Skip to main content
Antimicrobial Agents and Chemotherapy logoLink to Antimicrobial Agents and Chemotherapy
. 1985 Dec;28(6):751–755. doi: 10.1128/aac.28.6.751

Comparison of amphotericin B and N-D-ornithyl amphotericin B methyl ester in experimental cryptococcal meningitis and Candida albicans endocarditis with pyelonephritis.

J R Perfect, D T Durack
PMCID: PMC180322  PMID: 4083860

Abstract

Amphotericin B and N-D-ornithyl amphotericin B methyl ester were compared for therapeutic efficacies against experimentally induced cryptococcal meningitis and Candida albicans endocarditis with pyelonephritis in rabbits. Antifungal activity of the two polyenes in vitro was similar for the yeasts used in these experiments. N-D-ornithyl amphotericin B methyl ester gave a slightly higher concentration in serum than amphotericin B did, but both drugs had similar elimination curves, and penetration into the cerebrospinal fluid was poor for both. Despite these similarities between the two polyenes, amphotericin B was much more effective than N-D-ornithyl amphotericin B methyl ester in the treatment of cryptococcal meningitis in rabbits. For C. albicans endocarditis, both polyenes had similar cure rates, but in vitro measurement of fungicidal activity in serum did not predict treatment outcome. For C. albicans pyelonephritis, both polyenes showed efficacy; because higher doses of the less toxic methyl ester could be used, it sterilized the urinary tract more often than amphotericin B. These studies indicate that in vivo and in vitro experiments may be needed to predict the results of treatment with polyenes.

