Fungal Infections

What makes up a fungal cell wall?

- Beta glucans

- Mannoproteins

- Ergosterol

- Chitin

How do fungal infections compare to bacterial infections?

- More difficult to diagnose

- More difficult to treat

- Treated with antifungals

- Higher rates of morbidity/mortality with systemic infections

What are 5 reasons why fungal infections are increasing?

1. Immunosuppressive therapies

2. AIDS epidemic

3. Broad-spectrum antibiotics

4. Expansion of immunocompromised population

5. Central venous catheters

Name 4 common yeasts

1. Candida spp.

2. Cryptococcus neoformans

3. Trichosporon spp.

4. Malassezia fufur

Name 4 common dimorphic fungi

1. Histoplasmosis

2. Blastomycosis

3. Sporotrichosis

4. Coccidioidomycosis

Name 4 common molds

1. Aspergillus spp.

2. Mucormycosis

3. Pseudallescheria boydii

4. Penicillium marneffei

5. Fusarium spp.

Which invasive fungi can cause systemic infections?

1. Histoplasmosis

2. Blastomycosis

3. Coccidioidomycosis

4. Candidiasis

5. Cryptococcosis

6. Aspergillosis

What is Histoplasmosis caused by?

Inhalation of dust-borne microconidia of the dimorphic fungus H.capsulatum. Often found in bat and bird droppings

Histoplasmosis can become _______________ especially in patients with AIDS

acutely disseminated disease

What are some symptoms/signs associated with Histoplasmosis?

- Fever/chills

- Weight loss

- Night sweats

- Enlargement of the spleen, liver, or lymph nodes

- Anemia

How are AIDS patients with Histoplasmosis treated?

- Intensive 12-week primary induction therapy followed by lifelong suppression

- Induction: Amphotericin B 50-100 mg/kg/day for 12 weeks

- Suppression: Itraconazole 200 mg PO BID

What is Blastomycosis caused by?

Inhalation of conidia (B.dermatitidis), which convert to the yeast form in the lung. Isolated from soil containing decayed vegetation, decomposed wood, and pigeon manure

Why is Blastomycosis danergous?

It can disseminate to virtually every other body organ

What is used to treat Blastomycosis?

Amphotericin B and itraconazole

What causes Coccidioidomycosis?

Coccidioides immitis arthroconidia inhaled into the respiratory tree

Coccidioidomycosis is also know as...

Valley fever

How is Coccidioidomycosis treated?

Azole antifungals or Amphotericin B. Treatment is difficult

What causes Cryptococcosis?

Inhalation of cryptococcus, which is found in soil (pigeon droppings). Causes a non-contagious, systemic mycotic infection that can disseminate

How is Cryptococcosis treated?

Systemic antifungal therapy, control of elevated intracranial pressure (ICP) and supportive care. Amphotericin B, flucytosine, or fluconazole could be considered

What is common between histoplasmosis, coccidiomycosis, crytococcosis, and blastomycosis?

Their origin is through inhalation of fungal particles and they can all become disseminated diseases

Where does candida colonize? How are infections commonly acquired?

Skin, GI tract, URT, and GU tract. Acquired via GI tract or IV catheters

What is the most common/aggressive candida spp.? What is it susceptible to?

C. albicans, sensitive to fluconazole

Which tissues does candida tropicalis infect? What is it susceptible to?

Deep tissue infections (myositis), susceptible to fluconazole

Can fluconazole be used to treat candida glabrata?

Borderline susceptible, dose needs to be over 800 mg/day

Candida parapsilosis causes _______ infections

CVC

Can fluconazole be used to treat candida krusei?

NO, resistant to fluconazole, seen in immunocompromised

Invasive candidiasis can be seen as what kinds of infections?

1. Abdominal abscess

2. Endocarditis

3. CNS infection

4. Osteomyelitis

What are 10 risk factors for invasive candidiasis?

1. Barrier disruption

2. Broad-spectrum antimicrobials

3. TPN

4. Burns

5. Chemo

6. Deficits in cell-mediated immunity (corticosteroids)

7. Quantitative or qualitative neutrophil dysfunction (chem, corticosteroids, neutropenia)

8. Metabolic dysfunction (diabetes, renal failure)

9. LOS in ICU

10. Colonization

What is an emerging type of candida?

C. auris

In which candida spp. are we seeing some resistance to amphotericin B?

C. lusitaniae

What is included in the general treatment strategy for treating candida infections?

