Antifungal Drugs and Fungal Infections

Classification of Antifungal Drugs

• Polyene antibiotics: amphotericin B, natamycin, nystatin
• Azole derivatives: clotrimazole, fluconazole, ketoconazole, itraconazole, posaconazole, voriconazole
• Allylamine drugs: terbinafine
• Echinocandin drugs: caspofungin
• Other antifungal agents

Fungal Infections

• Divided into three main groups:
  • Systemic mycoses: soft tissue infections, UTIs, PNA, meningitis, septicemia
  • Subcutaneous mycoses: sporotrichosis
  • Superficial mycoses: infections of nails, skin, and mucous membranes caused by dermatophytes and yeasts

Superficial Dermatophyte Infections

• Causative agents: Epidermophyton, Microsporum, Trichophyton spp.
• Manifest as rash with pruritus and erythema
• Ringworm presents as annular, scaly rash with clear center
• Examples:
  • Onychomycosis (tinea unguium): dermatophyte infection of nails
  • Tinea pedis (athlete's foot): infection of feet
  • Tinea corporis (ringworm of the body): infection of body
  • Tinea cruris (jock itch): infection of groin area

Superficial Yeast Infections

• Causative agents: Candida spp., usually C. albicans
• Present as oral candidiasis (thrush), vulvovaginal candidiasis, or candidiasis infections of axilla, groin, or gluteal folds (diaper rash)
• Less common causes: M. furfur, M. ovalis
  • M. furfur causes tinea versicolor (pityriasis versicolor)
  • Both yeasts cause seborrheic dermatitis

Subcutaneous Mycoses

• Often caused by puncture wounds contaminated with soil fungi
• Examples:
  • Chromomycosis
  • Pseudallescheriasis
  • Sporotrichosis

Systemic Mycosis

• Chronic and indolent: blastomycosis, coccidioidomycosis, histoplasmosis
• Invasive and life-threatening: aspergillosis, candidiasis, cryptococcosis, mucormycosis

Blastomycosis

• Fungal infection of humans and other animals caused by Blastomyces dermatitidis
• Endemic to North America
• Clinical symptoms similar to histoplasmosis
• Flu-like illness, acute illness resembling bacterial pneumonia, chronic illness mimicking TB/lung cancer, fast progressive disease like ARDS, skin lesions, bony lytic lesions

Coccidioidomycosis

• Also known as "valley fever", "California fever", and "San Joaquin Valley fever"
• Fungal disease caused by Coccidioides immitis or Coccidioides posadasii
• Endemic in certain parts of Arizona, California, Nevada, New Mexico, Texas, Utah, and northern Mexico
• 60% are asymptomatic, 40% have varied symptoms:
  • Classic triad ("desert rheumatism") of fever, joint pain, and erythema nodosum

Histoplasmosis

• Also known as "cave disease", "spelunker's lung", and "Ohio Valley disease"
• Fungal infection caused by Histoplasma capsulatum
• Found in soil, often associated with decaying bat guano or bird droppings
• Primarily affects lungs, called disseminated when other organs affected
• Can be fatal if left untreated

Aspergillosis

• Wide variety of diseases caused by fungi from genus Aspergillus
• Majority of cases in people with underlying TB or COPD but with otherwise healthy immune systems
• Most common occurs in form of chronic pulmonary aspergillosis, aspergilloma, or allergic bronchopulmonary aspergillosis

Cryptococcosis

• Potentially fatal fungal disease caused by Cryptococcus neoformans and Cryptococcus gattii
• Acquired by inhalation of infectious material from environment; found worldwide in soil
• Defining opportunistic infection for AIDS (but also seen with lymphomas, sarcoid, liver cirrhosis, and patients on long-term steroid therapy)

Mucormycosis

• Any fungal infection caused by fungi in the order of Mucorales
• Characterized by hyphae growing in and around blood vessels; potentially life-threatening in diabetic or severely immunocompromised individuals

Antifungal Drugs

• Classification:
  • Polyene antibiotics (e.g., amphotericin B)
  • Azole derivatives (e.g., clotrimazole, fluconazole)
  • Allylamine drugs (e.g., terbinafine)
  • Echinocandin drugs (e.g., caspofungin)
  • Other antifungal agents

