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. 1982 Nov;22(5):763–770. doi: 10.1128/aac.22.5.763

Interactions among amphotericin B, 5-fluorocytosine, ketoconazole, and miconazole against pathogenic fungi in vitro.

F C Odds
PMCID: PMC185657  PMID: 6295266

Abstract

Interactions among amphotericin B, 5-fluorocytosine, ketoconazole, and micoconazole were tested for all possible paired and triple drug combinations and all four drugs combined against three isolates of Candida albicans, three Candida spp., two isolates of Cryptococcus neoformans, and three isolates Aspergillus fumigatus. An assay for inhibitory activity was developed in which growth in the presence of an antifungal agent was expressed as a percentage of the growth in drug-free cultures. For nearly all of the antifungal combinations, the interaction was additive against most fungal isolates. Drug combinations that included amphotericin B and ketoconazole were most often synergistic, i.e., amphotericin plus ketoconazole, amphotericin plus 5-fluorocytosine plus ketoconazole, and amphotericin plus 5-fluorocytosine plus ketoconazole plus miconazole, whereas the combination of ketoconazole plus miconazole showed the strongest tendency towards antagonism. The data in this screening survey provide a basis for further studies of drug interactions in vivo and in vitro.

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Selected References

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

  1. Ball E. H., Forbes E. C., Gentles J. C. Unusual response of a yeast to imidazole antifungals. Sabouraudia. 1981 Dec;19(4):287–294. doi: 10.1080/00362178185380461. [DOI] [PubMed] [Google Scholar]
  2. Beggs W. H., Sarosi G. A., Andrews F. A. Synergistic action of amphotericin B and rifampin on Candida albicans. Am Rev Respir Dis. 1974 Nov;110(5):671–673. doi: 10.1164/arrd.1974.110.5.671. [DOI] [PubMed] [Google Scholar]
  3. Beggs W. H., Sarosi G. A., Steele N. M. Inhibition of potentially pathogenic yeastlike fungi by clotrimazole in combination with 5-fluorocytosine or amphotericin B. Antimicrob Agents Chemother. 1976 Jun;9(6):863–865. doi: 10.1128/aac.9.6.863. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Beggs W. H., Sarosi G. A., Walker M. I. Synergistic action of amphotericin B and rifampin against Candida species. J Infect Dis. 1976 Feb;133(2):206–209. doi: 10.1093/infdis/133.2.206. [DOI] [PubMed] [Google Scholar]
  5. Bennet J. E. Flucytosine. Ann Intern Med. 1977 Mar;86(3):319–321. doi: 10.7326/0003-4819-86-3-319. [DOI] [PubMed] [Google Scholar]
  6. Berenbaum M. C. A method for testing for synergy with any number of agents. J Infect Dis. 1978 Feb;137(2):122–130. doi: 10.1093/infdis/137.2.122. [DOI] [PubMed] [Google Scholar]
  7. Dougherty P. F., Yotter D. W., Matthews T. R. Microdilution transfer plate technique for determining in vitro synergy of antimicrobial agents. Antimicrob Agents Chemother. 1977 Feb;11(2):225–228. doi: 10.1128/aac.11.2.225. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Dupont B., Drouhet E. In vitro synergy and antagonism of antifungal agents against yeast-like fungi. Postgrad Med J. 1979 Sep;55(647):683–686. doi: 10.1136/pgmj.55.647.683. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Galgiani J. N., Stevens D. A. Antimicrobial susceptibility testing of yeasts: a turbidimetric technique independent of inoculum size. Antimicrob Agents Chemother. 1976 Oct;10(4):721–728. doi: 10.1128/aac.10.4.721. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Hoeprich P. D., Finn P. D. Obfuscation of the activity of antifungal antimicrobics by culture media. J Infect Dis. 1972 Oct;126(4):353–361. doi: 10.1093/infdis/126.4.353. [DOI] [PubMed] [Google Scholar]
