Download PDF
Nuklearmedizin 1993; 32(02): 82-86
DOI: 10.1055/s-0038-1629648
Originalarbeiten
Schattauer GmbH

Prophylaktische Inhalation von Amphotericin B bei invasiver Aspergillose: Verteilungsstudie

Prophylactic Inhalation of Amphotericin B in Invasive Pulmonary Aspergillosis: Distribution Study
G. Barzen
1   Aus der Strahlenklinik und Poliklinik
,
J. Beyer
2   Der Medizinische Klinik und Poliklinik des Universitätsklinikums Rudolf Virchow
,
G. Farshidfar
3   Und dem Institut für Diagnostikforschung an der Freien Universität Berlin. FRG
,
W. Kramp
3   Und dem Institut für Diagnostikforschung an der Freien Universität Berlin. FRG
,
W. Richter
1   Aus der Strahlenklinik und Poliklinik
,
R. Felix
1   Aus der Strahlenklinik und Poliklinik
› Author Affiliations
Further Information

Publication History

Eingegangen: 29 September 1992

26 October 1992

Publication Date:
05 February 2018 (online)

Also available at
    Permissions and Reprints

Zusammenfassung

Die Prophylaxe der invasiven pulmonalen Aspergillose, die bei immunsuppri- mierten Patienten mit einer hohen Mortalität einhergeht, ist bisher unbefriedigend. Da die systemische (parenterale) Therapie mit Amphotericin B (AMB) bei nur eingeschränkter Wirksamkeit relativ viele unerwünschte Wirkungen nach sich zieht, wird in ersten Studien die inhalative Prophylaxe mit druckluftvernebeltem AMB erprobt, ohne daß bisher die intrapulmonale Verteilung von AMB untersucht worden ist. In der vorliegenden Studie wurde daher die intrapulmonale Verteilung von 99mTc-markiertem AMB szintigraphisch untersucht und die Partikelgröße bestimmt. Es zeigte sich, daß sich AMB homogen in der Lunge verteilt, die peripheren Lungenabschnitte erreicht und mit einer Halbwertszeit von ca. 14 h ausreichend lange in der Lunge verbleibt, um antimykotisch wirksam zu sein. Somit kann die AMB-Inhalation zur Prophylaxe mit dem hier untersuchten System empfohlen werden.

Summary

Invasive pulmonary aspergillosis (IPA) during periods of immunosuppression or prolonged neutropenia is a serious condition with high mortality. Prophylaxis is unsatisfactory because of the low effectiveness of systemic administration of amphotericin B (AMB) and because of its side effects. Prophylactic inhalation of AMB by means of a nebulizing system may be able to reduce the incidence of IPA. Therefore, we studied the distribution of nebulized 99mTc-labeled AMB and estimated its particle size. AMB is homogenously distributed in the lung and partly deposited in the terminal respiratory unit; it remains there with a half-life of at least 14 h. Therefore, prophylaxis of IPA with AMB nebulized as described can be recommended.