Full text

PDF
751

Selected References

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

  1. Bennett J. V., Brodie J. L., Benner E. J., Kirby W. M. Simplified, accurate method for antibiotic assay of clinical specimens. Appl Microbiol. 1966 Mar;14(2):170–177. doi: 10.1128/am.14.2.170-177.1966. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bindschadler D. D., Bennett J. E. A pharmacologic guide to the clinical use of amphotericin B. J Infect Dis. 1969 Oct;120(4):427–436. doi: 10.1093/infdis/120.4.427. [DOI] [PubMed] [Google Scholar]
  3. Bistoni F., Vecchiarelli A., Mazzolla R., Puccetti P., Marconi P., Garaci E. Immunoadjuvant activity of amphotericin B as displayed in mice infected with Candida albicans. Antimicrob Agents Chemother. 1985 Apr;27(4):625–631. doi: 10.1128/aac.27.4.625. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bonner D. P., Tewari R. P., Solotorovsky M., Mechlinski W., Schaffner C. P. Comparative chemotherapeutic activity of amphotericin B and amphotericine B methy ester. Antimicrob Agents Chemother. 1975 Jun;7(6):724–729. doi: 10.1128/aac.7.6.724. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Dismukes W. E., Stamm A. M., Graybill J. R., Craven P. C., Stevens D. A., Stiller R. L., Sarosi G. A., Medoff G., Gregg C. R., Gallis H. A. Treatment of systemic mycoses with ketoconazole: emphasis on toxicity and clinical response in 52 patients. National Institute of Allergy and Infectious Diseases collaborative antifungal study. Ann Intern Med. 1983 Jan;98(1):13–20. doi: 10.7326/0003-4819-98-1-13. [DOI] [PubMed] [Google Scholar]
  6. Ellis W. G., Sobel R. A., Nielsen S. L. Leukoencephalopathy in patients treated with amphotericin B methyl ester. J Infect Dis. 1982 Aug;146(2):125–137. doi: 10.1093/infdis/146.2.125. [DOI] [PubMed] [Google Scholar]
  7. Gadebusch H. H., Pansy F., Klepner C., Schwind R. Amphotericin B and amphotericin B methyl ester ascorbate. I. Chemotherapeutic activity against Candida albicans, Cryptococcus neoformans, and Blastomyces dermatitidis in mice. J Infect Dis. 1976 Nov;134(5):423–427. doi: 10.1093/infdis/134.5.423. [DOI] [PubMed] [Google Scholar]
  8. Galgiani J. N., VanWyck D. B. Ornithyl amphotericin methyl ester treatment of experimental candidiasis in rats. Antimicrob Agents Chemother. 1984 Jul;26(1):108–109. doi: 10.1128/aac.26.1.108. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Graybill J. R., Kaster S. R. Experimental murine aspergillosis. Comparison of amphotericin B and a new polyene antifungal drug, SCH 28191. Am Rev Respir Dis. 1984 Feb;129(2):292–295. [PubMed] [Google Scholar]
  10. Hauser W. E., Jr, Remington J. S. Effect of antibiotics on the immune response. Am J Med. 1982 May;72(5):711–716. doi: 10.1016/0002-9343(82)90534-4. [DOI] [PubMed] [Google Scholar]
  11. Hoeprich P. D. New antifungal drugs in the therapy of systemic mycoses. Scand J Infect Dis Suppl. 1978;(16):74–79. [PubMed] [Google Scholar]
  12. Howarth W. R., Tewari R. P., Solotorovsky M. Comparative in vitro antifungal activity of amphotericin B and amphotericin B methyl ester. Antimicrob Agents Chemother. 1975 Jan;7(1):58–63. doi: 10.1128/aac.7.1.58. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Keim G. R., Sibley P. L., Yoon Y. H., Kulesza J. S., Zaidi I. H., Miller M. M., Poutsiaka J. W. Comparative toxicological studies of amphotericin B methyl ester and amphotericin B in mice, rats, and dogs. Antimicrob Agents Chemother. 1976 Oct;10(4):687–690. doi: 10.1128/aac.10.4.687. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Kim H., Lin C. High-pressure liquid chromatographic method for determination of Sch 28191 in biological fluids. Antimicrob Agents Chemother. 1984 Jan;25(1):45–48. doi: 10.1128/aac.25.1.45. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Kim H., Loebenberg D., Marco A., Symchowicz S., Lin C. Comparative pharmacokinetics of Sch 28191 and amphotericin B in mice, rats, dogs, and cynomolgus monkeys. Antimicrob Agents Chemother. 1984 Oct;26(4):446–449. doi: 10.1128/aac.26.4.446. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Kobayashi G. S., Little J. R., Medoff G. In vitro and in vivo comparisons of amphotericin B and N-D-ornithyl amphotericin B methyl ester. Antimicrob Agents Chemother. 1985 Mar;27(3):302–305. doi: 10.1128/aac.27.3.302. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Lawrence R. M., Hoeprich P. D. Comparison of amphotericin B and amphotericin B methyl ester: efficacy in murine coccidioidomycosis and toxicity. J Infect Dis. 1976 Feb;133(2):168–174. doi: 10.1093/infdis/133.2.168. [DOI] [PubMed] [Google Scholar]
  18. Lawrence R. M., Hoeprich P. D., Jagdis F. A., Monji N., Huston A. C., Schaffner C. P. Distribution of doubly radiolabelled amphotericin B methyl ester and amphotericin B in the non-human primate, Macaca mulatta. J Antimicrob Chemother. 1980 Mar;6(2):241–249. doi: 10.1093/jac/6.2.241. [DOI] [PubMed] [Google Scholar]
  19. Lefler E., Brummer E., Perlman A. M., Stevens D. A. Activities of the modified polyene N-D-ornithyl amphotericin methyl ester and the azoles ICI 153066, Bay n 7133, and Bay l 9139 compared with those of amphotericin B and ketoconazole in the therapy of experimental blastomycosis. Antimicrob Agents Chemother. 1985 Mar;27(3):363–366. doi: 10.1128/aac.27.3.363. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Oblack D. L., Hewitt W. L., Martin W. J. Comparative in vitro susceptibility of yeasts to amphotericin B and three methyl ester derivatives. Antimicrob Agents Chemother. 1981 Jan;19(1):106–109. doi: 10.1128/aac.19.1.106. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Perfect J. R., Durack D. T. Treatment of experimental cryptococcal meningitis with amphotericin B, 5-fluorocytosine, and ketoconazole. J Infect Dis. 1982 Sep;146(3):429–435. doi: 10.1093/infdis/146.3.429. [DOI] [PubMed] [Google Scholar]
  22. Perfect J. R., Lang S. D., Durack D. T. Chronic cryptococcal meningitis: a new experimental model in rabbits. Am J Pathol. 1980 Oct;101(1):177–194. [PMC free article] [PubMed] [Google Scholar]
  23. Ryley J. F., Wilson R. G., Barrett-Bee K. J. Azole resistance in Candida albicans. Sabouraudia. 1984;22(1):53–63. [PubMed] [Google Scholar]
  24. Sande M. A., Bowman C. R., Calderone R. A. Experimental Candida albicans endocarditis: characterization of the disease and response to therapy. Infect Immun. 1977 Jul;17(1):140–147. doi: 10.1128/iai.17.1.140-147.1977. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Stiller R. L., Bennett J. E., Scholer H. J., Wall M., Polak A., Stevens D. A. Correlation of in vitro susceptibility test results with in vivo response: flucytosine therapy in a systemic candidiasis model. J Infect Dis. 1983 Jun;147(6):1070–1077. doi: 10.1093/infdis/147.6.1070. [DOI] [PubMed] [Google Scholar]
  26. Täuber M. G., Sande M. A. Principles in the treatment of bacterial meningitis. Am J Med. 1984 May 15;76(5A):224–230. doi: 10.1016/0002-9343(84)90268-7. [DOI] [PubMed] [Google Scholar]

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

RESOURCES