4th most common nosocomial blood infection
candida
Oval or spherical shaped, unicellular organisms
yeasts
Multicellular with branching, thread like filaments (hyphae) that knit to form a mat-like structure (mycelium)
mold
dimorphic
can exist as either a yeast or a mold form - depending on conditions
heterotrophic
reliant on their environment for nutrients and other required & essential substances
telemorph
sexual reproduction of yeast
anamorph
asexual reproduction of yeast
What MOA can you not use in fungus?
protein synthesis inhibitors because it’s too close to our protein synthesis
Azotemia
seen with amphotericin in ~80%. Decreased renal function. abnormally high levels of nitrogen-containing compounds such as urea or creatinine. It is largely related to insufficient filtering of blood by the kidneys. It can lead to uremia if not controlled
azole MOA
Inhibits ergosterol formation
blocks lanosterol->ergosterol
azole with the least CYP450 interaction
Posaconazole
echinocandin with the least CYP12450 interaction
Anidulafungin
griseofulvin MOA
inhibiting microtubule so disrupts flow and movement inside cell also disrupts mitosis
endemic mycoses
able to cause disease in healthy hosts; only present in certain areas
opportunistic mycoses
cause disease if your immune system isn’t working correctly; can get regardless of where you live
endemic mycoses ex:
histoplasmosis
blastomycosis
coccidioidomycosis
opportunistic mycoses ex:
candidiasis
cryptococcosis
aspergillosis
risk factors for fungal infections
- organ & bone transplant
- cytotoxic chemo
- indwelling IV catheters, burns, surgery or trauma
- broad-spectrum ABX
candida that is resistant to fluconazole
C. krusei
C. glabrata- somewhat resistant- need high doses
candidemia
candida in the blood
positive germ tube test
indicates C. albicans in healthy person
or could be C. dubliniensis in HIV
all patients with candidemia require
eye exam to rule out candida endophthalmitis
fluconazole treatment for C. albicans, C. parapsilosis, C. tropicalis
6mg/kg/day
fluconazole treatment for C. glabrata
12mg/kg/day
DO NOT USE for C. krusei
predisposing factors for aspergillosis
prolonged neutropenia (>7 days) chronic high dose steroids cytotoxic agents- chemo broad spectrum ABX cell transplantation
galactomannan postitve test
diagnostic of aspergillosis
unique CT scan
halo signs i n aspergillosis
empiric therapy for aspergillosis
1st line: voriconazole
2nd line: lipid form Amp B
salvage therapy in Aspergillosis
vori + echinocandin
lipid Amp B + echinocandin
or posaconazole
primary cryptococcosis presentation
always in the lungs- lungs, rales (rattling), SOB
Cryptococcal meningitis presentation
more serious
kernig’s & Brudzinki’s sign
in AIDs pts sxs are less specific
cryptococcosis diagnosis
cryptococcal antigen test or analysis of CSF- fungal (>lymphocytes)
cryptococcus pulmonary mild-moderate treatment
fluconazole
alt: itraconazole, ampB
cryptococcus severe pulmonary and CNS treatment
induction: ampB+ flucytosine +/- fluconazole
alt: mono lipid ampB
maintenance: only in AIDs pts- fluconazole until CD4>200
what should NOT be used to treat cryptococcus?
echinocandins
histoplasmosis is an endemic in
Ohio & mississippi river valleys
histoplasmosis diagnosis
antigent test- quick
direct mircoscopic exam w/ 10% KOH
histopathologic exam & culture
histoplasmosis mild-moderate treatment
treatment is usually not needed unless symptoms > 1 month
itraconazole
histoplasmosis moderately severe-severe treatment
ampB 1-2weeks then itraconazole
methylprednisolone 1-2 weks with acute respiratory complications
blastomycosis endemic in
Ohio and mississippi river valleys
acute pulmonary blastomycosis is either
asymptomatic or self-limited
stays in your system & will be reactivated “disseminate”
reactivation of blastomycosis
chronic pulmonary- weight loss, TB, CNS involvement
blastomycosis pulmonary disseminated disease (non-CNS) Mild-moderate treatment
itraconazole
blastomycosis pulmonary disseminated disease (non-CNS) life-threatening treatment
ampB for 1-2 weeks then itraconazole
blastomycosis CNS disease
ampB (lipid form preferred) then azole (flu, itra, vori)
histoplasmosis/blastomycosis response to therapy by:
- resolution of radiologic, serologic, & micro parametes
2. improvement in SXS
histoplasmosis/blastomycosis: after initial course of therapy in AIDs pts:
lifelong suppressive therapy with oral azoles until CD4>200
asymptomatic histoplasmosis
do NOT treat
can treat blastomycosis
risk factors for primary coccidiodomycosis
non identified
risk factors for severe coccidiodomycosis
very serious infection
race, prego, immuno-compromised, male, neonates, pts w/ B/AB blood
clinical presentation of coccidiodomycosis
60% asymptomatic, primary pneumonia, chronic persistent pneumonia- hemoptysis(coughing blood), valley fever-rash, disseminated disease- CNS
coccidiodomycosis asymptomatic treatment
NO treatment
Coccidiodomycosis primary respiratory or disseminated (non-CNS) infection treatment
azole- first line fluconazole or itraconazole for bone disease
ampB
duration- months to years; sometimes lifelong suppressive therapy
coccidiodomycosis disseminated CNS treatment
fluconazole for life
amp B intrathecal therapy +/- itra or fluconazole
itra for life
good CSF penetration fungal agents
fluconazole, voriconazole, fluctosine
flucytosine MOA
enters fungal cells by a cytosine-specific permease & disrupts nucleic acids by inhibiting thymidylate synthetase
flucytosine has a synergistic effect with:
AmB
Black box warning for itraconazole
In patients with heart failure due to ionotropic effect
host range
which host can be infected determined by specific binding of the virus to the cell
what are the three classes of viruses?
