Exam 5: Fungal Infections + Antifungal Agents Flashcards by TheOneandOnly Ash

What are some important characteristics of candida infections?

-Part of normal flora
-Cause mild infections (oropharyngeal or esophageal candidiasis, uncomplicated candiduria, vulvovaginal candidiasis)
-Can also cause severe disease (catheter-associated infections and disseminated disease)
*Increased mortality of empiric antifungal therapy is delayed 12 hours (needs to be caught early)

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What is aspergillus?

A mold found in the soil

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What is the most common location for aspergillus infection?

Pulmonary system

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What are some important characteristics of Aspergillus infections?

-Disease in immunocompromised patients
-Very difficult to treat

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What are the endemic fungi pathogens?

Histoplasma capsulatum
Blastomyces species
Coccidioides species

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Which 2 endemic fungi pathogens are found in Indiana?

Histoplasma capsulatum
Blastomyces species

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What is the most common crytpococcus species found in the US?

Cryptococcus neoformans

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What is cryptococcus and where does it primarily affect in the body?

Encapsulated yeast

Primarily effects the CNS

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What organisms is Amphotericin B first line for?

Cryptococcus
Blastomyces
Histoplasma
Mucor

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Amphotericin B is commonly used as the first-line agent for what kind of fungal infections?

Systemic Invasive

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What are some facts about Amphotericin B?

Poorly absorbed, requires IV

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What is the dosing of the different forms of Amphotericin B?

Deoxycholate: 0.5-1 mg/kg/day

Liposomal: 3-5 mg/kg/day

Lipid: 5 mg/kg/day

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What are the side effects of Amphotericin B?

“Amphoterrible”

Infusion related reaction
-pretreat with acetaminophen or antihistamines

NEPHROTOXICITY
-Increase in Scr and BUN
-prevent with fluids

Electrolyte abnormalities
-Hypokalemia
-Hypomagnesemia

Anemia

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What are some fast facts about flucytosine?

Great bioavailability

Penetrates into CSF

Primarily excreted unchanged in the urine

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What is the main use of Flucytosine?

Combo therapy with AmphoB for Cryptococcal meningitis

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What is Flucytosine used 1st line for?

Cryptococcus

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What are the main adverse effects of Flucytosine?

Hematologic
-Bone Marrow Suppression

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What do we need to monitor with Flucytosine therapy?

CBC
Platelets
SCr
BUN

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Which azole drug is not renally dose adjusted?

Ketoconazole

*metabolized by the liver

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How is the clinical use of ketoconazole limited?

NEVER be used orally for first-line therapy

-due to hepatotoxicity and endocrine side effects

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What are some important characteristics of Fluconazole?

Good bioavailability

Decent CSF concentration

Excreted unchanged in the urine
-Dose reduce in renal insufficiency

DOSE BASED ON TOTAL BODY WEIGHT

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What is Fluconazole first line for?

Invasive candidiasis

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What is the dosing of Fluconazole for Invasive candidiasis?

C albicans: 800 mg (12 mg/kg) loading dose, then 400 mg (6 mg/kg) daily

C. glabrata: 800 mg daily (loading dose 1200-1600) -dependent on susceptibility

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What phases of Cryptococcal Meningitis is fluconazole used in?

Consolidation
Maintenance

*not induction because it is inferior to Amphotericin B + Flucytosine

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What is the main adverse effect of Fluconazole?

QTc Prolongation

Fluconazole is a 1st line agent for which pathogens?

Candida albicans Candida parappsilosis Candida tropicalis Candida lustitaniae Coccidioides

Itraconazole is predominately metabolized by what?

CYP450 3A4 isoenzyme (inhibitor)

What is the active metabolite of Itraconazole?

Hydroxyitraconazole

What is an important fact about Itraconazole metabolism?

Clearance decreases with higher doses due to saturable hepatic metabolism

What is an important fact about Itraconazole absorption?

Dependent on gastric acidity -capsules are better absorbed with food intake Oral solution is better absorbed in fasting state and not affected by gastric acidity

What is Itraconazole first-line for?

Histoplasmosis Blastomycosis

What is the dosing of Itraconazole for Histoplasmosis?

