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Antifungal therapy in the management of chronic candidiasis
Antifungal therapy in the management of chronic candidiasis Benson J. Horowitz, MD Hartford, Connecticut The most pathogenic Candida species are identified and the structure of imidazole compounds and their mechanism of action on yeast cells are described. Not all yeast species react in the same way to imidazole preparations, and these actions are documented. (AM J OesTET GVNECOL 1988;158:996.)
Key words: Candida albicans, Candida tropicalis, imidazoles, butoconazole
Nine Candida species are commonly recognized as being pathogenic in humans (Table I). In an attempt to identify the same species that have been reported in the literature, we developed a reliable culture technique and then obtained vaginal samples from 175 consecutive patients.' Our results were similar to those reported by others: Among our first 175 patients, 65% were infected with Candida albicans and 23% with C. tropicalis. Only one patient had an infection due to C. glabrata, a species more commonly seen in England than in the United States. Interestingly, three cases of infection caused by Saccharomyces cerevisiae-brewer's or baker's yeast-were identified, as were six cases attributed to dermatophytes. Another important finding was that not all yeast species react in the same way to imidazole preparations. I C. tropicalis and C. glabrata, for example, are more resistant than C. albicans. In addition, a tenfold dose increase is necessary with drugs such as nystatin and miconazole to eliminate C. tropicalis and C. glabrata when compared with C. albicans in vitro. It should be pointed out that these results reflect only species differences; strain differences remain to be investigated.
Table I. Candida species commonly found in human disease C. albicans C. guilliermondii C. krusei C. parapsilosis C. stellatoidea
C. tropicalis C. glabrata C. pseudotropicalis C. viswanathii
From RipponjW: Medical mycology. 3rd ed. Philadelphia: WB Saunders, 1982.
Drug treatment of candidiasis
Structure of imidazole compounds The structure of the basic imidazole consists of a simple five-atom ring-three carbons and two nitrogensplus a side chain. Various radicals have been added to the side chain to produce compounds such as clotrimazole, miconazole, econazole, ketoconazole, and, more recently, butoconazole. Imidazole compounds have a profound effect on the endocrinologic characteristics of the cell wall of the yeast organism. At least they interfere with the cytochrome P-450 process at four stages: the 14demethylation process, the 17-desmolase reaction, the 11 13-hydrolase reaction, and side-chain cleavage. Because of these effects, imidazole compounds may be thought of as "antihorrnones."
Because of their mode of action, imidazoles are able to destroy a yeast organism only if the cell wall of the organism is dependent on ergosterol synthesis, as are most Candida species. To kill an organism that has a large amount of ergosterol in its cell wall, an increased concentration of an imidazole will be necessary. On the other hand, an organism such as C. tropicalis lacks ergosterol in its cell wall and thus will not be killed by drugs designed to interfere with ergosterol synthesis. One exception to this principle is butoconazole. This agent's spectrum of activity includes the C. tropicalis organism; the drug therefore may eliminate this organism more effectively than do other imidazoles. Another possibility for treating yeast infections is the pyrimidines. These drugs, instead of acting on the cell wall, are converted into the chemotherapeutic agent 5fluorouracil in the cell nucleus, where they destroy deoxyribonucleic acid or ribonucleic acid. In summary, in recent years, our knowledge of Candida species and the treatment of vulvovaginal candidiasis has increased. We have learned that yeast organisms may be resistant to one imidazole, necessitating the ase of another imidazole compound that has a specific action against that particular organism. The advent of newer agents with a wider spectrum of activity against Candida species, such as butoconazole, has expanded treatment options.
From the Department of Obstetrics and Gynecology, Mt. Sinai Hospital. Reprint requests: Benson J. Horowitz, MD, 449 Farmington Ave., Hartford CT 06105.
1. Horowitz B], Edelstein SW, Lippman L. Candida tropicalis vulvovaginitis. Obstet Gynecol 1985;66:29.
996
REFERENCE
Key words: Candida albicans, Candida tropicalis, imidazoles, butoconazole
Nine Candida species are commonly recognized as being pathogenic in humans (Table I). In an attempt to identify the same species that have been reported in the literature, we developed a reliable culture technique and then obtained vaginal samples from 175 consecutive patients.' Our results were similar to those reported by others: Among our first 175 patients, 65% were infected with Candida albicans and 23% with C. tropicalis. Only one patient had an infection due to C. glabrata, a species more commonly seen in England than in the United States. Interestingly, three cases of infection caused by Saccharomyces cerevisiae-brewer's or baker's yeast-were identified, as were six cases attributed to dermatophytes. Another important finding was that not all yeast species react in the same way to imidazole preparations. I C. tropicalis and C. glabrata, for example, are more resistant than C. albicans. In addition, a tenfold dose increase is necessary with drugs such as nystatin and miconazole to eliminate C. tropicalis and C. glabrata when compared with C. albicans in vitro. It should be pointed out that these results reflect only species differences; strain differences remain to be investigated.
Table I. Candida species commonly found in human disease C. albicans C. guilliermondii C. krusei C. parapsilosis C. stellatoidea
C. tropicalis C. glabrata C. pseudotropicalis C. viswanathii
From RipponjW: Medical mycology. 3rd ed. Philadelphia: WB Saunders, 1982.
Drug treatment of candidiasis
Structure of imidazole compounds The structure of the basic imidazole consists of a simple five-atom ring-three carbons and two nitrogensplus a side chain. Various radicals have been added to the side chain to produce compounds such as clotrimazole, miconazole, econazole, ketoconazole, and, more recently, butoconazole. Imidazole compounds have a profound effect on the endocrinologic characteristics of the cell wall of the yeast organism. At least they interfere with the cytochrome P-450 process at four stages: the 14demethylation process, the 17-desmolase reaction, the 11 13-hydrolase reaction, and side-chain cleavage. Because of these effects, imidazole compounds may be thought of as "antihorrnones."
Because of their mode of action, imidazoles are able to destroy a yeast organism only if the cell wall of the organism is dependent on ergosterol synthesis, as are most Candida species. To kill an organism that has a large amount of ergosterol in its cell wall, an increased concentration of an imidazole will be necessary. On the other hand, an organism such as C. tropicalis lacks ergosterol in its cell wall and thus will not be killed by drugs designed to interfere with ergosterol synthesis. One exception to this principle is butoconazole. This agent's spectrum of activity includes the C. tropicalis organism; the drug therefore may eliminate this organism more effectively than do other imidazoles. Another possibility for treating yeast infections is the pyrimidines. These drugs, instead of acting on the cell wall, are converted into the chemotherapeutic agent 5fluorouracil in the cell nucleus, where they destroy deoxyribonucleic acid or ribonucleic acid. In summary, in recent years, our knowledge of Candida species and the treatment of vulvovaginal candidiasis has increased. We have learned that yeast organisms may be resistant to one imidazole, necessitating the ase of another imidazole compound that has a specific action against that particular organism. The advent of newer agents with a wider spectrum of activity against Candida species, such as butoconazole, has expanded treatment options.
From the Department of Obstetrics and Gynecology, Mt. Sinai Hospital. Reprint requests: Benson J. Horowitz, MD, 449 Farmington Ave., Hartford CT 06105.
1. Horowitz B], Edelstein SW, Lippman L. Candida tropicalis vulvovaginitis. Obstet Gynecol 1985;66:29.
996
REFERENCE