Schlüsselwörter

Invasive pulmonale Aspergillose - Amphotericin B - Inhalation

Key words

Invasive pulmonary aspergillosis - amphothericin B - inhalation
 

  • LITERATUR

  • 1 Aisner J, Murillo J, Schimpff SC, Steere AC. Invasive aspergillosis in acute leukemia: correlation with nose cultures and antibiotic use. Ann Intern Med 1979; 90: 4-9.
    CrossrefPubMedGoogle Scholar
  • 2 Beyer J, Sicgert W, Barzen G. et al. Aerosol application of amphotericin B (AMB) as prevention of aspergillus pneumonia. Proc ASCO 1992; 11: 387 Abstr 1347..
    Google Scholar
  • 3 Gauwenbcrgh G. Prophylaxis of aspergillosis in immunocompromised patients. In: Aspergillus and Aspergillosis. Vandcn HBossche, Mackenzie DWR, Cauwenbergh G. (eds). New York: Plenum Press; 1987
    Google Scholar
  • 4 Chopra S, Taplin GV, Tashkin DP, Elam D. Lung clearance of soluble radioaerosols in sklcroderma. Am Rev Resp Dis. 1991 121. (Suppl Abstract).
    PubMedGoogle Scholar
  • 5 Conneally E, Caffcrkey MT, Daly PA, Kearie CT, McCann SR. Nebulized amphotericin B as prophylaxis against invasive aspergillosis in granulocytopenic patients. Bone Marrow Transplant 1990; 05: 403-6.
    Google Scholar
  • 6 Denning DW, Stevens DA. Antifungal and surgical treatment of invasive aspergillosis: review of 2121 published cases. Rev Infect Dis 1990; 12: 1147-201.
    CrossrefPubMedGoogle Scholar
  • 7 Eisenberg RS, Oatway WH. Nebulization of amphotericin B. Am Rev Resp Dis 1971; 103: 289-92.
    PubMedGoogle Scholar
  • 8 Heinemann V, Scholz P, Jehn U. Inhalation of amphotericin B as prophylactic antifungal treatment during intensive leukemia therapy. Ann Hematol. 1992 78. (Suppl 1): Abstr 144, A 110..
    PubMedGoogle Scholar
  • 9 Jeffery GM, Beard MEJ, Ikram RB. et al. Intranasal amphothericin B reduces the frequency of invasive aspergillosis in neutropenic patients. Am J Med 1991; 90: 685-92.
    CrossrefPubMedGoogle Scholar
  • 10 Jorgensen C, Dreyfus F, Vaixeler F. et al. Failure of amphotericin B spray to prevent aspergillosis in granulocytopenic patients. Nouv Rev Fr Hematol 1989; 31: 327-8.
    PubMedGoogle Scholar
  • 11 Karp JE, Merz WG, Charache P. Response to empiric amphotericin B during antileukemic therapy-induced granulocytopenia. Rev Infect Dis 1991; 13: 592-9.
    CrossrefPubMedGoogle Scholar
  • 12 Kilburn KH. The innocuousness and possible therapeutic use of aerosol amphotericin B. Rev Resp Dis 1959; 80: 441-2.
    Google Scholar
  • 13 Marrow PE. Physics of airborne particles and their deposition in the lung. Ann NY Acad Sei 1980; 353: 71-80.
    CrossrefPubMedGoogle Scholar
  • 14 Maschmeyer G, Link H, Hiddemann W. et al. Interventional antimicrobial strategy in febrile neutropenic patients. Onkologie 1990; 13: 38-42.
    PubMedGoogle Scholar
  • 15 Meunier F. New methods for delivery of antifungal agents. Rev Infect Dis 1989; 11 (Suppl. 07) 1605-12.
    CrossrefPubMedGoogle Scholar
  • 16 Minti BD, Jordan C, Jones JG. Rapid improvement in abnormal pulmonary epithelial permeability after stopping cigarettes. Br Med J 1981; 282: 1183-6.
    CrossrefPubMedGoogle Scholar
  • 17 Munz D. Messung der resorptiven Clearance bei verschiedenen Lungenkrankheiten: Vergleich mit spirometrischcn Daten und Gasaustauschgrößen. Inaugural-Disser- tation, Freiburg i.Br. 1980
    PubMedGoogle Scholar
  • 18 Myers SE, Devine SM, Topper RL. et al. A phase I trial of prophylactic aerosolized amphothericin B in patients at risk for prolonged neutropenia. Blood 1991; 78 Abstr 925, 234.
    Google Scholar
  • 19 Niki Y, Bernhard EM, Edwards FF. et al. Model of recurrent pulmonary aspergillosis in rats. J Clin Microbiol 1991; 29: 1317-22.
    PubMedGoogle Scholar
  • 20 Niki Y, Bernhard EM, Schmitt HJ. et al. Pharmacokinetics of aerosol amphotericin B in rats. Antimicrob Agents Chemother 1990; 34: 29-32.
    CrossrefPubMedGoogle Scholar
  • 21 Nilsson-Ehle I, Yoshikawa TT, Edwards JE, Schotz MC, Guze LB. Quantitation of amphotericin B with use of high-pressure liquid chromatography. J Infect Dis 1977; 135: 414-22.
    CrossrefPubMedGoogle Scholar
  • 22 Oehling A, Giron M, Subira ML. Aerosol chemotherapy in bronchopulmonary candidiasis. Respiration 1975; 32: 179-84.
    CrossrefPubMedGoogle Scholar
  • 23 Pannuti CS, Gingrich RD, Pfaller MA, Wenzel RP. Nosocomial pneumonia in adult patients undergoing bone marrow transplantation: a 9-year study. J Clin Oncol 1991; 09: 77-84.
    CrossrefPubMedGoogle Scholar
  • 24 Rhamc FS. Prevention of nosocomial aspergillosis. J Hosp Infect 1991; 18 (Suppl A): 466-72.
    CrossrefPubMedGoogle Scholar
  • 25 Rinderknecht J, Shaphiro L. Krauthammer et al. Accelerated clearance of small solutes from the lungs in interstitial lung disease. Am Rev Rcsp Dis 1980; 121: 105-17.
    Google Scholar
  • 26 Rousey SR, Russler S, Gottlieb M, Ash RC. Low-dose amphotericin B prophylaxis against invasive aspergillus infections in allogenic bone marrow transplantation. Am J Med 1991; 91: 484-92.
    CrossrefPubMedGoogle Scholar
  • 27 Schmitt HJ, Bernhard EM, Häuser M, Armstrong D. Aerosol amphotericin B is effective for prophylaxis and therapy in a rat model of pulmonary aspergillosis. Antimicrob Agents Chemother 1988; 32: 1676-9.
    CrossrefPubMedGoogle Scholar
  • 28 Shcrertz RJ, Belani A, Kramer BS. et al. Impact of air filtration on nosocomial aspergillus infections. Am J Med 1987; 83: 709-18.
    CrossrefPubMedGoogle Scholar
  • 29 Talbot GH, Huang A, Provencher M. Invasive aspergillus rhinosinusitis in patients with acute leukemia. Rev Infect Dis 1991; 13: 219-32.
    CrossrefPubMedGoogle Scholar
  • 30 Thunnissen PLM, Sizoo W, Hendriks WDH. Safety and efficacy of itraconazole in prevention of fungal infections in neutropenic patients. Neth J Med 1991; 39: 84-91.
    PubMedGoogle Scholar
  • 31 Tricot G, Joosten E, Boogaerts M, Vande JPittc, Cauwenberg G. Ketoconazole for antifungal prophylaxis in patients with severe granulocytopenia: preliminary results from two non-randomized studies. Rev Infect Dis 1987; 09: 94-9.
    CrossrefPubMedGoogle Scholar
  • 32 Voilier AF, Peterson DE, De Jongh CA. et al. Aspergillus sinusitis in cancer patients. Cancer 1986; 58: 366-71.
    CrossrefPubMedGoogle Scholar
  • 33 Wash TJ, Dixon DM. Nosocomial aspergillosis: environmental microbiology, hospital epidemiology, diagnosis and treatment. Eur J Epidemiol 1989; 05: 131-42.
    CrossrefPubMedGoogle Scholar
  • 34 Weis T, Dorow P, Felix R. Alveoläre Deposition inhalierter Radioaerosolpartikel bei zentraler und peripherer Atemwegsobstruktion. Fortschr Röntgcnstr 1993; 138: 716-21.
    Google Scholar