Abstract
Susceptibility testing with the broth-dilution visual end-point method is inoculum dependent with miconazole and 5-fluorocystosine, but not with amphotericin B. Turbidimetric measurements of yeast growth in the presence of antifungal drugs were therefore performed. With miconazole and 5-fluorocytosine, over the range of concentrations studied, growth occurred until a plateau phase was reached. With drug present prior to log phase growth, a delayed onset of effect was noted which was proportional to the generation time of the organism. With amphotericin B, in contrast, there was sharp transition with increasing drug concentration from no inhibition to complete arrest of growth, and no relation of onset of effect to generation time. These findings provide a possible explanation of inoculum dependence; i.e., at higher inocula, partially inhibited but growing yeasts become visible at higher drug concentrations. Supporting evidence derives from observations with different starting inocula, varying time of reading end points, and other methods of studying growth inhibition. The delay in miconazole and 5-fluorocytosine effect described suggests that rapid methods of susceptibility testing should be utilized with cultures already in log phase.
Full text
PDF
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Benitez P., Medoff G., Kobayashi G. S. Rapid radiometric method of testing susceptibility of mycobacteria and slow-growing fungi to antimicrobial agents. Antimicrob Agents Chemother. 1974 Jul;6(1):29–33. doi: 10.1128/aac.6.1.29. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Block E. R., Jennings A. E., Bennett J. E. Variables influencing susceptibility testing of Cryptococcus neoformans to 5-fluorocytosine. Antimicrob Agents Chemother. 1973 Oct;4(4):392–395. doi: 10.1128/aac.4.4.392. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Drazin R. E., Lehrer R. I. Rubidium release: a rapid and sensitive assay for amphotericin B. J Infect Dis. 1976 Sep;134(3):238–244. doi: 10.1093/infdis/134.3.238. [DOI] [PubMed] [Google Scholar]
- 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]
- 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]
- Kotler-Brajtburg J., Medoff G., Schlessinger D., Kobayashi G. S. Characterization of the binding of amphotericin B to Saccharomyces cerevisiae and relationship to the antifungal effects. Antimicrob Agents Chemother. 1974 Dec;6(6):770–776. doi: 10.1128/aac.6.6.770. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Medoff G., Kobayashi G. S. Amphotericin B. Old drug, new therapy.?2110. JAMA. 1975 May 12;232(6):619–620. doi: 10.1001/jama.232.6.619. [DOI] [PubMed] [Google Scholar]
- Polak A., Scholer H. J. Mode of action of 5-fluorocytosine and mechanisms of resistance. Chemotherapy. 1975;21(3-4):113–130. doi: 10.1159/000221854. [DOI] [PubMed] [Google Scholar]
- Shadomy S., Kirchoff C. B., Ingroff A. E. In vitro activity of 5-fluorocytosine against Candida and Torulopsis species. Antimicrob Agents Chemother. 1973 Jan;3(1):9–14. doi: 10.1128/aac.3.1.9. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sreedhara Swamy K. H., Sirsi M., Ramananda Rao G. R. Studies on the mechanism of action of miconazole: effect of miconazole on respiration and cell permeability of Candida albicans. Antimicrob Agents Chemother. 1974 Apr;5(4):420–425. doi: 10.1128/aac.5.4.420. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Van Den Bossche H., Willemsens G., Van Cutsem J. M. The action of miconazole of the growth of Candida albicans. Sabouraudia. 1975 Mar;13(Pt 1):63–73. [PubMed] [Google Scholar]