Download - Opportunistic Fungi
Opportunistic Mycoses
Infections due to fungi of low virulence in patients who are immunologically compromised
PATHOGENIC FUNGI
• NORMAL HOST
• Systemic pathogens - 25 species• Cutaneous pathogens - 33 species• Subcutaneous pathogens - 10 species
• IMMUNOCOMPROMISED HOSTOpportunistic fungi - 300 species
MOST FREQUENT OPPORTUNISTIC INFECTIONS
• CANDIDA SPECIES
• ASPERGILLUS SPECIES
• MUCOR SPECIES
• CRYPTOCOCCUS
CANDIDA SP.
• Endogenous organism• Found in 40-80% of normal human beings –
present in the mouth, skin, gut and vagina• May be commensal or pathogenic• Frequently infects skin and mucosa but can
also cause pneumonia, septicemia or endocarditis in immunocompromised hosts
CANDIDA ALBICANSMorphology and Identification
• In culture or tissue, oval, budding yeast cells
• Pseudohyphae formation- chains of elongated cells that are constricted at the septations between cells
CANDIDAMorphology and Identification
• On blood agar, after 24 hours of incubation , moist opaque colonies are seen with yeasty odor
CANDIDAMorphology and Identification
• Germ tube or true hyphae formation distinguish Candida albicans from the rest of Candida sp.
CANDIDAClinical Findings
• CUTANEOUS and
MUCOSAL CANDIDIASIS
- oral thrush
- vulvovaginitis
- cutaneous – intertriginous infections
- onychomycosis
CANDIDAClinical Findings
CANDIDAClinical Findings
• SYSTEMIC CANDIDIASIS
• CHRONIC MUCOCUTANEOUS CANDIDIASIS
CANDIDADiagnostic Laboratory Tests
A. Specimens : swabs and scrapings from superficial lesions, blood, spinal fluid, tissue biopsies, urine, exudates, catheters
B. Microscopic Examination: using KOH, demonstrate the presence of pseudohyphae in scrapings or tissue specimens
C. Culture : 37oC; presence of pseudohyphaeD. Serology: not useful; lack sensitivity and
specificity
CANDIDA SP. Diagnostic Laboratory Tests
GERM TUBE TEST
- rapid screening test where the production of germ tubes by the cells is diagnostic for Candida albicans
CANDIDATreatment
• For mucocutaneous form: topical nystatin, ketoconazole, fluconazole
• For systemic infection: Amphotericin B
ASPERGILLUS
• Ubiquitous saprophyte
• A fumigatus – most common human pathogen
• Produces abundant conidia – easily aerosolized
which can be inhaled and invade the lungs
ASPERGILLUSEpidemiology
• Distributed worldwide
• Commonly found in soil, food, paint, air vents, disinfectants
ASPERGILLUSMorphology and Identification
• Produce conidial structure: long condiosphores with terminal vesicles on which phialides are seen
ASPERGILLUSPortal of Entry
INHALATION
ASPERGILLUSClinical Types
• Allergic – hypersensitivity to the organism
- respiratory symptoms may be
mild to alveolar fibrosis
ASPERGILLUSClinical Types
• Fungus ball (Aspergilloma) –recognized by x-ray, may be mistaken for TB cavity
• A colony of saprophytic mold growing in preformed cavity usually due to TB or sarcoidosis
• Patients cough up the fungus elements
ASPERGILLUSClinical Types
• Aggressive tissue invasion
- primarily a pulmonary disease but aspergilli disseminate to any organ
- may cause endocarditis, osteomyelitis, otomycosis, and cutaneous
ASPERGILLUSDiagnostic Laboratory Tests
• Specimens : sputum, other respiratory specimens, or lung biopsy
• Microscopic Examination: with KOH, presence of hyaline branching septate hyphae
ASPERGILLUSDiagnostic Laboratory Tests
• Culture
- require 1-3 weeks for growth
- assumes a variety of colors
- species differentiation is based on spore formation as well as their color, shape and texture
ASPERGILLUSDiagnostic Laboratory Tests
• SEROLOGY1. Immunodiffusion test – antibody detection
- presence of precipitin bands (5)- presence of 3 or more bands indicate more
severe disease 2. EIA to measure galactomannan
- highly specific (99%) but less sensitive (50%)
ASPERGIILUSTreatment
AMPHOTERICIN B
MUCORMYCOSIS
• ACUTE INFLAMMATION OF SOFT TISSUE, USUALLY FUNGAL INVASION OF THE BLOOD VESSELS
MUCORMYCOSIS
Order Mucorales of the class
Zygomycetes1. Rhizopus species
2. Mucor species
3. Absidia species
MUCORMYCOSISEpidemiology
• World-wide distribution
• Common in soil, food, organic debris, seen on decaying vegetables in the refrigerator and on moldy bread
• Rhinocerebral infection – major clinical form
• Frequently seen in the uncontrolled diabetic
MUCORMYCOSIS Clinical Finding
• Rhinocerebral infection:
- invasion of the sinuses, eyes, cranial bones and brain
- blood vessels are damaged, facial edema, bloody nasal exudate, orbital cellulitis
MUCORMYCOSISDiagnostic Laboratory Tests
• CULTURE• Grow rapidly on lab
media producing abundant cottony colonies.
