How should I treat fungal infections in an otherwise healthy adult, including topical therapy for skin and nail infections, oral therapy for candidiasis, and systemic therapy for invasive disease?

Treatment of Fungal Infections in Otherwise Healthy Adults

For superficial dermatophyte skin infections, use topical terbinafine or an azole cream once or twice daily for 1–4 weeks; for dermatophyte toenail onychomycosis, oral terbinafine 250 mg daily for 12 weeks is first-line; for oropharyngeal candidiasis, use oral fluconazole 200–400 mg daily for 14–21 days; and for invasive aspergillosis, initiate voriconazole or isavuconazole immediately. 1, 2, 3

Topical Therapy for Superficial Skin Infections

Dermatophyte Infections (Tinea Corporis, Cruris, Pedis)

• Apply topical allylamines (terbinafine, naftifine, butenafine) once daily for 1 week, which are fungicidal and achieve high cure rates with short treatment duration. 4, 5
• Alternatively, use topical azoles (clotrimazole, miconazole, ketoconazole) twice daily for 2–4 weeks, though these are fungistatic and require longer treatment. 5
• For persistent tinea pedis failing topical therapy, prescribe oral terbinafine 250 mg once daily for 1 week, which achieves faster clinical resolution than 4 weeks of topical clotrimazole. 4
• Instruct patients to dry thoroughly between toes after bathing, change socks daily, and apply antifungal powder to footwear to prevent recurrence. 4

Candida Skin Infections (Intertrigo, Paronychia)

• For Candida paronychia without nail plate invasion, apply topical imidazole (clotrimazole or miconazole) to affected nail folds until cuticle integrity is restored, which may require several months. 2
• If bacterial co-infection is suspected, alternate the antifungal with a topical antibacterial agent. 2
• For superficial cutaneous candidiasis (intertrigo, balanitis), topical azoles are effective and should be applied twice daily for 2–4 weeks. 1

Oral Therapy for Oropharyngeal and Esophageal Candidiasis

Oropharyngeal Candidiasis (Mild Disease)

• Prescribe clotrimazole troches 10 mg five times daily for 7–14 days, or miconazole mucoadhesive buccal 50-mg tablet applied once daily for 7–14 days. 1
• Alternatives include nystatin suspension 4–6 mL (100,000 U/mL) four times daily for 7–14 days. 1

Oropharyngeal Candidiasis (Moderate to Severe Disease)

• Administer oral fluconazole 100–200 mg daily for 7–14 days. 1
• For fluconazole-refractory disease, use itraconazole solution 200 mg once daily or posaconazole suspension 400 mg twice daily for 3 days then 400 mg daily for up to 28 days. 1

Esophageal Candidiasis

• Initiate oral fluconazole 200–400 mg (3–6 mg/kg) daily for 14–21 days as first-line therapy. 1
• For patients unable to tolerate oral therapy, use intravenous fluconazole 400 mg (6 mg/kg) daily, or an echinocandin (micafungin 150 mg daily, caspofungin 70-mg loading dose then 50 mg daily, or anidulafungin 200 mg daily). 1
• De-escalate to oral fluconazole once the patient can tolerate oral intake. 1
• For fluconazole-refractory esophageal candidiasis, use voriconazole 200 mg (3 mg/kg) twice daily or an echinocandin for 14–21 days. 1

Systemic Therapy for Nail Infections (Onychomycosis)

Dermatophyte Toenail Onychomycosis

• Prescribe oral terbinafine 250 mg once daily for 12 weeks (toenails) or 6 weeks (fingernails), which achieves mycological cure rates of 70–80% for toenails and 80–90% for fingernails. 1, 2, 6
• Obtain baseline liver function tests (ALT, AST) and complete blood count before initiating terbinafine. 2, 6
• Monitor for adverse effects including gastrointestinal upset, headache, and reversible taste disturbance (occurs in approximately 1 in 400 patients). 2
• For severe infections with extensive nail involvement, extend treatment duration to 16 weeks. 2
• Terbinafine demonstrates superior in vitro and in vivo activity compared with all other antifungal agents for dermatophyte infections. 2

Second-Line: Itraconazole for Dermatophyte Onychomycosis

• Use itraconazole when terbinafine is contraindicated or not tolerated: pulse dosing at 400 mg daily (200 mg twice daily) for 1 week per month for 3 pulses (toenails) or 2 pulses (fingernails). 1, 2
• Alternatively, use continuous dosing at 200 mg daily for 12 weeks. 2
• Itraconazole must be taken with food and acidic beverages for optimal absorption. 2
• Obtain baseline liver function tests and monitor hepatic function during therapy, especially with concomitant hepatotoxic medications. 2
• Itraconazole is contraindicated in heart failure due to negative inotropic effects and in pregnancy. 2
• Important drug interactions: itraconazole increases levels of warfarin, digoxin, ciclosporin, and simvastatin (increasing myopathy risk); it is contraindicated with terfenadine, astemizole, midazolam, and cisapride. 2

