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    Candida Albicans

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    Afi Adi Kirana
    This document discusses opportunistic fungal infections, focusing on Candida species. It describes Candida as commonly causing localized or systemic infections in immunocompromised patients. Key points include: - Candida albicans is the most common cause of invasive fungal infection. - Virulence factors include ability to switch phenotypes, form hyphae, adhere to surfaces, and produce lytic enzymes. - Infections can range from mucocutaneous to disseminated. Diagnosis involves microscopy, culture, and identification of species. Treatment involves antifungal drugs like amphotericin B and azoles.

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    Candida Albicans

    Uploaded by

    Afi Adi Kirana
    180 views44 pages
    This document discusses opportunistic fungal infections, focusing on Candida species. It describes Candida as commonly causing localized or systemic infections in immunocompromised patients. Key points include: - Candida albicans is the most common cause of invasive fungal infection. - Virulence factors include ability to switch phenotypes, form hyphae, adhere to surfaces, and produce lytic enzymes. - Infections can range from mucocutaneous to disseminated. Diagnosis involves microscopy, culture, and identification of species. Treatment involves antifungal drugs like amphotericin B and azoles.

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    This document discusses opportunistic fungal infections, focusing on Candida species. It describes Candida as commonly causing localized or systemic infections in immunocompromised patients. Key points include: - Candida albicans is the most common cause of invasive fungal infection. - Virulence factors include ability to switch phenotypes, form hyphae, adhere to surfaces, and produce lytic enzymes. - Infections can range from mucocutaneous to disseminated. Diagnosis involves microscopy, culture, and identification of species. Treatment involves antifungal drugs like amphotericin B and azoles.

    Copyright:

    © All Rights Reserved
    Download as PPT, PDF, TXT or read online from Scribd
    Download as ppt, pdf, or txt
    180 views44 pages

    Candida Albicans

    Uploaded by

    Afi Adi Kirana
    This document discusses opportunistic fungal infections, focusing on Candida species. It describes Candida as commonly causing localized or systemic infections in immunocompromised patients. Key points include: - Candida albicans is the most common cause of invasive fungal infection. - Virulence factors include ability to switch phenotypes, form hyphae, adhere to surfaces, and produce lytic enzymes. - Infections can range from mucocutaneous to disseminated. Diagnosis involves microscopy, culture, and identification of species. Treatment involves antifungal drugs like amphotericin B and azoles.

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    © All Rights Reserved
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    of 44

    Opportunistic Fungal Infections

    Candida
    Susan Richardson
    January 11, 2010
    1

    Opportunistic Fungal Infections

    Require impairment of host immunity to cause serious infection


    Clinical infection - localized to severe systemic infection
    Yeasts:
    Candida spp. (albicans, tropicalis, parapsilosis, krusei, glabrata, lusitaniae,
    kefyr, guilliermondii etc.)
    Cryptococcus neoformans
    Filamentous fungi:
    Aspergillus spp. (fumigatus, niger, flavus)
    Zygomycetes (Rhizopus, Mucor, Rhizomucor, Absidia)
    Fusarium spp.
    Penicillium spp. (marneffei)
    Pseudallescheria boydii (Scedosporium apiospermium)
    Curvularia spp.

    Predisposing Factors
    (Immunologic)

    Cancer (esp. hematological malignancy)


    Key defect: Neutropenia

    Organ Transplantation (bone marrow, liver,


    lung, kidney)
    Key defect: Neutropenia, Impaired T cell function

    Cellular Immune Dysfunction (AIDS,


    lymphoma, CMC)
    Key defect: Impaired T cell function
    3

    Predisposing Factors
    (Non-Immunologic)
    Chemotherapy (cytotoxic) - mucosal damage
    of GI, respiratory, GU tracts
    Antibiotics - Broad spectrum; loss of normal
    flora, esp. anaerobic
    Invasive devices - breach skin/mucosal
    defences, i.e. intravenous lines, urinary
    catheters, tracheostomies
    Invasive procedures - surgery, diagnostic
    biopsies

    Transmission of Opportunistic
    Fungi

    Candida, Trichosporon, Malassezia


    ENDOGENOUS
    unique strain
    colonization precedes infection
    antibiotic suppression of normal flora, fungal
    overgrowth

    EXOGENOUS
    hand carriage health care worker
    5

    Transmission of Opportunistic
    Fungi

    Aspergillus, Zygomycetes, other


    filamentous fungi, Cryptococcus
    EXOGENOUS
    inhaled conidia
    ventilation systems, construction, heliports, plants,
    environment
    direct contact - dressings, arm boards, burns,
    wounds
    6

    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)

    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)
    8

    Cell wall Candida albicans

    Candida - Pathogenicity / Virulence


    Factors
    C. albicans >>> virulent than other Candida
    species
    Rapid switching of expressed phenotype

    Enhanced ability to reassort and regulate genetic


    expression by chromosomal rearrangement and
    recombination
    phenotypic - nutrient stress produces different colony forms
    virulence factors (including antifungal resistance, e.g. C.
    lusitaniae vs. amphotericin B)

    10

    Candida - Pathogenicity / Virulence


    Factors

    Hyphal formation
    Hyphal formation is associated with tissue invasion
    ( yeast forms associated with epithelial colonization)
    spontaneous C.albicans non-hyphae-forming mutant
    shows decreased pathogenicity in a rat Candida vaginitis
    model
    Experimental renal infection - yeast and hyphae initiate
    renal lesions, but hyphae are essential for invasion of the
    renal pelvis.

