Susceptibility Testing

Testing Methods:

Yeast testing according to CLSI M27-A3

Mould testing according to CLSI M38-A2

Synergy testing according to both of the above documents with minor modifications to allow for combination testing.

The following antifungal agents are available for testing:

AMPHOTERICIN B (AMB) (Fungizone™, Ambisome™, Abelcet™) Yeast CPT 87186 Moulds CPT 87188

AMB binds to sterol in the cell membrane disrupting membrane integrity. This causes intracellular components to leak which ultimately leads to cell death. This agent is appropriate for most fungi but some notable in vitro resistance occurs with Aspergillus terreus, Scedosporium boydii, Scedosporium apiospermum, Lomentospora (formerly Scedosporium) prolificans, and Purpureocillium lilacinum (formerly Paecilomyces lilacinus). Please note that liposomal formulations do not lend themselves to testing according to CLSI methods. As the lipid does not add to antifungal activity but rather only facilitates delivery of the parent AMB in higher concentrations to the site of infection, we recommend testing only parent compound when interested in MICs for liposomal agents.

 

NYSTATIN (NYS) (Mycostatin™) CPT 87186 Moulds CPT 87188

NYS binds to sterol in the cell membrane disrupting membrane integrity. This causes the membrane it to leak intracellular components which ultimately leading to cell death.

 

NATAMYCIN (NAT) (Pimaricin™) CPT 87186 Moulds CPT 87188

NAT is similar to other polyenes but is available only as a topical for the treatment of eye infections.

 

5-FLUOROCYTOSINE (5-FC) (Ancobon™) Yeast CPT 87186, Moulds CPT 87188

5FC inhibits fungal cell wall synthesis. This agent should not be used as sole therapy as fungi are known to rapidly develop resistance.

 

CASPOFUNGIN (Cancidas™) Yeast CPT 87186, Moulds CPT 87188

CAS inhibits glucan synthesis which is a necessary component of the fungal cell wall. This agent has excellent activity against most Candida spp. but does not have activity against Cryptococcus spp. CAS has in vitro activity against aspergilli and possibly other moulds.

 

FLUCONAZOLE (FLU) (Diflucan™) Yeast CPT 87186, Moulds CPT 87188

FLU inhibits synthesis of ergosterol, a critical component in the fungal cell wall. This drug is widely used for the treatment of yeast infections but both acquired and innate resistance has been noted. This agent is not appropriate for aspergilli, member of the order Mucorales (causative agents of mucormycosis or zygomycosis), or fusaria. FLU has excellent penetration into the CNS.

 

ITRACONAZOLE (ITRA) (Sporonox™) Yeast CPT 87186, Moulds CPT 87188

ITRA inhibits synthesis of ergosterol, a critical component in the fungal cell wall. This drug is widely used for the treatment of both yeast and mould infections with excellent in vitro activity against the dematiaceous fungi.

 

VORICONAZOLE (VORI) (Vfend™) Yeast CPT 87186, Moulds CPT 87188

VORI inhibits synthesis of ergosterol, a critical component in the fungal cell wall. This agent is effective against both yeast and mould fungi. In vitro activity against Aspergillus spp., Scedosporium boydii, Scedosporium apiospermum, and Purpureocillium lilacinum (formerly Paecilomyces lilacinus) is excellent.

 

POSACONAZOLE Yeast CPT 87186, Moulds CPT 87188

POSA inhibits synthesis of ergosterol, a critical component in the fungal cell wall. This agent has very excellent in vitro activity against a wide range of fungi with MIC values usually lower than most other azoles.

 

ISAVUCONAZOLE Yeast CPT 87186, Moulds CPT 87188

ISA inhibits synthesis of ergosterol, a critical component in the fungal cell wall. This agent has very excellent in vitro activity against a wide range of fungi.  It is FDA approved for the treatment of invasive aspergillosis and mucormycosis.

 

MICONAZOLE (MON) (Monistat™) Yeast CPT 87186, Moulds CPT 87188

MON inhibits synthesis of ergosterol, a critical component in the fungal cell wall. Its use is limited to topical applications.

 

CLOTRIMAZOLE (CLOT) (Lotrimin™, Mycelex™) Yeast CPT 87186, Moulds CPT 87188

CLOT inhibits synthesis of ergosterol, a critical component in the fungal cell wall. Its use is limited to topical applications.

 

TERCONAZOLE (TERC) (Terazole™) Yeast CPT 87186, Moulds CPT 87188

TERC inhibits synthesis of ergosterol, a critical component in the fungal cell wall. Its use is limited to topical applications

 

TERBINAFINE (TERB) (Lamisil™) Yeast CPT 87186, Moulds CPT 87188

TERB inhibits squalene epoxidase which assists with synthesis of ergosterol. This agent has activity against many fungi with excellent activity against dermatophytic fungi. In vitro, this agent may enhance the activity of azoles in combination testing against a variety of fungi.

 

GRISEOFULVIN (GRIS) (Grifulvin ™, Fulvicin U/F™, Grisactin™) Yeast CPT 87186, Moulds CPT 87188

GRIS inhibits fungal mitosis. It is effective only against dermatophytic fungi and is not an appropriate choice for yeasts or non-dermatophytic moulds.

 

Susceptibility Testing of Antifungal – Interpretive Guideline for Candida species only

Generic Name Trade Name Formulation Test Range
Amphotericin B Fungizone

Ambisome

Abelcet

IV 0.03-16 µg/ml
Anidulafungin Eraxis IV 0.015-8 µg/ml
Caspofungin Cancidas IV 0.015-8 µg/ml
Micafungin Mycamine IV 0.015-8 µg/ml
Nystatin Biostatin Mycostatin Oral suspension Topical powder 0.06-32 µg/ml
Natamycin Neomycin Ointment 0.06-32 µg/ml
5-Fluocrocytosine Ancobon IV Capsule 0.125-64 µg/ml
Fluconazole Diflucan IV, Tablet, Oral Suspension, Topical 0.125-64 µg/ml
Itracontazole Sporonoz Capsule, Oral Suspension 0.03-16 µg/ml
Ketoconazole Nizoral Tablet, Topical 0.03-16 µg/ml
Voriconazole Vfend IV, Tablet, Oral Suspension 0.03-16 µg/ml
Posaconazole Noxafil IV, Oral Suspension, Tablet 0.03-16 µg/ml
Isavuconazole Cresemba IV, Capsule 0.03-16 µg/ml
Miconazole Monastat Micatin Topical 0.03-16 µg/ml
Terconazole Terazol Topical 0.125-64 µg/ml
Clotrimazole Cruex Clotrimaderm Topical 0.03-16 µg/ml
Terbinafine Lamisil Tablet, Topical 0.004-2 µg/ml
Griseofulvin Fulvicin Tablet, Topical 0.03-16 µg/ml

Synergy Studies

Yeast /Moulds CPT 87999 Any combination from the above listed drugs may be requested. Classic checkerboard dilution methods are employed with testing parameters as described in NCCLS documents M27-A3 and M38-A2.