Invasive Fungal Infections Flashcards
1
Q
Unicellular, reproduce by budding
A
yeasts
2
Q
multicellular, filamentous colonies
A
molds
3
Q
Yeast classification
A
- candida spp
2. cryptococcus spp
4
Q
Molds classifcation
A
- aspergillus spp
- coccidioidomycoses
- histoplasmosis
- blastomycosis
- mucormycosis
5
Q
most common cause of invasive fungal infections especially in hospitals and ICU
A
candida
6
Q
What are healthcare associated infections of candida (4)?
A
- broad spectrum antibiotic exposure
- corticosteroids
- dialysis
- prolonged use of intravascular catheters
7
Q
What are 5 different species of candida?
A
- candida albicans
- candida glabrata
- candida parapsilosis
- candida tropicalis
- candida krusei
8
Q
Most common and susceptible candida
A
candida albicans
9
Q
Most common candida in immunocompromised patients and organ transplant recipients
A
candida glabrata
10
Q
A multi drug-resistant germ that spreads in healthcare facilities and behaves more like Nosocomial Bacteria than traditional Fungi (i.e., it is more difficult to contain and decontaminate than most Fungi)
A
candida auris
11
Q
Challenges of Diagnosing Invasive Candidiasis (IC)
A
- nonspecific clinical signs and symptoms
- colonization vs infections
- candida endopthalmitis
- skin lesions
- muscle soreness
12
Q
Risk factors for getting candida (8)
A
- ICU stay of 7 or more days
- central IV lines
- neonates
- broad spectrum abx
- hemodialysis
- glucocorticoid use
- IV drugs use
- abdominal surgery
13
Q
Gold standard for diagnosing candida
A
blood cultures
14
Q
3 disadvantages of blood cultures for candida
A
- slow turn around time 2-3 days
- antifungal sensitivities can takes 7 or more days
- false negatives occur in 40-75% of cultures
15
Q
Disseminated candida
A
Candida likes to travel to highly perfused organs such as the Liver, Kidneys, and the Spleen, resulting in nodules
16
Q
Problems with Diagnosing Invasive Fungal Infections
A
- Poor Diagnostic Tools with long turnaround times
- Empiric Antifungal Therapy is often delayed, putting patients at a
heightened risk for mortality
17
Q
low resistance to Fluconazole (Diflucan®), making Fluconazole the drug of choice for this candida infection
A
candida albicans
18
Q
What has an Acquired Resistance to
Triazoles like Fluconazole (Diflucan®)
A
candida glabrata
19
Q
What has the highest rate of resistance to Fluconazole (above 80%),
but its’ high resistance does NOT confer cross-resistance to other Triazoles
A
candida krusel
20
Q
2nd most common Fungi seen in hospitals
A
Aspergillosis
21
Q
universal and occurs via inhalation
A
Aspergillosis
22
Q
found in soil, plants, and indoors (i.e., black mold in showers)
A
Aspergillosis
23
Q
most common invasive mold infection
A
Aspergillosis
24
Q
Aspergillosis resistant to amp B
A
A. terreus
25
ubiquitous in the environment, disease is most frequently seen in Immunocompromised patients
Aspergillosis
26
Aspergillosis Disease Presentation in Immunocompetent Hosts
Allergic Reaction, specifically
| Allergic Bronchopulmonary Aspergillosis (ABPA)
27
Aspergillosis Disease Presentation in Patients with Immune Impairment
1. Chronic Necrotizing Pulmonary Aspergillosis, or a
“Fungal Ball”
2. Fibrocavitary Aspergillosis
3. Aspergilloma (i.e., Fungal Ball)
28
Risk Factors for Invasive Aspergillosis (4)
1. Prolonged Neutropenia
2. Recipients of Hematopoietic Stem Cell Transplants (or Solid Organ Transplants)
3. HIV Stage 3 (AIDS)
4. Chronic Granulomatous Disease (i.e., COPD)
29
Radiographic Findings of aspergillosis
halo sign
| air crescent sign
30
A Dimorphic Endemic Fungi
Coccidioidomycosis
31
typically peaks in the fall (October) and late spring (May)
Coccidioidomycosis
32
Five Main Clinical Manifestations of Coccidioidomycosis
1. Acute Pneumonia
2. Chronic Progressive Pneumonia
3. Pulmonary Nodules and Cavities
4. Extrapulmonary Non-CNS (Non-Meningeal) Disease
5. Meningitis
33
Coccidioides – Acute Pneumonia
1. Onset: 1–3 weeks after exposure
2. Severe Headache (may be indicative of Meningitis), Severe Pleuritic Chest Pain, Fatigue lasting several weeks to months, Hilar or Paratracheal Adenopathy seen on Chest X-Ray
34
Sites of dissemination with coccidioides
1. extra pulmonary disease
| 2. meningitis
35
Extra-Pulmonary Disease
- Occurs in less than 5% of immune-competent patients
- Patients of African or Filipino ancestry are at an increased risk
(possible genetic predisposition)
