Yeast and yeast-like organisms - Revision history

Aidan at 23:18, 12 March 2022

2022-03-12T23:18:38Z

← Older revision		Revision as of 23:18, 12 March 2022
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	* [[Candida ~~species~~]]		* [[Candida]]
	* [[Cryptococcus ~~species~~]]		* [[Cryptococcus]]
	* [[Trichosporon ~~species~~]]		* [[Trichosporon]]
	* [[Malassezia furfur]]		* [[Malassezia furfur]]
	* [[Saccharomyces cerevisiae]]		* [[Saccharomyces cerevisiae]]
	* [[Rhodotorula ~~species~~]]		* [[Rhodotorula]]

	==''Cryptococcus'' ~~species~~==		==''Cryptococcus''==

	===Diagnosis of ''Cryptococcus'' meningitis===		===Diagnosis of ''Cryptococcus'' meningitis===
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	*A color reaction on '''concanavalin-glycine-thymol''' agar		*A color reaction on '''concanavalin-glycine-thymol''' agar
	**Creatinine deiminase is repressed by ammonia in ''C''. ''neoformans'' but not in ''C''. ''gattii''. This difference is manifested by a change in the color of the diagnostic media as the pH changes		**Creatinine deiminase is repressed by ammonia in ''C''. ''neoformans'' but not in ''C''. ''gattii''. This difference is manifested by a change in the color of the diagnostic media as the pH changes
	**Media containing L-canavanine and glycine with bromothymol blue as the color indicator for growth (CGB medium) can efficiently differentiate between these two species (~~''C.~~ gattii'' will produce a ~~color~~ change and ~~''C.~~neoformans'' will not)		**Media containing L-canavanine and glycine with bromothymol blue as the color indicator for growth (CGB medium) can efficiently differentiate between these two species ([[Cryptococcus gattii]] will produce a colour change and [[Cryptococcus neoformans]] will not)
	*They produce different sexual spores (impractical)		*They produce different sexual spores (impractical)
	*MALDI-TOF may be able to identify the different species		*MALDI-TOF may be able to identify the different species

Aidan: removed candida to own page

2020-08-26T12:52:38Z

removed candida to own page

← Older revision		Revision as of 12:52, 26 August 2020
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	~~==''~~Candida'' species==		* [[Candida species]]
			* [[Cryptococcus species]]

			* [[Trichosporon species]]
	===Identification===
			* [[Malassezia furfur]]

			* [[Saccharomyces cerevisiae]]
	*Any yeast that has growth on culture (blood, fluid, tissue) or seen on Gram stain gets subcultured to SAB-CG at 35º C.
			* [[Rhodotorula species]]
	**Growth rate: <7 days is rapid
	**Texture
	**Colour of surface and reverse
	*Do wet mount to confirm features of ''Candida''.
	*'''Microscopy''' for chlamydospores, pseudohyphae, hyphae, arthroconidia, blastoconidia formation, budding, capsules, pigmentation.
	**''C. glabrata'' is smaller, does not produce hyphae or pseudohyphae, produces blastoconidia, and grows as creamy yeast colonies.
	**Non-glabrata spp. usually exhibit single buddings and can have pseudohyphae (rarely true septate hyphae). Cannot identify species based on microscopy alone.
	*'''MALDI-ToF''' (Vitek MS), which provides a species. If ''C. haemolunii'' or ''C. famata'' identified on Vitek, need to rule out ''C. auris''.
	**If Vitek not ≥95% match, or identifies one of the two species above, then repeat the MALDI-ToF and set up Dalmau on cornmeal agar.
	*'''Dalmau technique:''' growth in adverse conditions (bile oxgall and corn meal) to help identify differences between species of yeast.
	**Light inoculum of single colony in a #-sign pattern with lines 1 inch apart. Cover streaks with coverslip and tamp down gently. Incubate at room temperature 18-72 hours.
	**Examine after 18-24 hours. Look for thick-walled chlamydospores (terminal refractory circles), blastoconidia morphology, and presence of pseudohyphae. Then continue incubating, examining daily.
	*Old-school enzymatic tests and assimilation assays.
	*'''Temperature tolerance test''' at 35-37º C, 42º C, and 45º C
	*'''Germ tube test:''' if positive, either ''C. albicans'' or ''C. dubliniensis''.

	{\| class="wikitable"
	!Species
	!Colony
	!Conidia
	!Pseudohyphae
	!Other
	!Other Tests
	\|-
	!''C. albicans''
	\|White to creamy, raised, pasty, smooth and soft, shiny and moist. May produce mycelial growth called “feet” or “roots”.
	\|Blastoconidia globose to oval.
	\|Well-developed, abundant with blastoconidia in clusters or grape-like arrangement at septa.
	\|Chlamydospores: round, large, thick-walled, usually single and mostly terminal forming on the tip of pseudohyphae, but some may be sessile. True hyphae may be present in older cultures.
	\|Growth at 42-45º C.
	\|-
	!''C. dubliniensis''
	\|Cream-coloured, glistening, waxy, usually smooth.
	\|Blastoconidia subspherical, identical to C. albicans.
	\|Well-developed with blastoconidia in grape-like arrangement.
	\|Chlamydospores: round, large, thick-walled, usually in pairs, triplets, and clusters of 1-3 and mostly terminal. True hyphae may be present, especially in older culture.
	\|Usually no growth at 42-45º C.
	\|-
	!''C. glabrata''
	\|Small, white to cream-coloured, shiny, pasty, and smooth.
	\|Terminal single budding, oval, and small. Typically arranged in dense groups.
	\|Absent, or rudimentary if present
	\|
	\|
	\|-
	!''C. krusei''
	\|Cream-coloured to tannish-white. Flat, dry, ground-glass appearance. Spreading edge with a delicate feathery periphery.
	\|Elongate, ellipsoidal to cylindrical. Cells are liberated and arranged parallel to the main axis appearing like logs on the stream.
	\|Initially sparse, often present on prolonged incubation. Elondated and slender, with blastoconidia forming a cross-matchstick or treelike branching appearance at the septa.
	\|
	\|
	\|-
	!''C. parapsilosis''
	\|White to creamy, shiny, moist, slightly flat, mostly smooth or partly or entirely wrinkled.
	\|Ovoid, single or in small clusters.
	\|Usually abundant, but may be slow to grow. Crooked or curved, relatively short, branched chains of pseudohyphae with clusters of blastoconidia at or between septa. Christmas-tree-like arrangement.
	\|Occasional presence of large hyphal elements called giant cells.
	\|
	\|-
	!''C. tropicalis''
	\|Cream-coloured to semiwhite, dull, dry, soft, smooth and creamy. May be wrinkled or have a mycelial fringe near the edge. Can have feet (root mycelium) similar to C. albicans.
	\|Oval. Single or in small groups or short chains at or between septa of pseudohyphae.
	\|Very active growth. Abundant, long and branched. Blastoconidia produced in verticils from the pseudohyphae.
	\|True hyphae may be present.
	\|
	\|-
	!''C. famata''
	\|White to cream coloured.
	\|Ellipsoidal.
	\|Absent.
	\|
	\|Weak growth at 40º C. Does not grow at 42º C.
	\|-
	!''C. auris''
	\|White to cream-coloured. Pink to beige on chromogenic agar (depending on the agar).
	\|Oval or elongated yeast cells, singly or in pairs or groups.
	\|Absent.
	\|
	\|Grows well at 42º C. Variable growth at 45º C. Cycloheximide-susceptible. Usually fluconazole-resistant.
	\|-
	!''C. guilliermondii''
	\|White to tan, slightly heaped, shiny, moist, and usually mucoid with smooth edge.
	\|Spherical to ellipsoidal.
	\|May be slow growing (up to 10 days), radiating from centre of masses of budding cells.
	\|Pseudohyphae not produced.
	\|May grow at 42 º C.
	\|}

