Skip to main content
Antimicrobial Agents and Chemotherapy logoLink to Antimicrobial Agents and Chemotherapy
. 1997 Oct;41(10):2238–2243. doi: 10.1128/aac.41.10.2238

Activity of liposomal nystatin against disseminated Aspergillus fumigatus infection in neutropenic mice.

T L Wallace 1, V Paetznick 1, P A Cossum 1, G Lopez-Berestein 1, J H Rex 1, E Anaissie 1
PMCID: PMC164099  PMID: 9333054

Abstract

The purpose of this study was to examine the activity of liposomal nystatin against a disseminated Aspergillus fumigatus infection in neutropenic mice. Mice were made neutropenic with 5-fluorouracil and were administered the antifungal drug intravenously for 5 consecutive days beginning 24 h following infection. Liposomal nystatin, at doses as low as 2 mg/kg of body weight/day, protected neutropenic mice against Aspergillus-induced death in a statistically significant manner at the 50-day time point compared to either the no-treatment, the saline, or the empty-liposome group. This protection was approximately the same as that for free nystatin, a positive control. Histopathological results showed that liposomal nystatin cleared the lungs, spleen, pancreas, kidney, and liver of Aspergillus and that there was no organ damage at the day 5 time point, which was after only three doses of liposomal nystatin. Based on these results in mice, it is probable that liposomal nystatin will be effective against Aspergillus infection in humans.

Full Text

The Full Text of this article is available as a PDF (203.5 KB).

