Nystatin toxicity

The spectrum of its activity is somewhat narrower than that of amphotericin and nystatin, but at the same time, it is less toxic. It exhibits especially pronounced activity against a few strains of Fusarium and Cefalosporium. Natamycin is a drug for treating superficial fungal infections, and it is used only for ophthalmologic purposes. Synonyms of this drug are pimafucin, pimaricin, tennecetin, and others. 

Nystatin (Mycostatin) is a polyene antifungal drug with a ring structure similar to that of amphotericin B and a mechanism of action identical to that of amphotericin B. Too toxic for systemic use, nystatin is limited to the topical treatment of superficial infections caused by C albicans. Infections commonly treated by this drug include oral candidiasis (thrush), mild esophageal candidiasis, and vaginitis. 

Nystatin is a polyene macrolide much like amphotericin B. It is too toxic for parenteral administration and is only used topically. Nystatin is currently available in creams, ointments, suppositories, and other forms for application to skin and mucous membranes. It is not absorbed to a significant degree from skin, mucous membranes, or the gastrointestinal tract. As a result, nystatin has little toxicity, although oral use is often limited by the unpleasant taste. 

Gramicidin is available only for topical use, in combination with other antibiotics such as neomycin, polymyxin, bacitracin, and nystatin. Systemic toxicity limits this drug to topical use. The incidence of sensitization following topical application is exceedingly low in therapeutic concentrations. 

Nystatin is available as an ointment for topical applications and as a suspension or tablet for oral administration. It is approved for oral administration at 100,000 lU/day for 7 days in chickens and turkeys by the Food and Drug Administration (FDA), but it is also used in cattle for treatment of genital mycoses. Nystatin is remarkably low in toxicity when given orally, but it is much more toxic after parenteral administration. 

Nystatin is a mixture of tetraene antifungals produced by cultures of Streptomyces noursei. The principal component is nystatin Ai (Figure 3.68), but the commercial material also contains nystatin A2 and A3, which have additional glycoside residues. Nystatin is too toxic for intravenous use, but has value for oral treatment of intestinal candidiasis, as lozenges for oral infections, and as creams for topical control of Candida species. 

Microbes also have a plasma membrane that resides adjacent to their cell wall. Polymyxins are amphipathic agents (containing both nonpolar, lipophilic and polar, lipophobic groups) that interact with phospholipids in microbial cell membranes. The result is disruption of the membrane and increased permeability. However, because microbial and mammalian cell membranes are not exceedingly dissimilar, polymixins can produce significant toxicity in humans (i.e., they have low selective toxicity). This is also true for the related drug nystatin. This is why these particular antibiotics are not generally used systemically and are usually restricted to topical application. 

Nystatin [nye STAT in] is a polyene antibiotic its structure, chemistry, mode of action, and resistance resemble those of amphotericin B. Its use is restricted to topical treatment of Candida infections because of its systemic toxicity. The drug is negligibly absorbed from the gastrointestinal tract, and it is never used par-enterally. It is administered as an oral agent ( swish and swallow ) for the treatment of oral candidiasis. Excretion in the feces is nearly quantitative. Adverse effects are rare because of its lack of absorption, but occasionally nausea and vomiting occur. 

Amphoteridn is a complex amphoteric polyene antibiotic that binds to cell membranes and forms a pore through which ions can pass, with consequences that include loss of potassium ions from within the cell. Since the antibiotic binds more readily to fungal cell membranes than mammalian, its action is relatively selective. It can potentiate the action of certain other antifungals. and it may be used with flucytosine. Also, it confers antifungal activity on rifampicin (normally antibacterial). As it has an appreciable renal toxicity, it needs to be used with caution in some patients. Nystatin is a polyene antibiotic similar in structure to amphotericin, often used for local treatment. 

Nystatin (too toxic for systemic use) is used topically for localized infections (e.g., candidiasis). 

Answer C. Fluconazole is distinctive in terms of its ability to penetrate into the CSF, reaching levels similar to those in the blood. It is effective against C. neoformans and has become the most appropriate drug to use in both prophylaxis and suppression because of its oral efficacy and low toxicity compared with amphotericin B. Flucytosine is also active against C. neoformans but is not used alone because of rapid emergence of resistance. Nystatin is too toxic for systemic use. 

The selective toxicity of antibiotics is, of course, not confined to bacterial pathogens. Some of the earliest discovered antibiotics possessed other types of activity. Thus griseofulvin (1939) and nystatin (1951) are antifungal agents, and the actinomycins (1940) are antineoplastic... 

Specific toxicity drug is concentrated in bacteria but not in mammalian cells. Combinations with nystatin not effective. Do not give to renal compromised patients. 

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