Antifungal Agents Part 2

Question 1

What is the spectrum of activity of echinocandins?

Answer 1

1st line: C. glabrata, C. krusei, C. lusitaniae, C. auris
C. albicans, C. tropicalis
may add micafungin to voriconazole in severe aspergillus infections

Question 2

Caspofungin

Answer 2

poor oral bioavailability - administered by IV infusion
no dosage adjustment for renal insufficiency or mild hepatic impairment

Question 3

What is the clinical use of caspofungin?

Answer 3

candidemia - 70mg loading dose on day 1, then 50mg q24h

Question 4

What are the adverse effects of caspofungin?

Answer 4

histamine-mediated symptoms - rash, facial swelling, pruritus, flushing
fever
phlebitis at infusion site
N/V, HA

Question 5

Micafungin

Answer 5

not absorbed orally - give IV
no dosage adjustment for renal dysfunction
drug interactions - not metabolized via CYP450 pathways

Question 6

What is the clinical use of micafungin?

Answer 6

candidemia - 100 mg daily

Question 7

What are the adverse effects of micafungin?

Answer 7

hyperbilirubinemia, N/D, eosinophilia, rash, pruritis, urticarial

Question 8

Anidulafungin

Answer 8

not absorbed orally - must be administered IV
not metabolized or renally eliminated –> undergoes slow chemical degradation
no dosage adjustments required for renal or hepatic dysfunction

Question 9

What are the adverse effects of anidulafungin?

Answer 9

histamine-mediated symptoms - rash, urticaria, flushing, pruritis, hypotension
diarrhea, increased LFTs, hypokalemia

Question 10

Rezafungin

Answer 10

long-acting echinocandin
no adjustments in renal or hepatic dysfunction
approved for candidemia and invasive candidiasis

Question 11

What are the adverse effects of rezafungin?

Answer 11

hypokalemia, diarrhea, fever

Question 12

Ibrexafungerp

Answer 12

new antifungal!
similar to echinocandins, through structurally different
available orally; bioavailability dependent on gastric acid
better absorbed with food
does not penetrate CNS

Question 13

What is the spectrum of activity of ibrexafungerp?

Answer 13

candida species, aspergillus species, pneumocystis
not active against mucor, fusarium, cryptococcus, histoplasmosis, blastomyces

Question 14

What is the clininical use of ibrexafungerp?

Answer 14

vulvovaginal candidiasis, recurrent also
contraindicated in pregnancy!! - use effective contraception during and for 4 days after treatment

Question 15

What are the adverse effects of ibrexafungerp?

Answer 15

N/V/D, abdominal pain, dizziness, does NOT cause QT prolongation

Question 16

What is the DOC for C. albicans?

Answer 16

fluconazole

Question 17

What is the DOC for C. glabrata?

Answer 17

echinocandins

Question 18

What is the DOC for C. parapsilosis?

Answer 18

fluconazole

Question 19

What is the DOC of C. tropicalis?

Answer 19

fluconazole

Question 20

What is the DOC of C. krusei?

Answer 20

echinocandins

Question 21

What is the DOC of C. lusitaniae?

Answer 21

fluconazole, echinocandins

Question 22

What is the DOC of C. auris?

Answer 22

echinocandins

Question 23

What is the DOC of cryptococcus?

Answer 23

fluconazole, amphotericin, flucytosine

Question 24

What is the DOC of blastomyces?

Answer 24

itraconazole

Question 25

What is the DOC of histoplasma?

Answer 25

itraconazole

Question 26

What is the DOC of coccidioides?

Answer 26

fluconazole

Question 27

What is the DOC of aspergillus?

Answer 27

voriconazole

Question 28

What is the DOC of mucor?

Answer 28

amphotericin

Question 29

What the oropharyngeal candidiasis?

Answer 29

infection of the oral mucosa with candida species most common opportunistic infection in people living with HIV

Question 30

What is esophageal candidiasis?

Answer 30

infection of the esophagus with candida species

Question 31

Oropharyngeal and esophageal candidiasis primary line of host defenses against superficial candida infections is what?

Answer 31

cell-mediated immunity (mediated by CD4 Tcells) prevalence of EC increased secondary to HIV and other severely immunocompromised pts

Question 32

What are the local risk factors for oropharyngeal and esophageal candidiasis?

Answer 32

use of inhaled steroids and antibiotics; dentures; xerostomia due to drugs, chemo, HSCT, radiotherapy to head/neck; smoking; disruption of oral mucosa caused by chemo and radiotherapy, ulcers, endotracheal intubation, trauma, burns

Question 33

What are the systemic factors for oropharyngeal and esophageal candidiasis?

Answer 33

drugs (cytotoxic agents, corticosteroids, immunosuppressants after organ transplantation, PPIs) neonates or elderly; HIV infection/AIDS (depletion of CD4, HIV viral load); diabetes; malignancies; nutritional deficiencies

Question 34

What is the clinical presentation of esophageal candidiasis?

Answer 34

dysphagia, odynophagia, and retrosternal chest pain; fever; plaques can be hyperemic or edematous with ulceration to diagnose: upper GI endoscopy with biopsy

Question 35

What is the treatment for oropharyngeal candidiasis?

Answer 35

treat for 7-14 days topical therapy for mild infection: clotrimazole 10mg troche 5x/day nystatin 100,000units/mL suspension, 5mL swish and swallow QID miconazole 50mg mucoadhesive buccal tablet, apply to upper gum region daily x7-14 days

Question 36

What is systemic treatment for oropharyngeal candidiasis?

Answer 36

fluconazole 100-200mg daily

Question 37

What is treatment for fluconazole reffractory OPC?

Answer 37

treat for >/=14 days (up to 28 days) itraconazole solution 200mg daily

Question 38

What is the treatment for esophageal candidiasis?

Answer 38

treat for 14-21 days systemic therapy always required!! fluconazole 200-400mg PO/IV daily itraconazole solution 200mg PO daily

Question 39

What is the treatment for EC fluconazole refractory?

Answer 39

treat for 21-28 days itraconazole solution 200mg PO daily

Question 40

What is vulvovaginal candidiasis?

Answer 40

infection in women with or w/o sx who have positive vaginal cultures for candida species (C. albicans) uncomplicated: sporadic infection that is susceptible to all forms of antifungal therapy regardless of treatment duration complicated: recurrent VVC, severe disease, non-candida albicans infection, host factors (DM, immunosuppression, pregnancy)

Question 41

What increases the risk of vulvovaginal candidiasis?

Answer 41

sexually active; oral-genital contact increases risk; contraceptive agents; antibiotic use!!; post-menopausal women taking HRT no established association with diet, douching, or tight-fitting clothing

Question 42

Vulvovaginal candidiasis - topical agents

Answer 42

uncomplicated VVC: cure rates 80-95% with topical or oral azoles, 70-90% with nystatin topical preparations can decrease efficacy of latex condoms and diaphragms

Question 43

What is the treatment for VVC? - OTC/topical

Answer 43

butoconazole 2% cream clotrimazole miconazole tioconazole

Question 44

What is the treatment for VVC? - prescription

Answer 44

prescription/topical: nystatin 100,000 units tab; terconazole cream or suppository prescription/oral: fluconazole 150mg tab, 1 tab PO x 1 day!!