s3 l25 opportunistic mycoses
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S3 L24: Opportunistic Mycoses by Dr. Antonio Camacho DDDeeeccceeemmmbbbeeerrr 111999,,, 222000111000
OPPORTUNISTIC MYCOSES
Infections due to fungi of low virulence in patients who are immunologicallycompromised
PATHOGENIC FUNGI
Normal hostoSystemic pathogens - 25 speciesoCutaneous pathogens - 33 speciesoSubcutaneous pathogens - 10 species
Immunocompromised hosto Opportunistic fungi - 300 species
HOST-PATHOGEN EQUILIBRIUM
OPPORTUNISTIC FUNGI
1. Saprophytic - from the environment2. Endogenous a commensal organism
Include many species from:
A (Aspergillus) To Z (Zygomyces)
MOST FREQUENT OPPORTUNISTIC INFECTIONS
Candida species Aspergillus species Mucorspecies Cryptococcus
Candida sp.
Endogenous organismFound in 40-80% of normal human beings present in the mouth, skin, gutand vagina
May be communal or pathogenicFrequently infects skin and mucosa but can also cause pneumonia,septicemia or endocarditis in immunocompromised hosts
MORPHOLOGY AND IDENTIFICATION
In culture or tissue: Oval, budding
yeast cells
Pseudohyphae formation- chains ofelongated cells that are constricted atthe septations between cells
On blood agar, after 24 hours of incubation,moist opaque colonies are seen with yeastyodor
Germ tube ortrue hyphae formationdistinguish Candida albicans from the rest ofCandida sp.
CLINICAL FINDINGS
CUTANEOUS and MUCOSAL CANDIDIASISooral thrushovulvovaginitisocutaneous intertriginous infectionsoonychomycosis
CHRONIC MUCOCUTANEOUS CANDIDIASIS
Chronic mucocutaneous candidiasis (CMC) isthe label given to a group of overlappingsyndromes that have in common a clinicalpattern of persistent, severe, and diffusecutaneous candidal infections.
These infections affect the skin, nails andmucous membranes.
DIAGNOSTIC LABORATORY TESTS
Specimens : swabs and scrapings from superficial lesions, blood, spinalfluid, tissue biopsies, urine, exudates, catheters
Microscopic Examination: using KOH, demonstrate the presence ofpseudohyphae in scrapings or tissue specimens
Culture : 37oC; presence of pseudohyphae
Serology: not useful; lack sensitivity and specificity
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GERM TUBE TEST
rapid screening test where the production of germ tubes by the cells isdiagnostic forCandida albicans
Treatment forCandida
oFor mucocutaneous form: topical nystatin, ketoconazole, fluconazoleoFor systemic infection: Amphotericin B
Aspergillus sp.
Aspergillus is a filamentous mold and is a ubiquitous fungus found in nature(soil, plant debris, and indoor air)
Ubiquitous saprophyteA fumigatus most common human pathogen
Produces abundant conidia easily aerosolized which can be inhaled andinvade the lungs
EPIDEMIOLOGY
Distributed worldwideCommonly found in soil, food, paint, air vents, disinfectants
Aspergillus is the second most commonly recovered fungus in opportunisticmycoses (following Candida spp).
The three principal entities are: allergic bronchopulmonary aspergillosis pulmonary aspergilloma invasive aspergillosis
Nosocomial occurence of aspergillosis due to catheters and other devices isalso frequently observed.
MORPHOLOGY AND IDENTIFICATION
Produce conidial structure: long condiosphores with terminal vesicles
Portal of Entry INHALATION
ASPERGILLOSIS
CLINICAL TYPESAllergicohypersensitivity to the organismo respiratory symptoms may be mild to alveolar fibrosisFungus ball (Aspergilloma)o recognized by x-ray, may be mistaken for TB cavity
oA colony of saprophytic mold growing in preformed cavity usually due toTB or sarcoidosis
oPatients cough up the fungus elementsAggressive tissue invasionoprimarily a pulmonary disease but
aspergillus disseminate to any organomay cause endocarditis, osteomyelitis,
otomycosis, and cutaneous
DIAGNOSTIC LABORATORY TESTS
Specimens : sputum, other respiratory specimens, or lung biopsy
Microscopic Examination: with KOH, presence of hyaline branching septatehyphae
Cultureo require 1-3 weeks for growthoassumes a variety of colorsospecies differentiation is based on spore formation as well as their color,
shape and texture
Serologyo Immunodiffusion test
antibody detection presence of precipitin bands (5) presence of 3 or more bands indicate more severe disease
oEIA to measure galactomannan highly specific (99%) but less sensitive (50%)
TREATMENT-AMPHOTERICIN B
Mucorsp.
