Opportunistic Infections -Fungi

Name 3 Opportunistic Genuses

1. Candida

2. Aspergillus

3. Mucorales

Is Candida albicans part of the normal flora?

Yes, 50% are colonized with Candida albicans → GI tract (mouth to anus) and vagina

→ Infection arises from one’s flora

Is Candida albicans monomorphic or polymorphic?

Switch from yeast to hyphae (temperature, pH, other environmental conditions)

Ability NOT shared by other species

Where are the sites of infection of Candida albicans?

Bloodstream, hepatosplenic candidiasis, disseminated infection, meningitis, foreign body infections, urinary tract infections, and other sites

CATETHERS ALLOW ENTRY SIGHT

Where are sites for colonization for Candida?

1. Skin → not a lot on skin, moist wounds can grow candida

2. Wounds

3. Sputum/respiratory tract

4. Urine → foley catheter → common in urine → take out '

5. Differentiate infection from colonization

Candida virulence factors - name 3

1. Mannoproteins

2. Biofilm formation

3. Proteinases

How do mannoproteins help candida with invading cells

1. Attachment to GI epithelial cells

2. Immune tolerance

How do biofilm formations help with candida albicans with virulence?

1. Foreign bodies → grows as a film on these

2. Vascular access devices, implants

3. Take out hardware

How do proteinases help with virulence with candida?

1. Facilitate invasion → blood stream infections (translocation)

2. Local invasion - hyphae

Describe our immune response when exposed to Candida

1. Innate immune response →neutrophils

2. Cell mediated immunity → Th1 and Th2 balance

3. Candida mannan - down regulate CMI

Give 3 step plan for treating what may be Candida

1. Gram negative coverage

2. Treat for Staph Aureus

3. Treat for Candida

Discuss skin with Candida, also are bacterial infections less or more common?

1. Drainage/moisture - increased colonization

2. Portal of entry - especially with wound contamination and/or open wounds

3. Break in normal barrier → catheter, surgical wounds, abrasions

4. Bacterial infections → more common

How does intubation play a role in Candida infections?

1. Foreign body, altered respiratory clearance mechanisms

2. Increased colonization → Candida pneumonia not likely

IF YOU FIND CANDIDA AT MULTIPLE SITES, IT IS MORE LIKELY

Add antifungal early on in ICU settings

Talk about vascular access devices (central + peripheral lines) and their role in Candida infections

1. Central lines are placed a lot longer than peripheral → higher chance to get infected

2. Provide port of entry and can have biofilm

3. Risk based pre-emptive treatment

4. Positive blood culture - always significant

   1. if found, remove access device and treat for 2-3 weeks

Do orthopedic implants need to be removed with Candida?

1. Post surgical infection

2. Orthopedic → can get infection of prosthetic device - requires removal and long term treatment

Is colonization common in urinary catheters? Are UTI’s common? Is treatment needed?

1. Catheter in place - colonization COMMON

   1. + urine culture for yeast

   2. Remove foley if possible

2. UTI = uncommon

   1. Sx of UTI in absence of bacteria or foley catheter

   2. Obstruction → increases risk of invasive infection

3. Treatment is uncommon

What is the 2nd most common Candida after albicans?

Candida glabrata → elderly in hospital

Resistance to fluconazole 30% of the time

What are some other Candida types?

1. Candida parapsilosis → exogenous source

2. Candida krusei → resistance, intrinsic 100%

3. Candida tropicalis

4. Candida auris → resistance (emerging pathogen)

What type of media does Candida grow on? Yeast or mold?

Yeast = grows on standard media

How quickly does Candida grow? What is an exception? Compare to bacteria

1. Most rapid growing, colonies look like bacteria (24 hours)

   1. 4-5x bigger than bacteria and are oval shaped

2. C. glabrata takes longer, 2-4 days

Describe how common other yeast infections are besides Candida

1. Other yeasts = rare → even in immunocompromised patients

2. In special situations → brain or meningitis (Cryptococcus neoformans)

What are some risk factors for febrile neutropenia?