	===Epidemiology===

	*Refer to [https://doi.org/10.1093/cid/cis697 Cleveland et al; CID 2012 55:1352].
	*The predominant species worldwide (and in Canada) is '''''C. albicans''''', by a wide margin, followed by ''C. glabrata'', ''C. tropicalis'', and ''C. parapsilosis''.
	*Non-''candida'' species are becoming more common, globally, over the past three decades.
	**''C. dubliniensis'' associated with HIV esophagitis.
	**''C. lusitaniae'' can develop resistance to amphotericin.
	**''C. guilliermondii'' is multidrug resistant.
	**''C. auris'' still rare but may be emerging. It can be misidentified as other yeasts (most commonly ''C. haemulonii'', but also ''C. famata'', ''Saccharomyces cerevisiae'', and ''Rhodotorula glutinis'').

	Sources: [https://dx.doi.org/10.1016/j.jcrc.2006.10.038 Laverdiere et al. ''J Crit Care''. 2007;22(3):245–250], [https://doi.org/10.1111/1469-0691.12539 Guinea. ''Clin Microbiol Infect''. 2014;20(Suppl 6):5-10].

	==''Cryptococcus'' species==		==''Cryptococcus'' species==

Aidan at 12:47, 26 August 2020

2020-08-26T12:47:53Z

Show changes

Aidan: /* Identification */ tidied table

2019-08-17T15:40:34Z

Identification: tidied table

Show changes

Aidan at 15:32, 17 August 2019

2019-08-17T15:32:18Z

← Older revision		Revision as of 15:32, 17 August 2019
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	= ''Candida'' species =		== ''Candida'' species ==

	== Identification ==		=== Identification ===

	* Any yeast that has growth on culture (blood, fluid, tissue) or seen on Gram stain gets subcultured to SAB-CG at 35º C.		* Any yeast that has growth on culture (blood, fluid, tissue) or seen on Gram stain gets subcultured to SAB-CG at 35º C.
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	</table>		</table>

	== Epidemiology ==		=== Epidemiology ===

	* Refer to [https://doi.org/10.1093/cid/cis697 Cleveland et al; CID 2012 55:1352].		* Refer to [https://doi.org/10.1093/cid/cis697 Cleveland et al; CID 2012 55:1352].
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	Sources: [https://dx.doi.org/10.1016/j.jcrc.2006.10.038 Laverdiere et al. ''J Crit Care''. 2007;22(3):245–250], [https://doi.org/10.1111/1469-0691.12539 Guinea. ''Clin Microbiol Infect''. 2014;20(Suppl 6):5-10].		Sources: [https://dx.doi.org/10.1016/j.jcrc.2006.10.038 Laverdiere et al. ''J Crit Care''. 2007;22(3):245–250], [https://doi.org/10.1111/1469-0691.12539 Guinea. ''Clin Microbiol Infect''. 2014;20(Suppl 6):5-10].

	= ''Cryptococcus'' species =		== ''Cryptococcus'' species ==

	== Diagnosis of ''Cryptococcus'' meningitis ==		=== Diagnosis of ''Cryptococcus'' meningitis ===

	* Microscopy:		* Microscopy:
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	The composite reference standard was defined as a CSF culture-positive (n = 459) or a culture-negative sample with ≥2 positive test results (e.g., India ink microscopy, CRAG latex, or CRAG LFA) and without an alternative etiologic explanation (n = 60). Source: [https://dx.doi.org/10.3201%2Feid2001.130906 Boulware ''et al''. ''EID''. 2014;20(1):45-53].		The composite reference standard was defined as a CSF culture-positive (n = 459) or a culture-negative sample with ≥2 positive test results (e.g., India ink microscopy, CRAG latex, or CRAG LFA) and without an alternative etiologic explanation (n = 60). Source: [https://dx.doi.org/10.3201%2Feid2001.130906 Boulware ''et al''. ''EID''. 2014;20(1):45-53].

	== ''Cryptococcus gattii'' and ''C. neoformans'' ==		=== ''Cryptococcus gattii'' and ''C. neoformans'' ===

	== Epidemiology of ''C. gattii'' ==		=== Epidemiology of ''C. gattii'' ===

	* Unlike ''C.neoformans, C. gattii'' has never been found from bird/bat guano. It is usually found in eucalyptus (River red and Forest red gum trees) and coniferous trees, specifically in Vancouver Island and the West Coast		* Unlike ''C.neoformans, C. gattii'' has never been found from bird/bat guano. It is usually found in eucalyptus (River red and Forest red gum trees) and coniferous trees, specifically in Vancouver Island and the West Coast
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	* More likely to cause cryptococcomas		* More likely to cause cryptococcomas

	== Distinguishing ''C. gattii'' and ''C. neoformans'' ==		=== Distinguishing ''C. gattii'' and ''C. neoformans'' ===

	* A color reaction on '''concanavalin-glycine-thymol''' agar		* A color reaction on '''concanavalin-glycine-thymol''' agar
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	* MALDI-TOF may be able to identify the different species		* MALDI-TOF may be able to identify the different species

	= Other yeasts of clinical importance =		== Other yeasts of clinical importance ==

