Amphotericin toxicity

The reports supporting a lack of significant nephrotoxicity all used liposomal amphotericin B, a formulation that is recommended when amphotericin toxicity (particularly nephrotoxicity) is considered to be a significant risk. This would seem to suggest that in patients taking eielosporin, the less nephrotoxic forms of amphotericin B are advisable. Renal function should be closely monitored during concurrent use. 

Naeg/ena is treatable with intravenous amphotericin B (15, Fungizone), a toxic dmg that must be used with caution. 

Amphotericin B (15) is an antifimgal macioHde antibiotic produced by Streptomjces nodosus that has been used as an alternative, albeit more toxic, dmg to the antimonials. It acts as a leishmanicide against the visceral and mucocutaneous forms of the disease. To overcome its potentially severe nephrotoxicity, the dmg must be adrninistered over an extended period of time. 

Flucytosine is contraindicated in patients with known hypersensitivity to the drug. Flucytosine is used cautiously in patients with bone marrow depression and with extreme caution in those with renal impairment. The drug is also used cautiously during pregnancy (Category C) and lactation. When flucytosine and amphotericin B are administered concurrently, the risk of flucytosine toxicity is increased. 

J. (1985). Ocular toxicity of intravitreally injected liposomal amphotericin B in rhesus monkeys. Am. J. Ophthalmol., 100, 259-263. 

Mehta, R., Lopez-Berestein, G., Hopfer, R., Mills, K., and Juliano, R. L. (1984). Liposomal amphotericin B is toxic to fungal cells but not to mammalian cells. Biochim. Biophys. Acta, 770. 230-234. 

Newman, M. S., Guo, L., McCalden, T. A., Levy, M., Porter, J., Wong, A., and Fielding, R. M. (1989). A colloidal dispersion of amphotericin B with reduced lethality and non lethal toxicity, Proc. AAPS Western Regional Meet., February 26-March 1, 1989. 

Tremblay, C., Barza, M., Szoka, F., Lahav, M., and Baum, J. (1985). Reduced toxicity of liposome-associated amphotericin B injected intravitreally in rabbits. Invest. Ophthalmol. Visual Sci., 26, 711-16. 

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. 

Response to antifungal therapy in invasive candidiasis is often more rapid than for endemic fungal infections. Resolution of fever and sterilization of blood cultures are indications of response to antifungal therapy. Toxicity associated with antifungal therapy is similar in these patients as described earlier with the caveat that some toxicities maybe more pronounced in crit-ically-ill patients with invasive candidiasis. Nephrotoxicity and electrolyte disturbances, with amphotericin B in particular, are problematic and may not be avoidable even with lipid amphotericin B formulations. Fluconazole and echinocandins are generally safer options, and are generally well tolerated. Decisions to use one class of agents over the other is principally driven by concerns of non-albicans species, patient tolerability, or history of prior fluconazole exposure (risk factor for non-albicans species.). 

Amphotericin B is generally preferred as initial therapy in patients with rapidly progressive disease, whereas azoles are generally preferred in patients with subacute or chronic presentations. Lipid formulations of amphotericin B have not been extensively studied for coccidioidomycosis but can offer a means of giving more drug with less toxicity. Treatments for primary respiratory disease (mainly symptomatic patients) are 3- to 6-month courses of therapy. 

Lipid-associated formulations of amphotericin B, liposomal amphotericin B (AmBisome) and amphotericin B lipid complex (Abelcet) have been approved for use in proven cases of candidiasis however, patients with invasive candidiasis have also been treated successfully with amphotericin B colloid dispersion (Amphotec or Amphocil). The lipid-associated formulations are less toxic but as effective as amphotericin B deoxycholate. 

Szlinder-Richert J, Cybulska B, Grzybowska J, Bolard J, Borowski E (2004) Interaction of amphotericin B and its low toxic derivative, N-methyl-N-D-fructosyl amphotericin B methyl ester, with fungal, mammalian and bacterial cells measured by the energy transfer method. II Farmaco 59 289-296. 

Amphotericin B (AmB) is a broad-spectrum antifungal agent that is the antibiotic of choice for disseminated fungal infections, particularly in immunocompromised patients. AmB is also used for the treatment of Leishmaniasis as a second-line treatment. However, its toxicity toward mammalian cells is often dose limiting, whatever its indication. 

Espuelas MS, et al. Polymeric carriers for amphotericin B in vitro activity, toxicity and therapeutic efficacy against systemic candidiasis in neutropenic mice. J Antimicrob Chemother 2003 52 419. 

Janoff AS, et al. Unusual lipid structures selectively reduce the toxicity of amphotericin B. Proc Natl Acad Sci USA 1988 85 6122. 

Janoff AS, et al. Amphotericin B lipid complex (ABLC ) a molecular rationale for the attenuation of AmB related toxicities. J Liposome Res 1993 3 451. 

Larabi M, et al. Toxicity and antileishmanial activity of a new stable lipid suspension of amphotericin B. Antimicrob Agents Chemother 2003 47 3774. 

Larabi M, et al. Study of the toxicity of a new lipid complex formulation of amphotericin B. J Antimicrob Chemother 2003 53 81. 

The antimykotie amphotericine is eneapsulated in liposomes and marketed as Am-Bisome" against severe systemic mycosis. The liposomal encapsulation reduces the toxicity of amphotericine while increasing the half-life of the drug and plasma level peaks [31], For stability reasons, the parenteral formulation is a lyophilized powder whieh has to be reeonstituted by adding the solvent just before administration. 

The applicahon of the cDNA microarray revealed that the fungicide appeared to affect a number of cellular processes. While the content of the Clontech microarray was rather limited, it provided a substanhal amount of new informahon regarding amphotericin B-mediated cellular 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. 

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