1. Antibacterial therapy

2. If patient is high risk or not responding to antibacterial therapy → add empiric coverage for candida

3. Other high risk:

   1. High dose corticosteroids, immunocompromised, HIV

What is an environmental mold that can come from black pepper or construction in older buildings?

Aspergillus

What is aspergillosis and who is at risk?

1. Normal hosts are NOT at risk → only immunocompromised

2. Concern for asthma and an allergy to it → allergic bronchopulmonary aspergillosis (asthma), aspergilloma (develop mass of fungus)

Can give corticosteroids

What is invasive aspergillosis?

Hyphae grow into tissue → invade blood cells → tissue death and necrosis

PROBLEM IN IMMUNOSUPPRESSIVE PATIENTS - back off of immunosuppressive therapy

What type of hyphae do aspergillus have? What are some specific species, which is most common?

1. Septate hyphae - branching 30 degree

2. Aspergillus fumigatus (most common)

3. Aspergillus flavus, niger, and terreus

How does aspergillus enter the body and what does our immune response look like?

1. Inhale conidia into lungs

2. Innate immune cells → prevent germination into hyphae

3. Cell mediated immune → contains (walls of) potential invasion of tissue

Allergic disease within aspergillus immunity

1. <1% of asthma patients

2. Refractory to treatment and non invasive

3. Treat with steroids

What is another name for aspergilloma. What is this?

1. Fungus ball

2. Growth of fungus (mass) in lung airspace, sinus, or other tissue

3. Non invasive, yet obstructive

Management of aspergilloma

1. Prolonged antifungal therapy

2. Surgical removal

Invasive Aspergillosis is when hyphae is grown into tissues. What population do we see this in?

Almost exclusively in severely immunocompromised patients, like in AIDs, organ transplant, BMT

GROWTH THROUGH BLOOD VESSELS LEADING TO TISSUE INFARCT → contiguous spread (difficult to control)

What to keep in mind if getting a culture of Aspergillus?

1. Aspergillus is in environment → there will be some contamination (sputum sits for 4 days)

2. Need to find susceptibility and lesions associated with aspergillus

3. Tissue biopsy required → most are too high risk or sick for this

4. Antigen = galactomannan, Fungitell is positive

Where are the 3 sites of invasive aspergillosis

1. Lung

2. Sinus

3. Disseminated

What is the mortality rate with invasive aspergillosis

Mortality 30-90% depending on underlying immune deficiency

Mucorales is another type of fungi. Where are they found?

Found in soil, bread, mold, decaying fruits/vegatables. Can get into CNS

Includes absidia, rhizopus, and mucor

Structure of mucorales?

Nonseptate hyphae wider than aspergillus, wide angle branching

How is management with mucorales?

1. Must be VERY AGGRESSIVE → antifungal therapy and surgery

2. Requires excessive surgeries

UP TO 10 mg of AMPOTERICIN B

Risk factors of Mucorales?

1. Severely immunocompromised

2. Diabetics, severe ketoacidosis

What diseases does mucorales cause?

1. Pulmonary infection

2. Rhinocerebral → penetrate nose and sinuses, can spread to nerves and blood vessels

What type of organism is pneumocytis? What does it cause primarily?

1. Classified as parasite, now a fungi due to features

2. Causes pneumonia in immunosuppressed persons → AIDs, high dose corticosteroids >20mg per day, long term immunosuppression

What is the main pneumocystis? Is it culturable?

1. Pneumocystis jirovecii

2. NOT CULTURABLE

Describe the cell wall and membrane of pneumocystis jirovecii

1. Thin

2. Not rigid typical of other fungi

3. Does contain glucan and NAG which are components of chitin

MEMBRANE CONTAINS CHOLESTEROL

What population has a problem with pneumocystitis? What is the main disease?

1. Humans with depressed T cell immunity → TH1 response plays major role

2. Pneumonia → dyspnea and hypoxia → nonproductive cough

3. Extrapulmonary lesions in ADVANCED AIDS

Amphotericin B forms ______ and gives people what sx when taking it?

1. Mycelles

2. Fever and chills→ shake and bake

3. Kidney function will go down