Antifungal Agents

Chapter 11: Antifungal Agents

Differences Between Fungi and Bacteria

• Cell Structure

  • Fungi have a rigid cell wall composed of chitin and various polysaccharides.

  • Cell membrane contains ergosterol.

• Resistance to Antibiotics

  • The protective layers of the fungal cell make fungi resistant to antibiotics.

  • Bacteria are inherently resistant to antifungal drugs due to their distinct cellular makeup.

Patients Susceptible to Fungal Infections

• Individuals at Higher Risk

  • Patients with AIDS and AIDS-related complex (ARC).

  • Patients taking immunosuppressant drugs.

  • Patients who have undergone transplantation surgery or cancer treatment.

  • Older adults who may have diminished protection against environmental fungi due to aging.

Systemic Antifungals

• General Information

  • Drugs used for treating systemic infections can be toxic to the host.

  • A culture should be obtained before treatment to ensure the appropriate drug is chosen.

  • It is crucial to avoid putting patients at additional risks for toxic adverse effects.

Use of Antifungals Across the Lifespan

Children

• Many antifungal drugs lack proven safety and efficacy in children.

• Drugs of Choice

  • Fluconazole, ketoconazole, terbinafine, and griseofulvin have established pediatric dosages and can be used for specific infections.

• Topical Agent Usage

  • Should not be applied over open or draining areas due to the risk of increased systemic absorption and toxicity.

  • Use of occlusive dressings, such as tight diapers, over affected areas should be avoided.

Adults

• Antifungal drugs can be highly toxic, thus they should be reserved for cases where the causative organism is identified.

• Over-the-Counter Preparations

  • Patients should follow instructions closely and report persistent issues to healthcare providers.

• Pregnant and Nursing Patients

  • Should avoid these drugs unless benefits clearly outweigh potential risks to the fetus or neonate.

  • Patients capable of becoming pregnant must be advised to use barrier contraception while using antifungals.

  • In severe cases of fungal infections that threaten life, potential risks of treatment must be carefully explained.

• Topical Agents

  • Should not be applied over open or draining areas due to risks of systemic absorption.

Older Adults

• Older individuals may be more prone to adverse effects from antifungal drugs and require careful monitoring.

• Hepatic Dysfunction

  • Increased risk of worsening hepatic issues and toxic effects are noted with drugs like ketoconazole, itraconazole, and griseofulvin.

  • Dosage may need adjusting and frequent monitoring is vital for this population.

• Renal Toxicity Risks

  • Certain agents such as amphotericin B, flucytosine, and griseofulvin can cause renal toxicity and should be used cautiously in individuals with renal impairment.

  • For fluconazole, dosages should be reduced in cases of renal dysfunction to avoid accumulation-related adverse effects.

Sites of Action of Antifungals

• Cell Membrane

  • Antifungal agents act at various locations in cellular structures such as:

  • Cilia with microtubules

  • Microtubules

  • Mitochondria

  • Rough and smooth endoplasmic reticulum

  • Golgi apparatus

  • Lysosomes

  • Nucleus (nuclear membrane, nuclear pore, nucleolus, polyribosomes)

Azole Antifungals

• Indications

  • Used for treating systemic and topical fungal infections.

• Mechanism of Action

  • Bind to sterols, causing either cell death or interference with cell replication, depending on the fungus type and drug concentration.

• Pharmacokinetics

  • Varies by specific drug.

• Contraindications and Cautions

  • Hepatic and renal dysfunction, endocrine or fertility issues, pregnancy or lactation.

• Adverse Effects

  • Potential liver toxicity; severe effects on fetus or nursing baby.

• Drug-Drug Interactions

  • Numerous; consultation with a drug guide is advised.

Echinocandin Antifungals

• Indications

  • Treatment of fungal infections.

• Mechanism of Action

  • Inhibit glucan synthesis, leading to cell wall death.

• Pharmacokinetics

  • Generally given intravenously; onset and excretion vary by drug.

• Contraindications and Cautions

  • Pregnancy and lactation, hepatic impairment.

• Adverse Effects

  • Hepatic toxicity, serious hypersensitivity reactions, bone marrow suppression.

• Drug-Drug Interactions

  • Notable interactions with cyclosporine and caspofungin.

Other Antifungal Agents

• Agents Not Fitting into Classes

  • Amphotericin B (Abelcet, AmBisome)

  • Flucytosine (Ancobon)

  • Griseofulvin (Gris-Peg)

  • Nystatin (generic)

  • Terbinafine (Lamisil)

• Indications

  • Treatment of fungal infections.