1. Empiric or preemptive therapy = improve outcome

2. Remove foci for infection

3. Evaluate for disseminated disease

4. Continue treatment throughout neutropenia +/- period or post-engraftment

5. In critically ill, amphotericin B or caspofungin first, then fluconazole if susceptible

What are some common candida infection locations?

1. Mucocutaneous disease (oral, esophageal, dermatologic)

2. Fungemia (catheter-related, dissemination to reticulo-endothelial system, sepsis syndrome, mortality)

3. GU tract infection

4. GI and pulmonary colonizer

What are 3 uncommon candida infection locations?

1. Pneumonia

2. Endocarditis

3. Osteomyelitis

What is the predominant colonizing candida spp. in oropharyngeal and esophageal candidiasis?

C. albicans , can be any others as well

What is the most common opportunistic infection in patients with HIV?

oropharyngeal and esophageal candidiasis, can predispose patients to develop more invasive disease

What are some signs/symptoms to oropharyngeal candidiasis?

- Possibly asymptomatic

- Sore/painful tongue

- Metallic taste

- Dysphagia/odynophagia

- Diffuse erythema

- White patches on buccal mucosa, throat, tongue, gums

- Constitutional signs are absent

- Consider scraping of lesion to confirm

What are some signs/symptoms to esophageal candidiasis?

- Possibly asymptomatic

- Usually extension of OPC

- Dysphagia/odynophagia

- Retrosternal chest pain or epigastric pain

- fever

- Numerous plaques with ulceration

- Mucosal friability, lumen narrowing

- Upper GI endoscopy to exclude other Dx, obtain biopsy

What are 8 risk factors for oropharyngeal and esophageal candidiasis?

1. Use of steroids, antibiotics, dentures

2. Xerostomia

3. Smoking

4. Malignancy, BMT, chemotherapy

5. DM

6. HIV+

7. Extremes of age

8. Nutritional deficiencies

How common is candidemia?

4th most common bloodstream infection in US hospitals

What is the most common isolate of candidemia?

C. albicans

How is candidemia usually acquired?

Via GI tract, but can enter via indwelling IV catheters

Which patients are at higher risk of candidemia?

- ICU

- lymphoreticular or hematologic malignancies

- DM

- TPN

- CVC

- Taking high-risk meds

How long should candidemia therapy be continued after documented clearance of blood cultures?

2 weeks

How is candiduria acquired?

Often follows catheterization or treatment with broad spectrum antibiotics. Candida may be a colonizer, not always a pathogen

How is candiduria treated?

- Asymptomatic infections may clear spontaneously without treatment

- REMOVE the catheter

- Treat with oral fluconazole 200 mg/day for 14 days

How is aspergillosis acquired?

Inhalation of airborne conidia. Extremely high mortality the infects the sinuses/lungs and sometimes the CNS

Who is at highest risk for aspergillosis?

Immunocompromised, AML, HSCT with prolonged neutropenia

How can aspergillosis also manifest?

- Superficial or locally invasive infections of the ear, skin, appendages

- Allergic manifestations (mild asthma that can lead to bronchiectasis and granuloma formation)

- Aspergilloma aka FUNGUS BALLS

What are some signs/symptoms of pulmonary aspergillosis?

1. Pleuritic chest pain and friction rubs

2. Fever

3. Hemoptysis

What is used to diagnose invasive pulmonary aspergillosis?

1. High resolution CT (halo sign, late IA nodular lesions)

2. Glactomannan test (ELISA detects antigen released from A. hyphae)

What can cause a false positive in the glactomannan test?

Concomitant cyclophosphamdie, Zoysn, Augmentin, bifidobacterial infections, neonates

What can cause a false negative in the glactomannan test?

Concomitant use of antifungals

What is the first line treatment for invasive aspergillosis?

Voriconazole

Describe the frequency of mucormycosis

Once rare, now with increased frequency due to increase in immunosuppressed population

Which fungi infect the mucorales and cause mucormycosis?

1. Rhizomucor

2. Lichtheimia

3. Rhizopus

4. Mucor

5. Cunninghamella

Which drugs have good in vitro activity against mucormycosis?

Amphotericin B and posaconazole

Describe the "old era" of antifungals

- Amp B was a cornerstone

- Toxicity a limiting factor

- Limited options for prophylaxis or chronic therapy

- Limited spectrum of pathogens

- Combination therapy often not feasible

- less expensive

Describe the "new era" of antifungals

- several treatment options

- improved tolerability and availability of oral formulations

- expanding spectrum of pathogens

- combo therapy more common

- more expensive

What is the MOA of amphotericin B?

Binds to ergosterol in fungal membrane, disrupting membrane permeability/stability