Shared Flashcard Set

Details

Fungal Infections and Antifungal Drugs
Lecture 9 12/1/11
42
Biology
Professional
02/15/2012

Additional Biology Flashcards

 


 

Cards

Term
What are the major differences between Fungal and Bacterial Cell walls?
Definition
1) Fungi have Glucans (strength to cell coat), Mannans and Chitin (N-acetylgalactosamine).

2) Bacteria have murein, teichoic acid (gram positives), peptidoglycans
Term
How are fungi visualized under microscopy?
Definition
-Calciflour- brilliant white color
- Most will not gram stain, except Candida.
- Silver stain will stain cell wall
- PAS will stain polysacharide in cell wall
Term
You look under a microscope and the organism appears to be multicellular, with septated hyphae forming mycelium. You describe the organisms as "fuzzy."

What kind of organism are you looking at and how might you further characterize it?
Definition
Mold

- Colonial morphology, color and microscope appearance
Examples include Aspergillis, Mucor, Penicillium marneffei , Scedosporium and Fusarium.
Term
You look under a microscope and the organism appears to be unicellular, with round, smooth colonies and pseudohyphae.

What kind of organism are you looking at and how might you further characterize it?
Definition
Yeasts!

They reproduce by budding and can look like hyphae. You should do further biochemical experiments.

Examples include Candida spp. and Cryptococcus neoformans.
Term
What kind of fungi grows via budding in the parasitic stage, but forms hyphae in the saprophytic stage?
Definition
Dimorphic

Examples include **Histoplasma capsulatum**, Blastomyces dermatididis, Coccidioides immitis and Sporothrix schenckii
Term
How does Aspergillus mold cause hepatocellular carcinoma?
Definition
- Aflatoxin B1 (a kind of mycotoxin) is a problem in countries with chronic viral hepatitis (B and C).

- Food shortages lead to the consumption of contaminated foodts.
Term
Why are opportunistic fungal infections on the rise in the US?
Definition
More people are living in immunocompromised states.

Phagocytosis is most important resistance factor, followed by cellular immunity.
Term
What agent should only be used for mucosal mycoses?
Definition
1) Nystatin (Polyene)
Term
What agent should only be used for mucosal mycoses?
Definition
1) Nystatin (Polyene)
Term
How do Polyenes work to treat fungal infections?
Definition
Bind to ergosterol in cell membrane of fungi and increase membrane permeability (PCN of fungi).

1) Amphotericin B (Fungicidal with broad activity, but nephrotoxicity)

2) Nystatin (mucosal mycoses only)
Term
How do Azoles work to treat fungal infections?
Definition
Disrupt ergosterol biosynthesis (i.e. disrupt cell membrane) in a FUNGISTATIC manner.

1) Ketoconazole no longer used

2) Fluconazole not used for molds (Aspergilla, ect.)

3) Itraconazole used against Aspergilla

4) Voriconazole works against Candida and Aspergillus, bu tnot Mucorales

5) Posaconazole works against all

6) Imidazole works for cutaneous infections.
Term
Which Azole cannot be used to treat Molds?

Which was pulled from the market because of side effects?
Definition
1) Flutoconazole

2) Ketoconazole
Term
How do Echinocandins work to treat fungal infections?
Definition
The "fungins" (Caspofungin, Micafungin and Anidulafungin) inhibit 1,3 Beta-glucan synthase, interrupting cell walls

- Hepatic metabolism and well tolerated
- Treat Candida and Aspergillus (used for serious issues)
- Can't use for cryptococcus and zygomycetes.
Term
How do Antimetabolites work to treat fungal infections?
Definition
5-flucytosine interferes with DNA synthesis by non-competitive inhibition of thymidylate synthetase

- Not used in isolation, because resistance develops, so use with Amphotericin against cryptococcal meningitis.
Term
How do Allylamines work to treat fungal infections?
Definition
- Inhibit ergosterol synthesis like azoles, but through a different mechanism.

- Terbinafine (oral or topica) treats dermatophytes.
Term
How do Candida yeast infections normally occur and how to do you treat?
Definition
INFECTION
- Normal in mouth, GI and vagina

- Cellular immunity/granulocytes/mucous membranes have to be overcome, such as cases of surgery or antibiotic use.

- Manifests with oral "thrush", "diaper rash" and often blood infection or abscesses.

TREAT

- For topical, use Nystatin and Azoles
- For systemic, use Amphotericin B, Azoles and Echinocandins
Term
How do Cryptococcus neoformans yeast infections occur?
Definition
- Most patients are immunocompromised (CD4+ T cells inhibit neoformans directly)

-Fungus enters through respiratory tract, where it spreads in the blood to the CNS and can cause cryptococcal meningitis.

- Polysaccharide capsule inhibits phagocytosis
- Yeast produces melanin (oxidative stress) and grows at normal BP
Term
How do you diagnose/treat Cryptococcus neoformans yeast infections?
Definition
Often result in meningitis

1) Diagnose with
- India Ink for Capsule
-Cryptococcal polysaccharide antigens in blood and CSF
-Culture of organisms

2) Treat with Amphotericin + 5-flucytosine (anti-metabolite), and then maintain with Fluconazole (not for mold!)
Term
How does a Aspergillus mold infection arise/manifest?
Definition
-Can have 90% mortality in immunocompromised patients and often occurs in patients with Asthma or CF that have hypersensitivity reactions.

