Antifungal Antibiotics: Polyene Antibiotics

Amphotericin B is obtained from Streptomyces nodosus. Two types A & B but only B is used clinically because it is significantly more active in vivo. Amphotericin B is insoluble in water & is often used intravenously for systemic fungal infections. Rapidly decomposes on exposure to light. Mechanism of action The amphotericin B and other polyene antibiotics have high affinity for ______, present in fungal cell membranes.

High concentration of amphotericin B directly disrupts the fungal cell membrane permeability and leakage of cellular contents. Amphotericin B is fungistatic at normal dosages, but it can become fungicidal at higher concentrations. Antimicrobial spectrum Amphotericin B have broad-spectrum antifungal against is useful against several systemic fungi including Candida, Histoplasma, Cryptococcus, Blastomyces, Coccidioides, Aspergillus and Sporithrix spp. Some algae and protozoa (e.g. Leishmania, Trypanosoma, Trichomonas and Entamoeba spp.) are sensitive to the polyene antibiotics. Amphotericin B is not effective against clinical ______.

Polyene antibiotics obtain from actinomyces MOA: The polyenes bind to ______ in the fungal cell membrane and promote leakiness which may contribute to fungal cell death.

Amphotericin B and other polyene antibiotics have high affinity for ______, present in fungal cell membranes. High concentration of amphotericin B directly disrupts the fungal cell membrane permeability and leakage of cellular contents.

Amphotericin B is poorly absorbed from the GI tract and, therefore, oral used only for gastrointestinal fungal infection. For systemic infection, it is given by repeated daily slow IV injections because it is not absorbed after IM or other parenteral routes. It distributes very unevenly throughout the body & can not pass the CSF, vitreous humour and amniotic fluid. For fungal meningitis, it has to be given ________.

It is extensively bound to plasma lipoproteins, longer terminal half-life of about 15 days. Drug eliminate via ________ & bile.

The nephrotoxicity generally occurs via two mechanisms intense renal vasoconstriction and binding of drug to membrane cholesterol in the renal tubular cell membrane. Other adverse effects includes anorexia, nausea, vomiting, anaemia, cardiac arrhythmias, CNS signs (if given intrathecally), hepatic dysfunctions and thrombophlebitis at injection site. Cats are more sensitive to the renal toxic effects. During the therapy monitored patient's renal function by urine analysis of ________ & creatinine.

Amphotericin B is effective antifungal agent mainly in dogs & other spp. for serious life-threatening systemic infections. It is usually diluted in 5% dextrose and administered _________.

Nystatin is primarily used for skin, mouth, intestinal or vaginal candidiasis in dogs, cats and birds. Dose: Dogs : 50,000- 150,000 Units (total), PO, 3 times daily. Cats: 1,00,000 Units (total), PO, 4 times ________.

Natamycin is used to treat fungal infections, including Candida, Aspergillus, Cephalosporium, Fusarium and Penicillium. Used to treat fungal keratitis in eye infection. Mainly used ________.