    Hyphae adhere more readily to host epithelial surfaces than do


    yeast cells (50x more adherent)
    11

    Candida - Pathogenicity / Virulence


    Factors

    Contact sensing - growth of hyphae on filters or


    membranes (thigmotropism)
    When placed on agar medium grow through pores and
    along grooves. Tissue penetration may be aided by
    following surface discontinuities and microscopic breaks

    Surface hydrophobicity
    Hydrophobic C. albicans at 25 C >>virulent than more
    hydrophilic C. albicans at 37 C
    Hydrophobic CA show increased adherence and more
    rapid hyphal germ tube formation
    12

    Candida Pathogenicity / Virulence Factors

    Surface virulence molecules (receptors,


    adhesins, pyrogens, and immunomodulators)
    Candida adhere to:
    epithelial cells (buccal, cervical, corneal, urinary,
    gastrointestinal mucosa), vascular endothelial cells,
    spermatozoa, plastics

    Candida form ligands to host components C3d, iC3b, fibrinogen, laminin, fibronectin,
    fucose receptors, N-acetylglucosamine receptors
    13

    Candida
    Pathogenicity / Virulence Factors

    Molecular mimicry
    Surface coat of molecules that mimics host components
    (decreases recognizability)
    C. albicans cells in the bloodstream become rapidly coated with
    host platelets via the fibrinogen-binding ligand.

    Lytic enzymes
    Hydrolases with broad substrate specificities (proteinase,
    phospholipase(s), lipase(s), acid phosphomonoesterase).
    Aspartyl proteinase - most potent or thoroughly studied.

    14

    Candida
    Pathogenicity / Virulence Factors

    Growth rate and undemanding nutrient


    requirements
    Virulent strains have shorter doubling times than
    attenuated strains
    C. albicans not fastidious, but nutritionally deprived
    mutants (auxotrophs for adenine, lysine, serine, uracil
    and heme) show decreased virulence

    15

    Candida

    Human commensal (endogenous)


    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
    16

    Candida - Clinical

    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
    17

    Mucosal candidiasis

    Oral thrush
    Vaginal candidiasis

    18

    Cutaneous candidiasis

    Diaper dermatitis
    Balanitis

    19

    Cutaneous candidiasis

    Onychomycosis and paronychia

    Chronic mucocutaneous candidiasis


    20

    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

    21

    Clinical profile
    Central catheter
    Parenteral nutrition
    Broad-spectrum
    antibiotics
    Neutropenia

    Very low birth weight22

    Disseminated candidiasis

    Endophthalmitis

    Disseminated skin lesion

    23

    Disseminated candidiasis

    Hypo-echoic splenic lesions

    24

    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

    25

    Candida species
    Top: Calcofluor White x400: Yeast and
    pseudohyphae

    Bottom: Gram stain x1000: Yeast and


    pseudohyphae

    26

    Pathology of disseminated
    candidiasis

    Yeast-like cells and septate hyphae


    GMS

    27

    Pathology of disseminated
    candidiasis

    Esophagus, vascular invasion, blastoconidia and pseudohyphae, PAS

    28

    Pathology of disseminated
    candidiasis

    Hematogenous renal candidiasis. Disseminated miliary abscesses,


    cortex and medulla. Necrotic papillae.
    29

    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

    30

    Yeast Identification

    31

    32

    33

    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
    34

    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
    35

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

    x1000
    x400
    x1000
    36

    Yeast identification

    C. parapsilosis
    Short, curved pseudohyphae

    C. guilliermondii
    Few, short pseudohyphae
    Clusters of blastoconidia at septae

    C. lusitaniae
    Slender, branched, curved pseudohyphae
    short chains of blastoconidia

    C. lipolytica

    37

    Elongated blastoconidia in short chains

    Yeast identification

    C. dubliniensis
    Terminal chlamydospores

    C. krusei
    Elongate blastoconidia
    Cross-matchsticks, tree-like

    C. tropicalis

    Graceful long pseudohyphae


    Single/small groups blastoconidia along pseudohyphae

    C. glabrata
    No pseudohyphae, small blastoconidia

    38

    Candida - Laboratory Diagnosis 3


    Candida

    antigen, antibody and


    metabolite detection
    NOT useful in routine practice
    Low sensitivity and specificity

    Polymerase chain reaction


    No more sensitive than blood culture in
    studies to date
    39

    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)
    40

    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
    41

    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

    42

    Candida antifungal susceptibility


    testing

    43

    Candida antifungal susceptibility


    testing

    44

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