	== ''Trichosporon'' ==		=== ''Trichosporon'' ===

	* Clinical Significance:		* Clinical Significance:
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	** Treatment with '''voriconazole'''		** Treatment with '''voriconazole'''

	== ''Malassezia furfur'' ==		=== ''Malassezia furfur'' ===

	* Clinical Significance:		* Clinical Significance:
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	** Yeast cells are phialides with colarettes, broad based buds		** Yeast cells are phialides with colarettes, broad based buds

	== ''Saccharomyces cerevisiae'' (“Baker’s Yeast”) ==		=== ''Saccharomyces cerevisiae'' (“Baker’s Yeast”) ===

	* Clinical Significance:		* Clinical Significance:
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	** Absence of hyphae		** Absence of hyphae

	== ''Rhodotorula'' ==		=== ''Rhodotorula'' ===

	* Clinical Significance:		* Clinical Significance:
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	** Urease positive		** Urease positive

	= ''Candida auris'' =		== ''Candida auris'' ==

	* Review the paper [https://dx.doi.org/10.1128/CMR.00029-17 Clin Micro Rev January 2018 31(1).]		* Review the paper [https://dx.doi.org/10.1128/CMR.00029-17 Clin Micro Rev January 2018 31(1).]

	== Identification Methods ==		=== Identification Methods ===

	* ''C. auris'' can often be misidentified using the usual methods, often mistaken for ''C. haemulonii''		* ''C. auris'' can often be misidentified using the usual methods, often mistaken for ''C. haemulonii''
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	* Sequencing		* Sequencing

	== Susceptibility Patterns ==		=== Susceptibility Patterns ===

	* There are no antifungal clinical breakpoints		* There are no antifungal clinical breakpoints
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	* CNS infections: Amphotericin B + 5-flucytosine		* CNS infections: Amphotericin B + 5-flucytosine

	== Infection Control Methods ==		=== Infection Control Methods ===

	* Chlorhexidine is active against it		* Chlorhexidine is active against it
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	** Thorough daily and terminal cleaning/disinfection using Environmental Protection Agency-registered disinfectant effective against ''C. difficile'' spores		** Thorough daily and terminal cleaning/disinfection using Environmental Protection Agency-registered disinfectant effective against ''C. difficile'' spores

	= Antifungal Susceptibility Testing of Yeast =		== Antifungal Susceptibility Testing of Yeast ==

	== Patterns of resistance ==		=== Patterns of resistance ===

	* '''''Candida'' spp:''' most species are susceptible to azoles including fluconazole, except ''C. glabrata'' (which may be dose-dependently susceptible) ''C. krusei'', and ''C. auris''. ''C. lusitaniae'' is resistant to ampho B. All are generally susceptible to echinocandins.		* '''''Candida'' spp:''' most species are susceptible to azoles including fluconazole, except ''C. glabrata'' (which may be dose-dependently susceptible) ''C. krusei'', and ''C. auris''. ''C. lusitaniae'' is resistant to ampho B. All are generally susceptible to echinocandins.
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	Source: [https://doi.org/10.1086/504492 Dodds Ashley ''et al''. ''CID'' 2006;43(Suppl 1):S28-S39] (''Candida'' etc.), [https://doi.org/10.1086/497832 Enache-Angoulvant, ''et al''. ''CID'' 2005;41(11):1559-1568] (''Saccharomyces''), [https://doi.org/10.1128/AAC.46.4.1144-1146.2002 Paphitou AAC 2002;46(4):1144-1146] (''Trichophyton'').		Source: [https://doi.org/10.1086/504492 Dodds Ashley ''et al''. ''CID'' 2006;43(Suppl 1):S28-S39] (''Candida'' etc.), [https://doi.org/10.1086/497832 Enache-Angoulvant, ''et al''. ''CID'' 2005;41(11):1559-1568] (''Saccharomyces''), [https://doi.org/10.1128/AAC.46.4.1144-1146.2002 Paphitou AAC 2002;46(4):1144-1146] (''Trichophyton'').

	== Mechanisms of resistance ==		=== Mechanisms of resistance ===

	* '''Azole resistance:''' triazoles inhibit C-14α demethylase (Erg11p), which is required for the synthesis of ergosterol from lanosterol. Ergosterol is required for proper cell membrane function. There are several mechanisms of resistance:		* '''Azole resistance:''' triazoles inhibit C-14α demethylase (Erg11p), which is required for the synthesis of ergosterol from lanosterol. Ergosterol is required for proper cell membrane function. There are several mechanisms of resistance:
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	* '''Sources:''' Lancet ID series, Mandell, [https://doi.org/10.1016/s1473-3099(02)00181-0 Sanglard and Odds. ''Lancet ID'' 2002;2(2):73-85].		* '''Sources:''' Lancet ID series, Mandell, [https://doi.org/10.1016/s1473-3099(02)00181-0 Sanglard and Odds. ''Lancet ID'' 2002;2(2):73-85].

	== Susceptibility testing ==		=== Susceptibility testing ===

	* '''Sensitire plates:''' used for Candida susceptibility testing, does colorimetric testing of broth microdilution.		* '''Sensitire plates:''' used for Candida susceptibility testing, does colorimetric testing of broth microdilution.

Aidan at 12:29, 16 August 2019

2019-08-16T12:29:41Z

← Older revision		Revision as of 12:29, 16 August 2019
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	* '''Further Reading:''' [https://dx.doi.org/10.1128%2FJCM.00937-12 Pfaller J Clin Microbiol 2012 50(9): 2846], CLSI M59 and M27, the SOP for yeast susceptibility reporting.		* '''Further Reading:''' [https://dx.doi.org/10.1128%2FJCM.00937-12 Pfaller J Clin Microbiol 2012 50(9): 2846], CLSI M59 and M27, the SOP for yeast susceptibility reporting.