Candida Onychomycosis

• Itraconazole is the preferred agent for Candida nail infections, achieving cure rates of 92% versus 40% with terbinafine. 1, 2
• Use pulse itraconazole 400 mg daily for 1 week per month for 3–4 months (toenails) or 2 months (fingernails). 2

Third-Line: Fluconazole

• Prescribe fluconazole 150–450 mg once weekly for at least 6 months for toenail infections when both terbinafine and itraconazole are unsuitable. 1, 2
• Obtain baseline liver function tests and complete blood count, with repeat testing during high-dose or prolonged therapy. 2

Adjunctive Topical Therapy for Onychomycosis

• Add amorolfine 5% lacquer applied once or twice weekly for 6–12 months to enhance cure rates and provide antimicrobial synergy. 1, 2
• Alternatively, use ciclopirox 8% lacquer applied once daily for up to 48 weeks. 1, 2
• Combination of topical and systemic treatments provides wider antifungal spectrum, improved fungicidal activity, increased cure rates, and suppression of resistant mutants. 2

Preventive Measures for Onychomycosis

• Decontaminate footwear by placing naphthalene mothballs in shoes and sealing in plastic bags for minimum 3 days to kill fungal arthroconidia. 2
• Apply antifungal powders inside shoes regularly and consider periodic spraying of terbinafine solution into shoes. 2
• Keep nails short and clean, wear cotton absorbent socks, and avoid sharing nail clippers. 2

Monitoring and Follow-Up

• Follow patients for at least 48 weeks (preferably 72 weeks) from treatment initiation to detect relapse. 2
• End-of-therapy culture is recommended, especially in high-risk groups, to confirm mycological clearance. 2
• Mycological cure rates are typically approximately 30% higher than clinical cure rates; complete nail normalization may lag behind eradication. 2

Systemic Therapy for Invasive Fungal Disease

Invasive Candidiasis and Candidemia

• Initiate echinocandins (caspofungin 70-mg loading dose then 50 mg daily, anidulafungin 200-mg loading dose then 100 mg daily, or micafungin 100 mg daily) as first-line therapy. 1, 3
• Obtain regular blood cultures to determine duration of treatment; continue therapy for 14 days after the first negative control blood culture. 3
• De-escalate to oral fluconazole once the patient is clinically stable and susceptibility results permit. 1

Invasive Pulmonary Aspergillosis

• Administer voriconazole or isavuconazole as first-line therapy for invasive pulmonary aspergillosis. 1, 3
• Treatment duration depends on disease severity and is recommended for 6–12 weeks. 3
• Therapeutic drug monitoring is recommended for voriconazole and posaconazole to ensure adequate levels and minimize toxicity. 3
• For Fusarium species infections, use high-dose intravenous voriconazole or posaconazole. 1

Cutaneous Aspergillus, Mucor, and Rhizopus Infections

• Aspergillus cutaneous infections should be treated with systemic voriconazole; surgical excision may be necessary when local infection cannot be controlled in neutropenic patients. 1
• For catheter site Aspergillus infections, remove the catheter in addition to systemic antifungal therapy. 1
• Cutaneous Mucor and Rhizopus infections require surgical debridement in addition to systemic antifungal therapy due to angioinvasive tendency. 1

Common Pitfalls and Caveats

• Obtain mycological confirmation (microscopy and culture) before initiating systemic antifungal therapy, as only about 50% of nail dystrophies are fungal. 1, 2
• The most common cause of treatment failure in onychomycosis is incorrect diagnosis made on clinical grounds alone. 1
• Even with optimal terbinafine therapy, a consistent failure rate of 20–30% is observed; contributors include poor compliance, inadequate drug absorption, immunosuppression, and subungual dermatophytoma obstructing drug penetration. 2
• Yeasts and non-dermatophyte molds are frequently secondary colonizers or saprophytes in previously damaged nails; address underlying nail trauma or chronic paronychia to prevent recurrence. 2, 7
• Fungicidal drugs (allylamines) are preferred over fungistatic drugs (azoles) for dermatophyte skin infections because patients often stop treatment when skin appears healed after about 1 week; fungi recur more often with fungistatic agents. 5
• Terbinafine is markedly less effective against Candida infections (approximately 40% cure) compared with itraconazole (approximately 92% cure); select itraconazole for Candida onychomycosis. 1, 2