- Fumigatus is most important, while niger can sometimes cause otitis externa

- Inhale spores that evade pulmonary macrophages and PMNs, go onto the lungs, enter the vessels and often disseminate to the CNS

1) Allergic bronchopulmonary aspergilliosis (ABPA)
2) Aspergilloma "fungus ball"

**Other manifestations as well, but these are most important)
Term
How do you diagnose/treat Aspergillus infections?
Definition
1) Diagnosis is DIFFICULT
- Try and grow samples on respiratory specimens
- Look at galactomannan antigen in blood and lavage fluid.

2) Treat with **Voriconazole**, or Amphotericin, posoconazole or itraconazole (NOT fluconazole)
Term
What is the drug of choice for Aspergillus spp.?

What drug would you be sure not to use?
Definition
1) Voriconazole

2) Fluconazole doesn't work on molds!
Term
What molds other than Aspergillus spp. cause disease in humans?
Definition
1) Zygomycoses

2) Sporotichosis

3) Dermatiaceous molds/Penicillium marneffei/Fusarium/Scedosporium
Term
When are you likely to see a Zygomycoses infection and how could you treat?
Definition
- Molds such as Mucor infect in context of immune disease, metabolic disease or hemocromatosis.

- High affinity for vascular structures, which leads to thromboembolisms and infarction (High mortality)

-Treat with **Amphotericin B**, or Posoconazole (only oral agent with activity)
Term
When are you likely to see a Sporotrichosis infection?
Definition
- "Rose Garden" disease occurring as non-healing, inflamed nodules.

- Can spread to lymph nodes (string of nodular lesions)
Term
What do you treat all dimorphic fungi with?
Definition
Amphotericin!

Histoplasma capsulatum, Coccidioides immitis, Blastomyces dermatidis
Term
A patient from the MIssissippi river valley presents with a mediastinal granuloma and fibrosis.

You run a urine sample and take a tissue biopsy. What do you see?
Definition
Probably Histoplasma capsulatum (Dimorphic fungi)

- Lucky to catch it since it is asymptomatic in >90% of infections!

- Treat with Amphotericin or maybe itraconazole (cutaneous)
Term
A patient from the Southwestern US presents with Pulmonary infection and you know it is a fungal infection. What could they have?
Definition
Based upon the Southwestern US, it is mst likely Coccidioides Immitis.

Ohio/Mississippi could be Histoplasma or Blastomyces (if it spread to skin)
Term
How does an infection from Pneumocystits jiroveci present?
Definition
- This one is special in that it lacks ergosterol and used to be classified as a protozoa.

- Produces pneumonia in T-cell impaired individuals.

- Can be prevented/treated by pumping up the CD4+ count with Bactrim.
Term
What is the most common dermatophyte and how does it present?
Definition
1) Anthropodophilic dermatophyte (human to human transmission) causes superfiscial fungal infections such as

- Trichophyton rubrum (athlete's foot or jock itch)

2) Diagnose with skin scratch and prescribe imidazoles topically, or terbinafine orally.
Term
A patient presents with oral thrush, vaginitis and an abscessing infection.

Which fungal species fits these symptoms and how might you treat?
Definition
Candida albicans.

- For topical, use Nystatin and Azoles

- For systemic, use Amphotericin B, Azoles and Echinocandins
Term
A patient presents with cutaneous lesions in the extremities.

Which fungus would most likely cause these lesions and how might you treat?
Definition
Sporothrix schenckii (not geographically restricted, Sporotrichosis Dimorphic Mold) occurs in "Rose gardners" and can cause non-healing, inflamed nodules that can spread to the lymph nodes.

Probably treat with the polyene, Amphotericin.
Term
What type of organism has Mycelium?
Definition
Mold (Aspergillus, Penicillium marneffei, Fusarium, Scedosporium)
Term
What side effects are associated with Amphotericin B use?
Definition
1) Nephrotoxicity

2) Fever

3) Hypokalemia and Hypomagnesemia
Term
What side effects are associated with Echinocandin use?
Definition
Caspofungin, Micafungin and Anindulafungin can cause histamine-like reactions, but are usually well tolerated
Term
What side effects are associated with 5-Flucytosine use?
Definition
In patients with impaired renal function

1) Bone marrow suppression, rash and diarrhea.
Term
Why have C. glabrata infections become more and more prevalent in hospital settings, despite the previous prevalence of C. albicans?
Definition
Fluconazole use (Glabrata is less succeptible)
Term
Why do Cryptococcal yeast infections occur so commonly in immunocompromised patients?
Definition
CD4+ cells directly inhibit C. neoformans growth (by contact).
Term
How do Zygomycoses molds appear?
Definition
HIGH MORTALITY- treat with amphotericin B

Mucor, Absidia, Rhizopus, Rhizomucor

1) Broad, nonseptate hyphae with thick walls that branch at right angles.

2) look for in context of metabolic disease, hemochromatosis and immune deficiency.
Term
Which mold is endemic in Southeast Asia?
Definition
Penicillium marneffei (immunocompromised)
Term
Which mold is black?
Definition
Dematiaceous molds (black skin)
Term
Which mold appears in immunoCOMPETENT individuals post-trauma?
Definition
Scedosporium
Term
How do you treat microsporidia?
Definition
Diarrhea in immunosuppressed people with HIV.

1) Albendazole

2)**ART**
Supporting users have an ad free experience!