	[[Category:~~Mycology~~]]		[[Category:Microbiology]]
			[[Category:Yeasts]]

Aidan: /* Yeast and Yeast-like organisms */

2019-08-13T11:42:44Z

Yeast and Yeast-like organisms

← Older revision		Revision as of 11:42, 13 August 2019
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	= Yeast and Yeast-like organisms =

	= ''Candida'' species =		= ''Candida'' species =

Aidan at 11:15, 13 August 2019

2019-08-13T11:15:13Z

← Older revision		Revision as of 11:15, 13 August 2019
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	= Yeast and Yeast-like organisms =		= Yeast and Yeast-like organisms =

	== ''Candida'' species ==		= ''Candida'' species =

	=== Identification ===		== Identification ==

	* Any yeast that has growth on culture (blood, fluid, tissue) or seen on Gram stain gets subcultured to SAB-CG at 35º C.		* Any yeast that has growth on culture (blood, fluid, tissue) or seen on Gram stain gets subcultured to SAB-CG at 35º C.
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	</table>		</table>

	=== Epidemiology ===		== Epidemiology ==

	* Refer to [https://doi.org/10.1093/cid/cis697 Cleveland et al; CID 2012 55:1352].		* Refer to [https://doi.org/10.1093/cid/cis697 Cleveland et al; CID 2012 55:1352].
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	Sources: [https://dx.doi.org/10.1016/j.jcrc.2006.10.038 Laverdiere et al. ''J Crit Care''. 2007;22(3):245–250], [https://doi.org/10.1111/1469-0691.12539 Guinea. ''Clin Microbiol Infect''. 2014;20(Suppl 6):5-10].		Sources: [https://dx.doi.org/10.1016/j.jcrc.2006.10.038 Laverdiere et al. ''J Crit Care''. 2007;22(3):245–250], [https://doi.org/10.1111/1469-0691.12539 Guinea. ''Clin Microbiol Infect''. 2014;20(Suppl 6):5-10].

	== ''Cryptococcus'' species ==		= ''Cryptococcus'' species =

	=== Diagnosis of ''Cryptococcus'' meningitis ===		== Diagnosis of ''Cryptococcus'' meningitis ==

	* Microscopy:		* Microscopy:
Line 151:		Line 151:
	The composite reference standard was defined as a CSF culture-positive (n = 459) or a culture-negative sample with ≥2 positive test results (e.g., India ink microscopy, CRAG latex, or CRAG LFA) and without an alternative etiologic explanation (n = 60). Source: [https://dx.doi.org/10.3201%2Feid2001.130906 Boulware ''et al''. ''EID''. 2014;20(1):45-53].		The composite reference standard was defined as a CSF culture-positive (n = 459) or a culture-negative sample with ≥2 positive test results (e.g., India ink microscopy, CRAG latex, or CRAG LFA) and without an alternative etiologic explanation (n = 60). Source: [https://dx.doi.org/10.3201%2Feid2001.130906 Boulware ''et al''. ''EID''. 2014;20(1):45-53].

	=== ''Cryptococcus gattii'' and ''C. neoformans'' ===		== ''Cryptococcus gattii'' and ''C. neoformans'' ==

	==== Epidemiology of ''C. gattii'' ====		== Epidemiology of ''C. gattii'' ==

	* Unlike ''C.neoformans, C. gattii'' has never been found from bird/bat guano. It is usually found in eucalyptus (River red and Forest red gum trees) and coniferous trees, specifically in Vancouver Island and the West Coast		* Unlike ''C.neoformans, C. gattii'' has never been found from bird/bat guano. It is usually found in eucalyptus (River red and Forest red gum trees) and coniferous trees, specifically in Vancouver Island and the West Coast
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	* More likely to cause cryptococcomas		* More likely to cause cryptococcomas

	==== Distinguishing ''C. gattii'' and ''C. neoformans'' ====		== Distinguishing ''C. gattii'' and ''C. neoformans'' ==

	* A color reaction on '''concanavalin-glycine-thymol''' agar		* A color reaction on '''concanavalin-glycine-thymol''' agar
Line 170:		Line 170:
	* MALDI-TOF may be able to identify the different species		* MALDI-TOF may be able to identify the different species

	== Other yeasts of clinical importance ==		= Other yeasts of clinical importance =

	=== ''Trichosporon'' ===		== ''Trichosporon'' ==

	* Clinical Significance:		* Clinical Significance:
Line 188:		Line 188:
	** Treatment with '''voriconazole'''		** Treatment with '''voriconazole'''

	=== ''Malassezia furfur'' ===		== ''Malassezia furfur'' ==

	* Clinical Significance:		* Clinical Significance:
Line 202:		Line 202:
	** Yeast cells are phialides with colarettes, broad based buds		** Yeast cells are phialides with colarettes, broad based buds

	=== ''Saccharomyces cerevisiae'' (“Baker’s Yeast”) ===		== ''Saccharomyces cerevisiae'' (“Baker’s Yeast”) ==

	* Clinical Significance:		* Clinical Significance:
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	** Absence of hyphae		** Absence of hyphae

	=== ''Rhodotorula'' ===		== ''Rhodotorula'' ==

	* Clinical Significance:		* Clinical Significance:
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	** Urease positive		** Urease positive

	== ''Candida auris'' ==		= ''Candida auris'' =

	* Review the paper [https://dx.doi.org/10.1128/CMR.00029-17 Clin Micro Rev January 2018 31(1).]		* Review the paper [https://dx.doi.org/10.1128/CMR.00029-17 Clin Micro Rev January 2018 31(1).]

	=== Identification Methods ===		== Identification Methods ==

	* ''C. auris'' can often be misidentified using the usual methods, often mistaken for ''C. haemulonii''		* ''C. auris'' can often be misidentified using the usual methods, often mistaken for ''C. haemulonii''
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	* Sequencing		* Sequencing

	=== Susceptibility Patterns ===		== Susceptibility Patterns ==

	* There are no antifungal clinical breakpoints		* There are no antifungal clinical breakpoints
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	* CNS infections: Amphotericin B + 5-flucytosine		* CNS infections: Amphotericin B + 5-flucytosine

	=== Infection Control Methods ===		== Infection Control Methods ==

	* Chlorhexidine is active against it		* Chlorhexidine is active against it
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	** Thorough daily and terminal cleaning/disinfection using Environmental Protection Agency-registered disinfectant effective against ''C. difficile'' spores		** Thorough daily and terminal cleaning/disinfection using Environmental Protection Agency-registered disinfectant effective against ''C. difficile'' spores

	== Antifungal Susceptibility Testing of Yeast ==		= Antifungal Susceptibility Testing of Yeast =

