Mycology
Key Structures
Fungal cell wall
Great drug target as it's not in humans. The most important component are the glucans (50-60% cell wall). Beta-1,3-D-glucan especially is a site of action for Echinocandins.
Beta-D Glucan Assay (Fungitel) is a serum test to measure beta-D Glucan in cell wall.
BDG (+): Candida, Aspergillus, and Endemic Mycoses
BGD (-): Cryptococcus, Mucormycosis
Fungal plasma membrane
A bilayer composed of lipids and proteins. Ergosterol is the fungal analog of cholesterol. It is an important drug target for Polyenes (Amphotericin B) which increases the membrane permeability. Additionally, Triazoles inhibits ergosterol formation.
Microtubules
Composed of tubulin and responsible for intracellular transport. Griseofulvin binds to microtubules, and inhibits mitosis in metaphase.
TL;DR
Polyenes: Target membrane function
Echinocandins/Pneumocandins: Target cell wall synthesis
Azoles: Target Ergosterol synthesis
Pyrimidine analogs: Target nucleic acid synthesis
Fungal Types
Yeasts
Fungi that reproduce via budding.
Examples
- Candida Albicans
- Cryptococcus Neoformans
Molds
Characterized by hyphae and grows via apical elongation. It is identified with Conidiophores and Sporangiophores.
Examples
- Aspergillus
- Zygomyctes/Mucor
Dimorphic Fungi
Can exist as a yeast or mold form. Mold in the cold, yeast in the heat.
Examples
- Blastomyces Dermatitidis
- Coccidioides immitis
Candida
A yeast. Can be germ tube (+) or germ tube (-). Every positive Candida culture is infectious, not an accidental contaminant, and must be dealt with swiftly.
It is an exception to mold/cold, yeast/heat. It forms germ tubes at 37 degrees as a mold. At around 20 degrees, it turns into a yeast displaying pseudohyphae.
Major risk factors
- Broad spectrum antibiotics
- Neutropenia
- HIV
- Indwelling vascular catheters
- Chemotherapy/steroids
Muco-cutaneous manifestations
- Oropharyngeal candidiasis (thrush): HIV-defining illness
- Candida esophagitis: HIV-defining illness
- Yeast-vaginitis
- Cutaneous: Intertrigo, Folliculitis, Balanitis, Paronychia
Treatment
Includes Echinocandins for suspicion of C. albicans or Fluconazole once confirmed.
Aspergillus
A mold. It consists of septate hyphae and branches at 45 degree angles.
Major risk factors
- Prolonged neutropenia
- Solid organ/stem cell transplant recipients, especially allogeneic bone marrow transplantation with Graft-versus-host disease
- TNF-alpha antagonists (infliximab)
- Corticosteroids
- Chronic granulomatous disease
Clinical manifestations
- Allergic broncho-pulmonary aspergillus (ABPA): Type I Hypersensitivity reaction with eosinophilia and increased IgE
- Aspergilloma (fungus ball): Grown within pre-existing cavity
- Invasive pulmonary aspergillosis (IPA): Invades vasculature and presents with cavitary lesions and pulmonary nodules
Treatment
Azoles, Echinocandins, or Amphotericin B
Mucormycosis
A mold. This review focuses on Rhizopus and Mucormycosis. Characterized by broad and ribbon-like, non-septate hyphae that branch irregularly and/or at right angles.
The Rhizopus species can thrive in high glucose and acidic environments and it is equipped with a ketone reductase. Growth is favored in iron overload and the use of deferoxamine.
Major risk factors
- Diabetic ketoacidosis
- Diabetes mellitus
- Prolonged neutropenia
- Transplant
- Hematologic malignancies
Clinical manifestations
- Rhino-orbital-cerebral: Diabetic ketoacidosis
- Pulmonary: Hematologic malignancies
- Gastrointestinal: Diabetes mellitus
Treatment
Surgical debridement followed by Azoles and Amphotericin B
Dermatophytes
A mold. Filamentous fungi responsible for cutaneous infection. Some types include Trichophton, Microsporum, and Epidermohyton.
