24. Infectious Diseases III: Antifungals + Antivirals Flashcards
Zygomycetes refers to a class of fungi which includes ___ and __ species; invasive disease caused by these species is commonly referred to as “____”
Mucor
Rhizopus
Mucormycosis
Aphotericin B coverage
Broad-spectrum
Active against:
Yeasts - most Candida species and Cryptococcus neoformans
Molds - Aspergillus species and Zygomycetes
Dimorphic fungi - Histoplasma capsulatum, Blastomyces dermatitidis, and Coccidioides immitis
There are two types of Amphotericin B formulations: conventional and lipid. Which one is a/w fewer toxicities?
Lipid formulations are a/w fewer toxicities (e.g. decreased infusion reactions, decreased nephrotoxicity) compared to conventional (deoxycholate) formulations
Boxed warning for Amphotericin B
Medication errors confusing lipid (AmBisome and Abelcet) vs conventional formulation (dexoxycholate)
Conventional dose should not exceed 1.5mg/kg/day (verify product name and dose if it exceeds 1.5 mg/kg/day)
Conventional amphotericin B should NOT exceed _____mg/kg/day
1.5mg/kg/day
Side effects for amphotericin B
Infusion-related: fever chills, HA, malaise, rigors, decreased or increased bP, thrombophlebitis, N/V
Decreased K, Mg, nephrotoxicity, enamia
Ambisome: severe back/chest pain with first dose
Preparation notes for amphotericin B
Compatible with D5W ONLY
Lipid formulations must be filtered during preparation
Which amphotericin B formulation must be filtered during preparation
Lipid formulations
Which amphotericin B formulation requires premedication to reduce infusion related reactions?
Conventional (deoxycholate) formulation
What should you give as premedication before amphotericin B deoxycholate administration (30-60min before)?
APAP or NSAID
Diphenhydramine and/or hydrocortisone
NS bolus to decrease risk of nephrotoxicity
± meperidine to decrease duration of severe rigors
What color is amphotericin B (both lipid and conventional formulations)?
Yellow-orange
Amphotericin B was ordered for one of your transplant patients for fungal infection. Current med list includes tacrolimus. What is your concern with the new medication?
Additive risk of nephrotoxicity with other nephrotoxic agents like aminoglycosides, cisplatin, polymixins, cyclosporine, loop diuretics, NSAIDs, radiocontrast dye, tacrolimus, and vancomycin
Amphotericin B can increase risk of digoxin toxicity d/t ____
hypokalemia
Use caution with any agent that decreases K or Mg
MOA Flucytosine
Penetrates fungal cells and is converted to fluorouracil, which competes with uracil and interferes with fungal RNA and protein synthesis
Patient cultures were positive for Candida infection. Doctor prescribed flucytosine monotherapy regimen. What is your concern
D/t resistance, flucytosine should NOT be used alone. Recommended in combination with amphotericin B for treatment of invasive cryptococcal (e.g. meningitis) or Candida infections.
Boxed warning for flucytosine (5-FC) (Ancobon)
Use with extreme caution in pts with renal dysfunction; monitor hematologic, renal and hepatic status
Side effects for flucytosine (5-FC) (Ancobon)
Myelosuppression (anemia, neutropenia, thrombocytopenia)
Others: increased SCr, BUN, liver injury, increased bilirubin, many CNS effects, hypoglycemia, decreased K, and aplastic anemia
MOA of azole antifungals
Decrease ergosterol synthesis and cell membrane formation
Azole antifungal use is sometimes limited d/t drug interactions caused by _____
CYP450 (mainly 3A4) inhibition
Fluconazole has coverage against C. albicans, C. parapsilosis, and C. tropicalis but limited efficacy against ___ and ___ d/t resistance
C. qlabrata
C. krusei
Common uses for Fluconazole
Many infections, including yeast infections (e.g oral, esophageal, vaginal) and nail bed infections (onychomycosis)
Common uses for itraconazole
Dimorphic fungi (Blastomycoes and Histoplasma) and nail bed infections
____ is the treatment of choice for Aspergillus
Voriconazole
Fluconazole (Diflucan) dosing
50-800mg PO/IV daily
Vaginal candidiasis: 150mg PO x1
CrCl ≤50: decrease dose by 50%
Which azole antifungal requires renal dose adj?