	=== Patterns of resistance ===		== Patterns of resistance ==

	* '''''Candida'' spp:''' most species are susceptible to azoles including fluconazole, except ''C. glabrata'' (which may be dose-dependently susceptible) ''C. krusei'', and ''C. auris''. ''C. lusitaniae'' is resistant to ampho B. All are generally susceptible to echinocandins.		* '''''Candida'' spp:''' most species are susceptible to azoles including fluconazole, except ''C. glabrata'' (which may be dose-dependently susceptible) ''C. krusei'', and ''C. auris''. ''C. lusitaniae'' is resistant to ampho B. All are generally susceptible to echinocandins.
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	Source: [https://doi.org/10.1086/504492 Dodds Ashley ''et al''. ''CID'' 2006;43(Suppl 1):S28-S39] (''Candida'' etc.), [https://doi.org/10.1086/497832 Enache-Angoulvant, ''et al''. ''CID'' 2005;41(11):1559-1568] (''Saccharomyces''), [https://doi.org/10.1128/AAC.46.4.1144-1146.2002 Paphitou AAC 2002;46(4):1144-1146] (''Trichophyton'').		Source: [https://doi.org/10.1086/504492 Dodds Ashley ''et al''. ''CID'' 2006;43(Suppl 1):S28-S39] (''Candida'' etc.), [https://doi.org/10.1086/497832 Enache-Angoulvant, ''et al''. ''CID'' 2005;41(11):1559-1568] (''Saccharomyces''), [https://doi.org/10.1128/AAC.46.4.1144-1146.2002 Paphitou AAC 2002;46(4):1144-1146] (''Trichophyton'').

	=== Mechanisms of resistance ===		== Mechanisms of resistance ==

	* '''Azole resistance:''' triazoles inhibit C-14α demethylase (Erg11p), which is required for the synthesis of ergosterol from lanosterol. Ergosterol is required for proper cell membrane function. There are several mechanisms of resistance:		* '''Azole resistance:''' triazoles inhibit C-14α demethylase (Erg11p), which is required for the synthesis of ergosterol from lanosterol. Ergosterol is required for proper cell membrane function. There are several mechanisms of resistance:
Line 545:		Line 545:
	* '''Sources:''' Lancet ID series, Mandell, [https://doi.org/10.1016/s1473-3099(02)00181-0 Sanglard and Odds. ''Lancet ID'' 2002;2(2):73-85].		* '''Sources:''' Lancet ID series, Mandell, [https://doi.org/10.1016/s1473-3099(02)00181-0 Sanglard and Odds. ''Lancet ID'' 2002;2(2):73-85].

	=== Susceptibility testing ===		== Susceptibility testing ==

	* '''Sensitire plates:''' used for Candida susceptibility testing, does colorimetric testing of broth microdilution.		* '''Sensitire plates:''' used for Candida susceptibility testing, does colorimetric testing of broth microdilution.
Line 560:		Line 560:
	* '''Species-specific breakpoints:''' (by CLSI and EUCAST) the distribution of wild-type MICs differs between species, with the previous species-independent breakpoints often very far from the ECV. Using the species-independent breakpoints, then, may not detect the development of new resistance until much later.		* '''Species-specific breakpoints:''' (by CLSI and EUCAST) the distribution of wild-type MICs differs between species, with the previous species-independent breakpoints often very far from the ECV. Using the species-independent breakpoints, then, may not detect the development of new resistance until much later.
	* '''Further Reading:''' [https://dx.doi.org/10.1128%2FJCM.00937-12 Pfaller J Clin Microbiol 2012 50(9): 2846], CLSI M59 and M27, the SOP for yeast susceptibility reporting.		* '''Further Reading:''' [https://dx.doi.org/10.1128%2FJCM.00937-12 Pfaller J Clin Microbiol 2012 50(9): 2846], CLSI M59 and M27, the SOP for yeast susceptibility reporting.

			[[Category:Mycology]]

Maintenance script: Imported from text file

2019-08-11T18:06:01Z

Imported from text file

New page

= Yeast and Yeast-like organisms =

== ''Candida'' species ==

=== Identification ===

* Any yeast that has growth on culture (blood, fluid, tissue) or seen on Gram stain gets subcultured to SAB-CG at 35º C.
** Growth rate: <7 days is rapid
** Texture
** Colour of surface and reverse
* Do wet mount to confirm features of ''Candida''.
* '''Microscopy''' for chlamydospores, pseudohyphae, hyphae, arthroconidia, blastoconidia formation, budding, capsules, pigmentation.
** ''C. glabrata'' is smaller, does not produce hyphae or pseudohyphae, produces blastoconidia, and grows as creamy yeast colonies.
** Non-glabrata spp. usually exhibit single buddings and can have pseudohyphae (rarely true septate hyphae). Cannot identify species based on microscopy alone.
* '''MALDI-ToF''' (Vitek MS), which provides a species. If ''C. haemolunii'' or ''C. famata'' identified on Vitek, need to rule out ''C. auris''.
** If Vitek not ≥95% match, or identifies one of the two species above, then repeat the MALDI-ToF and set up Dalmau on cornmeal agar.
* '''Dalmau technique:''' growth in adverse conditions (bile oxgall and corn meal) to help identify differences between species of yeast.
** Light inoculum of single colony in a #-sign pattern with lines 1 inch apart. Cover streaks with coverslip and tamp down gently. Incubate at room temperature 18-72 hours.
** Examine after 18-24 hours. Look for thick-walled chlamydospores (terminal refractory circles), blastoconidia morphology, and presence of pseudohyphae. Then continue incubating, examining daily.
* Old-school enzymatic tests and assimilation assays.
* '''Temperature tolerance test''' at 35-37º C, 42º C, and 45º C
* '''Germ tube test:''' if positive, either ''C. albicans'' or ''C. dubliniensis''.

