Fungal Diseases and Antifungals Flashcards
7 classes of antifungal agents
- azoles
- Triazoles
- Imidazoles - polyenes
- echinocandins
- mitotic inhibitors
- allyamines
- fluctyosine (Ancobon)
- ibrexafungerp (Brexafemme)
fluconazole (Diflucan)
Triazoles - azoles
itraconazole (Sporanox)
Triazoles - azoles
Voriconazole (Vfend)
Triazoles - azoles
posaconazole (Noxafil)
Triazoles - azoles
isavuconazole (Cresemba)
Triazoles - azoles
clotrimazole (Mycelex)
Imidazoles - azole
miconazole (Monistat)
Imidazoles - azole
ketoconazole (Nizoral)
Imidazoles - azole
terconazole (Terazol)
Imidazoles - azole
tioconazole (Vagistat)
Imidazoles - azole
econazole (Spectazole)
Imidazoles - azole
sulconazole (Exelderm)
Imidazoles - azole
which type of azole has the tendency to have better distribution, fewer SE, fewer DDI
triazoles
which azole is for systemic or cutaneous infections
triazoles
which azole is primarily topicals
imidazoles
which azole is primarily topicals
imidazoles
MOA that Inhibits synthesis of ergosterol
azoles
DDI of azoles
- CYP 450 inhibitors and inducers
* Inhibitors - slow down azole metabolism
- Grapefruit juice, alcohol (binge), several antibiotics and stomach acid-reducing products
* Inducers - speed up azole metabolism
- Alcohol (chronic), several anticonvulsants - Not recommended with certain BZDs
which azole may have less DDI than others
fluconazole
SE of azole
- GI upset
- HA
- taste changes
- Major:
- hepatotoxicity
- prolonged QT
- seizures
- leukopenia
- thrombocytopenia
CI of azole
- hypersensitivity to rx
- coadministration with drugs that can cause same SE
caution with azole in who?
- hepatic or renal impairment
- pregnancy
- greatest risks with systemic therapy, 1st trimester
what is the prototype azole drug
fluconazole (diflucan)
which azole has the most limited spectrum of activity
Candida albicans, Cryptococcus
Fluconazole (Diflucan)
indications for fluconazole
- superficial fungal infections
- uncomplicated systemic infections
Gets into CSF well
Drug of choice against histoplasmosis, sporotrichosis, blastomycosis
Itraconazole (Sporanox)
Variable bioavailability
Drug of choice for invasive aspergillosis
Voriconazole (Vfend)
Gets into CSF well
which azoles have
very broad-spectrum
used for invasive fungal infections in immunocompromised pts, or resistant infections
- Posaconazole (Noxafil) - CSF
- isavuconazole (Cresemba) - brain tissue, no CSF
dosing for azoles
- mostly BID
- QD
- Econazole (Spectazole)
- ketoconazole (Nizoral)
efficacy of azoles
- mostly equal
- may have slightly more efficacy than older azoles (clotrimazole, miconazole)
- Econazole (Spectazole)
- ketoconazole (Nizoral)
- sulconazole (Exelderm)
which azoles are more expensive and inexpensive
- expensive
- Sulconazole (Exelderm) - no generic
- ketoconazole - inexpensive/OTC
- Clotrimazole
- miconazole
which antifungal binds to ergosterol in the fungal cell membrane, creating pores in the cell and causing leakage of cell contents
polyenes
why doesn’t polyenes bind to our cells
Our cells have similar molecules, but polyenes bind to
ergosterol with a greater affinity
which polyene is considered too toxic to use systemically
nystatin
which polyene is indicated for Severe, disseminated mycotic infection
has very broad spectrum of activity
Amphotericin B
SE of Amphotericin B
- infusion-related - fever, chills, N/V, headache
- Renal - renal impairment, nephrotoxicity
- Electrolytes - hypokalemia, hypomagnesemia, hyperchloremic acidosis
- Others - anemia, hypotension
which polyene is indicated for non-invasive candidal infections
- Oral, vulvovaginal, intertrigo
Nystatin
SE of nystatin
- Topical - local irritation, allergic reaction
- Oral - local irritation, allergic reaction, GI upset (N/V/D, abdominal pain)
which antifungal inhibits synthesis of β-(1,3)-d-glucan, needed for fungal cell walls
Echinocandins
caspofungin (Cancidas), anidulafungin (Eraxis), micafungin (Mycamine)
which antifungal class is indicated for invasive fungal infections
- Disseminated candidiasis
- Aspergillosis (especially in HIV+ patients)
Echinocandins
DDI with Echinocandins
minimal effect on CYP 450 system - fewer DDI than azoles
