What is the treatment for fungal nail infection?

Treatment of Fungal Nail Infection (Onychomycosis)

For dermatophyte onychomycosis (the most common type), terbinafine 250 mg daily is the first-line treatment: 6 weeks for fingernails and 12 weeks for toenails, achieving cure rates of 80-90% for fingernails and 70-80% for toenails. 1, 2, 3

Diagnostic Confirmation Required Before Treatment

• Never initiate treatment without mycological confirmation through microscopy with KOH and fungal culture. 2, 3
• Starting treatment based on clinical appearance alone is the most common cause of treatment failure, as many non-fungal nail dystrophies mimic onychomycosis. 3
• Dermatophytes (primarily Trichophyton rubrum) cause the majority of cases, but yeasts and non-dermatophyte molds require different treatment approaches. 1, 4

Treatment Algorithm by Causative Organism

Dermatophyte Onychomycosis (Most Common)

First-Line: Terbinafine

• Dosing: 250 mg once daily for 6 weeks (fingernails) or 12 weeks (toenails). 1, 2, 5
• Terbinafine is superior to itraconazole both in vitro (10 times lower MIC) and in clinical outcomes, with truly fungicidal activity. 1, 3
• Cure rates: 80-90% for fingernails, 70-80% for toenails. 2, 3
• Obtain baseline liver function tests (ALT and AST) before starting treatment, especially in patients with history of liver disease or excessive alcohol use. 5

Second-Line: Itraconazole

• Dosing options: 200 mg daily for 12 weeks continuously, OR pulse therapy 400 mg daily for 1 week per month (2 pulses for fingernails, 3 pulses for toenails). 1, 2
• Less effective than terbinafine for dermatophytes, with mycological cure rates around 54% and clinical cure rates of 14-26%. 2
• Reserve for patients with contraindications to terbinafine or treatment failures. 1

Candida Onychomycosis

First-Line: Itraconazole

• Dosing: 200 mg daily OR pulse therapy 400 mg daily for 1 week per month, for minimum 4 weeks (fingernails) or 12 weeks (toenails). 1, 2
• Itraconazole is the most effective agent when Candida invades the nail plate, with cure rates of 92% in pulse therapy regimens. 1
• Itraconazole is preferred over terbinafine due to shorter treatment duration, better cost-effectiveness, and superior efficacy against yeasts. 1, 2

Alternative: Fluconazole

• Dosing: 50 mg daily OR 300 mg weekly, for same duration as itraconazole. 1
• Use when itraconazole is contraindicated. 1

Terbinafine for Candida (Less Preferred)

• Requires prolonged treatment (16-48 weeks) to achieve 60-85% cure rates. 1, 6
• Only consider when azoles are contraindicated and patient can commit to extended therapy. 1

Non-Dermatophyte Molds

First-Line: Itraconazole

• Broader antimicrobial coverage than terbinafine for Aspergillus, Scopulariopsis, and other molds. 1
• Terbinafine demonstrates the lowest activity against most non-dermatophyte molds despite good dermatophyte activity. 1
• Clinical efficacy does not always correlate with in vitro susceptibility testing. 1

Special Population Considerations

Diabetic Patients

• Terbinafine is preferred due to lower risk of drug interactions and no hypoglycemia risk. 2
• Treatment is particularly important as onychomycosis significantly predicts foot ulcers and cellulitis in diabetics. 3

Immunocompromised Patients (HIV, Transplant Recipients)

• Terbinafine is preferred over itraconazole due to fewer drug interactions with antiretrovirals and immunosuppressive medications. 3
• Prevalence of onychomycosis is approximately 30% in HIV-positive patients. 3

Pediatric Patients

• Weight-based terbinafine dosing: 62.5 mg/day for <20 kg, 125 mg/day for 20-40 kg, 250 mg/day for >40 kg. 3
• Duration: 6 weeks for fingernails, 12 weeks for toenails. 3
• Cure rates are higher in children than adults. 2, 3

Patients on Multiple Medications

• Avoid itraconazole in patients taking statins, certain antiretrovirals, or those with heart failure due to significant drug interactions. 2
• Itraconazole interacts with numerous medications including cyclosporine, rifampin, cimetidine, and desipramine. 5

Role of Topical Therapy

• Topical agents (amorolfine 5% lacquer, ciclopirox 8% lacquer) are inferior to systemic therapy except for very distal infection or superficial white onychomycosis. 2, 3, 7
• Ciclopirox 8% achieves only 5.5-8.5% complete cure rates even with monthly professional nail debridement over 48 weeks. 7
• Consider topical therapy only as adjunct to systemic treatment or when systemic therapy is contraindicated. 2
• Application regimens: amorolfine once or twice weekly for 6-12 months; ciclopirox daily for up to 48 weeks. 2

Critical Monitoring and Follow-Up

• Reevaluate patients 3-6 months after initiating treatment. 3
• Minimum follow-up period should be 48 weeks (preferably 72 weeks) from treatment start to identify superior drug efficacy and detect relapse. 1, 2
• Optimal clinical effect occurs months after mycological cure due to time required for healthy nail outgrowth. 5
• Do not expect complete clinical normalization even with mycological cure, as nails may have pre-existing dystrophy from trauma or non-fungal disease. 3

Management of Treatment Failure (20-30% of Cases)

Common Causes:

• Poor adherence to treatment regimen. 3
• Poor drug absorption. 3
• Immunosuppression. 3
• Dermatophytoma (compact subungual fungal mass preventing drug penetration). 3
• Incorrect diagnosis (most common cause). 3

Strategies for Failure:

• Consider partial nail removal for dermatophytoma. 3
• Switch to alternative agent: if terbinafine failed, use itraconazole; if itraconazole failed, use terbinafine. 3
• Reconfirm diagnosis with repeat mycological testing. 3

Critical Safety Warnings

Terbinafine:

• Immediately discontinue and report symptoms of liver problems: persistent nausea, anorexia, fatigue, vomiting, right upper abdominal pain, jaundice, dark urine, or pale stools. 5
• Report taste or smell disturbances, which may become permanent even after discontinuation. 5
• Report depressive symptoms: sadness, worthlessness, sleep changes, loss of energy or interest, restlessness, mood changes. 5
• Photosensitivity reactions occur; minimize sun and artificial UV exposure. 5
• Serious skin reactions require immediate discontinuation. 5

Itraconazole:

• Contraindicated in heart failure patients. 2
• Multiple significant drug interactions require careful medication review. 2, 5

Prevention of Recurrence (25% Relapse Rate)

• Wear protective footwear in communal bathing facilities, gyms, and hotel rooms. 3
• Apply absorbent antifungal powders inside shoes regularly. 2, 3
• Spray terbinafine solution into shoes periodically. 2
• Keep nails short, wear cotton socks, avoid sharing nail clippers, and discard old footwear. 3

Common Pitfalls to Avoid

• Never treat without mycological confirmation—this is the leading cause of treatment failure. 2, 3
• Do not use inadequate treatment duration, as this results in higher relapse rates. 2
• Do not ignore drug interactions, particularly itraconazole with statins, antiretrovirals, and in heart failure. 2
• Do not expect immediate results; healthy nail outgrowth takes months after mycological cure. 1, 5
• Do not use concomitant systemic and topical antifungals, as this has not been studied and may reduce effectiveness. 7