<table>
<thead>
<tr class="header">
<th>Species</th>
<th>Colony</th>
<th>Conidia</th>
<th>Pseudohyphae</th>
<th>Other</th>
<th>Other Tests</th>
</tr>
</thead>
<tbody>
<tr class="odd">
<td>C. albicans</td>
<td>White to creamy, raised, pasty, smooth and soft, shiny and moist. May produce mycelial growth called “feet” or “roots”.</td>
<td>Blastoconidia globose to oval.</td>
<td>Well-developed, abundant with blastoconidia in clusters or grape-like arrangement at septa.</td>
<td>Chlamydospores: round, large, thick-walled, usually single and mostly terminal forming on the tip of pseudohyphae, but some may be sessile. True hyphae may be present in older cultures.</td>
<td>Growth at 42-45º C.</td>
</tr>
<tr class="even">
<td>C. dubliniensis</td>
<td>Cream-coloured, glistening, waxy, usually smooth.</td>
<td>Blastoconidia subspherical, identical to C. albicans.</td>
<td>Well-developed with blastoconidia in grape-like arrangement.</td>
<td>Chlamydospores: round, large, thick-walled, usually in pairs, triplets, and clusters of 1-3 and mostly terminal. True hyphae may be present, especially in older culture.</td>
<td>Usually no growth at 42-45º C.</td>
</tr>
<tr class="odd">
<td>C. glabrata</td>
<td>Small, white to cream-coloured, shiny, pasty, and smooth.</td>
<td>Terminal single budding, oval, and small. Typically arranged in dense groups.</td>
<td>Absent, or rudimentary if present</td>
<td></td>
<td></td>
</tr>
<tr class="even">
<td>C. krusei</td>
<td>Cream-coloured to tannish-white. Flat, dry, ground-glass appearance. Spreading edge with a delicate feathery periphery.</td>
<td>Elongate, ellipsoidal to cylindrical. Cells are liberated and arranged parallel to the main axis appearing like logs on the stream.</td>
<td>Initially sparse, often present on prolonged incubation. Elondated and slender, with blastoconidia forming a cross-matchstick or treelike branching appearance at the septa.</td>
<td></td>
<td></td>
</tr>
<tr class="odd">
<td>C. parapsilosis</td>
<td>White to creamy, shiny, moist, slightly flat, mostly smooth or partly or entirely wrinkled.</td>
<td>Ovoid, single or in small clusters.</td>
<td>Usually abundant, but may be slow to grow. Crooked or curved, relatively short, branched chains of pseudohyphae with clusters of blastoconidia at or between septa. Christmas-tree-like arrangement.</td>
<td>Occasional presence of large hyphal elements called giant cells.</td>
<td></td>
</tr>
<tr class="even">
<td>C. tropicalis</td>
<td>Cream-coloured to semiwhite, dull, dry, soft, smooth and creamy. May be wrinkled or have a mycelial fringe near the edge. Can have feet (root mycelium) similar to C. albicans.</td>
<td>Oval. Single or in small groups or short chains at or between septa of pseudohyphae.</td>
<td>Very active growth. Abundant, long and branched.
Blastoconidia produced in verticils from the pseudohyphae.</td>
<td>True hyphae may be present.</td>
<td></td>
</tr>
<tr class="odd">
<td>C. famata</td>
<td>White to cream coloured.</td>
<td>Ellipsoidal.</td>
<td>Absent.</td>
<td></td>
<td>Weak growth at 40º C. Does not grow at 42º C.</td>
</tr>
<tr class="even">
<td>C. auris</td>
<td>White to cream-coloured. Pink to beige on chromogenic agar (depending on the agar).</td>
<td>Oval or elongated yeast cells, singly or in pairs or groups.</td>
<td>Absent.</td>
<td></td>
<td>Grows well at 42º C. Variable growth at 45º C. Cycloheximide-susceptible. Usually fluconazole-resistant.</td>
</tr>
<tr class="odd">
<td>C. guilliermondii</td>
<td>White to tan, slightly heaped, shiny, moist, and usually mucoid with smooth edge.</td>
<td>Spherical to ellipsoidal.</td>
<td>May be slow growing (up to 10 days), radiating from centre of masses of budding cells.</td>
<td>Pseudohyphae not produced.</td>
<td>May grow at 42 º C.</td>
</tr>
</tbody>
</table>

=== Epidemiology ===

* Refer to [https://doi.org/10.1093/cid/cis697 Cleveland et al; CID 2012 55:1352].
* The predominant species worldwide (and in Canada) is '''''C. albicans''''', by a wide margin, followed by ''C. glabrata'', ''C. tropicalis'', and ''C. parapsilosis''.
* Non-''candida'' species are becoming more common, globally, over the past three decades.
** ''C. dubliniensis'' associated with HIV esophagitis.
** ''C. lusitaniae'' can develop resistance to amphotericin.
** ''C. guilliermondii'' is multidrug resistant.
** ''C. auris'' still rare but may be emerging. It can be misidentified as other yeasts (most commonly ''C. haemulonii'', but also ''C. famata'', ''Saccharomyces cerevisiae'', and ''Rhodotorula glutinis'').

[[File:media/image9.png]]

[[File:media/image7.png]]

Sources: [https://dx.doi.org/10.1016/j.jcrc.2006.10.038 Laverdiere et al. ''J Crit Care''. 2007;22(3):245–250], [https://doi.org/10.1111/1469-0691.12539 Guinea. ''Clin Microbiol Infect''. 2014;20(Suppl 6):5-10].

== ''Cryptococcus'' species ==

=== Diagnosis of ''Cryptococcus'' meningitis ===

* Microscopy:
** India ink can help identify encapsulated yeasts (50% of non-AIDS and 80% of AIDS will have CSF positive by India ink). India ink no longer done because antigen LFA way more sensitive and specific.
** GMS may help identify narrow-based budding.
* From culture:
** Christensen’s Urea: urease-positive yeast include ''Cryptococcus'', ''Trichosporon'', and ''Malassezia furfur''.
** Capsule present on India ink preparation.
** Characteristics include:
*** Colonies: Cream to tan in colour, slightly heaped, chiny, moist, and usually mucoid with smooth edge.
*** Conidia: Blastoconidia are round, budding attached to parent cells by narrow necks.
*** Pseudohyphae: absent
*** Extra tests: India ink to demonstrate capsule; urease positive.
** Other methods to presumptively identify the yeast are to perform a rapid urease test or to inoculate the yeast onto Staib’s birdseed, DOPA, or caffeic acid media (in which colonies will produce melanin and turn brown to black).
* Antigen detection (cryptococcal polysaccharide antigen)
** Latex agglutination (Sn & Sp 90%)
** ELISA (Sn & Sp 90%)
** Lateral flow assay (LFA) (Sn & Sp 95-100%); sensitivity higher in AIDS

[[File:media/image13.png|Performance characteristics of cryptococcal diagnostic assays in persons with suspected meningitis, Uganda and South Africa]]

The composite reference standard was defined as a CSF culture-positive (n = 459) or a culture-negative sample with ≥2 positive test results (e.g., India ink microscopy, CRAG latex, or CRAG LFA) and without an alternative etiologic explanation (n = 60). Source: [https://dx.doi.org/10.3201%2Feid2001.130906 Boulware ''et al''. ''EID''. 2014;20(1):45-53].