Acute inflammation of soft tissue, usually fungal invasion of the blood vessels
Organisms under the order MUCORALES of the class ZYGOMYCETES
1. Rhizopus species
2. Mucorspecies3. Absidia species
EPIDEMIOLOGY
World-wide distributionCommon in soil, food, organic debris, seen on decaying vegetables in therefrigerator and on moldy bread
Rhinocerebral infection major clinical form
Frequently seen in the uncontrolled diabetic
MUCORMYCOSIS
CLINICAL FINDING
Rhinocerebral infection:o results from germination of spores in nasal
passages and invasion of the hyphae intothe blood vessels causing thrombosis,infarction, and necrosis.
oblood vessels and nerves are damaged,facial edema, bloody nasal exudate, orbitalcellulitis
DIAGNOSTIC LABORATORY TESTS
Culture: Grow rapidly on lab media producing abundant cottony colonies.
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Direct examination: broad hyphae withuneven thickness, irregular branching andsparse septations
TREATMENT
Surgical debridement
Rapid administration of amphotericin B
Control of underlying disease
Crytococcus neoformans
Yeast with a thick polysaccharide capsule
Occurs worldwide in nature
Found in very large numbers in dry pigeon and chicken droppings
MORPHOLOGY AND IDENTIFICATION
Spherical cells that produce buds
Polysaccharide capsule surrounds theorganismCapsule may suppress T-cell function virulence factor
Phenoloxidase (melanin) also avirulent factor
PATHOGENESIS
INHALATION OF YEAST CELLS (AEROSOLIZED)
PRIMARY PULMONARY INFECTION(asymptomatic or flu-like illness)
In immunocompromised, may disseminate to
other organs preferentially to the CNS (meningoencephalitis)
CLINICAL FINDINGS
Meningoencephalitisoprolonged clinical course: begin with visual problems; headache, neck
stiffness, coma, death
Skin and lung infectionso formation of a granulomatous reaction with giant cellsoCryptococcoma: mass in the mediastinum
DIAGNOSTIC LABORATORY TESTS
o Specimens: spinal fluid, exudates, blood, urine, sputumo LACCASE PRODUCTION: (catalyzes formation of melanin)
differentiates C. neoformans and gattiifrom nonpathogenicCryptococcus
o INDIA INK TEST-demonstrates capsule of thisyeast
o Latex Agglutination test for antigen decreasing titer indicates a good prognosis
DIAGNOSTIC LABORATORY TESTS
LABORATORY FINDINGS
Cryptococcus neoformans in sputum,Wright Stain
Cryptococcus neoformans in bloodculture, Gram stain
TREATMENT
AMPHOTERICIN B + FLUOCYTOSINE: Standard for cryptococcalmeningitis
PREDISPOSING FACTORS
MalignanciesoLeukemiasoLymphomasoHodgkins DiseaseDrug therapiesoAnti-neoplasticsoSteroidso Immunosuppressive drugs
AntibioticsoOver-use or inappropriate use of antibiotics alter the normal flora allowing
fungal overgrowth
Therapeutic proceduresoSolid organ or bone marrow transplantoOpen heart surgeryo Indwelling cathetersoArtificial heart valvesoRadiation therapyOther FactorsoSevere burnsoDiabetesoTuberculosiso IV Drug use
AIDS
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SOME COMMON ASSOCIATIONS BETWEEN FUNGAL ORGANISMSAND DISEASE CONDITIONS
Cryptococcus Candida Aspergillus Zygomycetes
Diabetes melllitus
tuberculosis
lymphoma
Hodgkins disease
steroid therapy
immunosuppression
prolonged antibiotictherapy
prolonged IV catheter
prolonged urinarycatheter
corticosteroid therapy
Diabetes mellitus
hyperalimentationimmunosuppression
leukemia
corticosteroid
therapy
tuberculosis
immunosuppression
IV drug use
diabetes mellitus
leukemia
steroid therapy
IV therapy
severe burns
IMPROVING TREATMENT
New Drugs
New therapeutic regimen
Aggressive therapy
Conjunctive therapy
NEW DRUGS
EchinocandinsThird generation azoles
New classes of antifungal agents
NEW THERAPEUTIC REGIMENCombination Therapy1.Simultaneously administering two drugs2.Sequential Tx with two or more drugs3.Alternate Administration of two or moreAGGRESSIVE THERAPY FOR IMMUNOCOMPROMISED PATIENTS1.Prophylactic Anti-fungal agents at, or near, the time of chemotherapy2.Empirical Start therapy when patient at risk, i.e., fever and/or infiltrate
without response to anti-bacterials.
3.Pre-emptiveWhen there is some additional evidence of fungal infection(serology, isolate, etc.)
CONJUNCTIVE THERAPY FOR IMMUNOCOMPROMISED PATIENTSThe use of anti-fungal agents with immunotherapy (interferon, colony stimulatingfactors, interleukin
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