Exam 4 - Fungal (Kays) Flashcards
what are the most common fungal pathogens?
Candida species Aspergillus species Cryptococcos neoformans Zygomycetes Endemic Fungi (related to your region)
What are types of Zygomycetes
Rhizopus
Absidia
Mucor
what are types of endemic fungi
histoplasma capsulatum
blastomyces species
coccidioides immitis
Is it a yeast or a mold?
Candidia
yeast
Is it a yeast or a mold?
Aspergillus
mold
Is it a yeast or a mold?
cryptococcus
yeast
Which fungal pathogen?
is enacpsulated and
primarily affects CNS and respiratory tract
cryptococcus neoformans
Which fungal pathogen?
risk factor includes penetrating injuries from natural disasters?
Zygomycetes
Which fungal pathogen?
is common in midwestern states/happens from exposure to bat guano/cave exploration/from contrstruction
histoplasma capsulatum
Which fungal pathogen?
common in southwestern US
coccidiodies
what is the most common species of Candidia?
C. Albicans
what is the most drug resistant species of Candidia?
C. Auris
Candida species:
increased mortality if empiric antifungal therapy doesn’t happen within ______
12 hours
Candida species:
what are some risk factors for invasive candidiasis
prolonged ICU stay central venous catheters prolonged therapy with broad spec abx receive parenteral nutrition recent surgery (esp abdominal) hemodialysis diabetes...
PD parameter for Amphotericin B?
Peak/ MIC
PK of Amphotericin?
CSF?
Renal / Hepatic?
PO or IV?
poor CSF penetration
no adjustment for Renal or hepatic needed
bad PO absorption – must do IV
Dosing Notes about Amphotericin?
do a TEST DOSE
can do bigger doses if use lipid formulations
Infused over 4- 6 hours!!
ADEs of Amphotericin?
Infusion related (fever, chills, arhtralgias, myalgias, N/V) & thrombophlebitis
Nephrotoxicity
Hypo kalemia and magnesemia
Bicarb wasting
anemia
How to manage Amphotericin infusion related rxns?
pre-treat - APAP, antihistamines, anti-nausea meds
add hydrocortisone to infusion
TOLERANCE WILL DEVELOP
give slower rxn to help with thrombophlebitis
MOA of flucytosine
5-FC enters fungal cell — gets made into 5-FU and gets into fungal RNA and stops protein synthesis
or inhibits thymidylate synthetase and interferes with DNA synthesis
Flucytosine is used mainly for what fungal pathogen?
Cryptococcus
PK of Flucytosine?
CSF?
Renal/hepatic?
PO or IV?
great CSF
renal adjsut!!/excreted in urine (HD and PD pull it out)
great PO absorption – oral!
drug interactions of amphotericin?
nephrotoxic agents (bc more nephrotoxicity) Digoxin/Skeletal muscle relaxants -- hypokalemia risk \+ Flucytosine = better therapeutic effect but toxicityyyy
ADE of flucytosine?
Bone marrow suppression
Normal dose for Flucytosine
100 - 150 mg/kg day
and DIVIDED in 4 doses
Monitoring for Flucytosine
CBC/Platelets (because marrow suppression)
SCr/BUN (because renal adjsut)
Ketoconazole MOA?
inhibits egosterol synthesis
via inhibiting lanosterol 14 a demethylase
also membrane gets wack without egosterol = leakage
Ketoconazole:
-cidal or - static
static
PK of Ketoconazole:
CSF?
Renal/Hepatic adjustments?
PO or IV?
negligible CSF
metabolized by liver extensively
PO absorption is related to gastric pH
Ketoconazole:
Oral absorption: related to gastric pH how?
inversely! lower pH (more acidic) = more absorption
ADEs of Ketoconazole?
Hepatoxicity
Endocrine: Menstural irregularities, Hair loss, libido/sperm issues, and Gynecomastia
Drug interactions of Ketoconazole?
It is a POTENT CYP3A4 inhibitor:
therefore — anticoag, rifampin, cyclosporine/tacrolimus/sirolimus, phenytoin
ALSO
anything that decreases stomach acid (H2RA, PPIs antacids)
PK of Itraconazole:
CSF?
Renal/hepatic?
PO or IV?
poor CSF liver metab (NO renal adjust) PO dependent on acidity!! take with cola for capsules (oral solution - acidity doesnt matter)
Itraconazole ADEs
Hepatoxicity
CHF – boxed warning
Avoid (CONTRAINDICATED) in pregnant/nursing women
peripheral neuropathy
Boxed warning for itraconazole?
CHF!! (present or history) negative inotropic effect
Drug interactions for Itraconazole?
PPIs/H2RAs/Antacids - because acidity needed
CYP3A4 interactions
PK of Fluconazole:
CSF?
Renal/Hepatic?
PO or IV?
great CSF
needs renal adjustment
PO absorption is great
ADEs of Fluconazole
QT prolongation
Elevation in hepatic transaminase
Voriconazole:
Does it cover Aspergillus, Mucor, or both?
Aspergillus - NO MUCOR
PK of Voriconazole:
CSF?
Renal/Hepatic?
PO or IV?
IDK about CSF…
renal adjust when IV!!!! (not oral)
great PO availability
Oral Voriconazole tips?
acid reducers do NOT matter for this
this is best 1 hour BEFORE OR AFTER a meal
ADEs of Voriconazole
Visual disturbances
Elevated LFTs
Phototoxic skin rxns
Adjust Voriconazole for renal elimination when?
Adjust when IV and CrCl < 50 mL/min
PK of Posaconazole?
CSF?
Renally or Hepatic?
PO or IV
idk about CSF…
Renally adjustment needed
PO – needs acidic to be absorbed
IV - RENAL ADJUST
when do you avoid Posaconazole and Voriconazole due to renal issues
when IV formulation and CrCl is < 50 mL/min
Drug interactions for Posaconazole?
CYP 4 dayz
and acid reducers!
ADes of Posaconazole
Elevated LFTs/billirubin
hypokalemia
Rash
PK of Isavuconazole
PO or IV?
Renal/hepatic?
PO has great bioavail - so PO or IV is fine
NO renal adjustment needed
NO hepatic adjustment needed
Why do some IV azoles need to be avoided when CrCl is < 50 mL/min
something to do with their formulation having cyclodextrin??
Isavuconazole does not have cyclodextrin = does not need renal adjustment
ADEs of Isavuconazole
increased LFTs
infusion related reaction
*NO QT PROLONGATION actually SHORTENS QT
what is an abnormal Qt interval?
male over 450 ms
females over 470 ms
Contraindications for Isavuconazole?
coadministration of any strong CYP3A4 inhibitors or inducers
patients with familial SHORT qt syndrome (this drug will shorten QT)
Examples of strong CYP3A4 inhibitors:
Ketoconazole
high dose ritonavir
Examples of strong CYP3A4 inducers
CBZ
rifampin
St. Johns Wort
Long acting barbiturates
MOA of Caspofungin
glucan synthesis inhibitor = prevents from fungal cell wall from being made
The echinocandin drugs have what suffix?
-fungin
spectrum of echinocandin?
Candida and aspergillus
Azole antifungals affect cell ______
Echinocandins affect cell ______
Azole: affect cell membrane
Echinocandins: cell wall
which echinocandin needs to be dose reduced with hepatic dysfunction
caspofungin
Echinocandins:
PO or IV?
IV!!
very poor bioavailability
VVC stands for?
vulvovaginal candidiasis
Complicated or uncomplicated VVC?
sporadic infection that is susceptible to all forms of antifungal therapy regardless of treatment duration
uncomplicated
Complicated or uncomplicated VVC?
Recurrent VVC
complicated
Complicated or uncomplicated VVC?
Severe disease
complicated
Complicated or uncomplicated VVC?
Non-candida albicans infection
complicated
Complicated or uncomplicated VVC?
Candida albicans infection
uncomplicated
Complicated or uncomplicated VVC?
diabetes/immunocomproised/pregnancy
complicated
VVC:
Candida species - mono, di, or tri morphic
di
patient education for VVC? Avoid \_\_\_\_\_\_\_\_ to prevent worsening irritation Keep genital area \_\_\_\_\_\_\_\_\_ \_\_\_\_\_\_ to soothe the skin \_\_\_\_\_\_\_\_ not recommended
avoid harsh soaps
keep it clean and dry
cool baths to soothe
do not douche
Pharm Treatment of VVC:
Topical preparations can decrease efficacy of what?
latex condoms and diaphragms
Pharm Treatment of VVC:
Oral or Topical treatment is better?
Equally therapeutic
Pharm Treatment of VVC:
Treat for how long if uncomplicated?
can be 1 day.. (1 dose fluconazole)
or like 3 - 7 for various topical treatments
Pharm Treatment of VVC:
Treat how long if complicated?
10 - 14 days!
do this if uncontrolled diabetes or immunocompromised
what does OPC stand for and what is it
oropharyngeal candidiasis aka THRUSH
candida infection of the oral mucosa
what does EC stand for and what is it
esophageal candidiasis
esophagus infection from candida
what is the primary line of defense against OPC and EC
cell mediated immunity (CD4 T cells)
LOCAL risk factors for OPC and EC?
steroids/abx dentures xerostomia due to drugs, chemo, radiotherapy to head/neck, and BMT(?) smoking any disruption to oral mucosa
patients with ______ have had much less incidence of OPC and EC due to great drug development
HIV
HAART is savin’ them
SYSTEMIC risk factors for OPC and EC?
