Chapter 63

Antifungal Susceptibility Testing,

Therapy, and Prevention
 Objectives (1 of 2)
 Name the documents available that contain the
current guidelines for antifungal susceptibility
testing
 Identify three circumstances during which
antifungal susceptibility testing may be of value
 List three areas of concern that complicate
interpretive guidelines
 Describe how amphotericin B is produced, how it
is administered, and its most significant adverse
reaction
 Objectives (2 of 2)
 Describe the mechanism of action of flucytosine
and how it is used in therapy
 Identify three echinocandin agents, and describe
their mechanisms of action
 Antifungal Susceptibility Testing
 Designed to provide data for the selection of the
correct antifungal agent
 Standardized methods must be used to insure
reproducibility
 Clinical Laboratory Standards Institute provides
guidelines for antifungal susceptibility testing
(AFST)
 CLSI Documents
 Standards for testing have been developed by the Clinical
Laboratory Standards Institute (CLSI)
 Guidelines are provided in four documents:
 M27-A3
• Reference method for broth dilution susceptibility testing of yeasts
 M38-A2
• Reference method for broth dilution susceptibility testing of filamentous
fungi
 M44-A2
• Method for antifungal disk diffusion susceptibility testing of yeasts and
molds (M51-A)
 A27-S4
• Reference method for broth dilution susceptibility testing of yeasts,
supplement
 Value of AFST
 Tests are costly and time-consuming
 Susceptibility testing may be of value:
 To determine antibiograms for isolates in an institution
 To aid in the management of patients with refractory
oropharyngeal candidiasis
 To aid in the management of patients who have
invasive candidiasis when the use of the azoles is
questioned in infections caused by non–Candida
albicans
 AFST Interpretations
 Problems that complicate interpretive guidelines:
 Physical condition of the patient (i.e., immunologic
status)
 Type of infection and ability of the drug to penetrate a
closed space (in the case of an abscess)
 Dose of the drug and its pharmacokinetics
 Susceptibility testing method used and serum level of
drug administered
 Azole Antifungal Agents (1 of 2)
 Disrupt the integrity of the cell membrane and
inhibit synthesis of ergosterol
 Common agents:
 Itraconazole
• Is used to treat systemic fungal pathogens
 Fluconazole
• Provides excellent activity toward Candida spp. and
Cryptococcus neoformans
• Candida auris, an emerging pathogen is resistant
Azole Antifungal Agents (2 of 2)
 Ketoconazole
• Is used for mild cases of paracoccidioidomycosis
 Itraconazole
• Provides a broader spectrum than ketoconazole
 Voriconazole
• Is active against Fusarium and fluconazole-resistant yeasts
• Is also used against systemic fungal isolates
 Posaconazole
• Effective against dermatophytes
 Isavuconazole
• Oral and parenteral for treatment of aspergillosis
 Polyene Macrolide Antifungal Agents
 Agents contain multiple conjugated double bonds and
one to three ring structures
 Amphotericin B
• Produced from Streptomyces noursei
• Intravenous treatment for systemic infections
 Nystatin
• Produced from Streptomyces noursei
• Treats oral or vulvovaginal candidiasis
 Griseofulvin
• Produced from Penicillium griseofulvin
• Is the oral agent for dermatophytoses
 5-Fluorocytosine (flucytosine)
• Inhibits protein and deoxyribonucleic acid (DNA) synthesis
• Acts synergistically with amphotericin B
 Amphotericin B Agents
 Are produced by  Resistant fungi include:
Streptomyces nodosus  Pseudallescheria boydii
 Are intravenously infused  Scedosporium prolificans
to treat:  Aspergillus terreus
 Invasive aspergillosis  Trichosporon spp.
 Candida spp.  Fusarium spp.
 Cryptococcus
 Mucorales members
 Bind to ergosterol in the
cell membrane
 May cause renal
insufficiency
 Echinocandin Agents
 Inhibit glucan synthesis (1,3--glucan synthase)
 Three echinocandins:
 Caspofungin
• Is used for Candida spp., including fluconazole-resistant
yeasts
• Has fungistatic properties against Aspergillus spp.
• C. neoformans is resistant to caspofungin
 Micafungin
 Anidulafungin
 Allylamines
 Terbinafine (Lamisil) and Naftifine
 Highly lipophilic
 Interferes with fungal cell wall synthesis
 Effective for topical treatments
 Selenium sulfide
 Shampoo for Malassezia furfur