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Airway biofilm disease: Clinical manifestations and therapeutic possibilities using macrolides

  • Review Article
  • Published:
Journal of Infection and Chemotherapy

Summary

From the investigation of DPB as it manifests in chronic persistent biofilm disease, it has been found that the most important factors are the excess antigen-antibody reaction (where alginate acts as the antigen) and the resultant formation of immune complex. The factors which specifically “link the disease state of infected DPB to” the effects of 14- and 15-membered macrolides are the inhibition of immune reaction induced by alginate and their inhibitory effect on alginate production, acting as antigens at the GMD level. Furthermore, the specificity of macrolides on these actions was also evident from the standpoint of structural activity.

The present serial processes represent an approach quite dissimilar to those of conventional reports, and the results thus obtained provide an entirely new facet to current knowledge. The pathologic category of DPB was first presented in Japan and its therapeutic approaches by 14- or 15-membered macrolides have likewise been developed in this country. In my opinion, “macrolide therapy”, i.e., long-term administration of 14- or 15-membered ring macrolides should be tried in patients with infected cystic fibrosis in Europe and North America due to the apparent therapeutic success of utilizing these macrolides in patients with Pseudomonas biofilm disease in Japan.

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References

  1. Yamanaka A, Saeki S, Tamura S, et al. The problems of chronic obstructive pulmonary disease: especially concerning diffuse panbronchiolitis. Intern Med 1969;23: 442–451.

    CAS  Google Scholar 

  2. Homma H, Yamanaka A, Tanimoto S, et al. Diffuse panbronchiolitis. A disease of the transitional zone of the lung. Chest 1983;83:63–69.

    CAS  PubMed  Google Scholar 

  3. Kobayashi H, Ohgaki N. Chronic airway infection—from viewpoint of biofilm disease. Respiration 1992;11:1266–1277.

    Google Scholar 

  4. Tanimoto H. A review of the recent progress in treatment of patients with diffuse panbronchiolitis associated withPseudomonas aeruginosa infection in Japan. Antibiot Chemother 1991;44:94–98.

    CAS  PubMed  Google Scholar 

  5. Kudoh S, Uetake K, Hagiwara K et al. A study on the clinical effect of low-dose, long-term administration of erythromycin on diffuse panbronchiolitis. The therapeutic results of 4 years. Jpn J Thorac Dis 1987;25:632–642.

    CAS  Google Scholar 

  6. Sawaki M, Mikami R, Mikasa K, et al. A study on longterm chemotherapy with erythromycin in patients with chronic lower respiratory infection. J Jpn Assoc Infect Dis 1986;60:37–44.

    CAS  Google Scholar 

  7. Yamamoto M, Kondo A, Tamura A, et al. Long-term therapeutic effect of erythromycin chemotherapy and new quionolone antibacterial agents on diffuse panbronchiolitis—retrospective comparative design. Jpn J Thorac Dis 1990;28:1305–1315.

    CAS  Google Scholar 

  8. Yamamoto M (Chairman). Annual report on the study of diffuse disseminated disease Grant-in-Aid from the Ministry of Health and Welfare in Japan. The therapeutic effect of erythromycin on DPB, a double-blind comparative study;1992:p.18.

  9. Takeda H, Miura H, Kobayashi H, et al. A study on long-term administration of TE-031 in patients with diffuse panbronchiolitis, J Jpn Assoc Infect Dis 1989;63:71–78.

    CAS  Google Scholar 

  10. Mikasa K, Sawaki M, Kita E, et al. Long-term chemotherapy using erythromycin for chronic lower airway infection: effectiveness of clarithromycin in erythromycin ineffective cases. J Jpn Assoc Infect Dis 1992;66:1097–1104.

    CAS  Google Scholar 

  11. Kobayashi H, Shimada K, Sano Y, et al. Study on azithromycin in treatment of diffuse panbronchiolitis. J Jpn Assoc Infect Dis 1995; 69:(6) (in press).

