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Microbiology

Antifungal Susceptibility

This section covers antifungal susceptibility testing (AFST), covering manual and automated methods, classes of antifungal agents, and intrinsic resistance patterns

Antifungal Susceptibility Testing (AFST)

  • Purpose: To determine the susceptibility of a fungal isolate to various antifungal agents, guiding appropriate therapy
  • Importance:
    • Guides antifungal therapy
    • Detects resistance
    • Monitors resistance trends
    • Optimizes dosing

Manual Methods

  • Broth Microdilution (BMD)
    • Principle: Two-fold dilutions of antifungals in broth; MIC is the lowest concentration inhibiting growth
    • Advantages: Gold standard, quantitative, versatile, inexpensive
    • Limitations: Labor-intensive, subjective, expertise required
  • Etest
    • Principle: Antifungal gradient on a strip; MIC is where the zone intersects the strip
    • Advantages: Easy to perform, quantitative, versatile
    • Limitations: More expensive, reading can be difficult

Automated Methods

  • Examples: Vitek 2, MicroScan, Sensititre
  • Principle: Automate inoculation, incubation, reading, and interpretation
  • Advantages: Faster, increased throughput, reduced labor, standardized
  • Limitations: Higher cost, limited species coverage, requires maintenance

Classes of Antifungal Agents

  • Azoles
    • Mechanism: Inhibit ergosterol synthesis
    • Types: Fluconazole, itraconazole, voriconazole, posaconazole, isavuconazole
    • Spectrum: Broad, but varies by azole and species
    • Considerations: Drug interactions, resistance, QT prolongation
  • Polyenes
    • Mechanism: Bind to ergosterol, disrupting the cell membrane
    • Types: Amphotericin B (D-AmB, lipid formulations), nystatin
    • Spectrum: Broad
    • Considerations: Toxicity (nephrotoxicity, infusion reactions), poor oral absorption
  • Echinocandins
    • Mechanism: Inhibit beta-1,3-glucan synthesis
    • Types: Caspofungin, micafungin, anidulafungin
    • Spectrum: Candida, Aspergillus
    • Considerations: Limited spectrum, IV only, resistance in C. glabrata
  • Allylamines
    • Mechanism: Inhibit squalene epoxidase
    • Types: Terbinafine, naftifine
    • Spectrum: Dermatophytes
    • Considerations: Limited to dermatophytes, hepatotoxicity
  • Flucytosine (5-FC)
    • Mechanism: Inhibits DNA and RNA synthesis
    • Spectrum: Cryptococcus, Candida, some molds
    • Considerations: Resistance, bone marrow suppression, hepatotoxicity
  • Griseofulvin
    • Mechanism: Disrupts microtubule function
    • Spectrum: Dermatophytes
    • Considerations: Limited to dermatophytes, long duration, drug interactions

Intrinsic Resistance Patterns

  • Definition: Inherent resistance due to genetic makeup, not prior exposure
  • Examples
    • Candida krusei: Fluconazole
    • Candida glabrata: Reduced azole susceptibility
    • Candida auris: Variable, often multidrug-resistant
    • Scedosporium spp.: Amphotericin B, many azoles
    • Fusarium spp.: Amphotericin B, many azoles
    • Mucorales: Voriconazole
  • Importance
    • Guides initial therapy
    • Avoids ineffective agents
    • Prevents treatment failure
    • Guides antifungal stewardship
  • Laboratory Considerations
    • Perform AFST on significant isolates
    • Follow quality control procedures
    • Report results accurately with interpretive comments
    • Communicate about intrinsic resistance patterns