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Tolerance and efficacy of amphotericin B inhalations for prevention of invasive pulmonary aspergillosis in haematological patients

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Abstract

The tolerance of aerosolised amphotericin B as prophylaxis against invasive pulmonary aspergillosis was investigated in 61 granulocytopenic periods in 42 patients treated for a haematologic malignancy. Each patient was to receive amphotericin B in doses escalating to 10 mg three times daily (t.i.d.), but only 20 (48%) patients managed to complete the scheduled regimen. One patient tolerated the full dose initially, but had to discontinue treatment when dyspnea developed as a result of pneumonia and acute respiratory distress. Another 22 patients (52%) experienced side effects, including eight (19%) who reported mild coughing and dyspnea but who tolerated the full dose and three (7%) patients whose dose was reduced to 5 mg t.i.d. Another six (14%) patients could tolerate only 5 mg t.i.d., and five (12%) others stopped treatment because of intolerance. Elderly patients (p<0.05) and those with a history of chronic pulmonary obstructive disease (p=0.09) were more likely to develop side effects during inhalation. Twelve (28%) patients developed proven or possible invasive fungal infections, but no correlation was established between infection and the total amount of amphotericin B inhaled. Inhalation of aerosolised amphotericin B is poorly tolerated and does not appear useful in preventing invasive pulmonary aspergillosis in granulocytopenic patients.

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References

  1. Saral R:Candida andAspergillus infections in immunocompromised patients. Reviews of Infectious Diseases 1991,13: 487–492.

    Google Scholar 

  2. Walsh TJ, Lee JW: Prevention of invasive fungal infections in patients with neoplastic diseases. Clinical Infectious Diseases 1993, 17, Supplement 2: 468–480.

    Google Scholar 

  3. Bodey GP, Bueltman B, Duguid W, Gibbs D, Hanak H, Mall G, Martino R, Meunier F, Milliken S, Naoe S, Okudaira M, Scevola D, van't Wout J: Fungal infections in cancer patients: an international autopsy survey. European Journal of Clinical Microbiology & Infectious Diseases 1992, 11: 99–109.

    Google Scholar 

  4. EORTC International Antimicrobial Therapy Cooperative Group: Empiric antifungal therapy in febrile neutropenic patients. American Journal of Medicine 1989, 86, 668–672.

    Google Scholar 

  5. Bennett JE: Toxicity of amphotericin B. In: Goodman Gilman A, Rall TW, Nies AS, Taylor P (ed): Goodman and Gilman's The Pharmacological Basis of Therapeutics. Pergamon Press, New York, 1990, 1167–1168.

    Google Scholar 

  6. Schmitt HJ, Bernard EM, Hauser M, Armstrong D: Aerosol amphotericin B is effective for prophylaxis and therapy in a rat model of pulmonary aspergillosis. Antimicrobial Agents and Chemotherapy 1988, 32: 1676–1679.

    Google Scholar 

  7. Jeffrey GM, Beard MJ, Ikram RB, Chua J, Allen JR, Heaton DC, Hart DN, Schousboe MI: Intranasal amphotericin B reduces the frequency of invasive aspergillosis in neutropenic patients. American Journal of Medicine 1991, 90: 685–691.

    Google Scholar 

  8. Conneally E, Cafferkey MT, Daly PA, Keane CT, McCann SR: Nebulized amphotericin B as prophylaxis against invasive aspergillosis in granulocytopenic patients. Bone Marrow Transplantation 1990, 5: 403–406.

    Google Scholar 

  9. Hertenstein B, Kern WV, Schmeiser T, Stefanic M, Bunjes D, Wiesneth M, Novotny J, Heimpel H, Arnold R: Low incidence of invasive fungal infections after bone marrow transplantation in patients receiving amphotericin B inhalations during neutropenia. Annals of Haematology 1994, 68: 21–26.

    Google Scholar 

  10. Meunier-Carpentier F, Snoeck R, Gerain J, Muller C, Klastersky J: Amphotericin B nasal spray as prophylaxis against aspergillosis in patients with neutropenia. New England Journal of Medicine 1984, 311: 1056.

    Google Scholar 

  11. Jorgensen CJ, Dreyfus F, Vaixeler J, Guyomard S, Maissot C, Belanger C, Brunet F, Giraud T, Dupuis-Camay P: Failure of amphotericin B spray to prevent aspergillosis in granulocytopenic patients. Nouvelle Revue Française d'Hematologie 1989, 31: 327–328.