MUCORMYCOSISDiagnostic Laboratory Tests
• DIRECT EXAMINATION:
- broad hyphae with uneven thickness, irregular branching and sparse septations
MUCORMYCOSISTreatment
Surgical debridement
Rapid administration of amphotericin B
Control of underlying disease
CRYPTOCOCCUS NEOFORMANS
• Yeast with a thick polysaccharide capsule
• Occurs worldwide in nature
• Found in very large numbers in dry pigeon and chicken droppings
CRYPTOCOCCUS NEOFORMANSMorphology and Identification
• Spherical cells that produce buds, charac-
teristic narrow-based
• Polysaccharide capsule surrounds the organism
• Capsule may suppress T-cell function – virulence factor
• Phenoloxidase (melanin) – also a virulent factor
CRYPTOCOCCUS NEOFORMANSPathogenesis
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)
CRYPTOCOCCUS NEOFORMANSClinical Findings
1. Meningoencephalitis
- prolonged clinical course: begin with visual problems;
headache,neck stiffnessm coma, death
2. Skin and lung infections- formation of a granulomatous reaction with giant cells
- Cryptococcoma: mass in the mediastinum
CRYPTOCOCCUS NEOFORMANSDiagnostic Laboratory Tests
• Specimens: spinal fluid, exudates, blood, urine, sputum
• INDIA INK TEST –
demonstrates capsule of this yeast
Latex Agglutination test for antigen
- decreasing titer indicates
a good prognosis
CRYPTOCOCCUS NEOFORMANSLaboratory Findings
• Cryptococcus neoformans in sputum,
Wright Stain
CRYPTOCOCCUS NEOFORMANSlaboratory findings
• Cryptococcus neoformans in blood culture, Gram stain
CRYPTOCOCCUS NEOFORMANSTreatment
• AMPHOTERICIN B
Predisposing Factors
Malignancies
• Leukemias
• Lymphomas
• Hodgkins Disease
Predisposing Factors
Drug therapies
• Anti-neoplastics
• Steroids
• Immunosuppressive drugs
Predisposing Factors
Antibiotics
Over-use or inappropriate use of antibiotics alter the normal flora allowing fungal overgrowth
Predisposing Factors
Therapeutic procedures
• Solid organ or bone marrow transplant
• Open heart surgery
• Indwelling catheters
• Artificial heart valves
• Radiation therapy
Predisposing Factors
Other Factors
• Severe burns
• Diabetes
• Tuberculosis
• IV Drug use
Predisposing Factors
AIDS
Some Common Associations between fungal organisms and Disease Condition
CRYPTOCOCCUS- Diabetes melllitus
- tuberculosis
- lymphoma
- Hodgkin’s disease
- steroid therapy
- immunosuppression
Some Common Associations between fungal organisms and Disease Condition
CANDIDA- prolonged antibiotic therapy- prolonged IV catheter- prolonged urinary catheter- corticosteroid therapy- Diabetes mellitus- hyperalimentation- immunosuppression
Some Common Associations between fungal organisms and Disease Condition
ASPERGILLUS
- leukemia
- corticosteroid therapy
- tuberculosis
- immunosuppression
- IV drug use
Some Common Associations between fungal organisms and Disease Condition
ZYGOMYCETES (MUCOR)- diabetes mellitus
- leukemia
- steroid therapy
- IV therapy
- severe burns
IMPROVING TREATMENT
1. New Drugs
2. New therapeutic regimen
3. Aggressive therapy
4. Conjunctive therapy
IMPROVING TREATMENT
New Drugs
Echinocandins
Third generation azoles
New classes of antifungal agents
IMPROVING TREATMENT
New Therapeutic Regimen
Combination Therapy
1. Simultaneously administering two drugs
2. Sequential Tx with two or more drugs
3. Alternate Administration of two or more
IMPROVING TREATMENT
AGGRESSIVE THERAPY
FOR IMMUNOCOMPROMISED PATIENTS
1. Prophylactic – Anti-fungal agents at, or near, the time of chemotherapy
IMPROVING TREATMENT
AGGRESSIVE THERAPY
FOR IMMUNOCOMPROMISED PATIENTS
2. Empirical – Start therapy when patient at risk, i.e., fever and/or infiltrate without response to anti-bacterials.
IMPROVING TREATMENT
AGGRESSIVE THERAPY
FOR IMMUNOCOMPROMISED PATIENTS
3. Pre-emptive –When there is some additional evidence of fungal infection (serology, isolate, etc.)
IMPROVING TREATMENT
CONJUNJUNCTIVE THERAPY
FOR IMMUNOCOMPROMISED PATIENTS
The use of anti-fungal agents with immunotherapy.
Immunotherapy
• Interferons
• Colony stimulating factors
• Interleukins
MYCOLGISTS have more
FUNGI