SE of Echinocandins
- Infusion-related - dyspnea, flushing, hypotension
- Common - GI upset, HA, fever, insomnia
- Serious - hepatotoxicity, hypokalemia, anemia
what antifungal has the possibility to act on cell wall and DNA synthesis
Mitotic Inhibitors (Griseofulvin)
how is Mitotic Inhibitors (Griseofulvin) absorbed best
with fatty meals
which antifungal is indicated for Dermatophyte (tinea) infections of hair and skin
Mitotic Inhibitors (Griseofulvin)
DDI with Mitotic Inhibitors (Griseofulvin)
- alcohol
- Can cause “disulfiram”-type rxn - contraceptives
- warfarin
- barbiturates
CI of Mitotic Inhibitors (Griseofulvin)
- allergy to med
- liver failure
- porphyria
- pregnancy
SE of Mitotic Inhibitors (Griseofulvin)
- HA, GI upset, skin rashes, dizziness
- Serious - hepatotoxicity, teratogenic, granulocytopenia
- Need weekly CBCs
what antifungal interferes with ergosterol synthesis
Terbinafine (Lamisil) - Allyamines
indications for allyamines
- Oral - onychomycosis, dermatophyte (tinea) infections of hair and skin
- Topical - Dermatophyte (tinea) infections of hair and skin
DDI with allyamines
numerous - certain beta-blockers, certain TCAs, tamoxifen, tramadol
CI with allyamines
allergy to med, liver disease
SE of allyamines
- HA, GI upset, skin rashes, taste disturbances
- Serious - hepatotoxicity, neutropenia
- Monitor LFTs and CBC before and during tx
- Liver damage usually reversible, but case reports of liver failure and death
which antifungal enters cells and is converted to 5-fluorouracil, which inhibits fungal RNA and protein synthesis
flucytosine (Ancobon)
which antifungal is indicated for
- adjunct treatment used in combination with amphotericin B
- For severe candidal or cryptococcal infections (immunocompromised pts)
flucytosine (Ancobon)
which medication has a BBW with possible renal failure
flucytosine (Ancobon)
SE of flucytosine (Ancobon)
BBW
1. Renal - renal failure
- increased renal function testing
2. GI - hepatic injury, hepatotoxicity, GI upset
3. Heme - pancytopenia/aplastic anemia
4. CNS - peripheral neuropathy, confusion, psychosis, dizziness, ataxia
which antifungal inhibits glucan synthase, used to make part of the cell wall
ibrexafungerp (Brexafemme)
First drug in new novel antifungal class, triterpenoids
which antifungal is indicated for Vulvovaginal candidiasis (single-day treatment option)
ibrexafungerp (Brexafemme)
CI for ibrexafungerp (Brexafemme)
allergy
pregnancy
SE of ibrexafungerp (Brexafemme)
-
GI - abdominal pain, nausea, diarrhea in 10-17%
- Rare - elevated AST/ALT, flatulence, vomiting - GU - vaginal bleeding, dysmenorrhea
- Other - rash, dizziness, back pain
what are the other Topical Therapies for Tineas
- Butenafine (Lotrimin)
- Tolnaftate (Tinactin)
- Naftifine (Naftin)
what topicals are OTC and indicated for dermatophytes (tineas)
- Butenafine (Lotrimin)
- Tolnaftate (Tinactin)
which topical antifungal is:
rx only, newly generic but still may be a little expensive
may be more effective than clotrimazole and miconazole
Indicated for dermatophytes (tineas)
Naftifine (Naftin)
what are the Topical Therapies for Onychomycosis
- Ciclopirox (Loprox, Penlac)
- Tavaborole (Kerydin)
- Efinaconazole (Jublia)
which topical:
- Expensive , but now generic, more effective than clotrimazole and miconazole
- Indicated for dermatophytes, onychomycosis, seborrheic dermatitis
Ciclopirox (Loprox, Penlac)
which topical:
- Expensive, but has a generic version; equally effective as ciclopirox
- Indicated for onychomycosis
Tavaborole (Kerydin)
which topical:
- Expensive (no generic)
- More effective than clotrimazole, miconazole, and even ciclopirox
- Indicated for onychomycosis
Efinaconazole (Jublia)
Risk factors for candidiasis
- Chronic disease - chronic kidney disease, cancer, HIV, DM
- Medications - corticosteroids, immunosuppressants, broad-spectrum abx
- Vascular access - IV drug use, intravascular catheters
- Other - recent surgery (especially abdominal), prolonged neutropenia, organ transplant
what fungal infection is part of normal flora of the mouth and esophagus or the lower respiratory tract are AIDS-defining opportunistic infections!
