3rd Year MBBS
Infection and Inflammation
Topic 22 — Fungal Infections and Antifungal Pharmacotherapy
Connect Aspergillus and Candida with their disease patterns, diagnostic clues and the major antifungal drug targets for rapid revision.
1. THE TOPIC IN ONE CONNECTED FLOW
Fungal disease depends on both the organism and the host. Aspergillus is mainly encountered as an inhaled environmental mould, whereas Candida may already colonize mucosal surfaces. Disease develops when the fungus produces an allergic response, colonizes an abnormal site or invades tissue. Antifungal drugs then act mainly by damaging fungal membrane ergosterol, blocking its synthesis or interfering with fungal growth.
Aspergillus: inhaled conidia
Candida: mucosal colonizer
Immune impairment, abnormal cavity or loss of microbial balance
Allergy, colonization or tissue invasion
Pulmonary disease, hemoptysis, mucosal candidiasis or invasive infection
Hyphal or yeast morphology, microscopy, histology and culture
Ergosterol, sterol synthesis or fungal microtubules
Amphotericin B / nystatin → bind ergosterol → membrane leakage;
azoles → inhibit 14-alpha-demethylase → reduced ergosterol;
terbinafine → inhibits squalene epoxidase → reduced ergosterol + squalene accumulation;
griseofulvin → disrupts fungal microtubules → impaired mitosis.
2. KEY CLINICAL CONNECTIONS
Inhaled conidia
→
septate acute-angle branching hyphae
→
cavity colonization or invasive growth
→
hemoptysis or tissue necrosis.
Vascular invasion
→
thrombosis
→
ischemia, hemorrhage and necrosis.
Normal mucosal colonization
→
disturbed flora or weakened barriers
→
overgrowth
→
pseudohyphal / hyphal invasion
→
candidiasis.
Budding yeast + pseudohyphae
→
supports laboratory recognition when matched with the clinical site.
Amphotericin B
→
ergosterol binding
→
fungal membrane pores
→
strong systemic antifungal effect
→
nephrotoxicity and infusion reactions.
Liposomal formulation
→
altered tissue distribution
→
lower renal exposure
→
reduced nephrotoxicity.
3. AIM HIGH-YIELD INTEGRATION REVIEW
septate hyphae with acute-angle branching strongly support Aspergillus when seen in the appropriate clinical specimen.
hyphal invasion of vessels causes thrombosis and reduced blood supply, explaining hemorrhagic infarction and tissue necrosis.
fungal colonization forms an intracavitary mass and may produce hemoptysis without the widespread tissue invasion seen in invasive disease.
disruption of normal flora or epithelial defence permits overgrowth, while budding yeast and pseudohyphae provide useful diagnostic morphology.
amphotericin B and nystatin bind ergosterol; amphotericin B is used for severe systemic infection, whereas nystatin is mainly used locally.
both reduce ergosterol, but azoles inhibit 14-alpha-demethylase while terbinafine inhibits squalene epoxidase and causes squalene accumulation.
acidic gastric conditions support absorption, hepatic metabolism is important, and CYP inhibition explains significant drug interactions.
deposition in newly formed keratin limits dermatophyte invasion, while disruption of fungal microtubules inhibits cell division.
Amphotericin B and nystatin bind existing ergosterol; azoles and terbinafine inhibit ergosterol synthesis; griseofulvin acts on fungal microtubules.