Fluconazole
Boxed warnings for itraconazole
Can worsen or cause HF; do NOT use to treat onychomycosis in pts with ventricular dysfunction or hx of HF
Can increase plasma conc of certain drugs and lead to QT prolongation and ventricular tacharrhythmias, including TdP
Boxed warnings for Ketoconazole
Hepatotoxicity (has led to liver transplantation and/or death)
QT prolongation
Use PO tabs only when other effective antifungal therapy is unavailable or not tolerated and the benefits outweigh risks (hepatotoxicity, DDIs)
____ was the first azole antifungal, but d/t toxicities and many DDIs, it is now most often used topically
Ketoconazole
Which formulation of ketoconazole is OTC?
Nizoral A-D (topical)
Class ADE for azole antifungals
Increased LFTs
QT prolongation (Except isavuconazonium)
Many drug interactions
Others: HA, N/V, abd pain, rash/pruritus, dizziness, hair loss (or possible hair growth), altered hair texture with ketoconazole shampoo
All azoles are cleared hepatically except ____ which requires renal dose adj
fluconazole
Which azole antifungals penetrate the CNS adequately to treat fungal meningitis?
Fluconazole and voriconazole
Which azole antifungals use sulfobutyl ether beta-cyclodextrin (SBECD) vehicles and may worsen renal function in pts with eGFR <50 d/t accumulation?
(Note: PO preferred in these patients)
Voriconazole (Vfend)
Posaconazole (Noxafil)
Contraindications for voriconazole
Coadministration with barbiturates (long-acting), carbamazepine, efaviren (≥400 mg/day), ergot alkaloids, pimozide, quinidine, rifabutin, rifampin, ritonavir (≥800 mg/day), sirolimus, or St. John’s wort
Warnings for voriconazole
Hepatotoxicity
Visual disturbances (optic neuritis and papilledema)
Phototoxicity
QT prolongation (correct K, Ca, and Mg prior to initiating treatment)
Others: nephrotoxicity, avoid in pregnancy, infusion-related reactions, SJS/TEN, skeletal adverse effects (fluorosis, periostitis), pancreatitis
ADEs for voriconazole
Visual changes (~20%)
Increaed LFTs, Increased SCr, CNS toxicity (hallucinations, HA, dizziness), photosensitivity, increased/decreased K
How should Vfend be taken?
Voriconazole (Vfend) should be taken on an EMPTY stomach at least 1 hr before or after a meal; hold tube feedings for 1 hour before and after doses
Counseling points for voriconazole (Vfend)
Take on empty stomach at least 1 hr before or after meal
Use caution when driving at night d/t vision changes
Avoid direct sunlight
Suspension: shake for 10 seconds before each use; do NOT refrigerate
Which azole antifungal is the prodrug of isavuconazole
Isavuconazonium sulfate (Cresemba)
All azole antifungals affect QT. What is unique about isavuconazonium?
Causes QT shortening, not prolongation
Which azole antifungal requires a filter (0.2-1.2 micron) during administration d/t possible particulates?
isavuconazonium
All azoles are moderate-strong CYP___ inhibitors
3A4
Which azole antifungals inhibit CYP2C9? What drug are we concerned about when using these azoles?
Fluconazole and voriconazole
Warfarin - monitor INR
PPIs and cimetidine can decrease the absorption of which azole antifungal?
Posconazole suspension
Should be stopped during therapy to avoid treatment failure
Which azole antifungals require acidic gut for proper absorption?
Itraconazole (Sporanox brand capsules) and ketoconazole
Separate antacids 2 hrs before and after doses
If PPIs or H2RAs must be used while on ketoconazole, take an acidic beverage (non-diet cola) to provide an acidic environment for absorption
If PPIs or H2RAs must be used while on ketoconazole, what do you recommend to ensure proper absorption?
take an acidic beverage (non-diet cola) to provide an acidic environment for absorption
Azoles can (increased/decrease) concentrations of apixaban and rivaroxaban. Monitor s/sx of bleeding.
