Skip to main content
NCBI home page
Antimicrobial Agents and Chemotherapy logoLink to Antimicrobial Agents and Chemotherapy
. 1993 Dec;37(12):2762–2765. doi: 10.1128/aac.37.12.2762

Efficacy of intravenous itraconazole against experimental pulmonary aspergillosis.

H M Miyazaki 1, S Kohno 1, Y Miyazaki 1, K Mitsutake 1, K Tomono 1, M Kaku 1, H Koga 1, K Hara 1
PMCID: PMC192807  PMID: 8109952

Abstract

The efficacy of intravenous itraconazole solubilized in hydroxypropyl-beta-cyclodextrin was assessed in a rat model of Aspergillus fumigatus pneumonia. Immunosuppressed rats were infected by intratracheal inoculation of A. fumigatus conidia. Intravenous administration of various doses of itraconazole was started immediately after infection and continued once a day for 7 days. A 10-mg dose of intravenous itraconazole per kg was as effective on survival as 1 mg of amphotericin B per kg daily (a survival rate of 100% in 28 days), while treatment with 1 mg/kg did not increase the survival rate. The 50% lethal dose of intravenous itraconazole given to immunosuppressed and uninfected rats for 7 days was 24.5 mg/kg/day. A microbiological assay to estimate accumulation in tissue after five daily intravenous administrations of itraconazole at 10 mg/kg showed that itraconazole and its active metabolites were present in the lungs for at least 6 h, reaching the MIC as previously described (B. Dupont and E. Drouchet, Rev. Infect. Dis. 9(Suppl. 1):71-76, 1987; A. Espinel-Ingroff, S. Shadomy, and R. J. Gebhart, Antimicrob. Agents Chemother. 26:5-9, 1984). Intravenous itraconazole was considered to be worth evaluating in clinical trials of aspergillosis.