DNA, RNA & retroviral
DNA virus examples
smallpox, chickenpox, herpes, hep B, CMV, HPV
RNA virus examples
rabies, polie, influenza, colds, MMR, Hep A & Hep C
RNA retroviral virus examples
HIV & human T-cell leukemia
RNA virus MOA
replicate entirely in host cytoplasm
uncoating
the release of viral nucleic acids
current agents _____ eliminate dormant viruses
do NOT
acyclic guanosine analogs lack
a cyclic sugar (ribose)
acyclic guanosine analog drugs
acyclovir,valacyclovir, penciclovir, famciclovir, ganciclovir, valganciclovir
acyclic guanosine analog MOA
viral thmidine kinase adds first PO4 and then host cell kinase ass the other 2. Gets incorporated into viral DNA. Has no 3’OH so DNA chain is terminated!
cidofovir is an analog of
cytidine
cidofovir already has one P, so it
bypasses the need for viral thymidine kinase
cidofovir diphosphate (3Ps) inhibits
DNA polymerase & also is a chain terminator (no 3’OH)
foscarnet MOA
inhibits viral nucleic acid synthesis by noncompetitive inhibition of the pyrophosphate binding site on viral DNA polymerase
first FDA approved antisense therapy for viral infection
fomivirsen
rimantadine & amantadine MOA
inhibit viral uncoating & assembly of new components. Active against Influenza A. cyclic cage structure
analogs of sialic acid
oseltamivir & zanamivir
flu A & B incl H1N1
oseltamivir & zanamivir MOA
inhibit neuraminidase & block release of progeny virus from host cell
antiviral agents used to treat Hep B & C
adefovir
recombinant & natural IFNs
lamivudine & telbivudine
ribavirin
acyclic adenosine monophosphate analog
adefovir
Lamivudine & telbivudine MOA
nucleoside analogs of C & T. block chain elongation
in contrast with other agents, ribavirin has
a ribose sugar.
ribavirin MOA
inhibits the enzyme inosine-5-PDH which decreases synthesis of GTP. Also inhibits post-transcriptional processing of viral mRNA (5’ capping)
herpes zoster aka
shingles
shingles is characteristically
unilateral
postherapetic neuralgia (PHN)
pain that persists >120 days after onset of shingles rash
treatment of shingles recommended in:
> 50yo, more severe cases, immunocompromised
goals of shingles treatment
accelerate resolution, limit severity & duration of pain & reduce risk of complications
steroids & antivvirals do NOT prevent
postherpetic neuralgia
prevention of CMV
valganciclovir, possibly ganciclovir, brincidofovir underinfestigation
CMV treatment
ganciclovir & valganciclovir are first line
antigenic drift
a mechanism for variation in viruses that involves the accumulation of mutations within the genes that code for antibody-binding sites.
antigenic shift
the process by which two or more different strains of a virus, or strains of two or more different viruses, combine to form a new subtype having a mixture of the surface antigens of the two or more original strains.. larger change
7th leading cause of death in the US
influenza
immunity to influenza ___ develops in childhood
c
hemagluttin (Hx)
involved in host cell binding prior to viral entry
neuramidase (Nx)
necessary for viral release and propagation
____ flu vaccine recommended in children 2-8 if available
live attenuated
influenza prophylactic agents
oseltamivir, zanamivir
pts who should receive prophylaxis or therapy for flu
hospitalized pts, pts with severe, complicated or progressive illness, pts which higher risk of flu complications