- Pregnant women are also at an increased risk
36
Meningitis
-more commonly seen
| in Stage III HIV (AIDS) patients
37
dismorphic fungi endemic to Ohio and Mississippi river valleys
histoplasmosis
38
histoplasmosis
- grows in rich soil in bird and bat droppings
| - most common endemic mycosis causing human infection
39
Disseminated histoplasmosis
- symptomatic pts usually immunocompromised
- chills, fever, anorexia, weight loss
- GI tract, diffuse ulcerations of the mucosa
- CNS involvement not common
40
histoplasmosis chronic or mild to moderate infection treatment
1. itraconazole preferred for non-severe infections
| 2. alt: amp b or fluconazole
41
histoplasmosis moderately severe to severe or CNS disease
lipid formulation of amp B followed by intraconazole
42
yeast with a thick polysaccharide capsule that blunts a
| patients’ immune response
Cryptococcus
43
Epidemiology Cryptococcus neoformans
- Immune Compromised
| - Clinical manifestations: Pulmonary Disease and Meningitis
44
Epidemiology Cryptococcus gatti
- Immune Competent
| - Clinical manifestations: Cryptococcomas, Neurological involvement, Prolonged therapy
45
“Necrotizing Fasciitis of the Fungal World”
Mucormycosis
46
one fungal infection that can affect Immune Competent patients, as well as Immunocompromised patients
Mucormycosis
47
Mucormycosis Risk Factors in Immune Competent Individuals
1. Major Trauma / Inoculation and Contaminated Lacerations
2. Surgery and Use of Contaminated Materials
3. ICU Stay with High Acuity
4. Iron Chelation Therapy, specifically with Deferoxamine
5. Burns
48
Mucormycosis Risk Factors in Immunocompromised Individuals
1. Diabetes, specifically Diabetic Ketoacidosis (DKA)
2. Uremia / Metabolic Acidosis
3. Hematological Malignancies, particularly Leukemias
4. Stem Cell Transplant
5. Solid Organ Transplant
6. Immunosuppressive Drugs (i.e., Corticosteroids)
49
Mucormycosis clinical presentation
-Infarction and Necrosis of Host Tissue
- usually begins in Nasal Turbinates (i.e., the Rhino-Orbital-Cerebral) or
Alveoli (Pulmonary)
50
Management of Candidemia Preferred Initial Therapy
Echinocandins (may be Oral Therapy if isolates are
| susceptible to oral Antifungal agent) At least 2 weeks if no dissemination has occurred to other sites
51
Management of Candidemia Alternative Therapy
Fluconazole (Diflucan®) may be considered in non-
| critically ill patients who are unlikely to have Fluconazole-Resistant Candida spp.
52
Management of Candidemia precautions
i. Remove Central Venous Catheters if possible
ii. A Dilated Ophthalmological Examination should be performed prior to initiating
therapy to look for sites of dissemination
iii. Repeat blood cultures daily to establish Clearance
53
Aspergillosis Treatment
-Voriconazole
- If an Aspergillosis patient cannot tolerate Voriconazole, we may deescalate to
Amphotericin B
54
Coccidioides Treatment
-the drug of choice is Fluconazole
(Diflucan®), 400 mg or more IV (or PO) daily
- alt: itraconazole po only
55
Cryptococcal Treatment Mild-to-Moderate Pulmonary Disease
Fluconazole (Diflucan®) Oral Therapy
56
Cryptococcal Treatment Severe Pulmonary Disease OR Cryptococcal Meningitis
- Amphotericin B IV PLUS 5-Flucytosine for 2 wks. Minimum
| - Maintenance Therapy – Fluconazole (Diflucan®) 12 mg / kg initially, then 6 mg / kg for 6–12 months
57
Mucormycoses Treatment
- Liposomal Amphotericin B (L-AmB®), 5–10 mg / kg / day
| - Alt: Posaconazole (Noxafil®) PO tablets or Isavuconazole (Cresemba®)
58
Mechanism of Action – Decrease Ergosterol Synthesis by inhibiting Fungal Cytochrome P450 enzymes (i.e., Lansterol14 Demethylase). This prevents Fungal Cells from incorporating Ergosterol into the plasma membranes of newly formed Fungal Cells, drastically reducing their growth
triazole
59
Mechanism of Action – Bind to Ergosterol in Fungal Plasma Membrane and
forms “Pores” in the Fungal Cell Membranes. These pores disrupt membrane
permeability, allowing intracellular molecules to “leak out”
Polyenes (Amphotericin B)
60
Mechanism of Action – Inhibit Fungal Cell Wall Synthesis by inhibiting Beta-(1,3)- D-Glucan Synthesis; Beta-(1,3)-D-Glucan Synthesis is a polysaccharide component of Fungal Cell Walls
Echinocandins
61
Mechanism of Action – 5-Flucytosine (5-FC) gets converted into 5-Fluorouracil
(5-FU), which gets incorporated into Fungal RNA to inhibit Fungal Protein
synthesis
5-Flucytosine (5-FC) – DNA / RNA Synthesis Inhibitor