  12. Goswami SK, Kivity S, Marom Z. Erythromycin inhibits respiratory glycoconjugate secretion from human airways in vitro. Am Rev Respir Dis 1990;141:72–78.

    CAS  PubMed  Google Scholar 

  13. Tamaoki A, Sakai N, Isono K, et al. Erythromycin inhibition transport across airway epithelial cells in dogs. Respiration 1990;9:1036–1039.

    CAS  Google Scholar 

  14. Miyake M, Taki F, Taniguchi H. Erythromycin reduces the severity of bronchial hyperresponsiveness in asthma. Chest 1991;99:670–675.

    Google Scholar 

  15. Ramphal R, Guay C, Pier GB.Pseudomonas aeruginosa adhesins for tracheobronchial mucin. Infect Immun 1987;55:600–603.

    CAS  PubMed  Google Scholar 

  16. Johanson JD. Antibiotic uptake by alveolar macrophage. J Lab Clin Med 1980;95:429–436.

    Google Scholar 

  17. Tulkens PM. Intracellular activity. In: Neu HC, Young LS Zinner SH (eds) The new macrolides, azalides and streptogramines. New York: Marcel Dekker, 1993:41–46.

    Google Scholar 

  18. Takeshita K, Yamagishi I, Harada M, et al. Immunological and anti-inflammatory effects of clarithromycin: inhibition of interleukin 1 production of murine peritoneal macrophages. Drugs Exp Clin Res 1989;15:527–533.

    CAS  PubMed  Google Scholar 

  19. Katahira J, Kikuchi K, Shibata Y, et al. Kinetic studies on the effect of macrolides on cytokine production. Chemotherapy 1991;39:678–686.

    CAS  Google Scholar 

  20. Kita E, Sawaki M, Nishikawa F, et al. Enhanced interleukin production after long-term administration of erythromycin stearate. Pharmacology 1990;41:179–183.

    Google Scholar 

  21. Prokesch RC, Hand WL. Antibiotic entry into human polymorphonuclear leukocytes. Antimicrob Agents Chemother 1982;21:373–380.

    CAS  PubMed  Google Scholar 

  22. Horwitz MA, Siberstein SC. Intracellular multiplication of Legionnaries disease bacteria (Legionella pneumophilia) in human monocytes is reversibly inhibited by erythromycin and ripfampin. J Clin Invest 1983;70:15–21.

    Google Scholar 

  23. Eyrand A, Descotes J, Lombard JY, et al. Effects of erythromycin, josamycin and spiramycin on rat polymorphonuclear leukocyte chemotaxis. Chemotherapy 1986;32:379–382.

    Google Scholar 

  24. Naess A, Solberg CO. Effects of two macrolide antibiotics on human leukocyte membrane receptors and functions. APMIS 1988;96:503–508.

    CAS  PubMed  Google Scholar 

  25. Nelson S, Summer WR, Terry PB, et al. Erythromycin-induced suppression of pulmonary antibacterial defenses. Am Rev Respir Dis 1987;136:1207–1212.

    CAS  PubMed  Google Scholar 

  26. Miyachi Y, Yoshioka A, Imamura S, et al. Effect of antibiotics on the generation of reactive oxygen species. J Invest Dermatol 1986;86:449–453.

    CAS  PubMed  Google Scholar 

  27. Roszkowski K, Beuth J, Ko G, et al. Comparative study on macrolides erythromycin and clarithromycin antibacterial activity and influence on immune responses. Zentralbl Bakteriol 1990;273:518–530.

    CAS  PubMed  Google Scholar 

  28. Anderson R, Fernandes AC, Eftychis HE. Studies on the effects of administration of a single 500 mg oral dose of erythromycin stearate on leukocyte motility and transformation and on release in vitro prostaglandin E2 by stimulated leukocytes. J Antimicrob Chemother 1984;14:41–50.

