Invasive Fungal Infections

Question 1

General Fungal Classifications

Answer 1

• Yeasts: unicellular, reproduce by budding (candida, cryptococcus)
• Molds: multicellular, filamentous colonies (aspergillus, blastolycosis, histoplasmosis)

Question 2

Rapid Diagnostic Tests of IFIs

Answer 2

1. B-D-glucan
2. Mannan antigen/Anti-mannan antibody
3. Nucleic acid PCR
4. Galactomannan

Question 3

B-D-glucan

Answer 3

• Species: Candida, Aspergillosis, PJP
• Low sensitivity and specificity
• Limitations: Doesn’t detect cryptococcus or zygomycetes, controversy surrounding optimal cutoff value

Question 4

Mannan/Anti-manna Tests

Answer 4

• Species: Candida species
• Highest sensitivity/specificity when used in combination
• Both tests have better specificity than sensitivity

Question 5

Nucleic Acid PCR

Answer 5

• Species: Candida species
• High sensitivity and specificity
• Limitations: Using too early may decrease sensitivity

Question 6

Galactomannan

Answer 6

• Species: Aspergillus and some other molds
• Relatively high sensitivity and specificity
• Limitations: not as sensitive in non-neutropenic patients

Question 7

Invasive Candidiasis Epidemiology

Answer 7

• Most common IFI
• Usually healthcare associated infections: broad antibiotic use, corticosteroids, dialysis
• 40-50% mortality rate

Question 8

Candida Auris

Answer 8

• Emerging pathogen
• Behaves more like nosocomial bacteria than traditional fungi
• Drug-resistant and spreads in healthcare facilities

Question 9

Diagnosis IC Difficulties

Answer 9

• Nonspecific clinical signs/symptoms
• Colonization vs infection
• Physical exam: candida endophthalmitis, skin lesions, muscle soreness

Question 10

IC Risk Factors

Answer 10

• Central venous catheters
• Candida colonization
• Increasing severity of illness
• Broad spectrum antibiotic use
• Abdominal trauma/surgery
• Dialysis
• Parental nutrition
• Corticosteroids
• Certain surgical patients: recurrent GI perforation, anastomotic leaks, acute necrotizing pancreatitis

Question 11

Diagnosis Candidiasis

Answer 11

• Blood cultures = gold standard
• 2-3 day turn-around time
• 40-75% false negative rate

Question 12

Candidemia Treatment Guidelines

Answer 12

• Fluconazole: acceptable in select patients (non-critically ill, no prior triazole therapy)
• Lipid AmB: recommended for suspected azole/echinocandin-resistant candida infections
• Voriconazole: effective but not advantageous over fluconazole

Question 13

Susceptibility Testing

Answer 13

• Azole Susceptibility: recommended for all blood stream isolates
• Echinocandin Susceptibility: consider for patients previously receiving an echinocandin or with prior C.glabrata or parapsilosis infections

Question 14

Managing Candidemia

Answer 14

• Remove central venous catheters if possible
• Dilated opthalmological examination
• Repeat blood cultures daily to establish clearance
• Duration of therapy minimally 2 week if no metastatic complications

Question 15

Aspergillosis Epidemiology

Answer 15

• Ubiquitous mold existing all over world
• Exposed via inhalation
• Most common invasive mold infection
• A. fumigatus is most common species

Question 16

Aspergillosis Disease Spectrum

Answer 16

• Immunocompetent Hosts: allergic reaction, ABPA
• Immune impairment: chronic necrotizing pulmonary aspergillosis (fungal ball, fibrocavitary aspergillosis)
• Immune compromised: acute, invasive aspergillosis, lower respiratory tract infection and hematogenous dissemination into other tissues

Question 17

IA Risk Factors

Answer 17

• Prolonged neutropenia (degree and duration)
• Recipients of hematopoietic stem-cell transplants or solid organ transplants (highest after lung transplants)
• HIV Stage 3 (AIDS)
• Chronic granulomatous disease

Question 18

Radiographic Findings

Answer 18

• Halo sign: solid nodule filling with hemorrhage and edema fluid, earlier sign
• Air-crescent sign: air between infarcted lung and surrounding lung parenchyma, late sign