    Google Scholar 

  12. Beyer J, Barzen G, Risse G, Weyer C, Miksits K, Dullenkopf K, Huhn D, Siegert W: Aerosol amphotericin B for prevention of invasive pulmonary aspergillosis. Antimicrobial Agents and Chemotherapy 1993, 37: 1367–1369.

    Google Scholar 

  13. Myers SE, Devine SM, Topper RL, Ondrey M, Chandler C, O'Toole K, Williams SF, Larson RA, Geller RB: A pilot study of prophylactic aerosolized amphotericin B in patients at risk for prolonged neutropenia. Leukaemia and Lymphoma 1992, 8: 229–233.

    Google Scholar 

  14. Erjavec Z, de Vries-Hospers HG, van Kamp H, van der Waay D, Halie MR, Daenen S: Comparison of imipenem versus cefuroxime plus tobramycin as initial empiric therapy in febrile granulocytopenic patients and efficacy of vancomycin and aztreonam given in case of failure — a prospective randomized study. Scandinavian Journal of Infectious Diseases 1994, 26: 585–595.

    Google Scholar 

  15. Sterk PJ, Plomp A, van de Vate JF, Quanjer PH: Physical properties of aerosols produced by several jet- and ultrasonic nebulizers. Bulletin of European Physiopathology of Respiration 1984, 20: 65–72.

    Google Scholar 

  16. Denning DW, Lee JY, Hostetler JS, Pappas P, Kauffman CA, Dewsnup DH, Galgiani JN, Graybill JR, Sugar AM, Catanzaro A: NIAID Mycosis Study Group multicenter trial of oral itraconazole therapy for invasive aspergillosis. American Journal of Medicine 1994, 97: 135–144.

    Google Scholar 

  17. Behre GF, Schwartz S, Lenz K, Ludwig WD, Wandt H, Schilling E, Heinemann V, Link H, Trittin A, Boenisch O, Treder W, Siegert W, Hiddeman W, Beyer J: Aerosol amphotericin B inhalations for prevention of invasive pulmonary aspergillosis in neutropenic cancer patients. Annals of Haematology 1995, 71: 287–291.

    Google Scholar 

  18. Touw DJ, Brimicombe RW, Hodson ME, Heijerman HGM, Bakker W: Inhalation of antibiotics in cystic fibrosis. European Respiratory Journal 1995, 8: 1594–1604.

    Google Scholar 

  19. Gryn J, Goldberg J, Johnson E, Siegel J, Inzerillo J: The toxicity of daily inhaled amphotericin B. American Journal of Clinical Oncology 1993, 16: 43–46.

    Google Scholar 

  20. O'Doherty M, Thomas S, Page C, Bradbeer C, Nunan T, Bateman N: Pulmonary deposition of nebulised pentamidine isethionate: effect of nebuliser type, dose, and volume of fill. Thorax 1990, 45: 460–464.

    Google Scholar 

  21. Quieffin J, Hunter J, Schlechter MT, Lawson L, Ruedy J, Pare P, Montaner JS: Aerosol pentamidine-induced bronchoconstriction predictive factors and preventive therapy. Chest 1990, 100: 624–627.

    Google Scholar 

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Authors and Affiliations

  1. Department of Haematology, University Hospital Groningen, Hanzeplein 1, 9713, GZ, The Netherlands

    Z. Erjavec, S. M. G. J. Daenen & M. R. Halie

  2. Department of Medical Microbiology, University Hospital Groningen, Hanzeplein 1, 9713, GZ, The Netherlands

    H. G. de Vries-Hospers

  3. Department of Endocrinology, University Hospital Groningen, Hanzeplein 1, 9713, GZ, The Netherlands

    W. J. Sluiter

  4. Antonius Hospital, Sneek, The Netherlands

    G. M. H. Woolthuis

  5. Department of Haematology, University Hospital Nijmegen, The Netherlands

    B. de Pauw

Authors
  1. Z. Erjavec
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  2. G. M. H. Woolthuis
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  3. H. G. de Vries-Hospers
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  4. W. J. Sluiter
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  5. S. M. G. J. Daenen
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  6. B. de Pauw
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  7. M. R. Halie
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Erjavec, Z., Woolthuis, G.M.H., de Vries-Hospers, H.G. et al. Tolerance and efficacy of amphotericin B inhalations for prevention of invasive pulmonary aspergillosis in haematological patients. Eur. J. Clin. Microbiol. Infect. Dis. 16, 364–368 (1997). https://doi.org/10.1007/BF01726364

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