Can onychomycosis (nail fungus infection) be caused by a fungal infection if the potassium hydroxide (KOH) preparation of the nail is positive for fungal elements but the culture is negative for dermatophytes (fungi that cause skin, hair, and nail infections)?

From the Guidelines

Yes, onychomycosis can still be caused by a fungal infection even when KOH preparation is positive but culture is negative for dermatophytes. This discrepancy occurs because KOH preparation detects fungal elements but doesn't identify the specific organism, while cultures may fail due to prior antifungal treatment, improper sampling technique, or the presence of non-dermatophyte molds or yeasts that are harder to culture 1. Non-dermatophyte molds like Aspergillus, Fusarium, and Scopulariopsis, or yeasts like Candida species can cause nail infections but may require special culture media or techniques for growth.

Key Points to Consider

• KOH preparation is a sensitive test for detecting fungal elements, but it does not provide information on the specific type of fungus present.
• Culture of yeasts and nondermatophyte moulds should be interpreted carefully in each individual case, as they may be secondary infections or saprophytic in previously damaged nails 1.
• Treatment options may include topical antifungals like ciclopirox 8% nail lacquer applied daily for up to 48 weeks, or oral options such as terbinafine 250 mg daily for 12 weeks for fingernails or 12-16 weeks for toenails, or itraconazole 200 mg twice daily for 1 week per month, repeated for 2 months for fingernails or 3 months for toenails.
• For suspected Candida infections, fluconazole 150-300 mg weekly for several months may be effective.
• Proper diagnosis may require additional testing like PCR or histopathology in challenging cases.

Treatment Approach

Given the potential for non-dermatophyte molds or yeasts to cause onychomycosis, treatment should be guided by the clinical presentation and additional diagnostic testing, rather than relying solely on culture results. Terbinafine is considered a first-line treatment option for dermatophyte onychomycosis, but its effectiveness against non-dermatophyte molds or yeasts may vary 1. Therefore, treatment should be individualized and monitored closely for response.

From the FDA Drug Label

The trials compared 48 weeks of treatment with JUBLIA to the vehicle solution. The Complete Cure rate was assessed at Week 52 (4 weeks after completion of therapy). Complete cure was defined as 0% involvement of the target toenail (no clinical evidence of onychomycosis of the target toenail) in addition to Mycologic Cure, defined as both negative fungal culture and negative KOH

Onychomycosis can still be caused by a fungal infection even if the culture is negative for dermatophytes, as the KOH prep positive for fungal elements suggests the presence of a fungal infection. However, the type of fungus is not specified, and it may not be a dermatophyte.

• The drug label does not provide information on the specific types of fungi that can cause onychomycosis besides dermatophytes.
• A negative culture does not rule out a fungal infection, as some fungi may not be detected by culture 2.

From the Research

Onychomycosis Diagnosis and Treatment

• Onychomycosis is a fungal infection of the nail, causing discoloration and thickening of the affected nail plate 3.
• The diagnosis of onychomycosis can be confirmed by direct microscopic examination with a potassium hydroxide (KOH) wet-mount preparation, histopathologic examination of the trimmed affected nail plate, fungal culture, or polymerase chain reaction assays 4.
• A positive KOH prep of the nail for fungal elements but a negative culture for dermatophytes does not rule out onychomycosis, as non-dermatophyte moulds (NDMs) and yeast can also cause the infection 3, 5.

Fungal Infection Causes

• Onychomycosis can be caused by dermatophytes, non-dermatophytes, and yeast 5.
• Non-dermatophyte moulds (NDMs) are skin and laboratory contaminants, and their presence as an infectious agent requires multiple confirmations and repeated sampling 3.
• The presence of fungal elements in a KOH prep, even with a negative culture, suggests a fungal infection, which may be caused by NDMs or other fungi 6.

Treatment Options

• Treatment options for onychomycosis include oral antifungals, topicals, and devices 3, 4.
• Oral antifungals have higher cure rates and shorter treatment periods than topical treatments, but have adverse side effects such as hepatotoxicity and drug interactions 3, 4.
• Topical treatments, such as efinaconazole, have less serious side effects, but also have generally lower cure rates and much longer treatment regimens 7.