=== ''Cryptococcus gattii'' and ''C. neoformans'' ===

==== Epidemiology of ''C. gattii'' ====

* Unlike ''C.neoformans, C. gattii'' has never been found from bird/bat guano. It is usually found in eucalyptus (River red and Forest red gum trees) and coniferous trees, specifically in Vancouver Island and the West Coast
* No specific seasonality, one study reports more cases in the fall and winter
* No human-to-human transmission (unless in solid organ transplantation of an infected organ)
* Unlike ''C. neoformans'', ''C. gattii'' usually affects immunocompetent individuals
* Incubation period is 1 year
* More likely to cause cryptococcomas

==== Distinguishing ''C. gattii'' and ''C. neoformans'' ====

* A color reaction on '''concanavalin-glycine-thymol''' agar
** Creatinine deiminase is repressed by ammonia in ''C''. ''neoformans'' but not in ''C''. ''gattii''. This difference is manifested by a change in the color of the diagnostic media as the pH changes
** Media containing L-canavanine and glycine with bromothymol blue as the color indicator for growth (CGB medium) can efficiently differentiate between these two species (''C. gattii'' will produce a color change and ''C.neoformans'' will not)
* They produce different sexual spores (impractical)
* MALDI-TOF may be able to identify the different species

== Other yeasts of clinical importance ==

=== ''Trichosporon'' ===

* Clinical Significance:
** Can cause Tinea blanca/White piedra which is a mycosis of the hair. Soft nodules composed of yeast cells and arthroconidia encompass the hair shaft. (Immunocompetent)
** Invasive human infection is most commonly due to ''Trichosporon asahii'' or, less commonly, ''T. mucoides''. This usually occurs in immunocompromised patients.
*** Trichosporonosis is an acute febrile illness with dissemination to deep organs with a 64% mortality rate.
*** Often hematuria and funguria given common renal involvement
*** May present with multiple red papules on skin
* Identification:
** Colonies are white to cream colored, moist and soft. Become irregularly wrinkled, dry, powdery or crumb-like with age.
** Blastoconidia are ovoid to ellipsoidal, 3.5-3.5-14 um, singly or in short chains but few in number
** RESISTANT to cyclohexidine
** ++ True hyphae
** Urease positive
** Treatment with '''voriconazole'''

=== ''Malassezia furfur'' ===

* Clinical Significance:
** Common skin colonizer
** Causes catheter-related sepsis, almost always in patients who are receiving parenteral lipids through a central line
** Described in neonates in the ICU, immunocompromised adults
** Can present with fever, bradycardia, thrombocytopenia
** M.globosa causes tinea versicolor
* Identification:
** Will NOT grow on routine media
** With olive oil overlay or use of specialized media (Dixon, Leeming-Notman): colonies are smooth, cream to yellowish brown, dry with age
** RESISTANT to cyclohexamide
** Yeast cells are phialides with colarettes, broad based buds

=== ''Saccharomyces cerevisiae'' (“Baker’s Yeast”) ===

* Clinical Significance:
** Considered an occasional digestive commensal organism
** Can cause fungemia especially in patients on probiotics with central lines/catheter-related infections
** ''S. cerevisiae'' invasive infection usually seen in immunocompromised patients, while ''S. boulardii'' usually seen in immunocompetent patients
** Has been very rarely described in esophagitis
* Identification:
** Colonies are white to cream, smooth and glabrous
** Evidence of multilateral budding
** Blastoconidia are globose to ellipsoidal
** Absence of hyphae

=== ''Rhodotorula'' ===

* Clinical Significance:
** Can cause fungemia usually in immunocompromised patients or patients with central lines
** The most common underlying diseases included solid and haematologic malignancies in patients who were receiving corticosteroids and cytotoxic drugs, the presence of CVC, and the use of broad-spectrum antibiotics.
** Can also cause localized infections i.e. meningitis, SSTI, prosthetic joint, peritoneal and ocular infections
* Identification:
** Colonies are pink, reddish or yellow. They are either slimy or dry.
** May have rudimentary hyphae, but ballistoconidia are absent
** Urease positive

== ''Candida auris'' ==

* Review the paper [https://dx.doi.org/10.1128/CMR.00029-17 Clin Micro Rev January 2018 31(1).]

=== Identification Methods ===

* ''C. auris'' can often be misidentified using the usual methods, often mistaken for ''C. haemulonii''
* Use chromogenic agar to differentiate between ''C. auris'' and ''C. haemulonii'' isolates using growth characteristics
** ''C. auris'' forms pink-to-beige colonies on chromogenic agar
** Grows well at 42 degrees
** No growth in cyclohexidine
** No hyphae or pseudohyphae
* MALDI-TOF is more accurate now that it’s been added to the database
* PCR assays are in development (likely most helpful in an outbreak setting)
* Sequencing

=== Susceptibility Patterns ===

* There are no antifungal clinical breakpoints
* Demonstrated failures and resistance to: fluconazole and other azoles i.e. voriconazole, itraconazole and isavuconazole
** Resistance to azoles likely caused by the Erg11 mutation
* Variability of susceptibility to Amphotericin B
* Therefore empiric therapy is suggested with echinocandins, especially Micafungin (unless it’s a CNS infection as there is no penetration)
* Combination therapy is being studied with Micafungin + Voriconazole
* CNS infections: Amphotericin B + 5-flucytosine

=== Infection Control Methods ===

* Chlorhexidine is active against it
** Decolonize patients with chlorhexidine gluconate body wash, chlorhexidine mouthwash, and chlorhexidine-impregnated pads on CVC exit sites
** Note: ''C. auris'' can survive up to 14 days on plastic
* Sodium hypochlorite and hydrogen peroxide can be used for cleaning surfaces
** With the exception of a water-based QAC and a 1:50 dilution of sodium hypochlorite, our data demonstrate that most disinfectants used in healthcare facilities are effective (>3-log10 reduction) against ''C. auris'' ([https://doi.org/10.1017/ice.2019.1 source]).
* Screening (new PIDAC 2019 guidelines exist, essentially CPE risk factor screening):
** Axilla and groin screening; additional sites as directed clinically or by previously positive sites
** Periodic reassessment for presence of colonization at 1- to 3-mo intervals
** For deisolation, 2 or more assessments 1 wk apart with negative results (off antifungals)
* Isolation (per CDC):
** Single room with standard and contact precautions;
** gown and gloves
** hand hygiene precautions
* Cleaning:
** Thorough daily and terminal cleaning/disinfection using Environmental Protection Agency-registered disinfectant effective against ''C. difficile'' spores

== Antifungal Susceptibility Testing of Yeast ==

=== Patterns of resistance ===

* '''''Candida'' spp:''' most species are susceptible to azoles including fluconazole, except ''C. glabrata'' (which may be dose-dependently susceptible) ''C. krusei'', and ''C. auris''. ''C. lusitaniae'' is resistant to ampho B. All are generally susceptible to echinocandins.
* '''''Trichosporon'':''' azoles tested appeared to be more potent than amphotericin B, and were likely fungicidal. However, [https://doi.org/10.1093/mmy/myt029 a more recent series] reports resistance to fluconazole (though continued susceptibility to other azoles).
* '''''Saccharomyces'':''' [https://doi.org/10.1086/497832 in one review of case reports], there was ''in vitro'' resistance to ampho B and dose-dependent susceptibility to fluconazole. However, rates of clinical response were similar and other researchers have found ''in vitro'' susceptibility to amphotericin. [https://doi.org/10.1111/myc.12604 A review of 7 cases] describes successful treatment with micafungin, caspofungin, and voriconazole.
* '''''Cryptococcus neoformans'':''' routinely susceptible to fluconazole and amphotericin, but ''not'' to echinocandins (does not have beta-D-glucan).

