Candidiasis A primary or secondary mycotic infection caused by members of the genus Candida. The clinical manifestations may be acute, subacute or chronic to episodic. Involvement may be localized to the mouth, throat, skin, scalp, vagina, fingers, nails, bronchi, lungs, or the gastrointestinal tract, or become systemic as in septicaemia, endocarditis and meningitis. Distribution: World-wide. Text slide.

Candida MOST COMMON invasive fungal infection in immunocompromised patients 4th most common cause of nosocomial blood stream infection Species implicated in human disease most often: C. albicans C. tropicalis C. parapsilosis C. krusei (fluconazole resistant) C. glabrata C. lusitaniae (amphotericin B resistant)

Thick cell wall of mannan and glucan polysaccharides Candida Thick cell wall of mannan and glucan polysaccharides Unicellular, budding (asexual) reproduction (blastospores) Filament formation Pseudohyphae (buds stay attached, constricted, chains of elongated blastospores) Hyphae (buds germinate)

Cell wall Candida albicans

Candida Human commensal (endogenous) Environmental (exogenous) skin, gastrointestinal, genitourinary tracts 5 - 15% carriage rate in normal people increased carriage with use of antibiotics Environmental (exogenous) much less common food, animals, soil hospital environment outbreaks have occurred

Candida - Clinical Children with T-cell abnormality Mucous membrane infections Thrush (oropharyngeal) Esophagitis Vaginitis Cutaneous infections Paronychia (skin around nail bed) Onychomycosis (nails) Diaper rash Balanitis Chronic mucotaneous candidiasis Children with T-cell abnormality

Candida - Clinical Urinary tract infection Fungemia Disseminated (systemic, invasive) infection Immunocompromised patients Cancer/chemotherapy Neonatal candidiasis Endophthalmitis (eye) Liver and spleen Kidneys Skin Brain Lungs Bone

Mucosal candidiasis Oral thrush Vaginal candidiasis

Cutaneous candidiasis Diaper dermatitis Balanitis

Cutaneous candidiasis Onychomycosis and paronychia Chronic mucocutaneous candidiasis

056. Oral candidiasis in an infant showing characteristic patches of a creamy-white to grey pseudomembrane composed of blastoconidia and pseudohyphae of C. albicans. Note the mouth of normal newborn infants has a low pH which may promote the proliferation of C. albicans. The infections are usually acquired during the birth process from mothers who had vaginal thrush during pregnancy. Clinical symptoms may persist until a balanced oral flora has been established. 056

057. Chronic oral candidiasis of the tongue and mouth corners (angular cheilitis) in an adult with an underlying immune deficiency. Note characteristic white pseudomembrane composed of cells and pseudohyphae of C. albicans. 057

058. Angular cheilitis an intertrigo and fissuring caused by maceration of the corners of the mouth is frequently complicated by chronic infection with C. albicans. Note the white pseudomembrane-like colonies in the mouth corners of this adult patient. (Courtesy Dr G. Hunter, Adelaide, S.A.). 058

059. Solar cheilitis in a young boy showing colonization of the lip by C. albicans. (Courtesy Dr G. Hunter, Adelaide, S.A.). 059

060. Candida granuloma of the forehead and angular cheilitis of the mouth in a young girl with chronic mucocutaneous candidiasis. Note thick crusted lesions of the scalp and forehead. C. albicans was isolated. 060

061. Interdigital candidiasis of the hands may develop particularly in persons whose hands are subject to continuing wetting, especially with sugar solutions or contact with flour. C. albicans was isolated. (Courtesy Dr G. Hunter, Adelaide S.A.). 061

062. Interdigital candidiasis of the feet explains l% of cases of "athletes foot" and must be distinguished from tinea pedis caused by dermatophytes. C. albicans was isolated. Compare this slide with slide 251 showing T. rubrum infection of foot. (Courtesy Dr G. Hunter, Adelaide, S.A.). 062

063. Intertriginous or flexural candidiasis of the groin may also mimic tinea cruris caused by a dermatophyte. Note erythematous scaling lesions with distinctive border and several small satellite lesions. C. albicans was isolated. (Courtesy Dr D. Hill, Adelaide, S.A.). 063

064. Intertriginous or flexural candidiasis behind the knee showing an extensive erythematous scaling lesion and several smaller satellite lesions caused by C. albicans. (Courtesy Dr G. Hunter, Adelaide, S.A.). 064

065. Satellite lesions of cutaneous candidiasis showing typical collars of scale. C. albicans was isolated. Note the presence of satellite lesions usually differentiates candidiasis from dermatophytosis. 065

068. Chronic candidiasis (onychomycosis) of thumb nails showing destruction of nail tissue. C. albicans was isolated. (Courtesy Dr G. Hunter, Adelaide, S.A.). 068

069. Chronic candidiasis (onychomycosis) of thumb nails showing destruction of nail tissue. C. albicans was isolated. (Courtesy Dr G. Hunter, Adelaide, S.A.). 069