Fungal Infections

• Divided into three main groups:
  • Systemic mycoses (e.g., soft tissue infections, UTIs, PNA, meningitis, septicemia)
  • Subcutaneous mycoses (e.g., sporotrichosis)
  • Superficial mycoses (infections of nails, skin, and mucous membranes caused by dermatophytes or yeasts)

Superficial Dermatophyte Infections

• Causative agents: Epidermophyton, Microsporum, and Trichophyton spp.
• Typical manifestations:
  • Rash with pruritus and erythema
  • Ringworm presents as annular, scaly rash with clear center
• Term for dermatophyte infections:
  • Onychomycosis (tinea unguium): dermatophyte infection of nails
  • Tinea pedis: athlete's foot
  • Tinea corporis: ringworm of the body
  • Tinea cruris: jock itch

Superficial Yeast Infections

• Causative agents: Candida spp. (usually C. albicans)
• Presentations:
  • Oral candidiasis (thrush)
  • Vulvovaginal candidiasis
  • Candidiasis infections of axilla, groin, or gluteal folds (diaper rash)
• Less common causes: M. furfur (tinea versicolor, seborrheic dermatitis) and M. ovalis (seborrheic dermatitis)

Subcutaneous Mycoses

• Often caused by puncture wounds contaminated with soil fungi
• Examples: chromomycosis, pseudallescheriasis, and sporotrichosis

Systemic Mycosis

• Chronic and indolent (e.g., blastomycosis, coccidioidomycosis, histoplasmosis)
• Invasive and life-threatening (e.g., aspergillosis, candidiasis, cryptococcosis, mucormycosis)

Blastomycosis

• Fungal infection of humans and other animals caused by Blastomyces dermatitidis
• Endemic to North America
• Clinical symptoms: flu-like illness, acute illness resembling bacterial PNA, chronic illness mimicking TB/lung cancer, fast progressive disease like ARDS, skin lesions, bony lytic lesions

Coccidioidomycosis

• Also known as "valley fever," "California fever," and "San Joaquin valley fever"
• Fungal disease caused by Coccidioides immitis or C. posadasii
• Endemic in certain parts of AZ, CA, NV, NM, TX, UT, and northern Mexico
• 60% are asymptomatic, 40% have varied symptoms, including fever, joint pain, and erythema nodosum (classic triad, "desert rheumatism")

Histoplasmosis

• Also known as "cave disease," "spelunker's lung," and "Ohio valley disease"
• Fungal infection caused by Histoplasma capsulatum
• Found in soil, often associated with decaying bat guano or bird droppings
• Primarily affects lungs, can be fatal if left untreated

Aspergillosis

• Wide variety of disease caused by fungi from the genus Aspergillus
• Majority of cases occur in people with underlying TB or COPD but with otherwise healthy immune systems
• Most common forms: chronic pulmonary aspergillosis, aspergilloma, or allergic bronchopulmonary aspergillosis

Cryptococcosis

• Potentially fatal fungal disease caused by Cryptococcus neoformans and C. gattii
• Acquired by inhalation of infectious material from the environment
• Defining opportunistic infection for AIDS (but also seen with lymphomas, sarcoid, liver cirrhosis, and patients on long-term steroid therapy)

Mucormycosis

• Any fungal infection caused by fungi in the order of Mucorales
• Characterized by hyphae growing in and around blood vessels, potentially life-threatening in diabetic or severely immunocompromised individuals

Treating Fungal Infections

• Amphotericin B: typically used to treat severe mycoses
• Azoles: used for less severe infections
• New agents (e.g., voriconazole and caspofungin): used to treat invasive Candida and Aspergillus infections
• Flucytosine: usually given with amphotericin B to treat systemic cryptococcal or candida infections

This quiz covers the classification of antifungal drugs, including polyene antibiotics, azole derivatives, and echinocandin drugs, as well as types of fungal infections, such as systemic mycoses. Test your knowledge of these medicines and diseases.