The solution of amphotericin B is then reinjected through the tap. For severe infections, this procedure may need to be repeated many times.
Amphotericin B for injection is supplied as a sterile lyophilized cake or powder containing 50 mg of antibiotic with 41 mg of sodium deoxycholate to be dispersed in 10 mL of water. The infusion, providing 0.1 mg/mL, is prepared by further dilution (1:50) with 5% dextrose for injection. Normal saline cannot be used because it will break the micelles. The suspension should be freshly prepared and used within 24 hours. Even the powder should be refrigerated and protected from light.
Several sterile dosage forms32 with amphotericin B admixed with a lipid carrier have been developed with the goal of counteracting the dose-limiting toxicity of the drug following parenteral administration. These include amphotericin B colloidal dispersion (Amphocil, Amphocyte), which contains nearly equal parts of the drug and cholesterol sulfate in a suspension of disklike particles; Abelcet, a 1:1 combination of amphotericin B with l-a-dimyris-toylphosphatidylcholine (7 parts) and l-a-dimyristoylphos-phatidylglycerol (3 parts) to create a suspension of ribbonlike sheets; and liposomal amphotericin B (AmBisome), a small laminar vesicular preparation consisting of an approximately 1:10 molar ratio of amphotericin B and lipid (hydro-genated soy phosphatidyl choline, cholesterol, and dis-tearoylphosphatidylcholine in a 10:5:4 ratio) for an aqueous suspension.
The rationale behind these lipid preparations is simple: amphotericin B should have a greater avidity for the lipid vehicle than for cholesterol in cell membranes. Hence, tox-icity should be reduced. Lipid-associated amphotericin B should be drawn into the reticuloendothelial system, concentrating in the lymphatic tissues, spleen, liver, and lungs, where infectious fungi tend to locate. Lipases elaborated by the fungi and the host should release the drug from the lipid carrier, making it available to bind ergosterol in fungal cell membranes to exert its fungistatic and fungicidal activities.
Clinical use of each of the approved lipid preparations has shown reduced renal toxicity. Liposomal amphotericin B has been approved specifically for the treatment of pulmonary aspergillosis because of its demonstrated superiority to the sodium deoxycholate-stabilized suspension.
Amphotericin B is also used topically to treat cutaneous and mucocutaneous mycoses caused by C. albicans. The drug is supplied in various topical forms, including a 3% cream, a 3% lotion, a 3% ointment, and a 100-mg/mL oral suspension. The oral suspension is intended for the treatment of oral and pharyngeal candidiasis. The patient should swish the suspension in his or her mouth and swallow it. The suspension has a very bad taste, so compliance may be a problem. A slowly developing resistance to amphotericin B has been described. This is believed to relate to alterations in the fungal cell membrane.
Nystatin (Mycostatin) is a polyene antibiotic that was first isolated in 1951 from a strain of the actinomycete Streptomyces noursei by Hazen and Brown.33 It occurs as a yellow to light tan powder. Nystatin is very slightly soluble in water and sparingly soluble in organic solvents. The compound is unstable to moisture, heat, and light.
The aglycone portion of nystatin is called nystatinolide. It consists of a 38-membered macrolide lactone ring containing single tetraene and diene moieties separated by two methylene groups.34 The aglycone also contains eight hy-droxyl groups, one carboxyl group, and the lactone ester functionality. The entire compound is constructed by linking the aglycone to mycosamine. The complete structure of nystatin has been determined by chemical degradation and x-ray crystallography.35
Nystatin is not absorbed systemically when administered by the oral route. It is nearly insoluble under all conditions. It is also too toxic to be administered parenterally. Hence, it is used only as a topical agent. Nystatin is a valuable agent for the treatment of local and gastrointestinal monilial infections caused by C. albicans and other Candida species. For the treatment of cutaneous and mucocutaneous candidiasis, it is supplied as a cream, an ointment, and a powder. Vaginal tablets are available for the control of vaginal candidiasis. Oral tablets and troches are used in the treatment of gastrointestinal and oral candidiasis. Combinations of nystatin with tetracycline can be used to prevent monilial overgrowth caused by the destruction of bacterial microflora of the intestine during tetracycline therapy.
Although nystatin is a pure compound of known structure, its dosage is still expressed in terms of units. One milligram of nystatin contains not less than 2,000 USP units.
Natamycin (pimaricin; Natacyn) is a polyene antibiotic obtained from cultures of Streptomyces natalensis.
The natamycin structure consists of a 26-membered lactone ring containing a tetraene chromophore, an a, fi--unsaturated lactone carbonyl group, three hydroxyl groups, a carboxyl
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The term vaginitis is one that is applied to any inflammation or infection of the vagina, and there are many different conditions that are categorized together under this ‘broad’ heading, including bacterial vaginosis, trichomoniasis and non-infectious vaginitis.