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Testing Methods:
Yeast testing according to NCCLS M27-A2
Mould testing according to NCCLS M38-A
Synergy testing according both of the above documents with minor modifications to allow for combination testing.
Reference Ranges (NCCLS guidelines for yeast fungi only):
| Susceptible Dose |
| |
Susceptible (S) |
Dependent (SDD) |
Intermediate (I) |
Resistant (R) |
| Fluconazole |
<8 |
16-32 |
N/A |
>64 |
| Itraconazole |
<0.125 |
0.25-0.5 |
N/A |
>1 |
| 5FC |
<4 |
N/A |
8-16 |
>32 |
The following antifungal agents are available for testing:
AMPHOTERICIN B (AMB) (Fungizone™) Yeast CPT 87186 + 87187 Moulds CPT 87188 + 87187
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, Pseudallescheria boydii (Scedosporium apiospermium), Scedosporium prolificans, and Paecilomyces lilacinus. Please note that liposomal formulations do not lend themselves to testing according to NCCLS 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 + 87187 Moulds CPT 87188 + 87187
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 + 87187 Moulds CPT 87188 + 87187
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, zygomycetes, 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.
KETOCONAZOLE (KETO) (Nizoral™) Yeast CPT 87186, Moulds CPT 87188
KETO inhibits synthesis of ergosterol, a critical component in the fungal cell wall. This agent is effective against yeast and mould fungi. Of note is its activity against Paecilomyces lilacinus, an isolate that is resistant to many other antifungals.
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 Pseudallescheria boydii (Scedosporium apiospermium) and Paecilomyces lilacinus
is excellent.
POSACONAZOLE
(POSA) (currently available through clinical trials or compassionate use only) 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.
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 greatly enhances the
activity of azoles in combination testing against a
variety of fungi.
GRISIOFULVIN (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.
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-A2 and M38-A.
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