholar 

  28. Mearns MB. Cystic fibrosis. Arch Dis Child 1985; 60: 272–7

    PubMed  CAS  Google Scholar 

  29. Mearns MB, Hunt GH, Rushworth R. Bacterial flora of respiratory tract in patients wit fibrosis, 1950–1971. Arch Dis Child 1972; 47: 902–7

    PubMed  CAS  Google Scholar 

  30. Govan JRW, Glass S. The microbiology and therapy of cystic fibrosis lung infections. Rev Med Microbiol 1990; 1: 19–28

    Google Scholar 

  31. Gilligan PH. Microbiology of airway disease in patients with cystic fibrosis. Clin Microbiol Rev 1991; 4(1): 35–51

    PubMed  CAS  Google Scholar 

  32. Fitzsimmons SC. The changing epidemiology of cystic fibrosis. J Pediatr 1993; 122(1): 1–9

    PubMed  CAS  Google Scholar 

  33. Johansen HK, Kovesi TA, Koch C, et al. Pseudomonas aeruginosa and Burkholderia cepacia infection in cystic fibrosis patients treated in Toronto and Copenhagen. Pediatr Pulmonol 1998 Aug; 26(2): 89–96

    PubMed  CAS  Google Scholar 

  34. Botzenhart K, Dbring G. Ecology and epidemiology of Pseudomonas aeruginosa. In: Campa M, Bendinelli M, Friedman H, editor. Pseudomonas aeruginosa as an opportunistic pathogen. New York: Plenum Press, 1993: 1–18

    Google Scholar 

  35. Döring G, Bareth H, Gairing A, et al. Genotyping of Pseudomonas aeruginosa sputum and stool isolates from cystic fibrosis patients — evidence for intestinal colonization and spreading into toilets. Epidemiol Infect 1989 Dec; 103(3): 555–64

    PubMed  Google Scholar 

  36. Speert DP, Campbell ME, Davidson AGF, et al. Pseudomonas-aeruginosa colonization of the gastrointestinal tract in patients with cystic fibrosis. J Infect Dis 1993; 167(1): 226–9

    PubMed  CAS  Google Scholar 

  37. Agnarsson U, Glass S, Govan JRW. Fecal isolation of Pseudomonas aeruginosa from patients with cystic fibrosis. J Clin Microbiol 1989; 27: 96–8

    PubMed  CAS  Google Scholar 

  38. Döring G, Schaffar L, editors. Epidemiology of pulmonary infections by Pseudomonas aeruginosa in patients with cystic fibrosis: a consensus report. Paris: Association Francaise de Lutte Contra la Mucoviscidose, 1993: 1–25

    Google Scholar 

  39. Zimakoff J, Høiby N, Rosendal K, et al. Epidemiology of Pseudomonas aeruginosa infection and the role of contamination of the environment in a cystic fibrosis clinic. J Hosp Infect 1983; 4: 31–40

    PubMed  CAS  Google Scholar 

  40. Govan JRW, Nelson JW. Microbiology of lung infection in cystic fibrosis. Br Med Bull 1992; 48(4): 912–30

    PubMed  CAS  Google Scholar 

  41. Høiby N, Pedersen SS. Estimated risk of cross-infection with Pseudomonas aeruginosa in Danish Cystic Fibrosis patients. Acta Pediatr Scand 1989; 78: 395–404

    Google Scholar 

  42. Ojefflyi B. Polyagglutinable Pseudomonas aeruginosa from cystic fibrosis patients: a survey. APMIS 1994; 102Suppl. 46: 1–44

    Google Scholar 

  43. Pedersen SS, Koch C, Høiby N, et al. An epidemic spread of multiresistant Pseudomonas aeruginosa in a cystic fibrosis centre. J Antimicrob Chemother 1986; 17: 505–16

    PubMed  CAS  Google Scholar 

  44. Wolz C, Kiosz G, Ogle JW, et al. Pseudomonas aeruginosa cross-colonization and persistence in patients with cystic fibrosis. Use of a DNA probe. Epidemiol Infect 1989; 102: 205–14