Increase concentrations
MOA of echinocandins
Inhibit synthesis of beta (1,3)-D-glucan, an essential component of the fungal cell wall
Coverage of echinocandins
Most Candida species, including strains typically resistant to azole antifungals (e.g. C. galbranta, C. krusei)
Echinocandins are available only as ____
injections
Warnings for echinocandins
Histamine-mediated symptoms (rash, pruritus, facial swelling, flushing, hypotension)
Anaphylaxis
ADEs for echinocandins
generally well-tolerated and not a/w sig renal or hepatic toxicity
Incresad LFTs, HA, hypotension, increased/decreased K, decreased Mg, fever, N/V/D, hyperglycemia, anemia, increased SCr, rash, SJS/TEN (caspofungin)
Dosing frequency for echinocandins in general
Once daily
Do not require renal dose adj
Which echinocandin requires light-protection during administration?
Micafungin
Nystatin suspension, clotrimazole troches/lozenges, and buccal miconazole are useful for treating mild, localized ___ infections
Candida
Nystatin suspension directions for use
Swish in mouth and retain for as long as possible (several minutes) before swallowing
T/F: When using nystatin suspension, it is recommended to swish in mouth for a few seconds and then spit out
False - Swish in mouth and retain for as long as possible (several minutes) before swallowing
Griseofulvin is indicated for fungal infections of ____
skin, hair, and nails
Contraindications for griseofulvin
Pregnancy, severe liver disease, porphyria
Side effects for griseofulvin
Photosensitivity, increased LFTs
Others: HA, rash, urticaria, dizziness, leukopenia, severe skin reactions
Which formulation of terbinafine is OTC?
Lamisil AT (topical)
How should griseofulvin be taken?
Take with fatty mean to increase absorption with food/milk to avoid GI upset
Warnings for terbinafine
Hepatotoxicity
Others: taste/smell disturbance, depression, neutropenia, thrombotic thrombocytopenic purpura (TTP), hemolytic uremic syndrome (HUS), SJS/TEN/DRESS/erythema multiforme, can cause/worsen systemic lupus erythematosus
Side effects for terbinafine
Headache, increased LFTs
Others: skin rash, abd pain, pruritus, diarrhea, dyspepsia
Contraindications for terbinafine
chronic or active liver disease
Patient on hormonal contraceptives got a prescription for griseofulgin for a hair fungal infection. What is your concern with these medications?
Griseofulgin increase metabolism of hormonal contraceptives (estrogen and progestin) - may lead to contraceptive failure. Use nonhormonal form of contraception
Terbinafine is a strong CYP ___inhibitor and weak/moderate CYP___ inducer
2D6 inhibitors
3A4 inducer
Patient as dx with mild oropharyngeal infection (thrush). What is the common pathogen and the preferred regimen?
Candida albicans
Mild disease: topical antifungals (clotrimazole, miconazole)
What is the recommended regimen for candida albicans oropharyngeal infection (thrush) moderate-severe disease or HIV+ pts
fluconazole
What is the alternative regimen for candida albicans oropharyngeal infection (thrush)?
Nystatin
Preferred: topical antifungals (clotrimazole, miconazole for) for mild disease, fluconazole for mod-severe or HIV + pts
What is the preferred regimen for candida albicans esophageal infection?
fluconazole
What is the alternative regimen for candida albicans esophageal infection?
Echinocandin
Preferred: fluconazole
What is the preferred regimen for candida krusei and glabrata, all Candida species bloodstream infections?
Echinocandin
What is the alternative regimen for candida krusei and glabrata, all Candida species bloodstream infections?
Amphotericin B, high-dose fluconazole (susceptible isolates only)
Preferred is echinocandin
What is the preferred regimen for aspergillus?
Voriconazole
What is the alternative regimen for aspergillus?
Amphotericin B, isavuconazonium
Preferred is voriconazole
What is the preferred regimen for cryptococcus neoformans meningitis ?
Amphotericin B + flucytosine (5-FC)
What is the alternative regimen for cryptococcus neoformans meningitis ?
high-dose fluconazole + flucytosine (5-FC)
What is the preferred regimen for Dermatophytes nail bed infections?
Terbinafine or itraconazole (confirm fungal infection prior to treatment)
What is the alternative regimen for Dermatophytes nail bed infections?
Fluconazole
Preferred is terbinafine or itraconazole
What are some key counseling points for azole antifungal (class)?
Can cause liver damage, QT prolongation (Except isavuconazonium)
Many DDIs
What are some key counseling points for itraconazole?