200 mg PO TID x 3 days, then 200 mg PO BID

What are the main adverse effects of Itraconazole?

Hepatotoxicity Congestive heart failure (BOXED WARNING) QTc Prolongation

What monitoring must be done with Itraconazole therapy?

Drug monitoring

What serum trough concentration do we want Itraconazole to be at?

>0.5-1

What are some important facts about Posaconazole?

Absorption is affected by gastric pH -absorption decreases with PPIs

When do we absolutely want to avoid Posaconazole?

CrCl < 50

What is the main adverse effect of Posaconazole?

QTc Prolongation

What is Posaconazole first-line for?

Nothing -used as primary prophylaxis

What are some important facts about Voriconazole?

Significantly metabolized by CYP450 isoenzymes (2C19, 2C9, 3A4) No renal adjustment needed for oral dosing Absorption is not affected by H2 antagonists, PPIs, or antacids

When should we absolutely avoid IV Voriconazole?

CrCl < 50

What is the primary clinical use of Voriconazole?

Invasive aspergillosis

What are the adverse effects of Voriconazole?

Visual Disturbances Elevated liver function tests QTc Prolongation Phototoxic Skin Reactions Diffuse, painful periostitis (from excess fluoride found in the Voriconazole)

What is the clinical use of Isavuconazole?

Last Line Therapy

What is an important fact to remember about Isavuconazole adverse effects?

*It does NOT cause QTc prolongation (can actually shorten it) -use this in patients with prolonged QTc who are not tolerating other azoles

Which of the azoles has the least drug interactions?

Isavuconazole

The Echinocandins are first-line for what organisms?

C. glabrata C. krusei C. lusitaniae C. auris

What is the main clinical use of Caspofungin (Echinocandin)?

Candidemia

What are the side effects of Caspofungin?

Histamine-mediated symptoms* Fever Phlebitis at injection site N/V Headache *not used much because of SE

What are some important points to remember about Micafungin?

Given IV No dosage adjustment needed for renal dysfunction Not metabolized via CYP450

What is the main clinical use of Micafungin?

Candidemia

What are the side effects of Micafungin?

Hyperbilirubinemia Nausea Diarrhea Eosinophilia Rash, Pruritis, Urticaria

What are some important facts about Ibrexafungerp?

New antifungal agent Dependent on gastric acid Better absorbed with food Does not penetrate CNS

What is the clinical use of Ibrexafungerp?

*Vulvovaginal candidiasis is its only indication *extremely expensive drug so not routinely used

What must we check before initiating Ibrexafungerp?

Pregnancy status -contraindicated in pregnancy -use contraception during and for 4 days after treatment

What is the primary line of host defense against superficial Candida infections?

Cell-mediated immunity

How long is Oropharyngeal Candidiasis treated?

7-14 days

What is the preferred therapy for mild Oropharyngeal Candidiasis?

Topical Agents: Clotrimazole Nystatin Miconazole Fluconazole 100-200 mg daily

How do we adjust treatment of Refractory Oropharyngeal Candidiasis?

Treat >/= 14 days Use Itraconazole solution 200 mg daily for more broad coverage

What is our treatment regimen for Esophageal candidiasis?

Treat for 14-21 days Systemic therapy is required! Fluconazole 200-400 mg PO/IV daily (higher dose)

What is uncomplicated vulvovaginal candidiasis?

Sporadic infection that is susceptible to all forms of antifungal therapy regardless of duration

What is complicated vulvovaginal candidiasis?

Recurrent Severe disease Non-candida albicans infections Additional host factors (DM, immunosuppressed, pregnancy)

What is the main therapy for Uncomplicated vulvovaginal candidiasis?

OTC Topical agents Topical azole depending on patient's preference for dosage form

What is an important counseling point for topical azoles used for vulvovaginal candidiasis?

Can decrease the efficacy of latex condoms and diaphragms

What prescription product is commonly used for vulvovaginal candidiasis?

Fluconazole 150 mg tablet, 1 tablet po once

What are the symptoms of a candidiasis infection (not oropharyngeal)?

Fever Tachycardia Tachypnea Chills Hypotension

What is the preferred drug class for initial candidemia therapy (species not known)?

Echinocandins -Micafungin -Caspofungin -Anidulafungin

What is the preferred agent for targeted candidiasis therapy?

