Sm. Ani. Med - Systemic Mycoses 1

drraythe's version from 2015-11-24 20:18

general info

Question Answer
who is most like to get a systemic/disseminated mycotic infection?Immunosuppressed animals (immune mediated dz, Immunosuppressive therapy, splenectomy).
which organ removal will inc chances of systemic mycotic infxn?SPLEEN removal (big ol' filter)
ON EVERY R/O LIST EVERfungal, neoplasia, ehrlichia
what is the PRIMARY site of entry for fungi? 2 other common sites?MOSTLY RESP TRACT. Can also enter skin (esp through lesions) and GI tract (consumption)
(Dr C said..) blasto likes to go WHERE in the body? where does it usually come from?like to live in BONE AND LUNGS, usually goes through skin lesions (so you can impression smear a gross looking skin lesion and might get your answer)
clinical signs are Dependent upon system affected, however, some general CS of systemic fungal infection are...Weight loss, Lymphadenopathy, Pyrexia
two ways to get cytology to determine if infxn is fungal?(1) FLUIDS (taps) (2) Scrapes (skin or rectal scrapes)
If you wish to do histopathology on a possible fungal sample, what must you keep in mind in terms of processing the tissue?might need SPECIAL STAINS for fungi
what should you consider if you decide to do a fungal culture?Usually fungal cultures take a LONG time to grow, and then there are concerns about any fungi that might be zoonotic (and if it can affect animals, it probably can affect you)
How useful is serology for fungal dx?often NOT diagnostic. consider antigen vs antibody, as well as paired samples
Is tx of fungal infections easy?NO- v difficult and very expensive, and treatment often takes a long time (which Limits epidemiological data)
why is Pharmacologics of antifungals really difficult?only Partially understood, Resistance testing limited, Culture and susceptibility can have variable results, Tissue distribution of agents is different
which group(s) of antifungals target the MEMBRANE function?polyenes (amphotericin B also)
which group(s) of antifungals target the cell wall synthesis?echinocandins/penumocandins
which group(s) of antifungals target nucleic acid synth?pyrimidine analogue
which group(s) of antifungals target ergosterol synth?azoles and allylamines (ergosterol works kinda like cholesterol in their cell membrane..these drugs stop the production of it, so can't rebuild/repair membrane)
what do polyenes do and what are some examples?disrupt membrane fxn- amphotericin B (+lipid formation version), nystatin (liposomal nystatin)
what do echinocandins/pneumocandins do and what are some examples?inhibit cell wall synth- caspofungin, micafungin, anidulafungin
what do azoles do and what are some examples?disrupt ergosterol synthesis- fluconazole, ketoconazole, itraconazole, clotrimazole,
what do allylamines do and what is an example?inhibit ergosterol synth, terbinafine
what do pyrimidine analogues do? example?target nucleic acid synth- flucytosine
what is the main go-to antifungal?itraconazole
what are the 2 Microorganism produced antibiotics?Griseofulvin and amphotericin B
what should you know about Griseofulvin?'s basically never ever used. (wont be a correct choice on test) (pharm throwback: works on microtubules aka mitotic inhibitor)
what are the 6 types of antifungals she listed?(1) Microorganism produced antibiotics (AmB and griseo) (2) azole derivatives (3) Chitin synthesis inhibitors (cell wall aka echinocandins) (4) Allylamine derivatives (also inhibit ergosterol) (5) Potassium iodide (6) flucytosine (pyrimidine analogue)
Azole derivatives--> Imidazoles: which drug is in this category?ketoconazole
AmphB is the "gold standard" drug for fungal infections, but the downside is...It's awful side effects of HEPATIC AND RENAL TOX-- must monitor these pts!!! (...lipid complexed/Colloidal dispersion/Liposome encapsulated versions have less severe SEs)
what drug (azole) can you combine with AmphB to dec it's dose (And thus dec its side effects)ketoconazole (an imidazole) ( B KET) [she also said it in general under azoles being in combo]
Azole derivatives--> Triazoles: what 5 drugs are in this category?Fluconazole, Itraconazole, Clotrimazole, Enilconazole, Voriconazole
what is Fluconazole good for?(triazole) Good for CNS, urine, ocular (the flu makes you unable to think, you cant see straight, and you feel like piss)
what is Itraconazole good for?(triazole) Good for skin ( itra itchy skin)
what is Clotrimazole good for?(triazole) nasal aspergillosis (noses are like vags)
what is Voriconazole good for?(triazole) Newer—used for really resistant fungus (super expensive) (for the really voracious fungi pull out the big gun)
explain how azole antifungals workInhibit ergosterol synthesis Via Cytochrome P-450 enzyme complex
which group of antifungals are used for almost all SYSTEMIC mycoses?azoles
what must you keep in mind with azole drug doses?Need loading doses (higher initial dose to speed up process of reaching steady state ie the level you want in the body), and will take 14 days to reach steady state (same amount going in as coming out)
which azole tends to give the most side effects? What are the side effects? ketoconazole gives the most SEs, and tends to have ill effects on the Liver and adrenals. Monitor liver enzymes when on this drug! (KET is bad for the liver and it makes you tweak out)
which antifungal group tends to give more drug interaction problems, and why?the azoles, bc they dec ergosterol synth via inhibition of CYP450--> DRUG INTERACTIONS ABOUND!
what are the main side effects of azoles?liver and adrenal issues, sometimes skin issues with itraconazole. GI issues in CATS (divide dose)
which animal should you divide the dose of azoles with and why?cats, can give them GI issues
what IS amphotericin B?Macrolide antibiotic
how does amphotericin B work?Binds to sterols in fungal cell membranes (pokes holes in membrane this way)
what's the gold standard antifungal to compare newer antifungals to?AmphB
where does crypococcus like to live?IN CAT NOSES
Flucytosine works how?Inhibits DNA and RNA synth (which means it inhibits protein synth as well)
which drug is SYNERGISTIC with Amphotericin B?flucytosine (amphB pokes holes in membrane to let more flu get into the nuc to do its job)
what is a particular condition where you would want to combine AmphB and Flucytosine?Cats with cryptococcosis (likes their noses)
what is tissue distribution like for flucytosine?WIDE tissue distribution, can cross BBB
which antifungal can cross BBB?FLUCYTOSINE
what are the side effects of flucytosine?Diarrhea, Anorexia, Vomiting, Dose dependent bone marrow suppression (flucytosine goes into the nuc and the BBB and has side effects like cancer drugs)
which drug is in the Allylamine group?terbinafine
what kinda drug is terbinafine? how does it work?it's an allylamine, it works by Inhibiting ergosterol biosynthesis (like azoles)
what is terbinafine good for, and why?Well distributed in the skin, so good for Dermatophytosis, onychomycosis, and sporothrix
which antifungal is good for Dermatophytosis, onychomycosis, and sporothrix?terbinafine (well distributed in the skin) (I wear a turbin to cover the gross skin on my head)
which two drugs can you use in combination to help with tx of pythiosis?terbinafine and itraconazole, SYSTEMICALLY
what are the side effects of terbinafine?GI, hepatic, and cutaneous reactions (good for skin so can react with skin, hepatic just like azoles, and GI bc you shouldnt eat turbans)
granulomatous inflammation means...inflammation with MACROPHAGES
Pyogranulomatous inflammation means...inflammation with MACROPHAGES AND NEUTROPHILS
purulent inflammation means...inflammation with NEUTROPHILS
fungi usually cause what kinda inflammation?granulomatous (ie: MACROPHAGES)
since fungi can cause granulomatous dz, you should be aware of what possible side effect?HYPERCALCEMIA (its the "G" in goshdarnit)
miliary pattern in lungs could be 2 things...fungal infection, neoplasia
what's a weird dermy (skin) thing you see a lot with fungal infections?DEPIGMENTATION


