ID: Antifungals/Antivirals/OIs

Yeast examples

candida species

• c. albicans

• c. tropicalis

• c. parapsilosis

• c. glabrata

• c. krusei

cryptococcus neoformans

Mold examples

aspergillus species

zygomycetes (mucor and rhizopus species)

Dimorphic fungi examples

histoplasma capsulatum

blastomyces dermatitidis

coccidiodes immitis

amphotericin MOA

binds to ergosterol, alters cell membrane permeability and cell death

what is the spectrum of coverage for amphoB

broad-spectrum

what is amphoB active against?

• yeasts: most candida species and Cryptococcus neoformans

• molds: Aspergillus and zygomycetes

• dimorphic: all 3

diff between amphob deoxycholate and lipid formulations

deoxycholate: conventional formulation; many toxicities

lipid: active and lipid component; fewer toxicities (decreased inf rxns, decreased nephrotoxocity)

2 lipid formulations of amphotericin

Abelcet (amphotericin B lipid complex) 5mg/kg/d

AmBisome (liposomal amphotericin B 3-6 mg/kg/d

boxed warning of amphoB

medication errors have led to cardiopulmonary arrest

max dose of conventional amphoB

should not exceed 1.5/mg/kg/d

side effects of amphoB

• infused-related: fever, chills, HA, malaise, rigors

• hypoK, hypoMg

• nephrotoxicity

what liquid is amphoB only compatible with?

NS

which amphoB requires premedication?

deoxycholate

• APAP or NSAID

• diphenhydramine and/or hydrocortisone

what type of formulation of amphoB requires filter during preparation?

lipid formulations

flucytosine MOA

penetrates fungal cells and is converted to fluorouracil and interferes with fungal RNA and protein synthesis

can flucytosine be used alone?

NO

• development of resistance

what med should flucytosine be used in combo with?

amphoB for the treatment of invasive cryptococcal (meningitis) or candida infections

side effect of flucytosine

myelosuppression

azoles MOA

decrease ergosterol synthesis

azoles main inhibition

CYP3A4 inhibition

what doesn’t fluconazole cover?

• C. glabrata

• C. krusei

• molds are resistance!

covers: C. albicans, parapsilosis, tropicalis, cryptococcus and coccidioides

what does itraconazole cover?

dimorphic (blastomycoses and histoplasma)

what bug is voriconazole the DOC for?

Aspergillus

Class side effect of azoles (3)

• inc LFTs

• QT prolongation (except isavuconazole)

• many drug interactions

which is the only azole that requires renal dose adj?

fluconazole

which azole has led to hepatotoxicity to liver txp?

ketoconazole

which azole can cause HF?

itraconazole

which azole causes visual changes, phototoxicity, and hallucinations?

voriconazole

posaconazole counseling

• tablet dose does NOT equal suspension dose (diff bioavailability)

• take with food!

IV:PO of azoles

1:1

which azoles have SBECD vehicle?

voriconazole

posaconazole

• can accumulate in renal dysfx CrCl<50

fluconazole dose for vaginal candidiasis

150mg PO x 1

what formulation of itraconazole is better absorbed?

oral solution

(Sporanox, Tolsura)

which azole is available OTC?

Nizoral A-D shampoo

are all azoles hepatically cleared?

NO

• fluconazole is renally cleared

which azoles (2) penetrate the CNS?

• fluconazole

• voriconazole

treats fungal meningitis

ketoconazole boxed warning

hepatotoxic

QT prolongation

use PO tablets when other antifungal therapy is unavailable or not tolerated

which azole causes QT shortening?

isavuconazole

which azole should be taken on an empty stomach?

voriconazole

which azole requires a filter during administration IV?

isavuconazole

which azoles (2) inhibit CYP2C9?

fluconazole

voriconazole

• increase effects of warfarin (monitor INR)

what meds can decrease the absorption of posaconazole solution?

PPIs

cimetidine

what azoles require acidic gut for absorption?

• itraconazole capsules

• fluconazole

if PPIs or H2RAs are needed, take with an acidic beverage (non-diet cola)

what azole can dangerously increase with small dose increases (1st order kinetics)?

voriconazole

echinocandins MOA

inhibit the synthesis of beta (1,3)-D-glucan

• essential part of fungal cell wall

echinocandins activity

effective aginst most Candida species

• C. glabrate and C. krusei

should be used in combo for Aspergillus

only route for echinocandins

IV only

2 echinocandins (brand/generic)

Caspofungin (Cancidas)

Micafungin (Mycamine)

what 2 disease states is micafungin used for?

candidemia

esophageal candidiasis

T/F: all echinocandins are given once daily except rezafungin

TRUE

do echinocandins require renal dose adjustments?