Tabs and caps: take with food
Solution: take on empty stomach
Can cause heart failure
What are some key counseling points for posconazole?
Tabs: take with food
Suspension: take with a full meal or oral liquid nutritional supplement
What are some key counseling points for voriconazole?
Take on empty stomach at least 1 hr before or after meals
Can cause photosensitvity, vision changes
Store oral suspension at room temp
What are some key counseling points for nystatin?
Suspension: shake well before using
What are some key counseling points for terbinafine?
Oral terbinafine can cause liver damage
Can take several months after finishing treatment to see full benefit of this drug (takes time for new healthy nails to grow and replace infected ones)
Which influenza strains are the ones that commonly affect humans?
Influenza A and B
S/sx influenza
fever, chills, fatigue, myalgia, non-productive cough, sore throat, and HA
How does influenza spread?
via respiratory droplets (e.g. generated by coughing)
How long is someone contagious for when they have influenza?
1 day prior to developing symptoms and for up to 5-7 after becoming ill
Influenza vaccine is recommended for all patients ages ≥ ___ who have no contraindications
6 months
MOA of neuraminidase inhibitors (oseltamivir, zanamivir, and peramivir)
Reduce amt of virus in the body by inhibiting the enzyme which enables release of new viral particles from infected cells
Active against influenza A and B, decreasing duration of s/sx by about 1 day and reducing complications
To be most effective, neuraminidase inhibitors should be started within ____ of illness onset
48 hrs
Note: in hospitalized, severely ill pts and those at high risk of complications, should still start >48hr after symptom onset, though less benefit if started later
____ is an endonuclease inhibitor approved for the treatment and post-exposure prevention of influenza. It has the advantage of being a single-dose regimen.
Baloxavir marboxil (Xofluza)
Baloxavir marboxil (Xofluza) should be started within ____ of symptom onset
48 hrs
Oseltamivir (Tamiflu) treatment dosing, age >12yo
75 mg BID x 5 days
Oseltamivir (Tamiflu) ppx dosing, age >12yo
75mg daily x 10 days
T/F: Oseltamivir (Tamiflu) does not require renal dose adj
False - CrCl ≤60 requires renal dose adj
Warnings for Oseltamivir (Tamiflu)
Neuropsychiatric events (sudden confusion, delirium, hallucinations, unusual behavior or self-injury)
SJS/TEN
Anaphylaxis
Which medication used for influenza cannot be used in asthma/COPD?
Zanamivir (Relenza Diskhaler) - inhaler formulation, can cause bronchospasm
Which medication used for influenza is x1 dose?
Baloxavir marboxil (Xofluza)
How is COVID-19 spread?
Respiratory droplets released when coughing or sneezing
Can be reduced by maintaining distance of at least 6 feet, mask we
S/sx of COVID-19
fever, chills, cough, SOB, fatigue, myalgia, loss of taste or smell, sore throat
What are some clinically significant herpes viruses?
Herpes simplex viruses 1 and 2 (HSV-1, HSV-2)
Varicella zoster virus (VZV)
Cytomegalovrius (CMV)
Epstein-Barr virus (EBV)
Human herpesviruses (HHV-6, HHV-7)
Kaposi sarcoma associated herpes virus (HHV-8)
Which herpes virus is most commonly a/w oropharyngeal disease
HSV-1
Which herpes virus is most commonly a/w genital disease
HSV-2
___ is the prodrug of acyclovir
Valcyclovir (Valtrex)
___ is the prodrug of penciclovir
Famciclovir
Warnings for antivrials for HSV and VZV
Caution in pts with renal impairment, the elderly, and/or those receiving nephrotoxic drugs
Infuse acyclovir over at least 1 hr and maintain adequate hydration to reduce risk of renal tubular damage
TTP/HUS has been reported in immunocompromised pts
Acyclovir dose is based on ___, including in obese patients
IBW
Cold sore eruption is preceded by a ____ (symptoms that occur before the lesions appear) of tingling, itching, or soreness
Prodrome
When is it the optimal time to take topical or oral medication to reduce blister duration for cold sores?
Tingling, itching, or soreness occurs
Which topical treatment for cold sores is OTC
Docosanol (Abreva)
Docosanol (Abreva) dosing for cold sores
Apply 5x daily at first sign of outbreak
Acyclovir (Zovirax) dosing for cold sores
Apply 5x daily for 4 days
For genital herpes, when must treatment be initiated?
