Amphotericin antifungal activity

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. 

Topical formulations of nystatin and of amphotericin B are useful in the management of Candida albicans infections of the skin. Both antibiotics are ineffective against dermatophytes. The use of nystatin is limited to topical treatment of cutaneous and mucosal Candida infections because of its narrow spectrum and its negligible absorption from the gastrointestinal tract. Hypersensitivity reactions are rare. It is not known whether topical nystatin can cause fetal harm when used by a pregnant woman. Amphotericin B has broader antifungal activity but its topical use is restricted to Candida. Topical use of amphotericin B has shown minimal absorption through the skin and is well tolerated. Limited human surveillance data do not indicate any harm to mother or fetus, but relative safety is still unknown. 

Amphotericin B has a wide spectrum of antifungal activity. It is active against... 

Flucytosine is converted into the anti metabolite 5-fluorouracil that inhibits thymidilate synthetase, thereby disrupting DNA synthesis. It also interferes with protein synthesis by incorporation of fluorouracil into RNA in place of uracil. Although active against most Candida species, its spectrum of antifungal activity, overall, is narrow. Since resistance can develop rapidly it is usually coadministered with another agent and its main value is that it facilitates a reduction in the dose (and, presumably, the toxic effect) of amphotericin when co-prescribed in this way. The main adverse effects are marrow aplasia and hepatotoxicity. 

Intrapetacin A and intrapetacin B isolated from L. intrapetiolaris, when examined in antifungal assay with Aspergillus niger spores, induced a good zone of inhibition of fungal growth if compared with amphotericin B activity [4]. 

K. M. Wasan and J. S. Conklin, Evaluation of renal toxicity and antifungal activity of free and liposomal amphotericin B following a single intravenous dose to diabetic rats with systemic candidiasis, Antimicrob. Agents Chemother. 40 1806-1810, (1996). 

Mode of action Ketoconazole interacts with C-14 a-demethylase (a cytochrome P-450 enzyme) to block demethylation of lanosterol to ergosterol, the principal sterol of fungal membranes Figure 34.4). This inhibition disrupts membrane function and increases permeability. Ketoconazole acts in an additive manner with flucytosine against Candida, but antagonizes amphotericin B s antifungal activity. 

Finally, there remain some effects of ansamycins of which the significance and the biochemical targets are as yet unknown these include the combined action of rifamycin and amphotericin B on fungal cells, and the antibacterial and antifungal activity of naphthomycin and geldanamycin. 

Adams, M.L. Andes, D.R. Kwon, G.S. Amphotericin b encapsulated in micelles based on poly(ethylene oxide)-block-poly(l-amino acid) derivatives exerts reduced in vitro hemolysis but maintains potent in vivo antifungal activity. Biomacromolecules 2003, 4, 750-757. 

Wasan KM, Rosenblum MG, Cheung L, and Lopez-Berestein G. Influence of lipoproteins on renal cytotoxicity and antifungal activity of amphotericin B. Antimicrob Agents Chemother 38 223-227,1994. 

Anaissie E, Paetznick V, Proffitt R, et ai. Comparison ofthe in vitro antifungal activity of free and liposome-encapsulated amphotericin B. Eur J Clin Microbiol Infect Dis 1991 10 665-8. 

Table 3. Antifungal activity of amphotericin B in combination with anethole (15).

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

Bacillomycins (Fig. 8) were discovered as antifungal compounds by Peypoux et al. in 1980 and Eshita et al. in 1995 from B. subtilis K In bacillomycin L congeners, the antifungal activity increases directly with increases lipophilicity, and their antifungal activity is less potent than that of clinically available polyene antibiotics amphotericin B and nystatin ... 

Aspergillus spp. in vitro K Anidulafungin and itraconazole or voriconazole show a synergistic antifungal activity, while anidulafungin and amphotericin B show low in vitro activity against Aspergillus spp. and... 

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. 

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