    CAS  PubMed  Google Scholar 

  29. Takeshita K, Yamagishi I, Harada M, Otomo S, et al. Immunological and anti-inflammatory effects of clarithromycin: inhibition of interleukin 1 production of murine peritoneal macrophages. Drugs Exp Clin Res 1989;15:527–533

    CAS  PubMed  Google Scholar 

  30. Forsgren A, Schmeling D. Effect of antibiotics on chemotaxis of human leukocytes. Antimicrob Agents Chemother 1977;11:580–584

    CAS  PubMed  Google Scholar 

  31. Fernandes AC, Anderson R, Theron G, et al. Enhancement of human polymorphonuclear leukocyte motility by erythromycin in vitro and in vivo. S Afr Med J 1984;66:173–177.

    CAS  PubMed  Google Scholar 

  32. Oda H, Kadota J, Kohno S, et al. Erythromycin inhibits neutrophil chemotaxis in bronchoalveoli of diffuse panbronchiolitis. Chest 1994;106:1116–1123

    CAS  PubMed  Google Scholar 

  33. Kadota J, Sakito O, Kohno S, et al. A mechanism of erythromycin treatment in patients with diffuse panbronchiolitis. Am Rev Respir Dis 1993;147:153–159

    CAS  PubMed  Google Scholar 

  34. Kadota J, Sakito O, Kohno S, et al. Roxithromycin treatment in patients with chronic lower respiratory tract disease. J Jpn Assoc Infect Dis 1995;68:27–33

    Google Scholar 

  35. Arioka H. Effects of erythromycin on neutrophil chemotactic activity. Ther Res 1990;957–977.

  36. Kita E, Sanaki M, Okano D, et al. Suppression of virulence factors ofPseudomonas aeruginosa by erythromycin. J Antimicrob Chemother 1991;27:273–284.

    CAS  PubMed  Google Scholar 

  37. Mikasa K, Sanaki M, Kita E, et al. Therapeutic effect of long term chemotherapy with clarithromycin in erythromycin-ineffective patients with chronic lower airway infections. Chemotherapy 1994;42:430–435

    Google Scholar 

  38. Van Rensburg CEJ, Anderson R, Joone M, et al. Effects of erythromycin on cellular and humoral immune functions in vitro and in vivo. J Antimicrob Chemother 1981;8:467–474.

    PubMed  Google Scholar 

  39. Ohtam H. Study on pathogenetic role of alginate produced from mucoidPseudomonas aeruginosa in diffuse panbronchiolitis. J Jpn Assoc Infect Dis 1995;69:(5) (in press).

  40. Sakata K, Yajima H, Tanaka K. Erythromycin inhibits the production of elastase byPseudomonas aeruginosa without affecting its proliferation in vitro. Am Rev Respir Dis 1993;148:1061–1065.

    CAS  PubMed  Google Scholar 

  41. Hirakata Y, Kaku M, Tomono K, et al. Efficacy of erythromycin lactobionate for treatingPseudomonas aeruginosa bacteremia in mice. Antimicrob Agents Chemother 1992;36:1198–1203.

    CAS  PubMed  Google Scholar 

  42. Hiraka Y, Kaku M, Mizukane R. Potential effects of erythromycin on host defense systems and virulence ofPseudomonas aeruginosa. Antimicrob Agents Chemother 1992;36:1922–1927.

    Google Scholar 

  43. Molinari G, Guzman CA, Pesce A, et al. Inhibition ofPseudomonas aeruginosa virulence factors by subinhibitory concentrations of azithromycin and other macrolide antibiotics. Antimicrob Chemother 1993;31:681–688.

    CAS  Google Scholar 

  44. Mizukane R, Hirakata Y, Kaku M, et al. Comparative in vitro exoenzyme—Suppressing activities of azithromycin and other macrolide antibiotics againstPseudomonas aeruginosa. Antimicrob Agents Chemother 1994;38:528–533.

