Fungal Infections and Antifungal Drugs

Pityriasis (Tinea) Versicolor

• Superficial skin infection caused by yeast Malassezia furfur
• Characterized by pale or dark patches of skin
• Part of normal skin flora in majority of adults, but can cause problems
• Requires fatty acids for growth, so media must contain oil

Fungal Infections

• Poor range of antifungal drugs compared to antibacterials
• Interest in developing new drugs

Antifungal Drugs

• Amphotericin B: binds to ergosterol in cell membrane, broad spectrum, systemic
• Flucytosine: converted to fluorouracil, synergistic with amphotericin B
• Azoles (e.g. Fluconazole, Itraconazole): inhibit ergosterol synthesis, systemic
• Griseofulvin: accumulates in keratinized tissue, interacts with fungal microtubules, dermatophytes
• Nystatin: binds to ergosterol in cell membrane, topical

Histoplasma capsulatum

• Grows as mold in soil and culture, and as yeast or mold in animal tissues
• Intracellular parasite found in soil rich with bird and bat droppings
• Occurs in USA, endemic in Ohio and Mississippi River valleys
• Histoplasmosis: usually asymptomatic or flu-like symptoms with fever and cough
• 250,000 new cases each year in USA

Yeast Infections

• Candida
  • Appears as Gram-positive, oval budding yeast
  • Forms pseudohyphae in culture and tissues
  • On Sabouraud agar, produces soft, cream-colored colonies with characteristic yeasty smell
  • Submerged growth consists of pseudomycelia

Infections

• Mouth

  • Oral thrush: white patches inside mouth, most common in infants and AIDS patients
  • Enhanced by corticosteroids, antibiotics, high levels of glucose, and immunodeficiency

• Female genitalia

  • Vaginal thrush or vulvovaginitis: irritation, discharge, intense itching
  • Acid pH normally maintained by bacteria, suppressing Candida
  • Diabetes, pregnancy, progesterone, and antibiotics predispose

• Skin

  • Occurs in warm parts of body
  • Often follows immersion in hot water

• Nails

• Lungs and other organs

  • May be secondary infection of lungs, kidney, and other organs under predisposing conditions
  • Chronic mucocutaneous candidosis: sign of immunodeficiency in children

Ringworm (Tinea corporis, Tinea cruris)

• Dermatophytosis of non-hairy skin gives rise to annular lesions of ringworm
• Varying degrees of inflammation may be found
• Most common isolates: E. floccosum, T. rubrum, and T. mentagrophytes
• Treat with antifungal cream

Non-dermatophyte Superficial Infections

• Non-dermatophytes: faster growing, grow on Sabouraud agar only (pH altered and without cyclohexamide)
• Cause problems for immunocompromised patients with limited cellular immunity

Tinea capitis (Ringworm of the Scalp)

• Microsporum in childhood
• Trichophyton in adults
• Infection begins on skin of scalp and then down wall of hair follicle
• May appear as alopecia with scaling, black dot ringworm
• Trichophyton may also infect beard hair
• Treatment: remove hairs, treat with Griseofulvin or shampoo with Miconazole

Aspergillus

• Aspergillosis: group of mycoses caused by spp. of the filamentous fungus Aspergillus
• Infection comes from exogenous source
• Pulmonary aspergillosis may occur in distinct forms:
  • One: aspergilloma, fungus ball growing in a pre-existing cavity (e.g. tuberculosis)
  • Often asymptomatic or patient has a cough

Aspergillus

• Invasive aspergillosis: caused by A. fumigatus in immunocompromised patients
• Widespread destruction of tissue as fungus grows
• Treat with Amphotericin B
• Allergic aspergillosis: occurs in patients with elevated IgE levels
  • 10-20% of asthmatics react to A. fumigatus
• Treatment: corticosteroids

Coccidioides immitis

• Dissemination occurs in less than 0.5% of cases
  • Often immunocompromised patients
• Chronic cases: localized cavities in lungs filled with spherules (cylindrical bodies) of C. immitis
• Other tissues involved: bones, liver, meninges, brain, skin, and heart
• Can be treated with Amphotericin B
• High death rate in disseminated cases