Clinical manifestations
All of the Tinea infections: Tinea pedis (athletes foot), Cruris, Manuum, Corporis (ringworm), Capitis, and Faciei.
They can also elicit an an immunologic response to fungal antigens. It occurs distal to the initial infection and manifests as pruritic papulovesicular lesions.
Treatment
Topical antifungals (Azoles, Griseofulvin) as well as oral antifungals (Terbinafine).
Cryptococcus
A yeast. The three forms include C. neoformans, C. grubii, and C. gattii. Grows White, clear colored opaque colonies.
Assays: India ink (+), Urease (+), Laccase (+)
Cryptococcal Ag (cerebral spinal fluid, blood) is the diagnostic test of choice.
Major risk factors
Transmission includes inhalation of soil and depressed cell mediated immunity. Especially soil associated with pigeon and chicken droppings, in the case of C. neoformans.
Clinical manifestations
Meningitis is very important to note here.
- Pulmonary: nodules in parenchyma, infiltrates
- CNS: Meningitis, intracranial pressure on cranial nerves can lead to optic neuritis and vision loss
- Skin: Skin lesions
Treatment
Amphotericin B plus flucytosine (5-FC) and then fluconazole for maintenance.
Histoplasma capsulatum
Dimorphic fungus. Grows in soil, associated with chicken, starling, and bat excrement.
Biopsy will shows macrophages with small intracellular oval yeast forms. Histoplasma Ag (urine, serum) is the diagnostic test of choice.
Major risk factors
- Depressed cell mediated immunity
- Organ transplantation
- Defects in IFN-gamma-IL12 pathway
- Diabetes mellitus
Clinical manifestations
90% of cases are asymptomatic. It has the ability to disseminate to reticuloendothelial system, like the liver, spleen, and lungs. Will hide out and remain dormant in immunocompetent hosts until immunocompromised.
- Pulmonary: Acute diffuse histoplasmosis (multiple pulmonary nodules)
- Skin: erythema nodosum (large, painful nodules on shins) and erythema multiforme
- Progressive Disseminated Histoplasmosis (PDH): Includes oral ulcers, lymphadenopathy, and hepatosplenomegaly, among other symptoms
Treatment
Amphotericin B followed by Itraconazole
Coccidioidomycosis (Coccidioides immitus)
Dimorphic fungus. Also known as Valley Fever.
A giant spherule (yeast form) will be found on Hematoxylin and Eosin (H&E) stain, Pap smear, or KOH preparation. High IgM will be found first and then high IgG around 3 months later.
Major risk factors
- Depressed cell mediated immunity
- Pregnancy
Clinical manifestations
- Viral-like upper respiratory symptoms (Valley Fever)
- Pulmonary: Alveolar infiltrate or solitary pulmonary nodule, hilar and mediastinal lymphadenopathy
In Disseminated Coccidioidomycosis, it can move to skin and bones/joints and cause osteolytic lesions. It can also cause eosinophilic or basilar meningitis. There will be positive (+) CF (complement fixation) antibody in 70% of these cases.
Treatment
For acute infection there are no recommended therapies. For disseminated infections, Azoles are used.
Blastomyces Dermatitids
A dimorphic fungus. Transmitted through inhalation (dirt/wood) or animal bites.
Diagnosis includes broadly based budding yeast from sputum. Additionally, assay for Blastomyces antigen (urine, serum).
Clinical manifestations
Extra-pulmonary manifestations occur simultaneously with pulmonary manifestations.
- Acute pulmonary blastomycosis
- Alveolar infiltrates in lower lobes
- Verrucous (warts) and ulcerative lesions
Sporothrix schenckii
A dimorphic fungus. Exposure includes rose gardening (classic exposure), landscaping, and cats.
Clinical manifestations
- Lymphocutaneous
- Linear, nodular lymphangitis