071. Young infant with chronic superficial candidiasis showing spread to the mouth area and conjunctiva. Note erythematous scaling lesions with well marginated borders and small satellite lesions on the chin showing typical collar of scaling. C. albicans was isolated. (Courtesy Dr G. Hunter, Adelaide, S.A.). 071

075. Chronic candidiasis of the scalp in a child with an underlying immune deficiency caused by C. albicans. 075

Candida - Laboratory Diagnosis 1 Specimens - Blood, tissue (biopsy or autopsy), sterile fluid, urine, CSF, skin, respiratory secretions Microscopy (direct on specimen - except blood and urine) Gram stain, Calcofluor Histopathology (tissues) H & E - stain poorly GMS, PMS - stain well

Candida - Laboratory Diagnosis 2 Culture (all specimens) Colony morphology White, smooth, creamy, sometimes wrinkled Laboratory identification Unique color on chromagar Chlamydospore production (terminal vesicle) Germ tube production (in horse serum) beginning of true hypha (no constriction) C. albicans - Germ tube positive Other Candida - Germ tube negative Carbohydrate assimilation and fermentation (API 20C, Vitek2, RapID and reference) Urea and nitrate Microscopic morphology on Cornmeal Tween 80

Candida species Candida albicans Sabouraud Agar Morphology: Creamy white yeast, may be dull, dry irregular and heaped up, glabrous and tough Chromagar producing green pigmented colonies on specially designed medium to speciate certain yeasts based on color they produce

Candida species Germ tube: inoculation of yeast in horse serum incubated at 370C for 2 to 3 hours Germ Tube: Positive Germ tube is a continuous filament germinating from the yeast cell without constriction at the point of attachment. e.g. C. albicans, C. dubliniensis Germ Tube: Negative Shows constriction at the attachment site e.g. other Candida species, esp. C. tropicalis

Candida species Candida albicans Oxgall Agar large round and thick walled chlamydospores Cornmeal Agar clusters of blastospores along pseudohyphae at regular intervals x400 x1000 x400 x1000

076. Skin scraping mounted in 10%KOH from superficial candidiasis showing clusters of budding yeast cells and branching pseudohyphae. 076

077. Direct smear of urine from a patient with candidiasis of the kidney showing C. albicans in mycelial or tissue phase with blastoconidia budding from the pseudohyphae. 077

078. Periodic Acid-Schiff (PAS) stained section of post-mortem oesophagus showing invasion of blood vessel by C. albicans. Note blastoconidia and branched pseudohyphae. 078

079. Candida albicans on Sabouraud's dextrose agar showing typical cream coloured, smooth surfaced, waxy colonies. 079

080. Microscopic morphology of C 080. Microscopic morphology of C. albicans showing budding spherical to ovoid blastoconidia. 080

081. Screening test for the identification of C. albicans 081. Screening test for the identification of C. albicans. Production of germ tubes by C. albicans in serum or plasma after 2-3 hours incubation at 37OC. Note characteristic germ tubes. 081

082. Germ tube negative Candida species showing no production of germ tubes in plasma after 3 hours incubation at 37OC. Budding blastoconidia only are seen. 082

083. Confirmatory test for C. albicans 083. Confirmatory test for C. albicans. Production of large round, thick-walled vesicles (often incorrectly referred to as chlamydoconidia) on Difco chlamydospore agar. Trypan blue in the medium is absorbed strongly by these terminal vesicles. Numerous small blastoconidia and pseudohyphae are also present. 083

084. Uni-Yeast-Tek plate showing common assimilation tests and dalmau plate culture used for the identification of yeasts. Note morphological studies are essential for the satisfactory identification of yeasts. Also note the negative urease test indicating the ascomycetous nature of Candida albicans, the test organism. 084

086. Auxacolor yeast identification strip showing the identification of Candida.

087. CHROMagar Candida plate showing chromogenic colour change for C 087. CHROMagar Candida plate showing chromogenic colour change for C. albicans (green), C. tropicalis (blue), C. parapsilosis (white) and C. glabrata (pink). 087

092. Candida dubleniensis and Candida albicans on CHROMagar.

093. Candida dubleniensis and Candida albicans on Bird Seed Agar.

Candida - Treatment Remove infected intravenous lines Antifungal therapy for systemic infection Amphotericin B IV Azoles (fluconazole, itraconazole, voriconazole, posaconazole) orally, intravenous Flucytosine (only with Ampho B because of resistance) Echinocandins (caspofungin, micafungin)

Candida antifungal resistance Primary (inherent) resistance C. lusitaniae (amphotericin B) C. glabrata (fluconazole) C. krusei (fluconazole) Secondary (acquired) resistance Fluconazole, other azoles Amphotericin B 5-FC

Candida antifungal susceptibility testing Testing methodology Reference broth microdilution (CLSI) Commercial broth microdilution with alamar blue (Sensititre, YeastOne) E-test Disk diffusion (CLSI Vitek 2

Candida antifungal susceptibility testing

Candida antifungal susceptibility testing