{"id":203,"date":"2023-06-25T11:21:06","date_gmt":"2023-06-25T10:21:06","guid":{"rendered":"https:\/\/microregistrar.com\/?p=203"},"modified":"2023-06-25T11:22:49","modified_gmt":"2023-06-25T10:22:49","slug":"echinocandin","status":"publish","type":"post","link":"https:\/\/microregistrar.com\/?p=203","title":{"rendered":"Echinocandin"},"content":{"rendered":"\n

Echinocandins are a class of antifungals that prevent glucan synthesis pathways necessary for fungal cell wall formation. Echinocanins are antifungals that are widely used in clinical practice.
Three echinocandins are approved for clinical use \u2013 Caspofungin, Micafungin and Anidulafungin.
A fourth echinocandin \u2013 Rezafungin<\/a> is being developed.

Some other antifungals (some in development) that act of fungal cell walls \u2013<\/p>\n\n\n\n

Glucan synthase inhibitors<\/strong><\/td>Echinocandins<\/td>Caspofungin
Micafungin
Anidulafungin
Rezafungin<\/td><\/tr>
Glucan synthase inhibitors<\/strong><\/td>Triterpenoids (enfumafungin derivatives)<\/td>ibrexafungerp<\/td><\/tr>
Chitin synthase inhibitors<\/strong><\/td>Nikkomycins<\/td>Nikkomycin Z<\/td><\/tr>
GPI anchor pathway inhibitors<\/strong><\/td><\/td>manogepix\/fosmanogepix<\/td><\/tr><\/tbody><\/table><\/figure>\n\n\n\n


Source of Echinocandins<\/h2>\n\n\n\n
Caspofungin<\/strong><\/td>Synthetically modified pneumocandin B0 of Glarea lozoyensis (Zalerion arboricola).<\/td><\/tr>
Micafungin<\/strong><\/td>Synthetic modification of cyclic hexapeptide FR901370 derived from Coleophoma empetri<\/td><\/tr>
Anidulafungin<\/strong><\/td>Synthetic modification of echinocandin B0, produced by Aspergillus nidulans<\/td><\/tr><\/tbody><\/table><\/figure>\n\n\n\n

Mechanism of action<\/h2>\n\n\n\n
    \n
  • Echinocandin is a noncompetitive inhibitor of the enzyme \u03b2-(1,3)-glucan synthase<\/strong>.<\/li>\n\n\n\n
  • \u03b2-(1,3)-glucan synthase<\/strong> is required for synthesis of \u03b2-( 1,3)-glucan<\/strong> from uridine diphosphate-glucose<\/strong>.<\/li>\n\n\n\n
  • \u03b2-(1,3)-glucan<\/strong> is a structural component of the fungal wall.<\/li>\n\n\n\n
  • Loss of \u03b2-(1,3)-glucan<\/strong> leads to the loss of cell wall integrity.<\/li>\n\n\n\n
  • The affected cells lyse due to osmotic pressure.<\/li>\n<\/ul>\n\n\n\n

    Echinocandins also exhibit immunomodulatory activity<\/strong> \u2013 it unmasks\/releases glucans from the cell wall. This process enhances the phagocytic killing of fungus via dectin-1 receptor activation.<\/p>\n\n\n\n

    \"\"<\/figure>\n\n\n\n

    Mechanism of resistance:<\/strong><\/h2>\n\n\n\n
      \n
    • Mutation in the FKS gene:<\/strong> A part of the \u03b2-1-3-d-glucan synthase, the target of the echinocandins, is encoded by FKS gene.<\/li>\n\n\n\n
    • Low-level resistance has been associated with
      deletion of the GNSI gene and
      Overexpression of Sbe2p, a Golgi protein involved in cell wall formation.<\/li>\n<\/ul>\n\n\n\n

      Echinocandin resistance is associated with repeated\/chronic exposure and inadequate source control.<\/p>\n\n\n\n

      Drug adaptation: <\/strong>Organisms like C glabrata exhibit a phenomenon called drug adaptation. On using echinocandin, almost all susceptible fungal cells die, leaving a very small number (1 in 10^4-5). These cells exhibit stress response \u2013 chitin synthesis and chromosomal rearrangements\/repairs. These fungal cells are not resistant but show an adaptive response to the echinocandins.<\/p>\n\n\n\n