Full text

PDF
2762

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Arroyo J., Medoff G., Kobayashi G. S. Therapy of murine aspergillosis with amphotericin B in combination with rifampin of 5-fluorocytosine. Antimicrob Agents Chemother. 1977 Jan;11(1):21–25. doi: 10.1128/aac.11.1.21. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Campbell J. H., Winter J. H., Richardson M. D., Shankland G. S., Banham S. W. Treatment of pulmonary aspergilloma with itraconazole. Thorax. 1991 Nov;46(11):839–841. doi: 10.1136/thx.46.11.839. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Clark J. M., Whitney R. R., Olsen S. J., George R. J., Swerdel M. R., Kunselman L., Bonner D. P. Amphotericin B lipid complex therapy of experimental fungal infections in mice. Antimicrob Agents Chemother. 1991 Apr;35(4):615–621. doi: 10.1128/aac.35.4.615. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Denning D. W., Tucker R. M., Hanson L. H., Stevens D. A. Treatment of invasive aspergillosis with itraconazole. Am J Med. 1989 Jun;86(6 Pt 2):791–800. doi: 10.1016/0002-9343(89)90475-0. [DOI] [PubMed] [Google Scholar]
  5. Espinel-Ingroff A., Shadomy S., Gebhart R. J. In vitro studies with R 51,211 (itraconazole). Antimicrob Agents Chemother. 1984 Jul;26(1):5–9. doi: 10.1128/aac.26.1.5. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Fratamico P. M., Buckley H. R. Identification and characterization of an immunodominant 58-kilodalton antigen of Aspergillus fumigatus recognized by sera of patients with invasive aspergillosis. Infect Immun. 1991 Jan;59(1):309–315. doi: 10.1128/iai.59.1.309-315.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Graybill J. R., Ahrens J. Itraconazole treatment of murine aspergillosis. Sabouraudia. 1985 Jun;23(3):219–223. doi: 10.1080/00362178585380321. [DOI] [PubMed] [Google Scholar]
  8. Haynes K. A., Latge J. P., Rogers T. R. Detection of Aspergillus antigens associated with invasive infection. J Clin Microbiol. 1990 Sep;28(9):2040–2044. doi: 10.1128/jcm.28.9.2040-2044.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Hostetler J. S., Hanson L. H., Stevens D. A. Effect of cyclodextrin on the pharmacology of antifungal oral azoles. Antimicrob Agents Chemother. 1992 Feb;36(2):477–480. doi: 10.1128/aac.36.2.477. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Karp J. E., Burch P. A., Merz W. G. An approach to intensive antileukemia therapy in patients with previous invasive aspergillosis. Am J Med. 1988 Aug;85(2):203–206. doi: 10.1016/s0002-9343(88)80343-7. [DOI] [PubMed] [Google Scholar]
  11. Kreisel W., Köchling G., von Schilling C., Azemar M., Kurzweil B., Dölken G., Lindemann A., Blum U., Windfuhr M., Müller J. Therapy of invasive aspergillosis with itraconazole: improvement of therapeutic efficacy by early diagnosis. Mycoses. 1991 Sep-Oct;34(9-10):385–394. doi: 10.1111/j.1439-0507.1991.tb00800.x. [DOI] [PubMed] [Google Scholar]
  12. Latgé J. P., Moutaouakil M., Debeaupuis J. P., Bouchara J. P., Haynes K., Prévost M. C. The 18-kilodalton antigen secreted by Aspergillus fumigatus. Infect Immun. 1991 Aug;59(8):2586–2594. doi: 10.1128/iai.59.8.2586-2594.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Lopez-Berestein G., Bodey G. P., Fainstein V., Keating M., Frankel L. S., Zeluff B., Gentry L., Mehta K. Treatment of systemic fungal infections with liposomal amphotericin B. Arch Intern Med. 1989 Nov;149(11):2533–2536. [PubMed] [Google Scholar]
  14. Niki Y., Bernard E. M., Edwards F. F., Schmitt H. J., Yu B., Armstrong D. Model of recurrent pulmonary aspergillosis in rats. J Clin Microbiol. 1991 Jul;29(7):1317–1322. doi: 10.1128/jcm.29.7.1317-1322.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Patterson T. F., George D., Ingersoll R., Miniter P., Andriole V. T. Efficacy of SCH 39304 in treatment of experimental invasive aspergillosis. Antimicrob Agents Chemother. 1991 Oct;35(10):1985–1988. doi: 10.1128/aac.35.10.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Proffitt R. T., Satorius A., Chiang S. M., Sullivan L., Adler-Moore J. P. Pharmacology and toxicology of a liposomal formulation of amphotericin B (AmBisome) in rodents. J Antimicrob Chemother. 1991 Oct;28 (Suppl B):49–61. doi: 10.1093/jac/28.suppl_b.49. [DOI] [PubMed] [Google Scholar]
  17. Rogers T. R., Haynes K. A., Barnes R. A. Value of antigen detection in predicting invasive pulmonary aspergillosis. Lancet. 1990 Nov 17;336(8725):1210–1213. doi: 10.1016/0140-6736(90)92831-2. [DOI] [PubMed] [Google Scholar]
  18. Saag M. S., Dismukes W. E. Azole antifungal agents: emphasis on new triazoles. Antimicrob Agents Chemother. 1988 Jan;32(1):1–8. doi: 10.1128/aac.32.1.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Schmitt H. J., Bernard E. M., Häuser M., Armstrong D. Aerosol amphotericin B is effective for prophylaxis and therapy in a rat model of pulmonary aspergillosis. Antimicrob Agents Chemother. 1988 Nov;32(11):1676–1679. doi: 10.1128/aac.32.11.1676. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Tucker R. M., Williams P. L., Arathoon E. G., Stevens D. A. Treatment of mycoses with itraconazole. Ann N Y Acad Sci. 1988;544:451–470. doi: 10.1111/j.1749-6632.1988.tb40443.x. [DOI] [PubMed] [Google Scholar]
  21. Van Cutsem J., Van Gerven F., Van de Ven M. A., Borgers M., Janssen P. A. Itraconazole, a new triazole that is orally active in aspergillosis. Antimicrob Agents Chemother. 1984 Oct;26(4):527–534. doi: 10.1128/aac.26.4.527. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Warnock D. W., Turner A., Burke J. Comparison of high performance liquid chromatographic and microbiological methods for determination of itraconazole. J Antimicrob Chemother. 1988 Jan;21(1):93–100. doi: 10.1093/jac/21.1.93. [DOI] [PubMed] [Google Scholar]
  23. Wilson E. V., Hearn V. M., Mackenzie D. W. Evaluation of a test to detect circulating Aspergillus fumigatus antigen in a survey of immunocompromised patients with proven or suspected invasive disease. J Med Vet Mycol. 1987 Dec;25(6):365–375. [PubMed] [Google Scholar]
  24. Wishart J. M. The influence of food on the pharmacokinetics of itraconazole in patients with superficial fungal infection. J Am Acad Dermatol. 1987 Aug;17(2 Pt 1):220–223. doi: 10.1016/s0190-9622(87)70194-7. [DOI] [PubMed] [Google Scholar]
  25. Yu B., Niki Y., Armstrong D. Use of immunoblotting to detect Aspergillus fumigatus antigen in sera and urines of rats with experimental invasive aspergillosis. J Clin Microbiol. 1990 Jul;28(7):1575–1579. doi: 10.1128/jcm.28.7.1575-1579.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Antimicrobial Agents and Chemotherapy are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES