Exam 5 Lecture 6 Flashcards
(78 cards)
Where are candida found? What type of infection do they cause? When is mortality increased?
Found in human GI tract as normal flora
Can cause mild infection such as oropharyngeal or esophageal candidiasis or more serious invasive infetions such as catheter associated infections and disseminated disease.
Increased mortality if empiric antfungal therapy delayed by 12 hrs
Risk factors for invasive candidiasis
Prolonged ICU stay
CV catheter
Prolonged therapy with broad spec antibacterial agents
Receipt of PN
Recent surgery
hemodialysis
DM
What are two fungi that are endemic? Who do they cause infection in and what disease may they cause?
Histoplasma capsulatum and blastomyces spp
May cause disseminated disease via a primary pulmonary infection. May cause disease in normal host but higher risk in HIV patients with suppressed cell immunity
What are two species of cryptococcus? What type of infection does it cause? Mortality
Cryptococcus neoformans and gatti
CNS side effects
30% mortality
broadest spec antifungal
Amphoterecin
MOA of amohoterecin
Binds to ergosterol and gets inserted into the fungal cytoplasmic membrane-> Disruption of the fungal cytoplasmic membrane.
Increased cell permeability-> leakage of sodium/potassium/cellular constituents, loss of membrane potential
cell death
When is amphoterecin 1st line
Systemic invasive infection such as
Cryptococcus
Blastomyces
Histoplasma
Mucor
what are the different doses for amphoterecin formulations
deoxycholate- usual 0.5-1 mg/kg/day
Liposomal- 3-5 mg/kg/day
Lipid complex- 5 mg/kg daily
Adverse effects of amphoterecin? Electrolyte abnormality?
NEPHROTOXICITY!!!! (can be permanent, dose dependent)
can increase Scr and BUN
Electrolyte abnormalities
-hypokalemia
-hypomagnesemia
-anemia
-bicarb wasting
How to prevent nephrotoxicity caused by amphoterecin
0.5-1 L NS over 30 min before AMB and 0.5-1L NS after infusion
extend infusion to help to 4 hours
What are infusion related rxns for amphoterecin? How to treat?
H/A, fever, chills, arthralgias, myalgias, N/V, hypotension
Pretreat with acetaminophen and antihistamines
What is the main use of flucytosine
Main use is combo therapy with AmphoB for cryptococcal meningitis
Bioavailabitily of flucytosine
Great bioavailability (>90%)
Penetrates into the CSF (75% of srum) (that is why it is used for cryptococcal meningitis)
how is flucytosine excreted? Is it renally dose adjusted?
85-95% excreted unchanged in the urine (removed by HD and PD)
Renally dose adjusted
do we dose adjust amphoterecin? Why or why not?
Can dose adjust if this occurs not for renal dysfunction, just to lessen side effects
What are goal peak and through concentrations of flucytosine? When are they drawn? What dose is associated with increased toxicity
goal peak 70-80 ug/ml
- DRawn 2 hours post dose after 3-5 days
Trough concentration 20-40 ug/ml
Peak concentration associated with increased toxicity
spectrum of activity of flucytosine? When is it first line
Candida and cryptococcus
First line in cryptococcus
flucytosine adverse effects
Hematologic effects (bone marrow suppression)
GI (N/V/D), pain, enterocolitis
What to monitor for flucytosine? Drug interactions?
Monitor- CBC, platelets, SCr, BUN
No significantd rug interactions
bioavailability of flucanozole? How is it excreted?
Bioavailability >90% and decent CSF concentration (60% if uninflamed, 80% in inflamed)
Excreted unchanged in urine
Do we renally adjust in flucanozole? What is dosing based on?
Dose reduce in renal insufficiency.
Dosing based on total body weight (npt adjusted)
Clinical use of flucanozole (1st line)
1st line in Invasive candidiases
Doses of flucanozole for C albicans and C glabrata
C. albicans; 800 mg (12 mg/kg) loading dose, then 400 mg (6mg/kg) daily
C glabrata- 800 mg daily (loading dose 1200-1600 mg) depending on susceptibility
Non first line uses of flucanozole
Prophylaxis in bone marrow transplant- 400 mg daily
Cryptococcal meningitis- alternative to amphotericin B +/- flucytosine for induction therapy