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Therapeutics 3 > Fungal Infections > Flashcards

Fungal Infections Flashcards

1
Q

What organisms can cause primary disease?

A
  • histoplasma capsulatam
  • blastomyces dermatitdis
  • coccidiodes immitis

endemic fungi, found in the soil

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2
Q

What organisms can cause secondary disease?

oppurtunistic infection, found in immunocompromised patients

A
  • candida spp.
  • aspergillus spp.
  • zygomycetes
  • fusarium spp.
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3
Q

What is the most common fungal pathogen found in tyhe ICU setting?

A

candida albicans

followed by candida glabrata

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4
Q

What is unique about the transmission of candida auris?

A

person to person transmission can occur

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5
Q

What is the preferred treatment for candida auris?

A

echinocandins

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6
Q

What is the diagnostic test for fungal infections?

A

1, 3 beta-D-glucan (BDG), primary component of most fungal cell walls

not specific, but negatives can rule out fungal infection

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7
Q

What is the candida score?

A

assists in diagnostic, candida score > 3 along with postive BDG suggests fungal infection
score is based on points:
- miltifocal colonization= 1 point
- surgery= 1 point
- parenteral nutrition= 1 point
- severe sepsis= 2 points

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8
Q

What is the primary treatment for invasive candida infection?

A

AZOLE ANTIFUNGALS
- imidazole= ketoconazole
- triazoles= fluconazole, itraconazole, voriconazole, posaconazole
- tetrazoles= oteseconazole

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9
Q

Which antifungals cause QTc prolongation?

A

azole antifungals

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10
Q

Which azole antifungal has the largest interaction with 2C9?

A

fluconazole

interacts with warfarin

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11
Q

What are the dosage forms of ketoconazole?

A

ketoconazole

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12
Q

What is the indication of fluconazole?

A
  • any candida infection, except C. auris, C. krusei, and C. glabrata
  • cryptococcal meningitis
  • prophylaxis of candida infection in high risk patients
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13
Q

Describe the absorption of fluconazole:

A

> 90% bioavaliability

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14
Q

Descibe the distribution of fluconazole:

A

good CNS penetration

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15
Q

How is fluconazole metabolized?

A

significant inhibitor of CYP2C9 (warfarin is highly affected), but 70% is excreted unchanged renally (renal adjustments required)

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16
Q

What is dosing of fluconazole?

A

systemic infection= 400mg+ IV/PO daily, therapeutic drug monitoring (TDM) needed, but TDM not needed for topical/local infections with dosing < 400mg

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17
Q

What drugs are echinocandins?

A
  • caspofungin
  • micafungin
  • anidulafungin
  • rezafungin
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18
Q

Describe the distribution of echinocandins:

A

large molecules, do NOT penetrate the CNS

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19
Q

What are the dosage forms of Echinocandins?

A

IV only

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20
Q

What is the dosing of Caspofungin?

A

loading dose of 70mg, MD of 50mg daily

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21
Q

What is the dosing of Micafungin?

A

100mg daily for candida or 150mg daily for aspergillus

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22
Q

What is the dosing of Anidulafungin?

A

loading dose of 200mg, MD of 100mg daily

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23
Q

What is the dosing of Rezafungin?

A

loading dose of 400mg, MD 200mg weekly

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24
Q

Which enchiocandin is associated with infusion-related reactions?

A

rezafungin

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25
Q

Which echinocandin can only be infused in the central line?

A

caspofungin

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26
Q

What is the indication of echinocandins?

A

all candida, including C. glabrata, C. krusei, and C. auris (drug of choice) and aspergillus (in combo with azoles)

no activity against cryptococcus or endemic fungi

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27
Q

What are echinocandins place in therapy?

A
  • candidemia and ivasive candida infection
  • preferred empiric treatment in immunocompromised patients
  • C. auris infections
  • esophageal candiditis
  • invasive aspergillosis in combo with azoles, monotherapy ok if intolerant to all other treatments
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28
Q

When may echinocandins be preferred over fluconazole for empiric treatment?

A
  • immunosuppressed patients
  • clinically unstable, ICU, or septic patients
  • history of C. glabrata, C. krusei, or C. auris
  • concurrent or extensive history of fluconazole use
  • high rate of C. glabrata at your site
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29
Q

At what site would you not treat a fungal infection?

A

urine/pneumonia

30
Q

Describe how aspergillus can take hold?

A

immunocompromised patients that have t-cell and b-cell dysfunction contributes to active disease which can be triggered by drugs such as: alemtuzumab, TNF-alpha inhibitors and more

31
Q

How is aspergillus diagnosed?

A

BOTH
- compatible host factors (immunocompromised)
- clincal and/or radiographic findings
PLUS
- proven culture
- probable bug through antigen
- possible infection (no direct testing results)

32
Q

What is the antigen test for aspergillus?

A

galactomannan (GM)

33
Q

What is the primary treatment for aspergillus?

A
  1. voriconazole, isavuconazole or posaconazole
  2. azole + echinocandins
  3. amphotericin B
34
Q

What is the place in therapy of voriconazole?

A

invasive aspergillus

35
Q

Describe the absorption of voriconazole:

A

food decrease bioavaliability, seperate dosing with meals

36
Q

Describe the distribution of voriconazole:

A

~ 50% CNS penetration and good ocular penetration

37
Q

Describe the metabolism of voriconazole:

A

inhibit CYP2C19, 3A4, and 2C9- interactions with warfarin, phenytoin, and sulfonylureas

38
Q

What are the adverse effects of voriconazole?