    CAS  PubMed  Google Scholar 

  45. Ras GJ, Anderson R, Taylor GW, et al. Clindamycin, erythromycin, and roxithromycin inhibit the proinflammatory interactions ofPseudomonas aeruginosa pigments with human neutrophils in vitro. Antimicrob Agents Chemother 1992;36:1236–1240.

    CAS  PubMed  Google Scholar 

  46. Costerton JW, Irvin RT, Cheng KJ. The bacterial glycocalyx in nature and disease. Ann Rev Microbiol 1981;35:299–344.

    CAS  Google Scholar 

  47. Kobayashi H. Bacteria-Host-Interaction. Respiration 1990;9:510–521.

    Google Scholar 

  48. Peters G, Locci R, Pulverer G. Adherence and growth of coagulase negativeStaphylococci on surface of intravenous catheters. J Infect Dis 1982;146:479–482

    CAS  PubMed  Google Scholar 

  49. Nickel JC, Gristina AG, Costerton JW. Electron microscopic study of an infected Foley catheter. Can J Surg 1985;28:50–52.

    CAS  PubMed  Google Scholar 

  50. Marrie TJ, Nelligan J, Costerton JW. A scanning and transmission electron microscopic study of an infected endocardial pacemaker lead. Circulation 1982;66:1339–1343.

    CAS  PubMed  Google Scholar 

  51. Nickel JC, Heaton J, Moreales A, et al. Bacterial biofilm in persistent penile prosthesis associated infection. J Urol 1986;135:586–588.

    CAS  PubMed  Google Scholar 

  52. Mills J, Pulliam L, Dall L, et al. Exopolysaccharide production by viridansStreptococci in experimental endocarditis. Infect Immun 1984;43:359–367

    CAS  PubMed  Google Scholar 

  53. Buxton TB, Horner J, Hinton A, et al. In vivo glycocalyx expression byStaphylococcus aureus phage type 52/52A/80 inS. aureus osteomyelitis. J Infect Dis 1987;156:942–946.

    CAS  PubMed  Google Scholar 

  54. Konstan MW, Berger M. Infection and inflammation of the lung in cystic fibrosis. In: Davis PB (ed) Lung biology in health and disease, vol 64: Cystic fibrosis. New York: Marcel Dekker, 1993;219–276.

    Google Scholar 

  55. Lam JS, Chan R, Lano K, et al. The production of mucoid microcolonies byPseudomonas aeruginosa within infected lungs in cystic fibrosis. Infect Immun 1980;28:546–556.

    CAS  PubMed  Google Scholar 

  56. Olson ME, Nickel JC, Khoury AE, et al. Amdinocillin treatment of catheter associated bacteria in rabbits. J Infect Dis 1989;159:1065–1072.

    CAS  PubMed  Google Scholar 

  57. Evans RC, Holmes CJ. Effect of vancomycin hydrochloride onStaphylococcus epidermidis biofilm associated with silicone elastomer. Antimicrob Agents Chemother. 1987;31:889–894.

    CAS  PubMed  Google Scholar 

  58. Kobayashi H. Bacterial biofilm. Kansensho 1991;21: 161–178 (in Japanese).

    Google Scholar 

  59. Kobayashi H. Relationship with host condition and pulmonary infection. J Jpn Soc Intern Med 1991;80: 663–668.

    CAS  Google Scholar 

  60. Baltimore RS, Christie CDC, Smith GJW. Immunohistopathologic localization ofPseudomonas aeruginosa in lungs from patients with cystic fibrosis. Am Rev Respir Dis 1989;140:1650–1661.

    CAS  PubMed  Google Scholar 

  61. Ohgaki N. Bacterial biofilm in chronic airway infection. J Jpn Assoc Infect Dis 1994;68:138–151.

    CAS  Google Scholar 

  62. Jensen E T, Kharazmi A, Lam K, et al. Human polymorphonuclear leukocyte response toPseudomonas aeruginosa grown in biofilms. Infect Immun 1990;58:2383–2385.

