{"id":447,"date":"2023-09-16T22:06:49","date_gmt":"2023-09-16T21:06:49","guid":{"rendered":"https:\/\/microregistrar.com\/?p=447"},"modified":"2023-09-16T22:06:49","modified_gmt":"2023-09-16T21:06:49","slug":"amphotericin-b","status":"publish","type":"post","link":"https:\/\/microregistrar.com\/?p=447","title":{"rendered":"Amphotericin B"},"content":{"rendered":"\n

Amphotericin B is a polyene antibiotic discovered in 1953 from the bacteria Streptomyces nodosus, in the Orinoco basin in Venezuela.<\/p>\n\n\n\n

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Its name is derived from its amphoteric property, being able to react to both acid and base. It is insoluble at normal pH; hence it is available as a buffered colloidal solution, with sodium deoxycholate as the dispersing agent. This preparation is called amphotericin B deoxycholate.<\/p>\n\n\n\n

The lipid formulations of this drug have been designed to reduce the toxicity associated with its use. There are three preparations available \u2013<\/p>\n<\/div>\n\n\n\n

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Mechanism of action<\/h4>\n\n\n\n

Amphotericin has two major mechanisms of action.<\/p>\n\n\n\n

    \n
  1. Disruption of the cell membrane and<\/li>\n\n\n\n
  2. Oxidative damage to the fungal cells.<\/li>\n<\/ol>\n\n\n\n

    The primary target of amphotericin B is the ergosterol. It disrupts the normal activity of the cell membrane, like endocytosis. However, the major damage is caused by the formation of pores, which leaks the intracellular ion from the cells, leading to cell death. Only potassium ions are leaked at low amphotericin B concentrations, but as the concentration increases, the pores become multimeric \u2013 leaking calcium, magnesium, and other ions.<\/p>\n\n\n\n

    Amphotericin also can auto-oxidise itself generative an oxidative burst, which damages the fungal cells.<\/p>\n\n\n\n

    Amphotericin is also known to have immunomodulatory activity \u2013 it may generate a pro-inflammatory response by binding to the Toll-like receptors. It can also enhance the antifungal activity of the macrophage and other inflammatory cells.<\/p>\n\n\n\n

    Mechanism of resistance<\/h4>\n\n\n\n

    Which fungi are inherently resistant to amphotericin B?<\/strong><\/p>\n\n\n\n

      \n
    • Amongst the Candida, Candida lusitaniae and Candida guilliermondii, tend to have variable MIC; however, they are often considered inherently resistant.<\/li>\n\n\n\n
    • Aspergillus terreus, produces a catalase, which reduces the effectiveness of amphotericin B, and it is considered inherently resistant.<\/li>\n\n\n\n
    • Other inherently resistant fungi are \u2013 Scedosporium prolificans, Trichosporon asahii, some fusarium spp. and chromoblastomycosis.<\/li>\n<\/ul>\n\n\n\n

      Mechanism of acquired amphotericin resistance:<\/strong><\/p>\n\n\n\n

        \n
      1. Alteration in the sterol content of the cell membrane. A mutation in the ERG gene could mediate this. The ergosterol biosynthesis is altered, leading to a higher concentration of sterol intermediates like lanosterol in the cell membrane. These intermediates have less affinity for amphotericin B.<\/li>\n\n\n\n
      2. Production of catalase may confer resistance to amphotericin B by reducing the effect of the oxidative burst.<\/li>\n\n\n\n
      3. Biofilm formation may confer resistance to multiple antifungal classes.<\/li>\n\n\n\n
      4. Altered cell membrane composition, like higher saturated fatty acid content, and
        altered cell wall content, like increased glucan content and decreased chitin content.<\/li>\n<\/ol>\n\n\n\n

        Spectrum<\/h4>\n\n\n\n
          \n
        • Yeast
          \u2013 Candida, Cryptococcus, Malassezia spp., Saccharomyces cerevisiae and Rodotorulla are usually sensitive
          \u2013 Trichosporin asahii is resistant
          (Some Candida spp. have higher MIC or are often resistant. They are \u2013 C. glabrata, C. Krusei, C. tropicalis, C. lusitaniae, C. guilliermondii, C. auris, C. haemulonii, and C. pseudohaemulonii.)<\/em><\/li>\n\n\n\n
        • Mould
          \u2013 Aspergillus, Mucorales are usually susceptible
          \u2013 Pseudallescheria boydii\/Scedosporium apiospermum, sporothrix, dermatophytes and fusarium have variable resistance.
          \u2013 Scedosporium prolificans, chromoblastomycosis are resistant.
          (Aspergillus terreus, Aspergillus alliaceus and some species of Fusarium are inherently resistant)<\/li>\n\n\n\n
        • Dimorphic fungi
          \u2013 Usually susceptible, however Penicillium marneffei is often resistant.<\/li>\n<\/ul>\n\n\n\n