NO

which echinocandin requires light protection during admin?

micafungin

Nystatin formulations (2)

suspension

tablet

what is nystatin used for (2)

oral candidiasis

intestinal infections

nystatin counseling

• suspension: swish in the mouth and retain for as long as possible (several minutes) before swallowing

what is griseofulvin indicated for?

fungal infections of the skin, hair, nails

what is griseofulvin contraindicated in?

pregnancy

side effects of griseofulvin

photosensitivity

inc LFT

griseofulvin counseling

take with a fatty meal to inc absorption or with food/milk to avoid GI upset

terbinafine notes

topical cream: Lamisil AT OTC

warnings: hepatotoxic

side effects: headahce, inc LFTs

clotrimazole formulations

10 mg troche/lozenge for oropharyngeal candidiasis

what antifungals are for mild oropharyngeal candidiasis? (candida albicans)

• miconazole

• clotrimazole

what antifungal is for severe oropharyngeal infection (thrush) (candida albicans)

fluconazole

preferred tx and alternative for candida albicans esophageal infection

preferred: fluconazole

alternative: echinocandin

preferred tx and alternative for candida krusei and glabrata (more resistant to azoles)

• all candida species blood stream infections

preferred: echinocandin

alternative: amphoB, high dose fluconazole (susceptible isolates only)

preferred tx and alternative for aspergillus invasive

preferred: voriconazole

alternative: isavuconazole + amphoB

preferred tx and alternative for cryptococcus neoformans meningitis?

preferred: amphoB + 5-FC

alternative: high dose fluconazole + 5-FC

preferred tx and alternative for dermatophytes nail bed infection

preferred: terbinafine or itraconazole

alternative: fluconazole

should itraconazole solution be taken with food?

NO, empty stomach!

should posaconazole tablets/suspension be taken with food?

YES

ages for influenza vaccine

≥6 months of age

neuraminidase inhibitors MOA (oseltamivir)

reduce the amount of virus in body by inhibiting enzyme which enables release of new viral particles

neuraminidase inhibitors are active against?

influenza A and B

what can neuraminidase inhibitors help with in flu?

decrease duration of symptoms by 1 day and reduce complications

when should neuraminidase inhibitors be given to be effective?

start within 48 hrs of illness

what is baloxavir marboxil used for?

endonuclease inhibitor: treatment and post-exposure prevention of influenza

single-dose regimen

oseltamivir (Tamiflu) dosing for flu treatment >12 yrs

75mg PO BID x 5 days

oseltamivir doing for ppx flu >12 yrs

75 mg PO daily x 10 days

how is oseltamivir dosed in pediatrics?

body weight

warnings/side effects of oseltamivir

warning: neuropsychiatric events

side effects: head ache, nausea/vomiting

Zanamivir (Relenza Diskhaler) notes

• treatment age ≥7 yrs (inhalation)

• ppx age ≥5 yrs

• warning: neuropsychatric, bronchospasm (avoid in COPD/asthma)

Peramivir (Rapivab) route

treatment for influezna in adults: IV

how many doses is baloxavir marboxil (Xofluza) in treatment and ppx?

1 dose

preferred outpatient treatment in COVID-19

nirmatrelvir/ritonavir (Paxlovid)

HSV-1 is most commonly associated with:

oropharyngeal disease

HSV-2 is most commonly associated with:

genital disease

3 antivirals for HSV and VZV?

1. acyclovir (Zovirax)

2. valcyclovir (Valtrex) - prodrug of acyclovir

3. famciclovir (prodrug of pinciclovir)

warnings of antivirals (-clovir)

• warnings

  • caution in renal impairment, elderly, and receiving nephrotoxic drugs

Acyclovir IV dosing should NOT use what weight?

do NOT use TBW in obese patients; use IBW or adjBW (if BMI >40) due to increased toxicity

when is the optimal time to take medication for herpes simplex labialis (cold sores)

during the prodrome period (sx that occur before lesions appear) of tingling, itching, soreness

what 2 antiviral topics are used for herpes labialis?

1. dosocanol (Abreva) OTC

2. acyclovir (Zovirax)

dosing for dosocanol for herpes labialis

apply 5x daily at first sign of outbreak, continue until healed

dosing for acyclovir cream for herpes labialis

apply 5 times daily for 4 days (can be used on genital sores)

gential herpes lesions

begin as papules or vesicles that rapidly spread

when should treatment be started for genital herpes

should be initiated during the prodrome period or within one day of lesion onset

acyclovir vs valacyclovir dosing

acyclovir

• dosed more frequently

valacyclovir

• prodrug of acyclovir

• can reach higher concentrations

• less frequent dosing can enhance adherence

bug/drug of viral encephalitis

bug: HSV

drug: IV acyclovir 10mg/kg/dose x Q8hr x 14-21 days

shingles rash description

itchy or tingly

painful

manifests unilaterally

cluster of fluid-filled blisters, often in a band

when should tx be started for HZV

within 72 hours of onset of zoster rash

how can pain be managed in HZV?

• topical medications

  • lidocaine patch, gel

• neuropathic medications

  • pregabalin

  • gabapentin

  • duloxetine

  • TCAs

• NSAIDs

• Opioids