During prodrome period or within 1 day of lesion onset
Compare acyclovir vs valacyclovir for genital herpes
Acyclovir - typically least expensive regimen but can be dosed up to 5x/day
Valacyclovir - prodrug of acyclovr; can reach higher conc than PO acyclovir; less frequent dosing = adherence
Note: if virus is resistant to acyclovir, it will also be resistant to valacyclovir, most likely famciclovir too
___ is the most commonly identified cause of viral encephalitis in the US (10-20% of cases)
HSV
HSV encephalitis is treated with ____
IV acyclovir 10mg/kg/dose Q8H x14-21 days
What virus is commonly referred to chicken pox?
Varicella zoster virus
Most adults in the US had chickenpox in their childhood. Virus can lie dormant in the nerve for decades without causing any symptoms. What is the recurrence of viral symptoms called?
Herpes zoster or shingles
Often as pts ages or acute stress
S/sx shingles
Itchy/tingly rash, very painful, and usually unilateral (only on one side of the body)
Antiviral therapy should be initiated at the earliest s/sx of shingles and is most effective when started within ___ of rash onset
72 hrs
Pain from shingles can be treated with ____
topical medications (Lidoderm patch, lidocaine gel), neuropathic pain meds (e.g. pregabalin, gabapentin, duloxetine, TCAs), NSAIDs, or opioids
Most shingles patients recover without long-term effects, but 5-10% have chronic pain called ____, can be debilitating
postherpetic neuralgia
ACIP recommends the shingles vaccines (Shingrix) in immunocompetent adults ages ___ and adults ages ____ who are or will be immunosuppressed
≥50yo
≥19yo
Herpes Zoster (Shingles) Treatment duration
7 days
What can be used to treat herpes zoster (Shingles)?
Acyclovir (Zovirax), Valacyclvoir (Valtrex), Famciclovir
____ is a double-stranded DNA virus within the herpes virus family (HHV-5)
Cytomegalovirus (CMV)
___ and ___ are treatments of choice for CMV infections. __ and ___ should be reserved for refractory cases
Ganciclovir and valganciclovir
Foscarnet and cidofovir
Ganciclovir preparation notes
Injection: reconstitute with sterile water, NOT bacterostatic water
Hazardous - special handling required
____ is the prodrug of ganciclovir (with better bioavailability)
Valganciclovir (Valcyte)
Boxed warnings for gancyclovir/valgancyclovir
Myelosuppression
Carcinogenic and teratogenic effects and inhibition of spermatogenesis in animals
IV ganciclovir to PO valganciclovir conversion
IV ganciclovir 5mg/kg = PO valganciclovir 900mg
Valganciclovir (Valcyte) solution storage instructions
Refrigerate, discard after 49 days
Boxed warnings for foscarnet (Foscavir)
Renal impairment (prehydartion recommended)
seizures d/t electrolyte imbalances (can lead to status epilepticus or death)
Infectious Epstein-Barr virus (EBV) is called ___and is transmitted through ___
mononucleosis or “mono”
Bodily fluids, primarily saliva and can be spread by kissing, sharing drinks or food, or by contact with an object that has been in mouth of an infected person (e.g. child’s toys)
S/sx of EBV
fatigue, fever, sore throat, and swollen lymph nodes
typically resolve in 2-4 weeks
Treatment for EBV
No drug treatment or vaccine exists for mononucleosis
A child with EBV developed a non-pruritic rash after using amoxicillin. Provider listed PCN as an allergy. Is this correct?
No - amoxicillin or ampicillin treatment in a child with EBV can cause a non-pruritic rash that appears similar to an allergy reaction; it is not and should not be included as an “allergy”
Osetlamivir (Tamiflu) key counseling points
Treatment should begin within 2 days (48hrs) of symptom onset
Can cause delirium
Acyclovir (Zovirax) and Valacyclovir (Valtrex) key counseling points
This medication dose not cure herpes infections (cold sores, chickenpox, shingles, or genital herpes). Use safe sex practices to lower transmission risk
Start treatment within 24 hrs of symptom onset
Acyclovir - drink plenty of fluids, topical cream can cause temporary burning and stinging
T/F: IV:PO ratio for all azoles is 1:1
True