          Adverse effects<\/h4>\n\n\n\n

          Some common adverse effects are<\/p>\n\n\n\n

            \n
          • Acute reaction \u2013 Fever, chill, hypotension, myalgia, || nausea, vomiting, headache, || tachypnoea.<\/li>\n\n\n\n
          • Renal adverse effects \u2013 renal failure, renal stone, renal tubular acidosis, azotemia, electrolyte imbalance.
            (two modes of toxicity \u2013 reduced blood flow to kidney and direct renal tubular toxicity)<\/li>\n\n\n\n
          • Hepatic abnormality (AmphotericinB should be discontinued).<\/li>\n\n\n\n
          • Blood \u2013 anaemia, leucopenia, thrombocytopenia, agranulocytosis, and eosinophilia.<\/li>\n\n\n\n
          • Skin reaction.<\/li>\n<\/ul>\n\n\n\n

            Indications<\/h4>\n\n\n\n
            Liposomal amphotericin B (AmBisome)<\/td>Severe systemic or deep mycosis.
            Febrile neutropenia not responding to the broad-spectrum antibiotics.
            Aspergillosis.
            Visceral leishmaniasis not responding to antimonial.<\/td><\/tr>
            Amphotericin B deoxycholate
            (Fungizone)<\/td>            		Systemic fungal infection.<\/td><\/tr>
            Amphotericin B lipid complex (Abelcet)<\/td>Severe invasive candidiasis.
            Severe systemic fungal infections \u2013 Aspergillus, Cryptococcal infection \u2013 disseminated \/meningitis.<\/td><\/tr><\/tbody><\/table><\/figure>\n\n\n\n

            Properties<\/h4>\n\n\n\n
              \n
            • Limited oral bioavailability. It is also inactivated by gastric acid. Hence the treatment for systemic fungal infection is used intravenously or through other direct installation routes (intrathecal, intraperitoneal, intracavitary, nebulised etc).<\/li>\n\n\n\n
            • Highly protein bound<\/li>\n\n\n\n
            • Mainly excreted in bile, with limited excretion in urine.<\/li>\n<\/ul>\n","protected":false},"excerpt":{"rendered":"

              Amphotericin B is a polyene antibiotic discovered in 1953 from the bacteria Streptomyces nodosus, in the Orinoco basin in Venezuela. […]<\/p>\n","protected":false},"author":1,"featured_media":448,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"site-sidebar-layout":"default","site-content-layout":"","ast-site-content-layout":"default","site-content-style":"default","site-sidebar-style":"default","ast-global-header-display":"","ast-banner-title-visibility":"","ast-main-header-display":"","ast-hfb-above-header-display":"","ast-hfb-below-header-display":"","ast-hfb-mobile-header-display":"","site-post-title":"","ast-breadcrumbs-content":"","ast-featured-img":"","footer-sml-layout":"","ast-disable-related-posts":"","theme-transparent-header-meta":"","adv-header-id-meta":"","stick-header-meta":"","header-above-stick-meta":"","header-main-stick-meta":"","header-below-stick-meta":"","astra-migrate-meta-layouts":"default","ast-page-background-enabled":"default","ast-page-background-meta":{"desktop":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"tablet":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"mobile":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""}},"ast-content-background-meta":{"desktop":{"background-color":"var(--ast-global-color-4)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"tablet":{"background-color":"var(--ast-global-color-4)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"mobile":{"background-color":"var(--ast-global-color-4)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""}},"ngg_post_thumbnail":0,"footnotes":""},"categories":[47],"tags":[152,151,153],"class_list":["post-447","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-antifungal","tag-ambisome","tag-amphotericin-b","tag-antifungal"],"_links":{"self":[{"href":"https:\/\/microregistrar.com\/index.php?rest_route=\/wp\/v2\/posts\/447","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/microregistrar.com\/index.php?rest_route=\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/microregistrar.com\/index.php?rest_route=\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/microregistrar.com\/index.php?rest_route=\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/microregistrar.com\/index.php?rest_route=%2Fwp%2Fv2%2Fcomments&post=447"}],"version-history":[{"count":1,"href":"https:\/\/microregistrar.com\/index.php?rest_route=\/wp\/v2\/posts\/447\/revisions"}],"predecessor-version":[{"id":452,"href":"https:\/\/microregistrar.com\/index.php?rest_route=\/wp\/v2\/posts\/447\/revisions\/452"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/microregistrar.com\/index.php?rest_route=\/wp\/v2\/media\/448"}],"wp:attachment":[{"href":"https:\/\/microregistrar.com\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=447"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/microregistrar.com\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=447"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/microregistrar.com\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=447"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}