    PubMed  CAS  Google Scholar 

  45. Tummler B, Koopmann U, Grothues D, et al. Nosocomial acquisition of Pseudomonas aeruginosa by cystic fibrosis patients. J Clin Microbiol 1991; 29(6): 1265–7

    PubMed  CAS  Google Scholar 

  46. Döring G. Pseudomonas aeruginosa epidemiology: major environmental reservoirs, routes of transmission and strategies for prevention. Pediatr Pulmonol 1991; Suppl. 6: 280

    Google Scholar 

  47. Cheng K, Sinyth RL, Govan JRW, et al. Spread of beta-lactam-resistant Pseudomonas aeruginosa in a cystic fibrosis clinic. Lancet 1996; 348(9028): 639–42

    PubMed  CAS  Google Scholar 

  48. Farrell PM, Shen GH, Splaingard M, et al. Acquisition of Pseudomonas aeruginosa in children with cystic fibrosis. Pediatrics 1997; 100(5): E21–9

    Google Scholar 

  49. Frederiksen B, Koeh C, Høiby N. Changing epidemiology of Pseudomonas aeruginosa infection in Danish cystic fibrosis patients (1974–1995). Pediatr Pulmonol 1999 Sep; 28(3): 159–66

    PubMed  CAS  Google Scholar 

  50. Jensen ET, Giwercman B, Ojeniyi B, et al. Epidemiology of Pseudomonas aeruginosa in cystic fibrosis and the possible role of contamination by dental equipment. J Hosp Infect 1997; 36: 117–22

    PubMed  CAS  Google Scholar 

  51. Pedersen SS. Lung infection with alginate-producing, mucoid Pseudomonas aeruginosa in cystic fibrosis. APMIS 1992; 100Suppl. 28: 5–79

    Google Scholar 

  52. Hudson VL, Wielinski CL, Regelmann WE. Prognostic implications of initial oropharangeal bacterial flora in patients with cystic fibrosis diagnosed before the age of two years. J Pediatr 1993; 122(6): 854–60

    PubMed  CAS  Google Scholar 

  53. Szaff M, Høiby N, Flensborg EW. Frequent antibiotic therapy improves survival of cystic fibrosis patients with chronic Pseudomonas aeruginosa infection. Acta Pediatr Scand 1983; 72: 651–7

    CAS  Google Scholar 

  54. Weaver LT, Green MR, Nicholson K, et al. Prognosis in cystic fibrosis treated with continuous flucloxacillin from the neonatal period. Arch Dis Child 1994; 70: 84–9

    PubMed  CAS  Google Scholar 

  55. Nelson JW, Tredgett MW, Sheehan JK, et al. Mucinophilic and chemotactic properties of Pseudomonas aeruginosa in relation to pulmonary colonization in cystic fibrosis. Infect Immun 1990; 58: 1489–95

    PubMed  CAS  Google Scholar 

  56. Lamblin G, Roussel P. Airway mucins and their role in defence against micro-organisms. Respir Med 1993; 87(6): 421–6

    PubMed  CAS  Google Scholar 

  57. Baker NR, Svanborg-Edén C. Role of alginate in the adherence of Pseudomonas aeruginosa. In: Høiby N, Pedersen SS, Shand GH, et al., editors (Schonfeld H, series editor). Pseudomonas aeruginosa infection. Antibiotics and chemotherapy. Vol. 42. Basel: Karger, 1989: 72–9

    Google Scholar 

  58. Ramphal R, Guay C, Pier GB. Pseudomonas aeruginosa adhesins for tracheobronchial mucin. Infect Immun 1987; 55: 600–3

    PubMed  CAS  Google Scholar 

  59. Johansen HK, Høiby N. Seasonal onset of initial colonisation and chronic infection with Pseudonionas-aeruginosa in patients with cystic fibrosis in Denmark. Thorax 1992; 47(2): 109–11