Fluconazole

What are the requirements to switch from IV to PO therapy for candidiasis infections?

Need susceptibilities Clinically stable Repeat negative blood cultures Been on appropriate therapy for 2 days Need to choose the most narrow spectrum agent

How long do we treat candidiasis infections?

14 days after first negative blood culture

What is our preferred therapy for Candidemia in neutropenic (immunocompromised) patients?

*Require broader therapy Echinocandin as initial therapy -Caspofungin Micafungin Anidulafungin Lipid form of Amphotericin B 3-5 mg/kg/day

What is the preferred therapy for C. albicans?

Fluconazole

What is the preferred therapy for C. glabrata?

Echinocandin

What are the preferred agents for C. parapsilosis?

Fluconazole Amphotericin

What is the preferred agent for C. tropicalis?

Fluconazole

What are the preferred agents for C. krusei?

Voriconaole Echinocandins Amphotericin

What are the preferred agents for C. lusitaniae?

Fluconazole Echinocandins

What is the preferred agent for C. auris?

Echinocandins

How are Histoplasmosis infections spread?

Chicken coops Inhalation of dust-borne pathogens

What is the presentation of disseminated histoplasmosis?

Fever, Chills, Fatigue, Weight loss, Night Sweats, Hepatosplenomegaly, Cough, Chest Pain, Dyspnea

What are the symptoms of CNS histoplasmosis?

Fever Headache Seizure Mental Status Changes

What is the treatment for Acute pulmonary histoplasmosis in an immunocompetent host?

Acute or Mild-Moderate Disease with symptoms < 4 weeks: No therapy needed Mild-Moderate Disease with symptoms > 4 weeks: Itraconazole 200 mg TID x 3 days, then 200 mg QD or BID for 6-12 weeks Severe: Lipid Amphotericin then Itraconazole for total of 12 weeks

What is the treatment for Disseminated Histoplasmosis in an immunocompromised host?

Lipid Amphotericin B 1-2 wks Then Itraconazole for 12 months

Blastomycosis has a high incidence of cross-reactivity with what other infection?

Histoplasmosis

What is the treatment for mild-moderate Blastomycosis?

Itraconazole

What is the treatment for Severe Blastomycosis?

Lipid Amphotericin B followed by Itraconazole

What is the treatment for Blastomycosis in the CNS?

Itraconazole

How long do we treat Blastomycosis?

12 months

What is the main therapy for Coccidioidomycosis infections?

Nothing, most patients do not need treatment

Who should we treat for Coccidioidomycosis infection?

Patients with: -Weight Loss > 10% -Intense night sweats for > 3 weeks -Infiltrates involving over half one lung or parts of both lungs -Antibody titers > 1:16 -Inability to work (extreme fatigue) for > 2 months

What is the treatment for a Coccidioidomycosis infection?

Primary Respiratory infection: -Fluconazole 400-800 mg PO/IV for 3-6 months Symptomatic Chronic Cavitary Pneumonia: -Fluconazole 400-800 mg PO/IV daily for 12 months Diffuse pneumonia with bilateral or miliary infiltrates: -Treat for 12 months

What is the therapy for Meningeal Coccidioidomycosis disease?

Fluconazole 400-1200 mg IV/PO daily

What is the most common form of cryptococcus in the US?

Cryptococcus neoformans

What is the clinical presentation of Cryptococcosis?

Pulmonary -rales, cough, SOB Meningitis

How do we diagnose Cryptococcosis?

*Lumbar Puncture* -for meningitis

What is the Induction therapy for a host with Cryptococcal Meningitis?

Amphotericin B + Flucytosine *4 weeks

What is the Consolidation therapy for a host with Cryptococcal Meningitis?

Fluconazole *8 weeks

What is the Maintenance therapy for a host with Cryptococcal Meningitis?

Fluconazole *6-12 months

What is the drug of choice for Invasive Pulmonary Aspergillosis?

Voriconazole

How long do we treat invasive pulmonary aspergillosis?

6-12 weeks

What is the main agent used for Aspergillosis prophylaxis?

Posaconazole

Exam 5: Fungal Infections + Antifungal Agents Flashcards

(102 cards)