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Oral ketoconazole and amphotericin B for the prevention of yeast colonization in patients with acute leukaemia
Journal
of Hospital
Infection
(1984) 5, 459-461
Letters
to the Editor
Sir,
Oral ketoconazole and amphotericin B for the prevention yeast colonization in patients with acute leukaemia
of
The report on the use of ketoconazole and amphotericin B for the prevention of yeast colonization (Donnelly et al., 1984) is the latest of a number of studies evaluating anti-fungal prophylaxis in neutropenic patients. Clearly the most effective regimen will be determined by trials of this nature. However, it has been shown that Candida albicans, initially sensitive to amphotericin B, becomes resistant to the drug after growth in subfungistatic concentrations of ketoconazole (Inder Jit Sud and Feingold, 1983). This is due to inhibition of the synthesis of ergosterol in the cell membrane by ketoconazole, ergosterol being essential for the fungicidal action of amphotericin B. Although conflicting results have been produced in a study of combined amphotericin B-ketoconazole therapy in experimental histoplasmosis and cryptococcosis (Graybill et al., 1980) care should be taken when using combinations of ketoconazole and amphotericin B, or when amphotericin B is used therapeutically in a patient receiving ketoconazole prophylaxis. It would be interesting to know, for those yeasts isolated after commencement of prophylaxis, if the MIC of amphotericin B was higher in patients receiving ketoconazole than in those receiving amphotericin B.
Public Health Laboratory, Luton & Dunstable Hospital, Lewsey Road, Luton LU4 ODZ
D. N. Looker
References Donnelly, J. P., Starke, I. D., Galton, D. A. G., Catovsky, D., Goldman, J. M. & Darrell, J. H. (1984). Oral ketoconazole and amphotericin B for the prevention of yeast colonization in patients with acute leukaemia. Journal of Hospital Infection 5, 83-91. Graybill, J. R., Williams, D. M., Van-Cutsen, E. & Drutz, D. J. (1980). Combination therapy of experimental Histoplasmosis and Cryptococcosis with amphotericin B and ketoconazole. Reviews of Infectious Diseases 2, 551-558. Inder Jit Sud & Feingold, D. S. (1983). Effect of ketoconazole on the fungicidal action of amphotericin B in Candida albicans. Antimicrobial Agents and Chemotherapy 23, 185-187.
459
of Hospital
Infection
(1984) 5, 459-461
Letters
to the Editor
Sir,
Oral ketoconazole and amphotericin B for the prevention yeast colonization in patients with acute leukaemia
of
The report on the use of ketoconazole and amphotericin B for the prevention of yeast colonization (Donnelly et al., 1984) is the latest of a number of studies evaluating anti-fungal prophylaxis in neutropenic patients. Clearly the most effective regimen will be determined by trials of this nature. However, it has been shown that Candida albicans, initially sensitive to amphotericin B, becomes resistant to the drug after growth in subfungistatic concentrations of ketoconazole (Inder Jit Sud and Feingold, 1983). This is due to inhibition of the synthesis of ergosterol in the cell membrane by ketoconazole, ergosterol being essential for the fungicidal action of amphotericin B. Although conflicting results have been produced in a study of combined amphotericin B-ketoconazole therapy in experimental histoplasmosis and cryptococcosis (Graybill et al., 1980) care should be taken when using combinations of ketoconazole and amphotericin B, or when amphotericin B is used therapeutically in a patient receiving ketoconazole prophylaxis. It would be interesting to know, for those yeasts isolated after commencement of prophylaxis, if the MIC of amphotericin B was higher in patients receiving ketoconazole than in those receiving amphotericin B.
Public Health Laboratory, Luton & Dunstable Hospital, Lewsey Road, Luton LU4 ODZ
D. N. Looker
References Donnelly, J. P., Starke, I. D., Galton, D. A. G., Catovsky, D., Goldman, J. M. & Darrell, J. H. (1984). Oral ketoconazole and amphotericin B for the prevention of yeast colonization in patients with acute leukaemia. Journal of Hospital Infection 5, 83-91. Graybill, J. R., Williams, D. M., Van-Cutsen, E. & Drutz, D. J. (1980). Combination therapy of experimental Histoplasmosis and Cryptococcosis with amphotericin B and ketoconazole. Reviews of Infectious Diseases 2, 551-558. Inder Jit Sud & Feingold, D. S. (1983). Effect of ketoconazole on the fungicidal action of amphotericin B in Candida albicans. Antimicrobial Agents and Chemotherapy 23, 185-187.
459