    PubMed  CAS  Google Scholar 

  60. Baker NR, Minor V, Deal C, et al. Pseudomonas aeruginosa exoenzyme-S is an adhesin. Infect Immun 1991; 59(9): 2859–63

    PubMed  CAS  Google Scholar 

  61. Feldman M, Bryan R, Rajan S, et al. Role of flagella in pathogenesis of Pseudomonas aeruginosa pulmonary infection. Infect Immun 1998; 66(1): 43–51

    PubMed  CAS  Google Scholar 

  62. Kharazmi A. Mechanisms involved in the evasion of the host defence by pseudomonas-aeruginosa. Immunol Lett 1991; 30(2): 201–6

    PubMed  CAS  Google Scholar 

  63. Elborn JS, Cordon SM, Shale DJ. Host inflammatory responses to first isolation of Pseudomonas aeruginosa from sputum in cystic fibrosis. Pediatr Pulmonol 1993; 15: 287–91

    PubMed  CAS  Google Scholar 

  64. Mathee K, Ciofu O, Sternberg C, et al. Mucoid conversion of Pseudomonas aeruginosa by hydrogen peroxide: a mechanism for virulence activation in the cystic fibrosis lung. Microbiology 1999; 145: 1349–57

    PubMed  CAS  Google Scholar 

  65. Goldstein W, Döring G. Lysosomal enzymes from polymorphonuclear leukocytes and proteinase inhibitors in patients with cystic fibrosis. Am Rev Respir Dis 1986; 134: 49–56

    PubMed  CAS  Google Scholar 

  66. Ammitzboll T, Pedersen SS, Espersen F, et al. Excretion of urinary collagen metabolites correlates to severity of pulmonary disease in cystic fibrosis. Acta Pediatr Scand 1988; 77: 842–6

    CAS  Google Scholar 

  67. Høiby N, Koch C. Pseudomonas acruginosa infection in cystic fibrosis and its management. Thorax 1990; 45: 881–4

    PubMed  Google Scholar 

  68. Tosi MF, Zakem H, Berger M. Neutrophil elastase cleaves C3Bi on opsonized pseudomonas as well as Cri on neutrophils to create a functionally important opsonin receptor mismatch. J Clin Invest 1990; 86(1): 300–8

    PubMed  CAS  Google Scholar 

  69. Bruce MC, Poncz L, Klinger JB, et al. Biochemical and pathologic evidence for proteolytic destruction of lung connective tissue in cystic fibrosis. Am Rev Respir Dis 1985; 332: 529–35

    Google Scholar 

  70. Suter S. The imbalance between granulocyte neutral proteases and antiproteases in bronchial secretions from patients with cystic fibrosis. In: Høiby N, Pedersen SS, Shand GH, et al., editors. (Schönfeld H, series editor) Pseudomonas aeruginosa infection: antibiotics and chemotherapy, vol. 42. Basel: Karger, 1989: 158–68

    Google Scholar 

  71. McElvaney N, Nakamura H, Birrer P, et al. Modulation of airway inflammation in cystic fibrosis. In vivo suppression of interleukin-8 levels on the respiratory epithelial surface by aerosolization of recombinant secretory leukoprotease inhibitor. J Clin Invest 1992; 89: 1296–301

    Google Scholar 

  72. Plotkowski MC, Tournier JM, Puchelle E. Pseudomonas aeruginosa strains possess specific adhesins for laminin. Infect Immun 1996; 64(2): 600–5

    PubMed  CAS  Google Scholar 

  73. Hata JS, Fick RB. Airway adherence of Pseudemonas-aeruginosa — mucoexopolysaccharide binding to human and bovine airway proteins. J Lab Clin Med 1991; 117(5): 410–22

    PubMed  CAS  Google Scholar 

  74. Kharazmi A. Interactions of Pseudomonas aeruginosa proteases with the cells of the immune system. In: Høiby N, Pedersen SS, Shand GH, et al., editors (Schönfeld H, series editor) Pseudomonas aeruginosa infection: antibiotics and chemotherapy, vol. 42). Basel: Karger, 1989: 42–9