      Properties:<\/strong><\/h2>\n\n\n\n
        \n
      • Poorly absorbed from the GI tract, hence IV preparations are available.
        (Micafungin topical preparation has been used in candida keratitis).<\/li>\n\n\n\n
      • Long T1\/2 (10-26 hrs) \u2013 once daily dose.<\/li>\n\n\n\n
      • Highly protein-bound (>95%)<\/li>\n\n\n\n
      • Caspofungin and micafungin undergo hepatic metabolism (dose adjustment in hepatic impairment, Child-Pugh >\/=7)<\/li>\n\n\n\n
      • Excretion \u2013 degraded into an inactive product which is primarily excreted in faeces.
        Poor glomerular filtration and tubular secretion (unsuitable for fungal UTI).<\/li>\n\n\n\n
      • Pregnancy \u2013 Class C pregnancy risk agent (animal studies have shown an adverse effect on the fetus, but there are no adequate studies in humans).<\/li>\n\n\n\n
      • Distribution \u2013 Extensively distributed in tissues but limited distribution to CNS and eye
        (not used in CNS\/eye infection).
        High concentration is achieved in liver, spleen and pulmonary alveolar space (but not in the pleural space).<\/li>\n\n\n\n
      • Synergy:
        Yeast \u2013 Echinocandin with amphotericin B, azoles \u2013 indifference\/variable
        Aspergillus \u2013 Echinocandin with amphotericin B\/azoles active against aspergillus \u2013 indifference or synergy can be seen.<\/li>\n<\/ul>\n\n\n\n

        Spectrum:<\/strong><\/h2>\n\n\n\n

        Candida:<\/strong><\/p>\n\n\n\n

          \n
        • Most active class of antifungal agents against Candida biofilms (in vitro, animal model).<\/li>\n\n\n\n
        • Prolonged post-antifungal effects against Candida (in vitro).<\/li>\n\n\n\n
        • Eagle effect has been observed in vitro.<\/li>\n\n\n\n
        • Fungicidal activity against \u2013 C. albicans, C. dubliniensis, C. glabrata, C. krusei, C. tropicalis.<\/li>\n\n\n\n
        • Fungistatic activity against \u2013 C guilliermondii, C. lusitaniae, C parapsilosis family (usually resistant).<\/li>\n\n\n\n
        • C parapsilosis family carries Fks polymorphism resulting in high MIC and
          breakthrough infection (It is often considered inherently resistant).<\/li>\n<\/ul>\n\n\n\n

          Cryptococcus:<\/strong> Inactive ((1\u21926)-\u03b2-d-glucan is the major component of the cell wall)<\/p>\n\n\n\n

          Trichosporon:<\/strong> Inactive ((1\u21926)-\u03b2-d-glucan is the major component of the cell wall)<\/p>\n\n\n\n

          Aspergillus: <\/strong>Fungistatic. (In Aspergillus -Echinocandin affects the growing tip of Aspergillus. The effect is measured by MEC \u2013 minimum effective concentration \u2013 min concentration at which the organism produces small compact highly branched hyphae<\/em>)<\/p>\n\n\n\n

          Endemic mycoses, Mucorales, Fusarium spp., Scedosporium spp:<\/strong><\/p>\n\n\n\n

            \n
          • No significant activity.<\/li>\n\n\n\n
          • Low (1\u21923)-\u03b2-d-glucan in the cell wall.<\/li>\n<\/ul>\n\n\n\n

            Use:<\/strong><\/h2>\n\n\n\n
              \n
            • Candidemia and invasive candidiasis<\/li>\n\n\n\n
            • Mucosal candidiasis.<\/li>\n\n\n\n
            • Refractory aspergillosis \u2013 salvage therapy\/2nd line\/adjuvant.<\/li>\n\n\n\n
            • Prophylaxis of invasive fungal infection in hematopoietic stem cell transplant recipients (micafungin).<\/li>\n\n\n\n
            • Neutropenic fever and suspected fungal infection \u2013 empiric treatment.<\/li>\n<\/ul>\n\n\n\n

              Adverse effect:<\/strong><\/h2>\n\n\n\n
                \n
              • GI adverse effects<\/li>\n\n\n\n
              • Headache<\/li>\n\n\n\n
              • LFT derangement (aminotransferase)<\/li>\n\n\n\n
              • Infusion site reaction.<\/li>\n<\/ul>\n","protected":false},"excerpt":{"rendered":"

                Echinocandins are a class of antifungals that prevent glucan synthesis pathways necessary for fungal cell wall formation. Echinocanins are antifungals […]<\/p>\n","protected":false},"author":1,"featured_media":207,"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":[47,12],"tags":[48,49],"class_list":["post-203","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-antifungal","category-mycology","tag-antifungals","tag-echinocandin"],"_links":{"self":[{"href":"https:\/\/microregistrar.com\/index.php?rest_route=\/wp\/v2\/posts\/203","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=203"}],"version-history":[{"count":3,"href":"https:\/\/microregistrar.com\/index.php?rest_route=\/wp\/v2\/posts\/203\/revisions"}],"predecessor-version":[{"id":208,"href":"https:\/\/microregistrar.com\/index.php?rest_route=\/wp\/v2\/posts\/203\/revisions\/208"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/microregistrar.com\/index.php?rest_route=\/wp\/v2\/media\/207"}],"wp:attachment":[{"href":"https:\/\/microregistrar.com\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=203"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/microregistrar.com\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=203"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/microregistrar.com\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=203"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}