C. albicans

Oral treatment offers the advantage of bringing all the lesions at all sites under control, in addition to the absence of unpleasant cosmetic effects. In certain cases, it may be preferable to use oral treatment for C. albicans vaginitis and for extensive and persistent pityriasis versicolor, a skin disorder caused by Pityrosporum orbiculare. In the case of onychomycosis, a combination treatment, topical plus systemic, is required. It is preferable to use oral treatment for deep and systemic mycoses, though intravenous or intrathecal treatment is sometimes required. 

In addition to tolnaftate and cetylpytidinium chlotide, the ointment also contains poly(ethylene glycol). This piepaiation is not active against C. albicans. 

Miconazole. Miconazole nitrate [22832-87-7] (Fig. 2), the 1-phenethyl-imidazole derivative first described in 1969, interferes at low doses with the cytochrome P-450 dependent ergosterol biosynthesis in yeasts and fungi. The result is accumulation of C-14 methylated sterols on the one hand and reduction of the ergosterol levels in the membranes on the other hand (12). Analogous to clotrimazole, this leads to a disturbance in the membranes it results in inhibition of ceU repHcation, mycelium development (in C. albicans) and finally, ceU death. High concentrations of miconazole, which may be achieved with topical use, disturb the orientation of phosphoHpids in the membranes, which produces leaks (13). 

Like the a2ole derivatives, it inhibits the biosynthesis of ergosterol. However, naftifine [65472-88-0] does not inhibit the cytochrome P-450 dependent C-14-demethylase, but the epoxidation of squalene. Squalene epoxidase cataly2es the first step in the conversion of squalene via lanosterol to ergosterol in yeasts and fungi or to cholesterol in mammalian cells. The squalene epoxidase in C. albicans is 150 times more sensitive to naftifine, C2 H2 N, than the en2yme in rat fiver (15). Naftifine is available as a 1% cream. 

Flucytosine-resistant strains can develop very rapidly. These mutants may have a disturbed 5-FC-metabohsm, or a compensatory mechanism for the disturbed nucleic acid functions. No cytosine permease was found in a resistant Cyptococcus neoformans strain, whereas cytosine deaminase was absent in resistant C. albicans strains. A deficiency of uridine monophosphate pyrophosphorylase occurs frequently in resistant C. albicans strains (1). 

Miconazole. Miconazole (Fig. 2, 7a) is also available as a sterile solution for intravenous infusion. Miconazole has a therapeutic effect on systemic mycoses due to C albicans A.spergillusfumigatus Cyptococcus neoformans Blastomyces dermatitidis Histoplasma capsulatum Coccidioides immitis Paracoccidioides brasiliensis and Petriellidum boydii. 

The superficial mycotic infections occur on the surface of, or just below, the skin or nails. Superficial infections include tinea pedis (athlete s foot), tinea cruris (jock itch), tinea corporis (ringworm), onychomycosis (nail fungus), and yeast infections, such as those caused by Candida albicans. Yeast infections or those caused by C. albicans affect women in the vulvovaginal area and can be difficult to control. Women who are at increased risk for vulvovaginal yeast infections are those who have diabetes, are pregnant, or are taking oral contraceptives, antibiotics, or corticosteroids. 

Another form of switching is well-known in C. albicans. This is the phenomenon of phenotypie switching (Soil 1992) whereby colony morphologies vary dramatieally (e.g. white, opaque, fiizzy, wrinkled.) These may seem trivial to the pharmacist or physician, but the variability extends far beyond the mere appearance of the colonies. It ean eneompass a vast array of bioehemical alterahons, anhgenicities and drug... 

Nystatin has a specific action on C. albicans and is of no value in the treatment of any other type of infection. It is poorly absorbed from the gastrointestinal tract even after very large doses, the blood level is insignificant. It is administered orally in the treatment of oral thrush and intestinal candidiasis infections. 

Amphotericin B is particularly effective against systemic infections caused by C. albicans and Cryptococcus neoformans. It is poorly absorbed from the gastrointestinal tract and is thus usually administered by intravenous injection under strict medical supervision. Amphotericin B methyl ester (Fig. 5.15C) is water-soluble, unlike amphotericin B itself, and can be administered intravenously as a solution. The two forms have equal antifungal activity but higher peak serum levels are obtained with the ester. Although the ester is claimed to be less toxic, neurological effects have been observed. An ascorbate salt has recently been described which is water-soluble, of similar activity and less toxic. 

The synthetic thiocarbamates, of which tolnaftate (Fig. 5.20J) is an example, also inhibit squalene epoxidase. Tolnaftate inhibits this enzyme from C. albicans, but is inactive against whole cells, presumably because of its inability to penetrate the cell wall. Tolnaftate is used topically in the treatment or prophylaxis of tinea. 

On the contrary, both crude and water extracts (containing both catechins and proanthocyanidins) obtained from Cocos nucifera L. husk fibre were in-acfive against both the yeasts C. albicans. Cryptococcus neoformans and the filamentous fungus Fonsecaea pedrosoi [62]. 

Candida albicans accounts for 80% of cases of OPC and esophageal candidiasis. Over the last 20 years, an increasing incidence of C. albicans resistance has been accompanied by an increased incidence of non-albicans species infections, including Candida glabrata, Candida tropicalis, Candida krusei, and Candida parapsilosis. In patients with cancer, non-albicans Candida species account for almost half of all cases.29... 

Sample staph. aureus B. subtilis Af. smegmatis C. albicans S. oerevisiae A. niger... 

BPH—benign prostatic hypertrophy BPM—breaths per minute beats per minute BUN—blood urea nitrogen C—mean plasma concentration Cmi]X—maximum plasma concentration Cmm—minimum plasma concentration C albicans—Candida albicans C. bofulinum—Clostridium frotu/irtum C. difficile—Clostridium difficile C. jejuni—Campylobacter jejuni C. neoformans—Cryptococcus neoformans Ca—calcium... 

Eight species of Candida are regarded as clinically important pathogens in human disease C. albicans, C. tropicalis, C. parapsilosis, C. krusei, C. stellatoidea, C. guilliermondii, C. lusitaniae, and C. glabrata. 

Three distinct presentations of disseminated C. albicans have been recognized (1) the acute onset of fever, tachycardia, tachypnea, and occasionally... 

No test has demonstrated reliable accuracy in the clinical setting for diagnosis of disseminated Candida infection. Blood cultures are positive in only 25% to 45% of neutropenic patients with disseminated candidiasis. Fluorescence in situ hybridization has excellent sensitivity and specificity in the identification of C. albicans from blood. 

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