View source for Candida

==Background==

*Most common medically-important genus of yeast

===Microbiology===

*Budding yeast
*Human pathogens include:
**[[Candida albicans]]
**[[Candida dubliniensis]]
**[[Candida glabrata]]
**[[Candida tropicalis]]
**[[Candida parapsilosis]]
**[[Candida krusei]]
**[[Candida guilliermondii]]
**[[Candida auris]]
*Species that only rarely cause disease in humans include: [[Candida albidus]], [[Candida catenulate]], [[Candida chiropterorum]], [[Candida ciferrii]], [[Candida famata]], [[Candida haemulonii]], [[Candida humicola]], [[Candida inconspicua]], [[Candida kefyr]], [[Candida lambica]], [[Candida lipolytica]], [[Candida norvegensis]], [[Candida pelliculosa]], [[Candida pintolopesii]], [[Candida pulcherrima]], [[Candida rugosa]], [[Candida utilis]] and [[Candida zeylanoides]]

====Identification====

*Any yeast that has growth on culture (blood, fluid, tissue) or seen on Gram stain gets subcultured to SAB-CG at 35º C.
*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) 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 [[Candida albicans]], by a wide margin, followed by [[Candida glabrata]], [[Candida tropicalis]], and [[Candida parapsilosis]]
*Non-''albicans'' species are becoming more common, globally, over the past three decades.
**[[Candida dubliniensis]] associated with HIV esophagitis
**[[Candida lusitaniae]] can develop resistance to amphotericin
**[[Candida guilliermondii]] is multidrug resistant
**[[Candida 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'').

==Clinical Manifestations==

===Fungemia===

*See also [[candidemia]]
*Risk factors include colonization, gastrointestinal mucosal disruption, total parenteral nutrition, and immunosuppression

===Oropharyngeal Candidiasis===

*Risk factors include immunosuppression including diabetes, inhaled corticosteroids, and denture used

===Esophageal Candidiasis===

*Risk factors include immunosuppression

===Vulvovaginal Candidiasis===

*Risk factors include colonization from recent antibiotic use, immunosuppression including diabetes, use of oral contraceptives, and pregnancy

===Candidal Infection of Skin and Nails===

*Risk factors include moisture and occlusion, immersion in water, and peripheral vascular disease
*Candidal skin infections can occur in moist body parts especially where skin occludes, and presents as a pruritic, erythematous rash with a poorly-defined edge that may have vesicles or pustules
*Candidal [[onychomycosis]] is most commonly caused by [[Candida albicans]] and [[Candida parapsilosis]], followed by [[Candida glabrata]] and [[Candida guilliermondii]]
*[[Paronychia]] can be caused by [[Candida albicans]]

===Cutaneous Congenital Candidiasis===

*Occurs in premature infants
*Presents as a generalized macular erythematous rash
*May become pustular, papular, or vescicular
*May desquamate

===Chronic Mucocutaneous Candidiasis===

*Occurs in people with T-cell defects, often related to [[Primary immunodeficiencies|primary immunodeficiency]]

===Urinary Tract Infection===

*Occurs in patients with diabetes, with indwelling urinary catheters, urinary obstruction, or recent urological procedures
*True infection most commonly occurs as a result of hematogenous dissemination rather than ascending infection or in patients who are immunocompromised
*''Candida'' species are a common contaminant of urine cultures, especially in women with vulvovaginal candidiasis
*They can also asymptomatically colonize the urinary system, causing asymptomatic candiduria

===Pulmonary Infections===

*Can occur from hematogenous spread
*Primary, isolated candidal [[pneumonia]] is very rare, and is associated with aspiration pneumonia
*[[Empyema]] can occur in patients with severe underlying diseases
*Candidal [[mediastinitis]] can happen after thoracic surgery, and is associated with high mortality
*[[Laryngitis]] or [[epiglottitis]] is rare and life-threatening

===Endocarditis===

*Most common fungal cause of [[infective endocarditis]]
*Risk factors include cardiac surgery, prior endocarditis, valvular disease, prosthetic valve, long-term central line, and intravenous drug use
*Clinically presents like bacterial [[Infective endocarditis|endocarditis]], but has a higher risk of embolic events
*Most commonly involves aortic and mitral valves

===Pericarditis and Myocarditis===

*Risk factors include thoracic surgery or immunosuppression
*[[Myocarditis]] is rare, occuring via hematogenous spread in immunocompromised patients
**Can have heart block and shock
*[[Pericarditis]] is also rare, often occurs after thoracic surgery, from hematogenous spread, or from contiguous spread

