antifungal

• Normal MRI of the brain, lumbar puncture revealing 330 WBC with 20% eosinophils, protein 75, and glucose 20
• Empiric therapy for bacterial meningitis with vancomycin and ceftriaxone unsuccessful after 72 hours
• White mold identified growing from CSF culture after 3 days
• Amphotericin B:

  • Binds to sterols in the fungal cell membrane
  • Causes loss of intracellular K+
  • Greater avidity to ergosterol
  • Enhances antifungal effect of flucytosine
  • Therapeutic uses include mucormycosis, aspergillosis, cryptococcosis, and more
  • Adverse effects include chills, fever, vomiting, headache, renal toxicity, and anemia
• Imidazoles/Triazoles:

  • Inhibit sterol biosynthesis
  • Therapeutic uses include systemic fungal infections like cryptococcal meningitis and vaginal candidiasis
• Ketoconazole:

  • Inhibits CYPP450
  • Adverse effects include primarily GI effects, hepatotoxicity, and endocrine effects
• Itraconazole:

  • Absorption reduced in fasting and reduced gastric acidity
  • Concentration decreased by concomitant use of certain drugs
  • Preferred over ketoconazole for nonmeningeal histoplasmosis
  • Adverse effects include hepatotoxicity and rash
• Fluconazole:

  • Completely absorbed, not affected by food or gastric acidity
  • Therapeutic uses include candidiasis, cryptococcosis, and more
  • No effect on CYP450 metabolizing steroid synthesis
• Flucytosine:

  • Combined with amphotericin for severe infections like cryptococcal meningitis
  • Converted into antimetabolite 5-fluorouracil
  • Given by IV infusion or orally
  • Unwanted effects are infrequent and include anemia, neutropenia, thrombocytopenia, and alopecia
• Clotrimazole:

  • Therapeutic uses include dermatophytosis, candidiasis, tinea versicolor, and fungal keratitis
• Miconazole:

  • Therapeutic uses include vulvovaginal candidiasis and tinea infections
  • Adverse effects include burning, itching, or irritation with vaginal application
• Griseofulvin:

  • Active against dermatophytes like Microsporum, Epidermophyton, and Trichophyton
  • Treatment need is very prolonged
  • Given orally and deposited in keratin precursor cells
  • Therapeutic uses include mycotic diseases of skin, hair, and nails
• Nystatin:

  • Binds to fungal sterols
  • Therapeutic uses include candidiasis of the intestine, mouth, and skin
  • Adverse effects include nausea and bitter taste
• Undecylenic acid:

  • Useful in the treatment of dermatomycosis, especially tinea pedis
  • Cure rate is 50% lower than imidazoles
• Benzoic acid & Salicylic acid (Whitfield's ointment):

  • Fungistatic benzoic acid and keratolytic salicylic acid
  • Used in the treatment of tinea pedis
  • Treatment lasts for several weeks to months
  • Mild irritation at the site of application