Antifungal Medications
Key Points
- Antifungals treat mycoses (fungal infections) by disrupting ergosterol biosynthesis in fungal cell membranes, increasing cellular permeability and causing cell death.
- Drug class is divided by scope: topical agents (imidazoles, allylamines) for superficial infections; systemic agents (azoles, polyenes) for invasive or disseminated fungal disease.
- Amphotericin B is the most potent systemic antifungal but carries significant nephrotoxicity and infusion reactions.
- Fluconazole is the most commonly used azole; inhibits CYP3A4 and CYP2C9 — extensive drug interactions.
- Opportunistic fungal infections (candidiasis, aspergillosis, cryptococcosis) are common in immunocompromised patients.
- Candida auris is an emerging fungal threat associated with difficult diagnosis/treatment and healthcare-facility outbreaks.
Mechanism of Action
Most antifungals disrupt ergosterol synthesis in the fungal cell membrane. Ergosterol is unique to fungi (analogous to cholesterol in human cell membranes), so targeting it allows selective fungal toxicity. Disruption of ergosterol biosynthesis increases membrane permeability → cellular contents leak → fungal cell death.
Amphotericin B (polyene class) directly binds to ergosterol and creates pores in the fungal cell membrane, causing irreversible leakage. This mechanism explains its potency and its adverse effects on renal tubular cells, which also contain ergosterol-like sterols.
Drug Classes and Agents
| Class | Examples | Route | Primary Indications |
|---|---|---|---|
| Azoles (triazoles) | Fluconazole (Diflucan), voriconazole, itraconazole | PO / IV | Oral thrush, vaginal candidiasis, cryptococcal meningitis, systemic candidiasis |
| Azoles (imidazoles) | Clotrimazole, miconazole, ketoconazole | Topical | Tinea pedis (athlete’s foot), tinea cruris (jock itch), tinea corporis (ringworm) |
| Polyenes | Amphotericin B, nystatin | IV / topical | Systemic fungal infections (aspergillosis, histoplasmosis, blastomycosis, candidiasis); nystatin for oral thrush / vaginal |
| Allylamines | Terbinafine | Topical / PO | Dermatophytic skin infections, onychomycosis (fingernail / toenail fungus) |
Fluconazole dosing (oropharyngeal or esophageal candidiasis): 200 mg PO on day 1, then 100 mg PO once daily for 2 weeks.
Nystatin dosing (oropharyngeal candidiasis): 400,000–600,000 units swish and swallow 4 times daily × 7–14 days (continue 48 hours after symptom resolution); swish for 30 seconds before swallowing, then do not eat or drink for 10–30 minutes.
Adverse Effects
| Drug/Class | Key Adverse Effects |
|---|---|
| Amphotericin B | Nephrotoxicity (most serious), flulike infusion reactions (fever/chills), hypotension, hypokalemia, hypomagnesemia; lipid formulations reduce toxicity |
| Fluconazole / azoles | Hepatotoxicity, QT interval prolongation, nausea, rash; inhibit CYP3A4/2C9 — increases levels of warfarin, cyclosporine, many others |
| Terbinafine (oral) | Hepatotoxicity (rare but serious) |
| Topical agents | Local skin irritation, rash |
Nursing Assessment
NCLEX Focus
Amphotericin B nephrotoxicity is the priority monitoring concern for IV antifungal therapy. Assess BUN and creatinine before and during therapy. Prehydration with 1 L normal saline before infusion can reduce renal toxicity.
Pre-administration:
- Screen for drug allergies and known hypersensitivity
- Review current medications for CYP3A4 drug interactions (especially with azoles)
- Check baseline kidney function tests (BMP or CMP) before systemic antifungal therapy
- Assess immune status — immunocompromised patients are highest risk for systemic mycoses
- Flag persistent or clustered facility fungal infections early and escalate culture/susceptibility follow-up for potential resistant organisms such as Candida auris
Monitoring:
- Monitor kidney function with renally eliminated antifungals (amphotericin B, fluconazole)
- Observe for infusion reactions during IV amphotericin B: premedicate with diphenhydramine, acetaminophen, and corticosteroids per protocol; infuse over 2–6 hours
- Monitor liver function tests for patients on oral terbinafine or prolonged azole therapy
Nursing Interventions
- Instruct clients to complete the full course of antifungal therapy even if symptoms resolve, to prevent resistance and recurrence
- Maintain adequate hydration during systemic antifungal therapy
- Monitor for anaphylaxis signs: shortness of breath, difficulty swallowing, rash, hypotension
- Topical agents: apply to clean, dry skin; do not use occlusive dressings unless specifically directed; avoid eye contact
- In tinea capitis care, reinforce that oral systemic therapy is usually required; shampoos or topical agents are adjuncts for transmission reduction, not cure.
Amphotericin B Infusion Reactions
IV amphotericin B commonly causes fever, chills, and hypotension during infusion — premedicate as ordered. Monitor renal function closely; nephrotoxicity can progress to acute kidney injury requiring dose reduction or drug discontinuation.
Related Concepts
- healthcare-associated-infections — Candidiasis is a common healthcare-associated infection in ICU patients with central lines.
- active-and-passive-immunity — Immunocompromised states increase susceptibility to opportunistic fungal infections.
- hypersensitivity-types-and-anaphylaxis-response — Antifungal hypersensitivity reactions may require emergency intervention.
- antibiotics — Broad-spectrum antibiotic use is a risk factor for secondary fungal superinfection (candidiasis).
- kidney-disease — Amphotericin B nephrotoxicity requires renal function monitoring.
- potassium-balance-disorders — Amphotericin B causes significant hypokalemia; electrolyte replacement is often needed.
- tinea-infection — Common superficial fungal syndromes with subtype-specific treatment routes and recurrence prevention.
Self-Check
- A nurse is administering IV amphotericin B. The client develops fever, chills, and rigors 30 minutes into the infusion. What are the priority nursing actions?
- Why should oral nystatin not be followed immediately by food or water after swallowing?
- A client on warfarin is newly prescribed fluconazole for vaginal candidiasis. What is the priority nursing concern?