• Clinical science

Antifungals

Abstract

Antifungals are used in the treatment of mycotic infections such as candidiasis, cryptococcal disease, aspergillosis, and dermatophytosis. They are primarily divided into four groups and are differentiated based on their chemical structure and specific spectrum of efficacy. Whereas intravenous broad-spectrum antifungals (such as fluconazole or lipid formulations of amphotericin B) cover almost all known fungi, topical agents (such as clotrimazole) often have a limited scope of activity. Hepatotoxicity, skin reactions, headaches and gastrointestinal symptoms are common side effects.

Substances

Substance class Active substance Mechanism of action Clinical use Characteristics Important adverse effects

Polyenes

  • Very broad spectrum of efficacy
  • Available as
  • Important contraindications
    • Renal dysfunction
    • Hepatic dysfunction
  • Pregnancy and breastfeeding: not generally recommended in breastfeeding mothers
Azoles Imidazole derivatives
  • Broad spectrum of efficacy
  • Children and newborns: safety and efficacy for patients < 3 years are not known
  • Local burning, reaction, and/or pruritus
  • Broad spectrum of efficacy
  • Children and newborns: safety and efficacy for patients < 16 years are not known
  • Broad spectrum of efficacy
  • Pregnancy and breastfeeding
  • Children and newborns
    • Ketoconazole: safety and efficacy for patients < 3 years are not known
    • Voriconazole: safety and efficacy for patients < 12 years are not known
    • Itraconazole: safety and efficacy for patients < 3 years are not known
  • Important contraindications
    • Cardiac arrhythmias (e.g., prolonged QT)
    • Severe cardiac insufficiency
    • Avoid cross-reactions with drugs metabolized by cytochrome P-450
  • Use with caution in patients with:
    • Renal dysfunction
    • Hepatic dysfunction
  • If given orally, discontinue PPIs, as they require a low pH to be absorbed

Triazole derivatives

Echinocandins

  • Inhibit synthesis of β-glucan (a component of the fungal cell wall)
  • Broad spectrum efficacy
  • Only minimal distribution to the CSF
  • Newborns: safety and efficacy for patients < 3 months are not known
  • Flushing
  • Hypotension
  • Respiratory failure
  • Hepatotoxicity
  • Gastrointestinal upset
  • Hypokalemia
  • Phlebitis/pain at injection site
  • Fever, shivering

Pyridone derivatives

Allylamine derivative

  • Inhibit fungal squalene epoxidase, which decreases ergosterol synthesis

Benzofurans

  • Narrow range of efficacy
  • Important contraindications: porphyria, hepatic failure
  • Children and newborns: safety and efficacy for patients < 2 years are not known
  • Avoid during pregnancy and breastfeeding
  • Hepatotoxicity
  • Rashes and severe skin reactions (e.g., Stevens-Johnson syndrome)
  • Urticaria
  • Carcinogenic
  • Teratogenic
  • Induces cytochrome P-450↓ concentration of many drugs metabolized by P-450 (e.g., warfarin)
Antimetabolites
  • Converted to 5-fluorouracil by fungal cytosine deaminase, which then inhibits DNA and RNA synthesis
  • Monotherapy: select cases of non-life-threatening infections such as genitourinary candida infections that are not covered by alternative drugs
  • Combination with amphotericin B: systemic fungal infections (especially cryptococcal meningitis)
  • Use with extreme caution in patients with renal impairment
  • Avoid during pregnancy and breastfeeding
  • Hepatic injury
  • Renal failure
  • Gastrointestinal (e.g. nausea)
  • Bone marrow suppression with pancytopenia


CNS penetration of fluconazole: “FLU through the blood-brain barrier”

Voriconazole is the drug of choice for inVasive aspergillosis.

References:[1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24]

Treatment of common fungal infections

Suggested treatment
Candidiasis

Aspergillosis

Cryptococcosis

Blastomycosis

Histoplasmosis

Coccidioidomycosis

Sporotrichosis

Tinea versicolor
Dermatophytosis

References:[25][26]