Drugs (cytotoxic, steroids, immunosuppressants after organ transplant) Neonates or elderly HIV infection/AIDS diabetes malignancy nutritional deficiencies
OPC or EC:
which one is more severe
EC
OPC or EC:
which one may have a fever more than the other
EC
OPC Treatment:
Treat for how long?
7 - 14 days
OPC Treatment:
If mild infection – treat how?
TOPICALLY
with clotrimazole troches or nystatin susp
or miconazole buccal tab
OPC Treatment:
If pt is refractory, cannot tolerate topical agents, have moderate - severe disease, or high risk for disseminated systemic disease (aka neutropenic) — treat how?
do SYSTEMIC
Fluconazole!!
Itraconazole
or Posaconazole
OPC Treatment:
If fluconazole refractory – treat how?
treat for 14 DAYS
kinda try any antifungal but itraconazole is good
(even try amphotericin…)
EC Treatment:
Treat for how long?
14 - 21 days?
EC Treatment:
Topical treatment when?
Systemic treatment when?
NEVER topical for EC
do SYSTEMIC!!
EC Treatment:
Treatment options?
Fluconazole…
itraconazole…
kinda whatever just do SYSTEMIC
EC Treatment:
If fluconazole refreactory – treat how?
treat for 21 - 28 days
itraconazole and like every other antifungal option…
Risk factors for fungal skin, hair, and nail infections?
prolonged exposure to sweaty clothes
failure to bathe regularly
lots of skinfolds
sedentary/confined to bed
how to treat tinea capitis
oral therapy — terbinafine daily 4 - 8 weeks (clean combs/brushes)
How to treat tinea unguium
aka onychomycosis ORAL therapy terbinafine: 6 - 12 wks or itraconazole 8 - 12 wks or fluconazole: 6 - 12 mos (toes need treated longer)
what are the different types of histoplasmosis
acute pulmonary
chronic pulmonary
disseminated
HIV infected pts
Acute Pulmonary Histoplasmosis treatment:
mIld-mod disease with sxs > 4 wks
itraconazole 6 - 12 weeks
Acute Pulmonary Histoplasmosis treatment:
if mod - severe disease?
amphotericin x 1 - 2 weeks THEN itraconazole
also medrol for first 1 - 2 weeks
Disseminated Histoplasmosis treatment:
if mod-severe disease?
amphotericin x 1 - 2 weeks then itraconazole for 12 months
Disseminated Histoplasmosis treatment:
if less severe disease?
itraconazole x 12 months
if C. glabrata strain — what drug(s) are preferred?
echinocandin
if C. parapsilosis strain — what drug(s) are preferred?
fluconazole or lipid amphotericin
if C. krusei strain — what drug(s) are preferred?
enchinocandin, lipid amphotericin, or vori
what antifungals cover mucor?
amphotericin
posaconazole
isavuconazole
what antifungal is the DOC for histoplasma
itraconazole
what antifungal is DOC for aspergillus
voriconazole
what fungi do echinocandins cover
candida and aspergillus
what fungi does 5-FC cover?
candida and cryptococcus
what fungi does ketoconazole cover?
candida ALBICANS and cryptococcus and histo
what two antifungal drugs cover everything but mucor
“everything” = candida, aspergillus, cryptococcus, histo, blasto, cocci
itraconazole and voriconazole
what does isavuconazole cover?
aspergillus
mucor
rhizopus
if we find candida in respiratory tract — what do we do?
nothing probably — its usually colonization/ candida does not cause pneumonia
if we find candida in the urine what do we do?
if asymptomatic and NOT high risk for dissemination — let it goooo
who are high risk pts for dissemination form candida UTI?
low birth weight infants
pts undergoing urologic procedure
neutropenic patients
which fungus is uncommon in HIV infected patients
aspergillus
galactomannan is a cell wall polysaccharide that is specific to the _________ fungus species and is detectable in serum/other body fluids
aspergillus
________ is the most important predisposing factor to the development of invasive aspergillosis
prolonged neutropenia (NOT HIV infection!)
DOC for invasive pulmonary aspergillosis
voriconazole
main drug to use for prophylaxis of aspergillosis
posaconazole
who would get aspergillosis prophylaxis
pts with neutropenia risk (cancer patients and bone marrow transplant pts)
which antifungal has a saturable metabolism/pk is NOT linear
voriconzaole
which antifungal agents need renal adjustment
flucytosine and fluconazole
voriconazole IV and posaconazole IV need to be avoided due to cyclodextrin build up in renal dysfunction
which antifungal agents need an acidic gastric environment to get absorbed
ketoconazole
itraconazole CAPSULE
posaconazole
what agents have cyclodextrin in them
IV voriconazole
and
IV posaconazole
what drugs used for cyptococcus infection?
amphotericin AND 5-FC