    Google Scholar 

  75. Döring G, Bulil V, Høiby N, et al. Detection of proteases of Pseudomonas aeruginosa in immune complexes isolated from sputum of cystic fibrosis patients. Acta Pathol Microbiol Scand Sect C 1984; 92: 307–12

    Google Scholar 

  76. Brown MRW, Collier PJ, Gilbert P. Influence of growth rate on susceptibility to antimicrobial agents — modification of the cell envelope and batch and continuous culture studies. Antimicrob Agents Chemother 1990; 34(9): 1623–8

    PubMed  CAS  Google Scholar 

  77. Giwercman B, Jensen ET, Høiby N, et al. Induction of beta-lactamase production in Pseudomonas-aeruginosa biofilm. Antimicrob Agents Chemother 1991; 35(5): 1008–10

    PubMed  CAS  Google Scholar 

  78. Jensen ET, Kharazini A, Lam K, et al. Human polymorphonuclear leukocyte response to Pseudomonas aeruginosa grown in biofilm. Infect Immun 1990; 58: 2383–5

    PubMed  CAS  Google Scholar 

  79. Anwar H, Strap JL, Costerton JW. Susceptibility of biofilm cells of Pseudomonas-aeruginosa to bactericidal actions of whole blood and serum. FEMS Microbiol Lett 1992; 92(3): 235–42

    Google Scholar 

  80. Pedersen SS, Høiby N, Espersen F, et al. Role of alginate in infection with mucoid Pseudomonas aeruginosa in cystic fibrosis. Thorax 1992; 47: 6–13

    PubMed  CAS  Google Scholar 

  81. Kronborg G, Hansen M, Svenson M, et al. Cytokines in sputum and serum from patients with cystic fibrosis and chronic Pseudomonas aeruginosa infection as markers of destructive inflammation in the lungs. Pediatr Pulmonol 1993; 15: 292–7

    PubMed  CAS  Google Scholar 

  82. Konstan MW, Berger M. Current understanding of the inflammatory process in cystic fibrosis: onset and etiology. Pediatr Pulmonol 1997; 24: 137–42

    PubMed  CAS  Google Scholar 

  83. Schiøtz PO, Clemmensen I, Høiby N. Immunoglobulins and albumin in sputum from patients with cystic fibrosis. A study of protein stability and presence of proteases. Acta Pathol Microbiol Scand Sect C 1980; 88: 275–80

    Google Scholar 

  84. Høiby N, Döring G, Schiøtz PO. The role of immune complexes in the pathogenesis of bacterial infections. Ann Rev Microbiol 1986; 40: 29–53

    Google Scholar 

  85. Konstan MW, Hilliard KA, Norvell TM, et al. Bronchoalveolar lavage findings in cystic fibrosis patients with stable, clinically mild lung disease suggest ongoing infection and inflammation. Am J Respir Crit Care Med 1995; 151(1): 260

    Google Scholar 

  86. Johansen HK. Potential of preventing Pseudomonas aeruginosa lung infections in cystic fibrosis patients: experimental studies in animals. APMIS 1996; 104Suppl. 63: 1–42

    Google Scholar 

  87. Auerbach HS, Kirkpatrick JA, Williams M, et al. Alternate-day prednisone reduces morbidity and improves pulmonary function in cystic fibrosis. Lancet 1985; II(8457): 686–8

    Google Scholar 

  88. Eigen H, Rosenstein BJ, Fitzsimmons S, et al. A multicenter study of alternate-day prednisone therapy in patients with cystic fibrosis. J Pediatr 1995; 126(4): 515–23

    PubMed  CAS  Google Scholar 

  89. Konstan MW, Byard PJ, Hoppel CL, et al. Effect of high-dose ibuprofen in patients with cystic fibrosis. N Engl J Med 1995; 332(13): 848–54

