Antifungal Medications

Cellular Biology and Pathophysiology of Fungi

Differentiation from Other Pathogens:
- Fungi are biologically distinct from bacteria and human cells.
- Cellular Structure: Fungi possess a rigid cell wall and a cell membrane structure that differs significantly from bacterial and human cell membranes.
- Treatment Limitations: Because of these structural differences, standard antibiotics (used for bacteria) and antivirals (used for viruses) are ineffective against fungal cells.
- Selective Toxicity: Antifungal medications must specifically target the unique components of the fungal cell to eradicate the infection without harming the host.
Patient Populations Susceptible to Systemic Fungal Infections:
- The following populations are at an increased risk for serious, systemic fungal infections (infections that enter the bloodstream):
  - Immunocompromised Patients: Individuals with weakened immune systems for any reason.
  - Antibiotic Therapy: Patients on long-term antibiotic regimens, which can disrupt normal flora and allow fungi to thrive.
  - Nutritional Status: Patients who are malnourished.
  - Disease States: Patients with diabetes or $AIDS$ .
  - Pregnancy: Pregnant patients are considered specifically susceptible.
  - Medical Treatments: Patients undergoing chemotherapy or receiving antineoplastic agents, and those on immunosuppressant drugs.

Classifications and Manifestations of Fungal Infections

Terminology:
- The prefix or root " $myco$ " specifically refers to fungus. Examples include mycoses, blastomycosis, and coccidioidomycosis.
Systemic Fungal Infections:
- These involve the bloodstream and internal organs; they are considered very difficult to eradicate and treat.
- Locations: Commonly found in the lungs (pulmonary) or the Central Nervous System ( $CNS$ ).
- Specific Examples:
  - Disseminated Candidiasis: Widespread infection through the body.
  - Aspergillus: A common systemic fungal infection.
  - Cryptococcal Meningitis: Fungal infection of the brain and spinal cord membranes ( $CNS$ ).
  - Histoplasmosis: Primarily affects the lungs.
  - Blastomycosis: Primarily affects the lungs.
  - Coccidioidomycosis: Primarily affects the lungs.
Superficial Fungal Infections:
- These affect the outer surfaces of the body and are more common and easier to treat than systemic types.
- Locations: Skin, nails, hair, or mucous membranes.
- Dermatophytes: Fungi that require keratin for growth ( $\text{Keratin}$ is found on the skin and nails).
- Specific Examples:
  - Oral Candidiasis (Thrush): Infection of the mouth.
  - Tinea Cruris (Jock Itch): Fungal infection of the groin area.
  - Tinea Pedis (Athlete's Foot): Fungal infection of the feet.
  - Candida Vulvovaginitis: Vaginal yeast infections.
  - Tinea Capitis: Ringworm of the scalp.

Systemic Antifungal Agents: Polyenes

Amphotericin B:
- Profile: An extremely potent drug reserved exclusively for very serious, potentially fatal systemic infections.
- Route: Administered only via Intravenous ( $IV$ ) infusion.
- Administration Guidelines:
  - Infusion Rate: Must be given very slowly over several hours, typically $4-6$ hours.
  - Test Dose: A small test dose may be administered to assess the patient's tolerance before the full dose is given.
  - Premedication: Patients are typically pre-medicated to manage unpleasant side effects. Premedication includes:
    - Antipyretics: Acetaminophen (to prevent fever/chills).
    - Antiemetics: Ondansetron ( $\text{Zofran}$ ) (to prevent nausea).
    - Antihistamines: Diphenhydramine ( $\text{Benadryl}$ ).
    - Corticosteroids: Methylprednisolone (to reduce inflammation and systemic reactions).
- Side Effects and Adverse Reactions during Infusion:
  - Fever and chills.
  - Nausea and vomiting.
  - Headaches and malaise/fatigue.
  - Hypotension (low blood pressure).
  - Thrombophlebitis (inflammation of the vein).
- Major Toxicities:
  - Nephrotoxicity: Toxic to the kidneys; renal function must be monitored closely.
  - Bone Marrow Depression: Results in decreased white blood cell ( $WBC$ ) counts, decreased red blood cell ( $RBC$ ) counts, and decreased platelets.
  - Neurotoxicity: Can cause numbness, tingling, visual changes, seizures, and peripheral neuropathies (damage to the central and peripheral nervous systems).
- Drug Interactions: The number of drug interactions is described as "Too Numerous To Count" ( $\text{TNTC}$ ).
- Lipid Preparation: There is a lipid-based formulation of Amphotericin B designed to increase the drug's efficacy while decreasing the severity of side effects.

Systemic Antifungal Agents: Azoles and Echinocandins

Azole Antifungals (Imidazoles):
- Identifier: Most drugs in this class end in the suffix "-azole."
- Prototype: Fluconazole ( $\text{Diflucan}$ ). Others include Ketoconazole.
- Note on Look-alikes: Lamisil is a look-alike, sound-alike drug name to be aware of.
- Fluconazole Characteristics:
  - Provides excellent coverage for various infections.
  - CSF Penetration: Can penetrate the Cerebrospinal Fluid ( $CSF$ ), making it effective for conditions like cryptococcal meningitis.
  - Vesicant Properties: If administered $IV$ , it is a vesicant. Extravasation can cause tissue necrosis.
  - Route: Available as $IV$ , oral, and topical (the topical form for yeast infections uses a much lower dosage and is generally well-tolerated).
  - Side Effects: More tolerable than Amphotericin B, but can cause $GI$ symptoms.
  - Hepatotoxicity: Hard on the liver; requires monitoring of liver enzymes.
Echinocandins:
- Identifier: Drugs ending in "-fungin" (e.g., Capsofungen, Micafungen).
- Route: Administered $IV$ for serious systemic infections.
- Adverse Effects:
  - Liver Toxicity: The primary side effect.
  - Hypersensitivity/Anaphylaxis: Can lead to hypotension, respiratory failure, and septic shock.
  - Mild Reactions: Infusion reactions, phlebitis, nausea, vomiting, diarrhea, and rashes.

Topical Antifungal Agents and Nursing Care

Topical Agents (OTC/Prescription):
- Examples: Monistat, Lotrimin, Tenactin.
- Nystatin:
  - Commonly used for oral candidiasis ( $Thrush$ ), particularly in oncology patients undergoing chemotherapy.
  - Oral Suspension (Swish/Spit or Swish/Swallow): Patients swish the liquid in the mouth as long as possible. If the infection is in the throat, they swallow; otherwise, they spit it out.
  - Lozenge/Troche: A tablet or cough-drop-like form that dissolves slowly in the mouth. Patients must not chew it or swallow it whole; the saliva containing the medication needs to remain in contact with the oral mucosa.
General Nursing Interventions and Patient Education:
- Course of Treatment: Instruct patients to take the entire course of the drug as prescribed, which may take weeks due to the stubborn nature of fungi.
- Topical Application Rules:
  - Do not use near open wounds.
  - Do not use occlusive dressings (e.g., plastic coverings) over the medication.
- Liver Function Monitoring:
  - Assess for signs of liver toxicity (especially with $IV$ azoles/echinocandins).
  - Signs of Hepatotoxicity: Fatigue, jaundice (yellowing of skin/eyes), right upper quadrant ( $RUQ$ ) pain, nausea, vomiting, darkened urine, light-colored (clay) stools, and increased bleeding or bruising.
- General Assessment: Monitor for the resolution of the fungal infection symptoms and monitor for $GI$ upset.