Question 19

IPA Treatment Guidelines

Answer 19

• Primary treatment: voriconazole, initiate early in those who are strongly suspected of IPA
• Alternatives: Liposomal AmB or isavuconazole
• Echinocandins are NOT recommended as primary therapy

Question 20

Histoplasmosis Capsulatum

Answer 20

• Dimorphic fungi found in Central and South America
• Most common endemic mycosis causing human infection
• Found from animal droppings and in caves/abandoned houses

Question 21

Disseminated Histoplasmosis

Answer 21

• Symptomatic patients are usually immunosuppressed
• Chills, fever, anorexia, weight loss
• GI tract: diffuse ulcerations of the mucosa (elevated liver enzymes and serum ferritin, pancytopenia)
• CNS involvement isn’t common

Question 22

Histoplasmosis Treatment Guidelines

Answer 22

• Chronic/Mild/Moderate: itraconazole is preferred for non-severe
• Alternatives: AmB or fluconazole
• Severe/CNS: Lipid formulation of AmB followed by itraconazole

Question 23

Coccidioidomycosis

Answer 23

-“Valley Fever”

Manifestations

• Acute pneumonia
• Chronic progressive pneumonia
• Pulmonary nodules and cavities
• Extrapulmonary non-meningeal disease
• Meningitis

Question 24

Coccidioides + Acute Pneumonia

Answer 24

• Onset: 1-3 weeks after exposure
• Indistinguishable from CAP
• Coccidio Sxs: severe headache and severe pleuritic chest pain, fatigue lasting weeks to month, hilar or paratracheal adenopathy (rarer)

Question 25

Coccidiodes + Sites of Dissemination

Answer 25

• Extra-pulmonary disease: skin, lymph nodes, bones and joints (uncommon in immunocompetent)
• Meningitis: most severe complication, substantial morbidity (diagnose with serum and CSF cultures)

Question 26

Coccidiodomycosis Treatment Guidelines

Answer 26

• Initiate treatment in symptomatic individuals/debilitating disease: Fluconazole >=400 mg PO daily
• Alternative: Itraconazole or AmB (or lipid formulation)
• Treatment of asymptomatic pulmonary nodule/cavities isn’t recommended

Question 27

Cryptococcus Epidemiology

Answer 27

• Neoformans: immunocompromised, pulmonary and meningitis manifestations, worldwide spread
• Gattii: immunocompetent, cryptococcomas and neurologic involvement, prolonged therapy, tropical/subtropical/temperate regions

Question 28

Cryptococcus Clinical Manifestations

Answer 28

• Blunted immune response
• Main Clinical Presentations: pulmonary infection, cryptococcal meningitis
• Can infect ANY organ of body: cutaneous, eye, prostate, bone, and joint

Question 29

Cryptococcal Treatment

Answer 29

• Mild-moderate pulmonary disease: Fluconazole
• Severe/Cryptococcal meningitis: AmB PLUS 5-FC x 2 weeks minimum (can replace with L-AmB)
• Maintenance: Fluconazole >= 6 mo

Combination of AmB and 5-FC reduces mortality in meningitis patients

Question 30

Murcormycoses

Answer 30

• MANY common mucorales

- Diagnosis usually made via pathology

Question 31

Murcormycoses + Immunocompetent Risk Factors

Answer 31

• Major trauma/contaminated lacerations
• Surgery and use of contaminated materials
• ICU stay with high acuity
• Iron chelation therapy
• Burns

Question 32

Murcormycoses + Immunocompromised Risk Factors

Answer 32

• Diabetes
• Uremia, metabolic acidosis
• Hematological malignancies
• Stem cell transplant
• Solid organ transplant
• Immunosuppressive drugs

Question 33

Murcormycoses Clinical Presentation

Answer 33

• Infarction and necrosis of host tissue
• Infection usually begins in nasal turbinates or alveoli
• Poor prognosis, mortality rates up to 90%

Question 34

Mucormycosis Treatment

Answer 34

• Combine surgical debridement and antifungal therapy
• Drug of choice: L-AmB
• Alternatives: Posaconazole, isavuconazole
• Correction of underlying host abnormalities
• Duration: resolution of signs of infection (usually months)