Selected References

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

  1. Anaissie E., Paetznick V., Proffitt R., Adler-Moore J., Bodey G. P. Comparison of the in vitro antifungal activity of free and liposome-encapsulated amphotericin B. Eur J Clin Microbiol Infect Dis. 1991 Aug;10(8):665–668. doi: 10.1007/BF01975823. [DOI] [PubMed] [Google Scholar]
  2. Andriole V. T., Miniter P., George D., Kordick D., Patterson T. F. Animal models: usefulness for studies of fungal pathogenesis and drug efficacy in aspergillosis. Clin Infect Dis. 1992 Mar;14 (Suppl 1):S134–S138. doi: 10.1093/clinids/14.supplement_1.s134. [DOI] [PubMed] [Google Scholar]
  3. BROWN R., HAZEN E. L., MASON A. Effect of fungicidin (nystatin) in mice injected with lethal mixtures of aureomycin and Candida albicans. Science. 1953 May 29;117(3048):609–610. doi: 10.1126/science.117.3048.609. [DOI] [PubMed] [Google Scholar]
  4. Broughton M. C., Bard M., Lees N. D. Polyene resistance in ergosterol producing strains of Candida albicans. Mycoses. 1991 Jan-Feb;34(1-2):75–83. doi: 10.1111/j.1439-0507.1991.tb00623.x. [DOI] [PubMed] [Google Scholar]
  5. Cahill K. M., Mofty A. M., Kawaguchi T. P. Primary cutaneous aspergillosis. Arch Dermatol. 1967 Nov;96(5):545–547. [PubMed] [Google Scholar]
  6. Chen W. C., Chou D. L., Feingold D. S. Dissociation between ion permeability and the lethal action of polyene antibiotics on Candida albicans. Antimicrob Agents Chemother. 1978 Jun;13(6):914–917. doi: 10.1128/aac.13.6.914. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Fendler J. H., Romero A. Liposomes as drug carriers. Life Sci. 1977 Apr 1;20(7):1109–1120. doi: 10.1016/0024-3205(77)90481-7. [DOI] [PubMed] [Google Scholar]
  8. GORDON L. E., SMITH C. E., WEDIN D. S. Nystatin (mycostatin) therapy in experimental coccidioidomycosis. Am Rev Tuberc. 1955 Jul;72(1):64–70. doi: 10.1164/artpd.1955.72.1.64. [DOI] [PubMed] [Google Scholar]
  9. Georgopapadakou N. H., Walsh T. J. Human mycoses: drugs and targets for emerging pathogens. Science. 1994 Apr 15;264(5157):371–373. doi: 10.1126/science.8153622. [DOI] [PubMed] [Google Scholar]
  10. Ghannoum M. A., Rex J. H., Galgiani J. N. Susceptibility testing of fungi: current status of correlation of in vitro data with clinical outcome. J Clin Microbiol. 1996 Mar;34(3):489–495. doi: 10.1128/jcm.34.3.489-495.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Guaschino S., Michelone G., Stola E., Lombardi G., Spinillo A., Viale P. Mycotic vaginitis in pregnancy: a double evaluation of the susceptibility to the main antimycotic drugs of isolated species. Biol Res Pregnancy Perinatol. 1986;7(1):20–22. [PubMed] [Google Scholar]
  12. HAZEN E. L., BROWN R. Fungicidin, an antibiotic produced by a soil actinomycete. Proc Soc Exp Biol Med. 1951 Jan;76(1):93–97. doi: 10.3181/00379727-76-18397. [DOI] [PubMed] [Google Scholar]
  13. HEBEKA E. K., SOLOTOROVSKY M. DEVELOPMENT OF RESISTANCE TO POLYENE ANTIBIOTICS IN CANDIDA ALBICANS. J Bacteriol. 1965 Jun;89:1533–1539. doi: 10.1128/jb.89.6.1533-1539.1965. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Hammond S. M. Biological activity of polyene antibiotics. Prog Med Chem. 1977;14:105–179. doi: 10.1016/s0079-6468(08)70148-6. [DOI] [PubMed] [Google Scholar]
  15. KINSKY S. C. COMPARATIVE RESPONSES OF MAMMALIAN ERYTHROCYTES AND MICROBIAL PROTOPLASTS TO POLYENE ANTIBIOTICS AND VITAMIN A. Arch Biochem Biophys. 1963 Aug;102:180–188. doi: 10.1016/0003-9861(63)90169-3. [DOI] [PubMed] [Google Scholar]
  16. Korting H. C., Ollert M., Georgii A., Fröschl M. In vitro susceptibilities and biotypes of Candida albicans isolates from the oral cavities of patients infected with human immunodeficiency virus. J Clin Microbiol. 1988 Dec;26(12):2626–2631. doi: 10.1128/jcm.26.12.2626-2631.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. LEHAN P. H., YATES J. L., BRASHER C. A., LARSH H. W., FURCOLOW M. L. Experiences with the therapy of sixty cases of deep mycotic infections. Dis Chest. 1957 Dec;32(6):597–614. doi: 10.1378/chest.32.6.597. [DOI] [PubMed] [Google Scholar]
  18. Lopez-Berestein G. Liposomes as carriers of antifungal drugs. Ann N Y Acad Sci. 1988;544:590–597. doi: 10.1111/j.1749-6632.1988.tb40459.x. [DOI] [PubMed] [Google Scholar]
  19. MANNING L. K., ROBERTSON L. A case of aspergillosis treated with nystatin. Br Med J. 1959 Feb 7;1(5118):345–346. doi: 10.1136/bmj.1.5118.345. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Meade R. H., 3rd Drug therapy reviews: clinical pharmacology and therapeutic use of antimycotic drugs. Am J Hosp Pharm. 1979 Oct;36(10):1326–1334. [PubMed] [Google Scholar]