    PubMed  CAS  Google Scholar 

  90. Sordelli DO, Macri CN, Maillie AT, et al. A preliminary study on the effect of antiinflammatory treatment in cystic fibrosis patients with Pseudomonas aeruginosa lung infection. Int J Immunopathol Pharmacol 1994; 7(2): 109–17

    Google Scholar 

  91. Bisgaard H, Pedersen SS, Nielsen KG, et al. Controlled trial of inhaled budesonide in patients with cystic fibrosis and chronic bronchopulmonary Pseudomonas aeruginosa infection. Am J Respir Crit Care Med 1997; 156(4): 1190–6

    PubMed  CAS  Google Scholar 

  92. Littlewood JM, Miller MG, Ghoneim AT, et al. Nebulised colomycin for early pseudomonas colonisation in cystic fibrosis. Lancet 1985; I(8433): 865–6

    Google Scholar 

  93. Valerius NH, Koch C, Høiby N. Prevention of chronic Pseudomonas-aeruginosa colonisation in cystic fibrosis by early treatment. Lancet 1991; 338(8769): 725–6

    PubMed  CAS  Google Scholar 

  94. Weaver LT, Green MR, Nicholson K, et al. Prognosis in cystic fibrosis treated with continuous flucloxacillin from the neonatal period. Arch Dis Child 1994; 70(2): 84–9

    PubMed  CAS  Google Scholar 

  95. Høiby N. Cystic fibrosis: infection. Schweiz Med Wschr 1991; 121(4): 105–9

    PubMed  Google Scholar 

  96. 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: 330–5

    PubMed  CAS  Google Scholar 

  97. Vazquez C, Municio M, Corera M, et al. Early treatment of Pseudomonas-aeruginosa colonization in cystic fibrosis. Acta Paediatr 1993; 82(3): 308–9

    PubMed  CAS  Google Scholar 

  98. 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: 88–92

    PubMed  CAS  Google Scholar 

  99. Konstan MW, Butler SM, Schidlow DV, et al. Patterns of medical practice in cystic fibrosis: part II. Use of therapies. Pediatr Pulmonol 1999; 28: 248–54

    PubMed  CAS  Google Scholar 

  100. Ramsey BW, Dorkin HL, Eisenberg JD, et al. Efficacy of aerosolized tobramycin in patients with cystic fibrosis. N Engl J Med 1993; 328(24): 1740–6

    PubMed  CAS  Google Scholar 

  101. Ramsey BW, Pepe MS, Quan M, et al. Intermittent administration of inhaled tobramycin in patients with cystic fibrosis. N Engl J Med 1999; 340(1): 23–30

    PubMed  CAS  Google Scholar 

  102. Regelmann WE, Elliott GR, Warwick WJ, et al. 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: 914–21

    PubMed  CAS  Google Scholar 

  103. Pedersen SS, Pressler T, Jensen T, et al. Combined imipenem/cilistatin and tobramycin therapy of multiresistant Pseudomonas aeruginosa in cystic fibrosis. J Antimicrob Chemother 1987; 19: 101–7

    PubMed  CAS  Google Scholar 

  104. Meyer KC, Lewandoski JR, Zimmerman JJ, et al. Human neutrophil elastase and elastase/alpha 1-antiprotease complex in cystic fibrosis — comparison with interstitial lung disease and evaluation of the effect of intravenously administered antibiotic therapy. Am Rev Respir Dis 1991; 144(3): 580–5

    PubMed  CAS  Google Scholar 

  105. Norman D, Elborn JS, Cordon SM, et al. Plasma tumour necrosis factor-alpha in cystic fibrosis. Thorax 1991; 46(2): 91–5

    PubMed  CAS  Google Scholar 

  106. Orenstein DM, Pattishall EN, Nixon PA, et al. Quality of well-being before and after antibiotic treatment of pulmonary exacerbation in patients with cystic fibrosis. Chest 1990; 98(5): 1081–4

    PubMed  CAS  Google Scholar 

  107. 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(4): 413–21

    PubMed  CAS  Google Scholar 

  108. Vic P, Ategbo S, Turck D, et al. Efficacy, tolerance, and pharmacokinetics of once daily tobramycin for pseudomonas exacerbations in cystic fibrosis. Arch Dis Child 1998; 78(6): 536–9

    PubMed  CAS  Google Scholar 

  109. Høiby N, Koch C. Maintenance treatment of chronic Pseudomonas aeruginosa infection in cystic fibrosis [editorial]. Thorax 2000; 55: 349–50

    PubMed  Google Scholar 

  110. Elborn JS, Prescott RJ, Stack BHR, et al. Elective versus symptomatic antibiotic treatment in cystic fibrosis patients with chronic Pseudomonas infection of the lungs. Thorax 2000; 55: 355–8

    PubMed  CAS  Google Scholar 

  111. Schiøtz PO. Local humoral immunity and immune reactions in the lungs of patients with cystic fibrosis. Acta Pathol Microbiol Scand Sect C 1981; Suppl. 276: 3–25

    Google Scholar 

  112. Schiøtz PO, Jorgensen M, Færø O, et al. A longitudinal study of immune complex activity and inflammatory response in sputum sol-phase of CF patients: influence of local steroid treatment. Acta Pediatr Scand 1983; 72: 283–7

    Google Scholar 

  113. Pedersen SS, Jensen T, Høiby N, et al. Management of Pseudomonas aeruginosa lung infection in Danish cystic fibrosis patients. Acta Pediatr Scand 1987; 76: 955–61

    CAS  Google Scholar 

  114. Sheldon CD, Assoufl BK, Hodson ME. Regular 3 monthly oral ciprofloxacin in adult cystic fibrosis patients infected with Pseudomonas aeruginosa. Respir Med 1993; 87(8): 587–93

    PubMed  CAS  Google Scholar 

  115. Høiby N. Diffuse panbronchiolitis and cystic fibrosis: East meets West. Thorax 1994; 49(6): 531–2

    PubMed  Google Scholar 

  116. Jaffe A, Francis J, Rosenthal M, et al. Long-term azithromycin may improve lung function in children with cystic fibrosis [letter]. Lancet 1998; 351(9100): 420

    PubMed  CAS  Google Scholar 

  117. Horrevorts AM, Witte JD, Degener JE, et al. Tobramycin in patients with cystic fibrosis: adjustment in dosing interval for effective treatment. Chest 1987; 92: 844–8

    PubMed  CAS  Google Scholar 

  118. Calien P, Lebourgeois M, Delacourt C, et al. Serum bactericidal test as a prognostic indicator in acute pulmonary exacerbations of cystic fibrosis. Pediatrics 1993; 91(2): 451–5

    Google Scholar 

  119. Høiby N, Friis B, Jensen K, et al. Antimicrobial chemotherapy in cystic fibrosis patients. Acta Pediatr Scand 1982; Suppl. 301: 75–100

    Google Scholar 

  120. Weber A, Degroot R, Ramsey B, et al. Probenecid pharmacokinetics in cystic fibrosis. Dev Pharmacol Ther 1991; 16(1): 7–12

    PubMed  CAS  Google Scholar 

  121. Jensen T, Pedersen SS, Høiby N, et al. Efficacy of oral fluoroquinolones versus conventional intravenous antipseudomonal chemotherapy in treatment of cystic fibrosis. Eur J Clin Microbiol 1988; 6: 618–22

    Google Scholar 

  122. Ciofu O, Giwercman B, Pedersen SS, et al. Development of antibiotic resistance in Pseudomonas aeruginosa during two decades of antipseudomonal treatment at the Danish CF center. APMIS 1994; 102(9): 674–80