===CNS Infections===

*Occurs following neurosurgery or with [[ventricular shunt infection]] or with hematogenous spread
*Can cause [[brain abscess]], [[meningitis]], or [[stroke]]
*Meningitis can be difficult to diagnose, and requires a large volume of CSF for improved sensitivity

===Ocular Candidiasis===

*From direct inoculation after ocular surgery or trauma, or with hematogenous spread
*Includes [[keratitis]], [[chorioretinitis]], and [[endophthalmitis]]

===Bone and Joint Infections===

*Rare cause of [[osteomyelitis]] and [[septic arthritis]]
*Usually from hematogenous spread; other risk factors include surgery, trauma, intraarticular injection, or [[diabetic foot infection]]
*Symptoms may only become apparent months after initial hematogenous seeding, especially with vertebral osteomyelitis

===Intraabdominal Infection===

*Risk factors include abdominal perforation, abdominal surgery, solid organ transplantation, anastomotic leaks, pancreatitis, and peritoneal dialysis

==Investigations==

*Urine culture if concern for cystitis
*Blood culture
**'''Never ignore candidemia!'''
**Requires an '''ophthalmology''' consult to rule out endophthalmitis (1-3% of cases)
**Echocardiogram if IVDU or prosthetic valve
*Germ tube test (GTT)
**If positive, indicates ''Candida  albicans'' or ''Candida  dubliniensis''
**Identifies fluconazole-sensitive Candidae

==Management==

*Invasive infections should be treated with an echinocandin until species and susceptibilities are available

=== Management by Site of Infection ===
*Superficial infections involving skin or mucosa: can be treated with either topical preparations or low-dose oral fluconazole
*Candidemia: see [[Candidemia#Management|management of candidemia]]
*Bone and joint infections
**Osteomyelitis: likely needs surgical debridement and removal of any implants. Duration of antifungals not well studied, but likely 3 to 12 months
**Septic arthritis: needs drainage and removal of implants. Duration of antifungals at least 6 weeks.

=== Fluconazole Susceptibility ===
{| class="wikitable"
!Species!!Resistance pattern
|-
|[[Candida albicans]]|| rowspan="4" |Generally [[fluconazole]] susceptible
|-
|[[Candida dubliniensis]]
|-
|[[Candida parapsilosis]]
|-
|[[Candida tropicalis]]
|-
|[[Candida glabrata]]||Often '''[[fluconazole]] resistant''', or dose-dependent susceptible
|-
|[[Candida krusei]]||Inherent '''[[fluconazole]] resistance'''
|-
|[[Candida lusitaniae]]||Often '''[[amphotericin]] resistant''' but [[fluconazole]] susceptible
|}

*See also [[Antifungal spectrum of activity]] and [https://doi.org/10.1086/504492 Pharmacology of Systemic Antifungal Agents, CID 2006]

=== Fluconazole-Susceptible Isolates ===

* [[Candidemia]]: [[fluconazole]] 12 mg/kg IV load followed by 6 mg/kg PO/IV daily
** Can use [[fluconazole]] 800 mg daily for isolates that show dose-dependent susceptibility
*[[Vaginal candidiasis]]: [[fluconazole]] 150 mg PO once, with or without intravaginal [[clotrimazole]]
*[[Oral thrush]]: [[fluconazole]] 100 mg po daily for 7 to 14 days
*[[Esophageal candidiasis]]: [[fluconazole]] 200 mg PO daily for 14 to 21 days
*[[Urinary tract infection]]: [[fluconazole]] 200 mg po daily for 7 to 14 days
* [[Intra-abdominal infections|Intraabdominal infection]]: [[fluconazole]] 400 mg PO daily 

== Further Reading ==

* ESCMID guideline for the diagnosis and management of ''Candida'' diseases 2012: non‐neutropenic adult patients. ''Clin Microbiol Infect''. 2012;18(Suppl. 7):19-37. doi: [https://doi.org/10.1111/1469-0691.12039 10.1111/1469-0691.12039]
* Clinical Practice Guideline for the Management of Candidiasis: 2016 Update by the Infectious Diseases Society of America. ''Clin Infect Dis''. 2016;62(4):e1-50: doi: [https://doi.org/10.1093/cid/civ933 10.1093/cid/civ933]
{{DISPLAYTITLE:''Candida''}}
[[Category:Yeasts]]