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Opportunistic Fungi

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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 HOST
Opportunistic 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 ALBICANS
Morphology and Identification
• In culture or tissue, oval,
budding yeast cells
• Pseudohyphae
formation- chains of
elongated cells that are
constricted at the
septations between cells
CANDIDA
Morphology and Identification
• On blood agar, after
24 hours of
incubation , moist
opaque colonies are
seen with yeasty odor
CANDIDA
Morphology and Identification
• Germ tube or true
hyphae formation
distinguish Candida
albicans from the
rest of Candida sp.
CANDIDA
Clinical Findings
• CUTANEOUS and
MUCOSAL
CANDIDIASIS
- oral thrush
- vulvovaginitis
- cutaneous –
intertriginous infections
- onychomycosis
CANDIDA
Clinical Findings
CANDIDA
Clinical Findings

• SYSTEMIC CANDIDIASIS

• CHRONIC MUCOCUTANEOUS
CANDIDIASIS
CANDIDA
Diagnostic Laboratory Tests

• Specimens : swabs and scrapings from


superficial lesions, blood, spinal fluid, tissue
biopsies, urine, exudates, catheters
• Microscopic Examination: using KOH,
demonstrate the presence of pseudohyphae in
scrapings or tissue specimens
• Culture : 37oC; presence of pseudohyphae
• 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
CANDIDA
Treatment

• 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
ASPERGILLUS
Epidemiology

• Distributed worldwide

• Commonly found in soil, food, paint, air


vents, disinfectants
ASPERGILLUS
Morphology and Identification
• Produce conidial
structure: long
condiosphores with
terminal vesicles on
which phialides are
seen
ASPERGILLUS
Portal of Entry

INHALATION
ASPERGILLUS
Clinical Types

• Allergic – hypersensitivity to the organism


- respiratory symptoms may be
mild to alveolar fibrosis
ASPERGILLUS
Clinical 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
ASPERGILLUS
Clinical Types

• Aggressive tissue invasion


- primarily a pulmonary disease but
aspergilli disseminate to any organ
- may cause endocarditis, osteomyelitis,
otomycosis, and cutaneous
ASPERGILLUS
Diagnostic Laboratory Tests

• Specimens : sputum, other respiratory


specimens, or lung biopsy

• Microscopic Examination: with KOH,


presence of hyaline branching septate
hyphae
ASPERGILLUS
Diagnostic 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
ASPERGILLUS
Diagnostic Laboratory Tests
• SEROLOGY
1. 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%)
ASPERGIILUS
Treatment

AMPHOTERICIN B
MUCORMYCOSIS

• ACUTE INFLAMMATION OF SOFT


TISSUE, USUALLY FUNGAL
INVASION OF THE BLOOD VESSELS
MUCORMYCOSIS

Order Mucorales of the class


Zygomycetes
1. Rhizopus species
2. Mucor species
3. Absidia species
MUCORMYCOSIS
Epidemiology
• 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
MUCORMYCOSIS
Diagnostic Laboratory Tests
• CULTURE
• Grow rapidly on lab
media producing abundant
cottony colonies.
MUCORMYCOSIS
Diagnostic Laboratory Tests
• DIRECT
EXAMINATION:
- broad hyphae with
uneven thickness,
irregular branching and
sparse septations
MUCORMYCOSIS
Treatment

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 NEOFORMANS
Morphology 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 NEOFORMANS
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)
CRYPTOCOCCUS NEOFORMANS
Clinical Findings
1. Meningoencephalitis
- prolonged clinical course: begin with visual problems;
headache,neck stiffnessm coma, death
4. Skin and lung infections
- formation of a granulomatous reaction with giant cells
- Cryptococcoma: mass in the mediastinum
CRYPTOCOCCUS NEOFORMANS
Diagnostic 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 NEOFORMANS
Laboratory Findings

• Cryptococcus
neoformans in sputum,
Wright Stain
CRYPTOCOCCUS NEOFORMANS
laboratory findings

• Cryptococcus
neoformans in blood
culture, Gram stain
CRYPTOCOCCUS NEOFORMANS
Treatment

• 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

3. New Drugs
4. New therapeutic regimen
5. Aggressive therapy
6. Conjunctive therapy
IMPROVING TREATMENT
New Drugs

Echinocandins
Third generation azoles
New classes of antifungal agents
IMPROVING TREATMENT
New Therapeutic Regimen
Combination Therapy

4. Simultaneously administering two drugs


5. Sequential Tx with two or more drugs
6. Alternate Administration of two or more
IMPROVING TREATMENT
AGGRESSIVE THERAPY
FOR IMMUNOCOMPROMISED
PATIENTS

• 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

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