Antifungal Agents

What Is a Fungus?

• Fungus
  • Composed of a rigid cell wall made up of chitin and various polysaccharides, and a cell membrane containing ergosterol
  • Protective layers of the fungal cell make the organism resistant to antibiotics

Patients Susceptible to Fungal Infections

• Patients with AIDS and AIDS-related complex (ARC)
• Patients taking immunosuppressant drugs
• Patients who have undergone transplantation surgery or cancer treatment
• Members of growing elderly population no longer protected from environmental fungi

Culture

• Culture is needed prior to prescribing antifungal agents
• Patients on antifungal agents are immuno-compromised at onset

Amphotericin B Indications

• Aspergillosis
• Leishmaniasis
• Cryptococcosis
• Blastomycosis
• Moniliasis
• Coccidioidomycosis
• Histoplasmosis
• Mucormycosis
• Candida infections (topically)

Amphotericin B

• Indications: progressive, potentially fatal fungal infections
• Pharmacokinetics: IV form, excreted in the urine
• Contraindication: kidney disease
• Adverse reaction: kidney failure

Systemic Antifungal Agents

• Caspofungin (Cancidas) (IV)
  • Approved for the treatment of invasive aspergillosis in patients who are refractory to other treatments
• Flucytosine (Ancobon) (oral)
  • Less toxic drug used for the treatment of systemic infections caused by Candida or Cryptococcus
• Nystatin (Mycostatin, Nilstat) (oral)
  • Used for the treatment of intestinal candidiasis; also available in a number of topical preparations

Voriconazole & Terbinafine

• Newer agents
• Voriconazole (Vfend)
  • Available in oral and IV forms
  • Treats invasive aspergillosis and serious infections caused by Scedosporium apiospermum and Fusarium species
• Terbinafine (Lamisil)
  • Blocks the formation of ergosterol
  • Inhibits a CYP2D6 enzyme system
  • Oral drug for the treatment of onychomycosis of the toenail or fingernail

Azoles

• Newer class of drugs used to treat systemic fungal infections
• Less toxic than amphotericin B
• Less effective than amphotericin B

Ketoconazole (Nizoral)

• Used orally to treat many of the same mycoses as amphotericin B
• Works by blocking the activity of a steroid in the fungal wall
• Has side effect of blocking the activity of human steroids, including testosterone and cortisol
• Pharmacokinetics: absorbed from the GI tract, metabolized in the liver, excreted in the feces
• Contraindications: not drug of choice for patients with endocrine or fertility problems
• Adverse reaction: hepatic toxicity
• Drug-to-drug interactions: many

Fluconazole (Diflucan)

• Not associated with the endocrine problems seen with ketoconazole
• Used to treat candidiasis, cryptococcal meningitis, and other systemic fungal infections
• Prophylactic agent for reducing the incidence of candidiasis in bone marrow transplant recipients
• Pharmacokinetics: available in oral and IV preparations, excreted unchanged in the urine
• Contraindications: renal dysfunction
• Adverse reactions:
• Drug-to-drug interactions: inhibits CYP450 and may be associated with drug-to-drug interactions

Itraconazole (Sporanox)

• An oral agent used for the treatment of assorted systemic mycoses
• Associated with hepatic failure
• Slowly absorbed from the GI tract, it is metabolized in the liver by the CYP450 system
• Excreted in the urine and feces

Sites of Action of Antifungal Agents

Sites of Action of Antifungal Agents

Overall Contraindications to Systemic Antifungal Agents

• Anyone with a known allergy
• Pregnant or lactating women (with the exception of terbinafine for life-threatening infections)
• Patients with renal or liver disease
  • Drug metabolism or excretion may be altered, or condition may worsen as a result of the actions of the drug

Overall Adverse Reactions to Systemic Antifungal Agents

• CNS effects
  • Headache, dizziness, fever, shaking, and chills
• GI effects
  • Nausea, vomiting, dyspepsia, and anorexia
• Hepatic dysfunction
• Dermatologic effects
  • Rash and pruritus associated with local irritation
• Renal dysfunction

Topical Antifungal Infections

• Caused by dermatophytes
• Tinea infections (ringworm)
  • Athlete’s foot (tinea pedis)
  • Jock itch (tinea cruris)
• Candida
  • Yeast infections of the mouth and vagina

Topical Antifungal Agents

• Action
  • Work to alter the cell permeability of the fungus, causing prevention of replication and fungal death
• Indication
  • Indicated only for local treatment of mycoses, including tinea infection
• Contraindication/caution
  • Limited to known allergy to any antifungal agent
• Adverse effects
  • Local effects include irritation, burning, rash, and swelling
  • When taken as a suppository or troche, nausea, vomiting, hepatic dysfunction, urinary frequency, burning, and change in sexual activity can occur
• Drug-to-drug interactions
  • None reported

Prototype Antifungal Agent

Fluconazole

Clotrimazole

Use of Antifungals Across the Lifespan

Drug Therapy Across the Lifespan

Nursing Considerations for Systemic Antifungal Agents

• Assessment (history and physical exam)
• Nursing diagnosis
• Implementation
• Evaluation

Nursing Considerations for Topical Antifungal Agents

• Assessment (history and physical exam)
• Nursing diagnosis
• Implementation
• Evaluation