{|
! Organism
! AmB
! Fluc
! Itra
! Vori
! Posa
! Anidula
! Caspo
! Mica
! Flucyt
|-
| ''Aspergillus'' spp.
| +
| –
| +
| +
| +
| +
| +
| +
| –
|-
| ''A. flavus''
| ±
| –
| +
| +
| +
| +
| +
| +
| –
|-
| ''A. fumigatus''
| +
| –
| +
| +
| +
| +
| +
| +
| –
|-
| ''A. terreus''
| –
| –
| +
| +
| +
| +
| +
| +
| –
|-
| ''A. niger''
| +
| –
| ±
| +
| +
| +
| +
| +
| –
|-
| ''Candida'' spp.
| +
| +
| +
| +
| +
| +
| +
| +
| +
|-
| ''C. albicans''
| +
| +
| +
| +
| +
| +
| +
| +
| +
|-
| ''C. glabrata''
| +
| SDD
| ±
| +
| +
| +
| +
| +
| +
|-
| ''C. krusei''
| +
| –
| ±
| +
| +
| +
| +
| +
| ±
|-
| ''C. lusitaniae''
| –
| +
| +
| +
| +
| +
| +
| +
| +
|-
| ''C. parapsilosis''
| +
| +
| +
| +
| +
| ±
| ±
| ±
| +
|-
| ''C. tropicalis''
| +
| +
| +
| +
| +
| +
| +
| +
| +
|-
| ''Crypto. neoformans''
| +
| +
| +
| +
| +
| –
| –
| –
| +
|-
| ''Coccidioides'' spp.
| +
| +
| +
| +
| +
| ±
| ±
| ±
| –
|-
| ''Blastomyces''
| +
| +
| +
| +
| +
| ±
| ±
| ±
| –
|-
| ''Histoplasma'' spp.
| +
| +
| +
| +
| +
| ±
| ±
| ±
| –
|-
| ''Fusarium'' spp.
| ±
| –
| –
| +
| +
| –
| –
| –
| –
|-
| ''Saccharomyces'' spp.
| ±
| SDD
| SDD
|
|
|
|
|
|
|-
| ''Scedosporium apiospermum''
| ±
| –
| ±
| +
| +
| –
| –
| –
| –
|-
| ''Scedosporium prolificans''
| –
| –
| –
| ±
| ±
| –
| –
| –
| –
|-
| ''Trichosporon'' spp.
| ±
| +
| +
| +
|
|
|
|
|
|-
| Zygomycetes
| ±
| –
| –
| –
| +
| –
| –
| –
| –
|}

Source: [https://doi.org/10.1086/504492 Dodds Ashley ''et al''. ''CID'' 2006;43(Suppl 1):S28-S39] (''Candida'' etc.), [https://doi.org/10.1086/497832 Enache-Angoulvant, ''et al''. ''CID'' 2005;41(11):1559-1568] (''Saccharomyces''), [https://doi.org/10.1128/AAC.46.4.1144-1146.2002 Paphitou AAC 2002;46(4):1144-1146] (''Trichophyton'').

=== Mechanisms of resistance ===

* '''Azole resistance:''' triazoles inhibit C-14α demethylase (Erg11p), which is required for the synthesis of ergosterol from lanosterol. Ergosterol is required for proper cell membrane function. There are several mechanisms of resistance:
** Induction of efflux pumps: most common mechanism, with various possible pumps
** Altered or overexpressed C-14α demethylase
** Rarely, alterations in sterol synthesis pathway
* '''Echinocandin resistance:''' echinocandins inhibit synthesis of 1,3-β-d-glucan, which is the main component of the cell wall. Resistance is conferred by mutations in the FKS gene (Fks1 for all species, as well as Fks2 in ''C. glabrata'') which encodes a subunit of glucan synthase. Ser-641 or Ser-645 account for more than 90% of resistance in ''C. albicans''. ''Cryptococcus'', by comparison, does not use that pathway and therefore has inherent resistance to echinocandins.
* '''Sources:''' Lancet ID series, Mandell, [https://doi.org/10.1016/s1473-3099(02)00181-0 Sanglard and Odds. ''Lancet ID'' 2002;2(2):73-85].

=== Susceptibility testing ===

* '''Sensitire plates:''' used for Candida susceptibility testing, does colorimetric testing of broth microdilution.
* Definitions
** '''Epidemiological cut-off value (ECV or ECOFF):''' the minimum MIC or MEC that separates fungi with acquired or mutational resistance and those without. They can be used to detect antimicrobial resistance in the lab, essentially discriminating wild-type from non-wild-type strains.
** '''Clinical breakpoint:''' the MIC or MEC that predicts clinical response to the antimicrobial, which is often based on the MIC distribution, PK/PD data, and clinical outcomes from trials.
** '''Wild-type strains:''' isolates with no mechanisms of acquired resistance or reduced susceptibility for the antifungal agent being evaluated.
* '''Amphotericin and ''Candida'':''' there is no clinical breakpoint for amphotericin B with Candida, so it is reported instead as an MIC. You should consult the ECV (CLSI or other) to make an educated guess at susceptibility.

[[File:./media/image3.png]]

Source: [https://doi.org/%2010.1128/JCM.02416-16 Lockhart, ''et al''. ''J Clin Microbiol'' 2017;55:1262-1268].

* '''Species-specific breakpoints:''' (by CLSI and EUCAST) the distribution of wild-type MICs differs between species, with the previous species-independent breakpoints often very far from the ECV. Using the species-independent breakpoints, then, may not detect the development of new resistance until much later.
* '''Further Reading:''' [https://dx.doi.org/10.1128%2FJCM.00937-12 Pfaller J Clin Microbiol 2012 50(9): 2846], CLSI M59 and M27, the SOP for yeast susceptibility reporting.