• Mechanism of Action

  • Function via various mechanisms to induce fungal cell death or stall further cell replication.

• Pharmacokinetics

  • Varies by agent.

• Contraindications and Cautions

  • Drug-dependent; amphotericin B can be cautiously used during pregnancy.

• Adverse Effects

  • Notable hepatic and renal toxicity, bone marrow suppression, rash, gastrointestinal effects.

• Drug-Drug Interactions

  • Amphotericin B should not be combined with other nephrotoxic agents.

Topical Antifungals

• Indications

  • Local treatment for various skin and mucous membrane mycoses.

• Mechanism of Action

  • Alter the cell permeability in fungi, preventing replication and leading to cell death.

• Pharmacokinetics

  • Not absorbed systemically.

• Contraindications and Cautions

  • Limited to known allergies to these drugs; avoid in areas with open lesions.

• Adverse Effects

  • Potential irritation, burning, rash, and swelling at the application site; gastrointestinal, hepatic, and urinary effects can arise when used as a suppository.

Nursing Considerations for Antifungal Therapy

Systemic Antifungal Agents

• Assessment Requirements

  • Check for contraindications or cautions such as a history of allergy, liver or renal dysfunction, pregnancy, or lactation.

  • Conduct a physical assessment to establish baseline data.

  • Obtain a culture of the infected area.

  • Perform renal and hepatic function tests and complete blood count (CBC).

Topical Antifungal Agents

• Assessment Requirements

  • Verify any known allergy to topical antifungal agents.

  • Conduct a physical assessment to establish baseline data.

  • Conduct culture and sensitivity testing.

  • Inspect the area of application for color, temperature, and evidence of lesions.

Prototype Antifungal Agent #1: Fluconazole

• Indications

  • Treatment of oropharyngeal, esophageal, and vaginal candidiasis; cryptococcal meningitis; systemic fungal infections; prophylaxis to decrease candidiasis incidence in bone marrow transplants.

• Mechanism of Action

  • Binds to sterols in the fungal cell membrane, altering membrane permeability; acts as fungicidal or fungistatic based on concentration and organism.

• Pharmacokinetics

  • Route:

    • Oral: Slow onset, peak in 1-2 hours, duration 2-4 days.

    • IV: Rapid onset, peak at the end of infusion, duration 2-4 days.

  • Half-Life: 30 hours; metabolized in the liver, excreted in urine.

• Adverse Effects

  • Include headache, nausea, vomiting, diarrhea, abdominal pain, and rash.

Prototype Antifungal Agent #2: Clotrimazole

• Indications

  • Treatment of oropharyngeal candidiasis (troche); prevention of oropharyngeal candidiasis in those undergoing radiation or chemotherapy; local treatment for vulvovaginal candidiasis; topical treatment for tinea pedis, tinea cruris, and tinea corporis.

• Mechanism of Action

  • Binds to sterols in the fungal cell membrane, leading to altered permeability and intracellular component leakage, resulting in cell death.

• Pharmacokinetics

  • Not absorbed systemically; pharmacokinetics generally unknown.

• Adverse Effects

  • Troche: nausea, vomiting, abnormal liver function tests. Topical: stinging, redness, urticaria, edema. Vaginal: lower abdominal pain, urinary frequency, burning or irritation in sexual partner.

Questions and Answers

Question #1

• Statement: Nystatin, taken orally, is used for the treatment of intestinal candidiasis. - Answer: True

• Rationale: Nystatin (generic) is effective in its oral form for treating candidiasis.

Question #2

• Which of the following is a contraindication of ketoconazole?

  • A) Patients with renal problems

  • B) Patients with fertility problems

  • C) Patients with hepatic problems

  • D) Patients with GI problems

• Answer: B. Patients with fertility problems

• Rationale: Ketoconazole is contraindicated in patients with endocrine or fertility issues due to its effects on sex hormones.

Question #3

• The nurse is caring for a patient with a fungal infection. Which of the following is an adverse effect of a topical antifungal medication?

  • A) Burning or irritation in the sexual partner

  • B) Abnormal kidney function tests

  • C) Upper abdominal pain

  • D) Urinary retention

• Answer: A. Burning or irritation in the sexual partner

• Rationale: Possible adverse effects associated with vaginal suppository usage include lower abdominal pain, urinary frequency, and burning or irritation in the sexual partner.

Conclusion

• The information covered includes differences between fungal and bacterial infections, populations at risk for fungal infections, various antifungal drugs, their mechanisms of action, indications, pharmacokinetics, adverse effects, and nursing considerations. This comprehensive overview serves to ensure effective and safe treatment of fungal infections.