  21. Mehta R. T., Hopfer R. L., Gunner L. A., Juliano R. L., Lopez-Berestein G. Formulation, toxicity, and antifungal activity in vitro of liposome-encapsulated nystatin as therapeutic agent for systemic candidiasis. Antimicrob Agents Chemother. 1987 Dec;31(12):1897–1900. doi: 10.1128/aac.31.12.1897. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Mehta R. T., Hopfer R. L., McQueen T., Juliano R. L., Lopez-Berestein G. Toxicity and therapeutic effects in mice of liposome-encapsulated nystatin for systemic fungal infections. Antimicrob Agents Chemother. 1987 Dec;31(12):1901–1903. doi: 10.1128/aac.31.12.1901. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Ng T. T., Denning D. W. Liposomal amphotericin B (AmBisome) therapy in invasive fungal infections. Evaluation of United Kingdom compassionate use data. Arch Intern Med. 1995 May 22;155(10):1093–1098. [PubMed] [Google Scholar]
  24. Oehling A., Giron M., Subira M. L. Aerosol chemotherapy in bronchopulmonary candidiasis. Respiration. 1975;32(2):179–184. doi: 10.1159/000193647. [DOI] [PubMed] [Google Scholar]
  25. PACE H. R., SCHANTZ S. I. Nystatin (mycostatin) in the treatment of monilial and nonmonilial vaginitis. J Am Med Assoc. 1956 Sep 22;162(4):268–271. doi: 10.1001/jama.1956.02970210008004. [DOI] [PubMed] [Google Scholar]
  26. PLOTNICK H., CERRI S. Treatment of oral histoplasmosis by local injection with nystatin. J Am Med Assoc. 1957 Sep 28;165(4):346–348. doi: 10.1001/jama.1957.72980220003009a. [DOI] [PubMed] [Google Scholar]
  27. PROCKNOW J. J., LOOSLI C. G. Treatment of the deep mycoses. AMA Arch Intern Med. 1958 Apr;101(4):765–802. doi: 10.1001/archinte.1958.00260160089013. [DOI] [PubMed] [Google Scholar]
  28. Powderly W. G., Kobayashi G. S., Herzig G. P., Medoff G. Amphotericin B-resistant yeast infection in severely immunocompromised patients. Am J Med. 1988 May;84(5):826–832. doi: 10.1016/0002-9343(88)90059-9. [DOI] [PubMed] [Google Scholar]
  29. ROBINSON R. C. Systemic moniliasis treated with mycostatin; case report. J Invest Dermatol. 1955 Apr;24(4):375–375. doi: 10.1038/jid.1955.51. [DOI] [PubMed] [Google Scholar]
  30. Sinclair A. J., Rossof A. H., Coltman C. A., Jr Recognition and successful management in pulmonary aspergillosis in leukemia. Cancer. 1978 Oct;42(4):2019–2024. doi: 10.1002/1097-0142(197810)42:4<2019::aid-cncr2820420451>3.0.co;2-b. [DOI] [PubMed] [Google Scholar]
  31. Stanley V. C., English M. P. Some effects of nystatin on the growth of four Aspergillus species. J Gen Microbiol. 1965 Jul;40(1):107–118. doi: 10.1099/00221287-40-1-107. [DOI] [PubMed] [Google Scholar]
  32. Stark J. E. Allergic pulmonary aspergillosis successfully treated with inhalations of nystatin. Report of a case. Dis Chest. 1967 Jan;51(1):96–99. doi: 10.1378/chest.51.1.96. [DOI] [PubMed] [Google Scholar]
  33. Stern J. C., Shah M. K., Lucente F. E. In vitro effectiveness of 13 agents in otomycosis and review of the literature. Laryngoscope. 1988 Nov;98(11):1173–1177. doi: 10.1288/00005537-198811000-00005. [DOI] [PubMed] [Google Scholar]
  34. Stevens D. A. Overview of amphotericin B colloidal dispersion (amphocil). J Infect. 1994 May;28 (Suppl 1):45–49. doi: 10.1016/s0163-4453(94)95971-4. [DOI] [PubMed] [Google Scholar]
  35. Terrell C. L., Hughes C. E. Antifungal agents used for deep-seated mycotic infections. Mayo Clin Proc. 1992 Jan;67(1):69–91. doi: 10.1016/s0025-6196(12)60281-x. [DOI] [PubMed] [Google Scholar]
  36. Than K. M., Naing K. S., Min M. Otomycosis in Burma, and its treatment. Am J Trop Med Hyg. 1980 Jul;29(4):620–623. doi: 10.4269/ajtmh.1980.29.620. [DOI] [PubMed] [Google Scholar]
  37. Thomas A. H. Suggested mechanisms for the antimycotic activity of the polyene antibiotics and the N-substituted imidazoles. J Antimicrob Chemother. 1986 Mar;17(3):269–279. doi: 10.1093/jac/17.3.269. [DOI] [PubMed] [Google Scholar]
  38. Tollemar J., Andersson S., Ringdén O., Tydén G. A retrospective clinical comparison between antifungal treatment with liposomal amphotericin B (AmBisome) and conventional amphotericin B in transplant recipients. Mycoses. 1992 Sep-Oct;35(9-10):215–220. doi: 10.1111/j.1439-0507.1992.tb00850.x. [DOI] [PubMed] [Google Scholar]
  39. Vedder J. S., Schorr W. F. Primary disseminated pulmonary aspergillosis with metastatic skin nodules. Successful treatment with inhalation nystatin therapy. JAMA. 1969 Aug 25;209(8):1191–1195. [PubMed] [Google Scholar]
  40. Weinstein J. N., Leserman L. D. Liposomes as drug carriers in cancer chemotherapy. Pharmacol Ther. 1984;24(2):207–233. doi: 10.1016/0163-7258(84)90035-4. [DOI] [PubMed] [Google Scholar]
  41. Woods R. A., Bard M., Jackson I. E., Drutz D. J. Resistance to polyene antibiotics and correlated sterol changes in two isolates of Candida tropicalis from a patient with an amphotericin B-resistant funguria. J Infect Dis. 1974 Jan;129(1):53–58. doi: 10.1093/infdis/129.1.53. [DOI] [PubMed] [Google Scholar]

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

RESOURCES