    CAS  PubMed  Google Scholar 

  63. Pier GB, Grout B, DesJardins D. Complement deposition by antibodies toPseudomonas aeruginosa mucoid exopolysaccharide (MEP) and non-MEP specific opsonins. J Immunol 1991;147:1869–1876.

    CAS  PubMed  Google Scholar 

  64. McCubbin M, Fick RB Jr. Pathogenesis of pseudomonas lung disease in cystic fibrosis. In: Fick BR Jr (ed)Pseudomonas aeruginosa the opportunist: pathogenesis and disease. London: CRC Press, 1993;189–211.

    Google Scholar 

  65. Veringa EM, Ferguson DA, Lambe DW, et al. The role of glycocalyx in surface phagocytosis of Bacteroides spp. in the presence and absence of clindamycin. J Antimicrob Chemother 1989;23:711–720.

    CAS  PubMed  Google Scholar 

  66. Kobayashi H. Chronic bronchitis. In: Neu HC, Young LS, Zinner SH (eds) The new macrolides azalides and streptogramins. New York: Marcel Decker, 1993;125–129.

    Google Scholar 

  67. Kobayashi H, Ohgaki N, Takeda H. Therapeutic possibilities for diffuse panbronchiolitis. Int J Antimicrob Agents 1993;3:81–86.

    Google Scholar 

  68. Fujimaki K, Ikeda K, Takahata M et al. Characteristics of biofilm formed byPseudomonas aeruginosa in vitro. Chemotherapy 1992;40:886–893.

    CAS  Google Scholar 

  69. Pier GB. Pulmonary disease associated withPseudomonas aeruginosa in cystic fibrosis: current status of the hostbacterium infection. J Infect Dis 1985;151:575–580.

    CAS  PubMed  Google Scholar 

  70. Høiby N.Pseudomonas aeruginosa infection in cystic fibrosis. Relation between mucoid strain ofPseudomonas aeruginosa APMIS 1974;82:551–558.

    Google Scholar 

  71. Kilbourne JP. Bacterial content and ionic composition of sputum in cystic fibrosis Lancet 1978;1:334–336.

    Google Scholar 

  72. Terry JM, Pine SE, Mattigly ST. Environmental conditions which influence mucoid conversion inPseudomonas aeruginosa PAO 1. Infect Immun 1991;59:471–477.

    CAS  PubMed  Google Scholar 

  73. Martin DR. Mucoid variation inPseudomonas aeruginosa induced by the action of phage. J Med Microbiol 1973;6:111–118.

    CAS  PubMed  Google Scholar 

  74. Miller RV, Rubero VJR. Mucoid conversion by phage ofPseudomonas aeruginosa strains from patients with cystic fibrosis. J Clin Microbiol 1984;19:717–719.

    CAS  PubMed  Google Scholar 

  75. Høiby N, Döring G, Schiøtz PO. Pathogenic mechanism of chronicPseudomonas aeruginosa infections in cystic fibrosis. Antibial Chemother 1987;39:60–76.

    Google Scholar 

  76. Thomassen MJ, Denko CA. Serum bactericidal effect onPseudomonas aeruginosa isolates from cystic fibrosis patients. Infect Immun 1981;33:512–518.

    CAS  PubMed  Google Scholar 

  77. Anwar H, Strap JL, Costerton JW. Susceptibility of biofilm cells ofPseudomonas aeruginosa to bacterial action of whole blood and serum. FEMS Microbiol Lett 1992;92:235–240.

    Article  Google Scholar 

  78. Kobayashi H. Pathogenesis of intractable respiratory infection. Respiration and Circulation 1993;41:3–11.

    CAS  Google Scholar 

  79. Luzar MA, Montie TC. A virulence and altered physiological properties of cystic fibrosis strains ofPseudomonas aeruginosa. Infect Immun 1985;50:572–576.

    CAS  PubMed  Google Scholar 

  80. Woods DE, Sokal DA, Bryan LF, et al. In vitro regulation of virulence inPseudomonas aeruginosa associated with genetic rearrangement. J Infect Dis 1991;163:143–149.

    CAS  PubMed  Google Scholar 

  81. Fagan M, Francis P, Hayward AC, et al. Phenotypic conversion ofPseudomonas aeruginosa in cystic fibrosis. J Clin Microbiol 1990;28:1143–1146.

    Google Scholar 

  82. Costerton JW, Cheng KJ, Geesey GG, et al. Bacterial biofilm in nature and disease. Ann Rev Microbiol 1987;41:435–464.

    CAS  Google Scholar 

  83. Ramphal R, Vishwanath S. Why isPseudomonas the colonizer and why does it persist? Infection 1987;15:281–287.

    Article  CAS  PubMed  Google Scholar 

  84. Houdret NR, Ramphal A, Scharfman JM et al. Evidence for the in vivo degradation of human respiratory mucins duringPseudomonas aeruginosa infection. Biochim Biophys Acta 1989;992:96–105.

    CAS  PubMed  Google Scholar 

  85. Saiman L, Ishimoto K, Lory S, et al. The effect of pilliation and exoproduct expression on the adherence ofPseudomonas aeruginosa to respiratory epithelial monolayers. J Infect Dis 1990;161:541–548.

    CAS  PubMed  Google Scholar 

  86. Ramphal R. The adhesion-receptor system ofPseudomonas aeruginosa: where are we now? Pediatr Pulmonol 1991, 6 (Suppl):140–141.

    Google Scholar 

  87. Prince A. Mini-review — Adhesins and receptors ofPseudomonas aeruginosa associated with infection of the respiratory tract. Microb Pathog 1992;13:251–260.

    CAS  PubMed  Google Scholar 

  88. Fick RB Jr. Pathogenesis of thePseudomonas lung lesion in cystic fibrosis. Chest 1989;96:158–164.

    PubMed  Google Scholar 

  89. Fick RB Jr. Pathogenetic mechanisms in cystic fibrosis lung disease — a paradigm for inflammatory airways disease. J Lab Clin Med 1993;121:632–634.

    PubMed  Google Scholar 

  90. Høiby N, Koch C. Cystic fibrosis.Pseudomonas aeruginosa infection in cystic fibrosis and its management. Thorax 1990;45:881–884.

    PubMed  Google Scholar 

  91. Bryan LE, Kureiski A, Rabin HR. Detection of antibodies toPseudomonas aeruginosa alginate extracellular polysaccharide in animals and cystic fibrosis patients by enzyme-linked immunosorbent assay. J Clin Microbiol 1983;18:276–282.

    CAS  PubMed  Google Scholar 

  92. Woods DE, Bryan LE. Studies on the ability of alginate to act as a protective immunogen against infection withPseudomonas aeruginosa in animals. J Infect Dis 1985;51:581–588.

    Google Scholar 

  93. Pier GB, DesJardin D, Grout M, et al. Human immune response toPseudomonas aeruginosa mucoid exopolysaccharide (alginate) vaccine. Infect Immun 1994;62: 3972–3979.

    CAS  PubMed  Google Scholar 

  94. Høiby N, Giwercman B, Jensen ET, et al. Immune response in cystic fibrosis-helpful or harmful? In: Escobar H, Baguero CF, Suárez L (eds) Clinical ecology of cystic fibrosis. Amsterdam: Elsevier Science Publishers, 1993;133–141.

    Google Scholar 

  95. Kobayashi H. Effective mechanism of macrolide antibiotics on diffuse panbronchiolitis. Jpn J Chemother 1995;43:96–101.

    Google Scholar 

  96. McGhee JR, Farrar JJ, Michalek SM, et al. Cellular requirements for lipopolysaccharide adjuvanticity. A role for both T lymphocytes and macrophages for in vitro responses particulate antigens. J Exp Med 1979;149:793–807.