Question Answer
what is the agent which causes blasto?Blastomyces dermatitidis
unique attribute of blasto which makes it easy to ID?BROAD BUDDING BASE (when it buds, it has more budding contact area than most others...)
what are the triggerwords for a blasto question?broad budding base, lungs and bone, water, (east and great lakes states like MI)
WHERE would you find blasto? (geographic)MS, OH, MO, TN, southern Great Lakes, and southern Mid-atlantic states
WHERE would you find blasto? (enviro)WATER!!! also, can sometimes uncover it in cases of soil disruption (bc soil saphrophyte)
WHO is most prone to blasto, and why?Young, male, large breed dogs--> ESP. sporting/hunting breeds (because they are more likely to be free roaming!)
what kinda fungi is blasto?Dimorphic fungus soil saphrophyte
most common way for blasto to get into the body?Inhaled condiophores which then Disseminate into LN, eyes, skin, bones, prostate
once blasto disseminates, how does it affect the immune system/ how does the body react?Macrophage activation leads to a Cell mediated immune response, resulting in Pyogranulomatous inflammation
what kinda inflammation is a result of blasto?Pyogranulomatous
how long is blasto incubation time?5-12wk
what are the CS of a blasto infection?Depends on body system affected, however, PULMONARY signs most common (since resp is usually route of infxn) which would be a cough. There is also Lymphadenopathy, Cutaneous signs (esp cats!), Ophthalmologic signs, Lameness (bone infection), Neurological (esp cats)
Dx--> what might you see on CBC/Chem?(she wrote "anything" i think she means anything abnormal, because it depends on the body system) might see HYPERcalcemia (bc granulomatous inflammation can cause hypercalcemia)
what would you see on Cytology/Histopathology of a blaso infected tissue?Pyogranulomatous inflammation
What kind of serology would you want to do for a suspected blasto infection?Antibody..Paired titers may be helpful early on
what are two definitive tests for blasto?(1) Organism identification- cytology, Histopathology (special stains!!), Culture (2) Antigen test
what should you know about culturing Blasto?Can take weeks and has zoonotic potential
what sample do you use for an antigen test for blasto?urine (send to Mira vista laboratory)
How do you treat a blasto infection? (no severe hypoxia)Itraconazole for at least 3-6 months, with a loading dose for the first 3-5days. Continue until no CS. (itra-itchy skin- I want to blast my itra skin off)
How do you treat a blasto infection if the pt is severely hypoxemic?Combination therapy with amphotericin B lipid complexed
what kind of supportive care should you provide pts with blasto?Fluids, O2, nutrition, +/- abx
how well do pts respond to tx? what factors can affect the prog?70% respond to tx, but Prognosis poorer if hypoxic and > 3 systems affected (Recurrence in 20% of dogs)