    PubMed  CAS  Google Scholar 

  123. Burns JL, VanDalfsen 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): 1190–6

    PubMed  CAS  Google Scholar 

  124. Giwercman B, Lambert PA, Rosdahl VT, et al. Rapid emergence of resistance in pseudomonas-aeruginosa in cystic fibrosis patients due to in vivo selection of stable partially depressed beta-lactamase producing strains. J Antimicrob Chemother 1990; 26(2): 247–59

    PubMed  CAS  Google Scholar 

  125. Giwercman B, Meyer C, Lambert PA, et al. High-level beta-lactamase activity in sputum samples from cystic fibrosis patients during antipseudomonal treatment. Antimicrob Agents Chemother 1992; 36(1): 71–6

    PubMed  CAS  Google Scholar 

  126. Robson M, Abbott J, Webb K, et al. A cost description of an adult cystic fibrosis unit and cost analyses of different categories of patients. Thorax 1992; 47(9): 684–9

    PubMed  CAS  Google Scholar 

  127. Moss RB. Drug allergy in cystic fibrosis. Clin Rev Allergy 1991; 9(1–2): 211–29

    PubMed  CAS  Google Scholar 

  128. Koch C, Hjelt K, Pedersen SS, et al. Retrospective clinical study of hypersensitivity reactions to aztreonam and six other beta-lactam antibiotics in cystic fibrosis patients receiving multiple treatment courses. Rev Infect Dis 1991; 13(S7): S608–11

    PubMed  Google Scholar 

  129. Pedersen SS, Jensen T, Osterhammel D, et al. Cumulative and acute toxicity of repeated high-dose tobramycin treatment in cystic fibrosis. Antimicrob Agents Chemother 1987; 31: 594–9

    PubMed  CAS  Google Scholar 

  130. Sone M, Schachern PA, Paparella MM. Loss of spiral ganglion cells as primary manifestation of aminoglycoside ototoxicity. Hear Res 1998; 115(1–2): 217–23

    PubMed  CAS  Google Scholar 

  131. Langford DT, Hiller J. Prospective, controlled study of a polyvalent pseudomonas vaccine in cystic fibrosis-three year results. Arch Dis Child 1984; 59: 1131–4

    PubMed  CAS  Google Scholar 

  132. Cryz SJ, Furer E, Que JU, et al. Clinical evaluation of an octavalent Pseudomonas-aeruginosa conjugate vaccine in plasma donors and in bone marrow transplant and cystic fibrosis patients. In: Homma JY, Tanimoto H, Holder IA, editors (Schönfeld H, series editor). Pseudomonas-aeruginosa in human diseases: antibiotics and chemotherapy, vol. 44). Basel: Karger, 1991: 157–62

    Google Scholar 

  133. Schaad UB, Lang AB, Wedgwood J, et al. Safety and immunogenicity of Pseudomonas aeruginosa conjugate-A vaccine in cystic fibrosis. Lancet 1991; 338(8777): 1236–7

    PubMed  CAS  Google Scholar 

  134. Pier GB. Vaccine potential of Pseudomonas aeruginosa mucoid exopolysaccharide (alginate). Antibiot Chemother 1991; 44: 136–42

    PubMed  CAS  Google Scholar 

  135. Johansen HK, Høiby N, Pedersen SS. Experimental immunization with Pseudomonas aeruginosa alginate induces IgA and IgG antibody responses. APMIS 1991; 99(12): 1061–8

    PubMed  CAS  Google Scholar 

  136. Johansen HK, Høiby N. Local IgA and IgG response to intratracheal immunization with Pseudomonas-aeruginosa antigens. APMIS 1992; 100(1): 87–90

    PubMed  CAS  Google Scholar 

  137. Moss RB. Antibody production in CF and possibilities for immunotherapy. Pediatr Pulmonol 1990; Suppl. 5: 66–7

    Google Scholar 

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Høiby, N. Prospects for the Prevention and Control of Pseudomonal Infection in Children with Cystic Fibrosis. Paediatr Drugs 2, 451–463 (2000). https://doi.org/10.2165/00128072-200002060-00004

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