  11. Huppert M., Pappagianis D., Sun S. H., Gleason-Jordan I., Collins M. S., Vukovich K. R. Effect of amphotericin B and rifampin against Coccidioides immitis in vitro and in vivo. Antimicrob Agents Chemother. 1976 Mar;9(3):406–413. doi: 10.1128/aac.9.3.406. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Kitahara M., Seth V. K., Medoff G., Kobayashi G. S. Activity of amphotericin B, 5-fluorocytosine, and rifampin against six clinical isolates of Aspergillus. Antimicrob Agents Chemother. 1976 Jun;9(6):915–919. doi: 10.1128/aac.9.6.915. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Kobayashi G. S., Cheung S. S., Schlessinger D., Medoff G. Effects of rifamycin derivatives, alone and in combination with amphotericin B, against Histoplasma capsulatum. Antimicrob Agents Chemother. 1974 Jan;5(1):16–18. doi: 10.1128/aac.5.1.16. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Kobbayashi G. S., Medoff G., Schlessinger D., Kwan C. N., Musser W. E. Amphotericin B potentiation of rifampicin as an antifungal agent against the yeast phase of Histoplasma capsulatum. Science. 1972 Aug 25;177(4050):709–710. doi: 10.1126/science.177.4050.709. [DOI] [PubMed] [Google Scholar]
  15. Kwan C. N., Medoff G., Kobayashi G. S., Schlessinger D., Raskas H. J. Potentiation of the antifungal effects of antibiotics by amphotericin B. Antimicrob Agents Chemother. 1972 Aug;2(2):61–65. doi: 10.1128/aac.2.2.61. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Lew M. A., Beckett K. M., Levin M. J. Antifungal activity of four tetracycline analogues against Candida albicans in vitro: potentiation by amphotericin B. J Infect Dis. 1977 Aug;136(2):263–270. doi: 10.1093/infdis/136.2.263. [DOI] [PubMed] [Google Scholar]
  17. Medoff G., Comfort M., Kobayashi G. S. Synergistic action of amphotericin B and 5-fluorocytosine against yeast-like organisms. Proc Soc Exp Biol Med. 1971 Nov;138(2):571–574. doi: 10.3181/00379727-138-35943. [DOI] [PubMed] [Google Scholar]
  18. Medoff G., Kobayashi G. S., Kwan C. N., Schlessinger D., Venkov P. Potentiation of rifampicin and 5-fluorocytosine as antifungal antibiotics by amphotericin B (yeast-membrane permeability-ribosomal RNA-eukaryotic cell-synergism). Proc Natl Acad Sci U S A. 1972 Jan;69(1):196–199. doi: 10.1073/pnas.69.1.196. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Montgomerie J. Z., Edwards J. E., Jr, Guze L. B. Synergism of amphotericin B and 5-fluorocytosine for candida species. J Infect Dis. 1975 Jul;132(1):82–86. doi: 10.1093/infdis/132.1.82. [DOI] [PubMed] [Google Scholar]
  20. Odds F. C. Laboratory evaluation of antifungal agents: a comparative study of five imidazole derivatives of clinical importance. J Antimicrob Chemother. 1980 Nov;6(6):749–761. doi: 10.1093/jac/6.6.749. [DOI] [PubMed] [Google Scholar]
  21. Odds F. C. Problems in the laboratory assessment of antifungal activity. Postgrad Med J. 1979 Sep;55(647):677–680. doi: 10.1136/pgmj.55.647.677. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Rifkind D., Crowder E. D., Hyland R. N. In vitro inhibition of Coccidioides immitis strains with amphotericin B plus rifampin. Antimicrob Agents Chemother. 1974 Dec;6(6):783–784. doi: 10.1128/aac.6.6.783. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Schwartz S. N., Medoff G., Kobayashi G. S., Kwan C. N., Schlessinger D. Antifungal properties of polymyxin B and its potentiation of tetracycline as an antifungal agent. Antimicrob Agents Chemother. 1972 Jul;2(1):36–40. doi: 10.1128/aac.2.1.36. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Shadomy S. Further in vitro studies with 5-fluorocytosine. Infect Immun. 1970 Oct;2(4):484–488. doi: 10.1128/iai.2.4.484-488.1970. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Shadomy S., Wagner G., Espinel-Ingroff E., Davis B. A. In vitro studies with combinations of 5-fluorocytosine and amphotericin B. Antimicrob Agents Chemother. 1975 Aug;8(2):117–121. doi: 10.1128/aac.8.2.117. [DOI] [PMC free article] [PubMed] [Google Scholar]

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