    Article  CAS  PubMed  Google Scholar 

  97. Høiby N, Axelsen NH. Identification and quantitation of preciptins againstPseudomonas aeruginosa in patients with cystic fibrosis by means of crossed immuno-electrophoresis with intermediated gel. APMIS 1973;81:298–308.

    Google Scholar 

  98. Berdischewsky M, Pollack M, Young LS, et al. Circulating immune complexes in cystic fibrosis. Pediatr Res 1980;14:830–833.

    CAS  PubMed  Google Scholar 

  99. Moss RB, Hsu YP. Isolation and characterization of circulating immune complexes in cystic fibrosis. Clin Exp Immunol 1982;41:301–308.

    Google Scholar 

  100. Döring G, Buhl B, Høiby N, et al. Detection of proteases ofP.aeruginosa in immune complexes isolated from sputum of cystic fibrosis patients. APMIS 1984;92:307–312.

    Google Scholar 

  101. Döring G, Obernesser HJ, Botzenhartk et al. Proteases ofPseudomonas aeruginosa patients with cystic fibrosis. J Infect Dis 1983;147:744–750.

    PubMed  Google Scholar 

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

    Google Scholar 

  103. Kronborg G, Shard GH, Fomsgaard A, et al. Lipopolysaccharide is present in immune complexes isolated from sputum in patients with cystic fibrosis and chronicPseudomonas aeruginosa lung infection. APMIS 1992;100:175–180.

    CAS  PubMed  Google Scholar 

  104. Hornick DB, Fick RB. The immunogloblin G subclass composition of immune complexes in cystic fibrosis. Implications for the pathogenesis of thePseudomonas lung lesion. J Clin Invest 1990;86:1285–1292.

    CAS  PubMed  Google Scholar 

  105. Schiøtz PO, Sørensen H, Høiby N. Activated complement in the sputum from patients with cystic fibrosis. APMIS 1979;87:1–5.

    Google Scholar 

  106. Kobayashi H. Fundamental study and clinical role of bacterial biofilms. J Jpn Soc Intern Med 1994;286–290.

  107. Liu J. FK 506 and cyclosporin, molecular probes for studying intracellular signal transduction. Immunol Today 1993;14:290–295.

    CAS  PubMed  Google Scholar 

  108. Pederson SS, Høiby N, Espersen F, et al. Role of alginate in infection with mucoidPseudomonas aeruginosa in cystic fibrosis. Thorax 1992;47:6–13.

    Google Scholar 

  109. Pederson SS, Kharazmi A, Espersen F.Pseudomonas aeruginosa alginate in cystic fibrosis sputum and the inflammatory response. Infect Immun 1990;58:3363–3368.

    Google Scholar 

  110. Roychoudhury S, May TB, Gill JF, et al. Purification and characterization of guanosine diphospho-D mannose dehydrogenase: a key enzyme in the biosynthesis of alginate byPseudomonas aeruginosa. J Biol Chem 1989;264:9380–9385.

    CAS  PubMed  Google Scholar 

  111. Roychoudhury S, Zielinski NA, DeVault JD, et al.Pseudomonas aeruginosa infection in cystic fibrosis: byosynthesis of alginate as a virulence factor. Antibiot Chemother 1991;44:63–67.

    CAS  PubMed  Google Scholar 

  112. Pugashetti BK, Vadas L, Wood RE, et al. GDP-mannose dehydrogenase and biosynthesis of alginate like polysaccharide in a mucoid strain ofPseudomonas aeruginosa. J Bacteriol 1982;153:1107–1110.

    Google Scholar 

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  1. First Department of Internal Medicine, Kyorin University, School of Medicine, 6-20-2, Shinkawa, 181, Mitaka, Japan

    Hiroyuki Kobayashi MD

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Kobayashi, H. Airway biofilm disease: Clinical manifestations and therapeutic possibilities using macrolides. J Infect Chemother 1, 1–15 (1995). https://doi.org/10.1007/BF02347725

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