A
  • CNS/visual disturbances (associated with trough/Cmin > 5.5 mg/L
  • liver enzyme elevations
  • bone pain (periostitis) with prolonged therapy
  • rash and photopsia
39
Q

Describe the dosing of voriconazole:

A

weight based IV dosing using adjBW

40
Q

What is the goal trough for voriconazole?

A

1-5.5 mg/L

41
Q

What is unique about the IV formulation of voriconazole?

A

contains beta-cyclodextrin solubilizer (SCEBD) which accumulates in the kidneys, caution in patients with CrCl < 50mL/min and is not recommended for CrCl < 30, but is removed in HD

42
Q

What is the primary use of isavuconazole?

A

invasive aspirgillus and zygomycosis

43
Q

What are the adverse drug effects of isavuconazole?

A
  • N/V/D, rash, headache, and peripheral edema
  • AST/ALT elevations
  • infusion related reactions (respiratory distress, dyspnea, and hypotension)
  • QT shortening (unlike other azoles which prolong)
44
Q

What is the dosing of isavuconazole?

A

loading dose 200mg IV/PO q8h for 2 days then 200mg IV/PO daily

IV formulation needs in-line filter

45
Q

What is the primary role of posaconazole?

A
  • prophylaxis to decrease risk of candida and aspergillus
  • invasive aspergillosis
  • zygomycoses infections
46
Q

Describe the distribution of posaconazole:

A

large Vd but limited CNS penetration due to P-gp substrate which becomes pumped out of the CNS

47
Q

Describe the metabolism of Posaconazole:

A

primarly metabolized by UGT and to a lesser extent CYP3A4 (strong inhibitor)

48
Q

When is therapeutic drug monitoring (TDM) be recommended for posaconazole?

A

oral suspension due to low and variable bioavaliability, but not commonly used for delayed release or IV formulations

49
Q

How is the oral suspension of posaconazole dosed?

A

200mg TID or 400mg BID, doses > 800mg do not produce any greater effect due to “ceiling effect”, must be administered with food (high fat meal) to increase AUC

50
Q

What are the dosage forms of amphotericin B?

A
  • conventional amphotericin B= amphotericin B deoxycholate (CAmB)
  • lipid formulations= amphotericin B lipid complex (ABLC), liposomal amphotericin B (L-AMB)
51
Q

What is the place in therapy of amphotericin B?

A

aspergillosis and zygomycetes, not recommended for candida

52
Q

What is the dosing of amphotericin B?

A
  • CAmB: 1-1.5 mg/kg/day (rarely exceeds 100mg/dose)
  • LF-AmB: 3-5mg/kg/day (doses almost always exceed 200mg/dose)
53
Q

Which dosage form of amphotericin B is safer?

54
Q

What are the adverse effects of conventional amphotericin B (CAmB)?

A
  • infusion related= fevers, chills, rigors, hypotension, arrhythmias, thrombophlebitis, headache
  • nephrotoxicity
  • hypokalemia
  • hypomagnesium
  • hypophosphatemia
  • hyponatremia
  • anemia
  • LFT elevation
55
Q

What drugs can be given prophylatically for infusion related reactions due to conventional amphotericin B (CAmB)?

A
  • fever= acetominophen
  • rigors= meperidine
  • hypotension= corticosteroids

all given 30 minutes prior to infusion

56
Q

What can be given prophylactically for nephrotoxicity due to coventional amphotericin B (CAmB)?

A

hydration and electrolyte replacement

57
Q

What are the monitoring parameters for coventional amphotericin B (CAmB)?

A
  • blood pressure, HR/rythmn, vitals, infusion rate
  • SCr
  • electrolytes (K, Mg, PO3)
  • liver function tests
  • hemoglobin and hematocrit
58
Q

How is histoplasmosis diagnosed?

A

antibody detection or urinary antigen

59
Q

What is the treatment for mild histoplasmosis?

A

itracontrole standard 2x/day for 6-12 weeks

60
Q

What is the treatment for moderate histoplasmosis?

A

itraconazole loading dose 3x for day one then standard dosing 2x/day dosing

TDM

61
Q

What is the treatment for severe histoplasmosis?

A

-LF-AmB daily for 1-2 weeks then itraconazole loading dose 3x day for 3 days then standard 2x/day dosing for 6-18 months

TDM

62
Q

What is the treatment for mild coccidioidomycosis?

A

fluconazole 400mg daily for 3-12 months

63
Q

What is the treatment for moderate coccidioidomycosis?

A

fluconazole > 400mg/day

64
Q

What is the treatment for severe coccidoioidomycosis?

A

LF-AmB for 1-2 weeks then fluconazole 800-1200mg daily for at least 12 months

65
Q

How must itraconazole capsules be dosed?

A

with food or with acidic pH- caution with pt on PPIs or H2 blockers

66
Q

How must Itraconazole solution be dosed?

A

on an empty stomach

67
Q

Which formulation of itraconazole has the best bioavaliability?

68
Q

What are the treatment options for zygomycetes (mucormycosis)?

A

amphotericin or isavuconazole

69
Q

What is the treatment for cryptococcal meningitis?

A

flucytosine (5-FC) in combination with AmB

70
Q

What are the adverse drug effects of flucytosine?

A
  • GI intolerance
  • myelosuppression

Therapeutics 3 (19 decks)

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