What causes recurrent thrush and what laboratory tests, such as fungal culture or Polymerase Chain Reaction (PCR), can be used to diagnose and manage it?

Causes and Laboratory Evaluation of Recurrent Thrush

What Causes Thrush

Thrush (oropharyngeal candidiasis) is caused by overgrowth of Candida species, most commonly Candida albicans, typically occurring in the setting of immunosuppression, antibiotic use, inhaled corticosteroids, or other factors that disrupt normal oral flora. 1 Recurrent thrush should prompt investigation for underlying immunodeficiency states, diabetes, HIV infection, or other conditions that impair immune function. 2

Laboratory Tests for Recurrent Thrush

Essential First-Line Testing

For recurrent or complicated oropharyngeal candidiasis, you should obtain a swab from the lesion for culture with species identification and antifungal susceptibility testing. 3, 1

Key diagnostic steps include:

• Swab the lesion directly and inoculate on selective fungal media to prevent bacterial overgrowth 3, 1
• Request species identification - this is mandatory because non-albicans species (like C. glabrata) may have different susceptibility patterns and require alternative treatment 3
• Order antifungal susceptibility testing - specifically recommended for recurrent cases and patients previously exposed to azole antifungals 3, 1

Important Diagnostic Considerations

• Culture may take 5-14 days to grow, so inform the laboratory you suspect Candida to ensure adequate incubation time 3
• Biopsy is not mandatory but can help distinguish true infection from colonization in unclear cases 3, 1
• PCR-based methods are NOT recommended - while they show promise in research settings, they have not been validated for clinical use in oropharyngeal candidiasis 3, 1

Additional Workup for Recurrent Cases

When thrush recurs despite appropriate treatment, investigate underlying causes:

• HIV testing - recurrent thrush is an AIDS-defining illness indicator
• Hemoglobin A1c - uncontrolled diabetes predisposes to candidiasis
• Complete blood count with differential - to evaluate for neutropenia or lymphopenia
• Immunoglobulin levels - if primary immunodeficiency suspected 2
• Consider genetic testing in unusual presentations (rare chromosomal abnormalities like Klinefelter syndrome have been reported) 2

Common Pitfalls to Avoid

• Do not rely on clinical appearance alone - symptoms and visual inspection cannot reliably differentiate Candida from other causes of oral lesions 4, 5
• Do not assume all Candida is C. albicans - approximately 10-20% of recurrent cases involve non-albicans species that may be azole-resistant 3, 6
• Negative culture does not exclude infection - some species grow slowly, and sampling error can occur with small specimens 3
• Do not treat asymptomatic colonization - Candida can be part of normal oral flora; treatment should be reserved for symptomatic infection 5

Antifungal Susceptibility Testing Interpretation

Use reference methods or validated commercial techniques (such as Etest™ or Sensititre YeastOne™) for susceptibility testing, but be aware that discrepant results may occur with borderline MIC values compared to reference methods. 3 Interpretation requires expertise, and you should ensure the laboratory uses appropriate species-specific breakpoints. 3