Question Answer
agent that causes histoplasmosis?Histoplasma capsulatum
what kinda fungi is histoplasma?Dimorphic Soil saprophyte
outbreaks of histo are associated with what kind of locations? (environmental)Chicken coops, bird roosts, bat habitats
what is the incubation period for histoplasmosis?12-16 day incubation
*Where does histo usually enter the body?Lungs or GI, and then can disseminate to LN, liver, spleen, BM, eyes...
*what kinda inflammation does histoplasma cause?Granulomatous inflammation (macrophages! potential hypercalcemia!)
WHO is most likely to get histoplasmosis?Younger animals <4 years (they are likely roaming!)
Where is histo most likely to be? (geographically)mid-east
how does histoplasma affect CATS?non-specific signs: depression, fever, weight loss, pale mm. Also Hepatomegaly and splenomegaly as well as Ophthalmologic signs
what are the Ophthalmologic signs of histoplasma, and WHO gets these?CATS! (herpes too, goodie.) Retinal pigment proliferation or edema and also Chorioretinitis, anterior uveitis, panophthalmitis
Which breeds of dogs are overrepresented for histoplasma?Male pointers, Weimaraners, and Brittneys
what are the clinical signs for histoplasma?CS dependent upon route of entry, however, GI signs are very prominent, like Often large intestinal diarrhea early on, Small intestinal signs as disease progresses, and less specific signs liek Fever, anorexia, depression, severe weight loss
Which is more prominent with histo- small or large bowel diarrhea/signs?LARGE first, small as dz progresses
what two clinical signs are gonna be really hinting towards histoplasma in DOGS?LARGE BOWEL diarrhea, and ASCITES
what three clinical signs are gonna be really hinting towards histoplasma in CATS?Ophthalmologic signs and hepatomegaly/splenomegaly
what information can a CBC yield for a histo infxn?variable depending on body system involved, but you should DO A SMEAR TO SEE IF YOU CAN FIND IT
what will you find on a chem panel for a cat or dog infected with histoplasma?Hypoalbuminemia and Hypercalcemia (granulomatous inflammation= hypercal, and hypoalb i can think of bc you can see it on a blood smear and alb is in the blood)
is serology useful for detecting histo? culture?no...not really... and culture rarely needed
what are the two definitive ways to dx histoplasmosis?(1) Organism identification- Cytology**(LARGE BOWEL= DO RECTAL SCRAPE), histolog (2) Antigen testing (mira vista labs)
which drug do you use to treat histoplasmosis? for how long?Itraconazole for 4-6mo, until resolution of clinical signs
how can you provide supportive care for the GI symptoms associated with histo?(remember GI= dog) provide Proper nutrition with a highly digestible diet +/- fiber, +/- anti-diarrheals. Possible ARE/SIBO tx (see other card)
what other treatment can you use to try to help with the GI symptoms of histo?ARE/SIBO tx aka antibiotic responsive entropathy/small intestinal bactrial overgrowth treatments to try to help
if there are resp symptoms with histoplasmosis, what can you provide for supportive care? provide O2 and Bronchodilators