Cryptococcus spp

There may be as great as a 1,000-fold variation in bacterial counts from leaf to leaf assayed from apparently similar leaves in similar canopy positions at the same sampling period (35,100). Most data sets obtained from plate counts of bean and corn leaves are described by a log normal distribution, indicating that on individual leaves or leaHets the spatial distribution of bacterial cells are not uniform within a canopy (35,100). A log normal distribution tends to reflect the fact that chance effects of random variables are acting on a large and diverse collection of objects (in this case bacteria). Interestingly, a similar study on wheat leaves indicated that bacterial counts were best described by a log normal distribution, but counts of yeasts (mainly Cryptococcus spp. and Sporobolomyces spp.) and Cladosporium spp. colonies appeared normally distributed (101). Much more work needs to be done, particularly with regard to host, host age, environmental factors, and position of the sample within a canopy, before the spatial distribution of these microbes can adequately be described. 

Amphotericin B has a broad spectrum of antifungal activity but is more effective against yeasts, in particular Candida and Cryptococcus spp., than... 

Pachysolen lonnophilus lipomices spp. Hansenula capsulotg H. HolstiT Cryptococcus spp. Torulopsis molischiona T. Pinus... 

Due to the rapid appearance of resistance, 5FC is only used as a combination partner for the intensive therapy of established severe fungal infections caused by Candida spp., Cryptococcus neoformans and Aspergillus sp. Anorexia, nausea, vomiting, diarrhoea and or abdominal pain occur in 6% of the patients. Of greater concern is the potential for bone marrow depression (seen in 5% of the patients, all with elevated 5FC levels). 

Amphotericin B is used to treat systemic disseminated fungal infections caused by Candida spp., Cryptococcus neoformans, and the invasive dimorphic fungi Aspergillus spp., Histoplasma capsulatum, Coccidioides immi-tis, Blastomyces dermatitidis, and Sporothrix schenckii). Intravenous amphotericin B remains the treatment of choice for serious invasive fungal infections unresponsive to other agents. 

Garlic has in vitro antifungal effects against Cryptococcus neoformans, Candida spp., Trichophyton, Epidermophyton, Microsporum, Aspergillus spp., and Mucor pusillus (40). When five volunteers consumed 10-25 mL of fresh garlic extract, urine samples had antifungal activity, but susceptibility from serum samples dropped significantly (42). 

Biotransformation, especially phase I metabolic reactions, cannot be assumed to be synonymous with detoxification because some drugs (although a minority) and xenobiotics are converted to potentially toxic metabolites (e.g. parathion, fluorine-containing volatile anaesthetics) or chemically reactive intermediates that produce toxicity (e.g. paracetamol in cats). The term lethal synthesis refers to the biochemical process whereby a non-toxic substance is metabolically converted to a toxic form. The poisonous plant Dichapetalum cymosum contains monofluoroacetate which, following gastrointestinal absorption, enters the tricarboxylic acid (Krebs) cycle in which it becomes converted to monofluorocitrate. The latter compound causes toxicity in animals due to irreversible inhibition of the enzyme aconitase. The selective toxicity of flucytosine for susceptible yeasts (Cryptococcus neoformans, Candida spp.) is attributable to its conversion (deamination) to 5-fluorouracil, which is incorporated into messenger RNA. 

Histoplasma capsulatum Coccidioides immitis Cryptococcus neoformans Candida spp. 

Flucytosine is a fluorinated pyrimidine related to fluorou-racil and floxuridine. It is a 5-fluorocytosine. Flucytosine has clinically useful activity against Cryptococcus neofor-mans, Candida spp., and the agents of chlomoblastomycosis. Within these species, determination of susceptibility in vitro has been extremely dependent on the method employed, and susceptibility testing perfonned on isolates obtained prior to treatment has not correlated with clinical outcome. 

Many other fungal mannans are heteropolymers based on an a-mannan chain [84, 55]. a-L-Rhamno-a-mannans with L-Rha al—>3, L-Rha al-2-L-Rha al—>3 and L-Rhal-4GlcAp 1 -2-L-Rhaa 1 —>3 side chains have been described. a-Gluco-a-mannans with single Glc residues attached to the mannan chain have been isolated from Ceratocystis spp. The capsular polysaccharides of the serotype of an encapsulated pathogenic yeast, Cryptococcus neoformans, have a main chain of a(l-3)... 

Flucytosine (ancobon) is clinically useful for Cryptococcus neoformans, Candida spp., and chromoblastomycosis. It is given orally at 100 mgAg/day, in divided doses at 6-hour intervals and is used predominantly in combination with amphotericin B. An all-oral regimen of flucytosine plus fluconazole has been advocated for therapy of AIDS patients with cryptococcosis, but the combination has substantial Gl toxicity without evidence that flucytosine improves the outcome. The combination of flucytosine with C-AMB runs the risk of substantial bone marrow suppression or colitis if the flucytosine dose is not promptly adjusted downward if amphotericin B—induced azotemia occurs. It is common practice in HIV-negative patients with cryptococcal meningitis to begin with C-AMB or ambisome plus flucytosine and change to fluconazole after the patient has improved. 

Flucytosine is a powerful antifungal agent used in the treatment of serious systemic fungal infections, such as Cryptococcus neoformans and Candida spp (Table 40.2). Flucytosine itself is not cytotoxic but, rather, is a pro-drug that is taken up by fungi and metabolized to 5-fluorouracil (5-FU) by fungal cytidine deaminase (Fig. 40.11) (51). Then, 5-FU is converted to 5-fluorodeoxyuridine, which as a thymidylate synthase inhibitor interferes with both protein and RNA biosynthesis. 5-Fluorouracil is cytotoxic and is employed in cancer chemotherapy (see Chapter 42). Human cells do not contain cytosine deaminase and, therefore, do not convert flucytosine to 5-FU. Some intestinal flora, however, do convert the drug to 5-FU, so human toxicity does result from this metabolism. Resistance rapidly develops to flucytosine when used alone, so it is almost always used in conjunction with amphotericin B. Use of flucytosine has declined since the discovery of fluconazole. 

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