Candidiasis
epidemiology of Oral Candidiasis
infants
elderly
DM
immune deficiency
after use of meds like antibiotics/steroids
symptoms for Oral Candidiasis
Early - asymptomatic
Later - abnormal or diminished taste, pain with eating/swallowing
pt has
Beefy red, edematous mucosa of oral cavity
+/- white plaques on tongue, palate, buccal mucosa, oropharynx
Plaques can be scraped off with a tongue depressor
what could be their diagnosis?
Oral Candidiasis
how do you diagnose oral candidiasis
- Often clinically
- KOH prep - budding yeasts, pseudohyphae
- Culture - + for candidal species - more accurate, longer to results
tx for oral candidiasis
- Topical Therapy
- Nystatin
- Clotrimazole
- Miconazole - Systemic Therapy
- Fluconazole
- May cut down to 100 mg after day 1 - Gentian Violet (alternative)
tx for 7-14 days
epidemiology of Esophageal Candidiasis
typically in HIV + or other severely
immunosuppressed pts; often also have oral thrush
if a pt is experiencing odynophagia, nausea, reflux, +/- oral thrush
what could be their diagnosis?
Esophageal Candidiasis
diagnosing Esophageal Candidiasis
endoscopy
tx for esophageal candidiasis
- Oral azoles
- Fluconazole (Diflucan)
- Itraconazole (Sporanox) - More costly, more nausea, must use solution rather than tablet - IV therapy
- Fluconazole (Diflucan)
if you are treating for esophageal candidiasis and have resistance to fluconazole, what could you use?
voriconazole, posaconazole, or an echinocandin
epidemiology of Vulvovaginal Candidiasis
Up to 75% of women will have at least once in their lifetime
HIV, pregnancy, antibiotic use, uncontrolled DM all up the risk
pt presents with
Discomfort - itching, burning, and pain around genital area
Discharge - thick, white, nonmalodorous, “cottage cheese”
what is their diagnosis?
Vulvovaginal Candidiasis
PE findings for Vulvovaginal Candidiasis
Erythematous, edematous mucosa
+/- erythema, edema, excoriations of external genitalia
Thick, white, curdy, “cottage cheese” discharge that is easily removed with a swab
diagnosing vulvovaginal candidiasis
Often can diagnose clinically
KOH prep - budding yeasts, pseudohyphae
Culture - + for candidal species - more accurate, longer to results
tx for vulvovaginal candidiasis
- Topical Therapy
- Miconazole (Monistat)
- clotrimazole (Mycelex)
- terconazole (Terazol) - Systemic Therapy
- Fluconazole (Diflucan)
- Ibrexafungerp (Brexafemme) - Recurrent/Prophylactic Therapy
- Azoles
- Probiotics - questionable benefit, but little harm - Alternative Tx
- Gentian Violet
- Boric Acid PV x 7 days
what increases risk of candidal intertrigo
- obesity
- occlusive or tight clothing
- sweating
- incontinence
- DM
- immunosuppression
- medications
during PE you find
Erythematous, macerated, well-defined plaques in skin folds
Satellite erythematous papules and pustules
what could it be?
intertrigo
how do you diagnose intertrigo?
- Often clinically
- KOH prep (skin scrapings) - budding yeasts, pseudohyphae
- Culture - + for candidal species - more accurate, longer to results
how do you diagnose intertrigo?
- Often clinically
- KOH prep (skin scrapings) - budding yeasts, pseudohyphae
- Culture - + for candidal species - more accurate, longer to results
tx for intertrigo
- Correcting underlying factors
- Weight loss, controlling DM, wearing different clothing, etc.
- Drying agents - talc, nystatin powder - Topical Therapy (until resolution)
- Topical azoles
- nystatin, BID - Systemic Therapy - if severe/extensive
- Fluconazole
tineas are caused by what organism
- Dermatophytes
- “feed” off keratin
- Infect skin, nails, and hair
- Epidermophyton, Trichophyton, Microsporum
if a pt presents with
Single or multiple scaly, circular patches on scalp
Alopecia; may see “black dots” at follicles
(broken-off hairs)
what do they have?
Tinea Capitis
Patches slowly enlarge over time
diagnosing tinea capitis
- clinically
- KOH prep and/or culture - usually only in
ambiguous/refractory cases
tinea capitis is MC seen in who?
children
Thought to spread via child-to-child contact
How is tinea corporis spread?
person-to-person contact
can be contracted from infected animals
pt presenting with
Center of lesion clearing, while a raised, advancing, scaly red border remains
what do they have?
Tinea Corporis
pt presenting with
Center of lesion clearing, while a raised, advancing, scaly red border remains
what do they have?
Tinea Corporis
how do you diagnose tinea corporis
- clinically
- KOH prep and/or culture - usually only in ambiguous/refractory cases
Tinea Cruris is MC in who? risk factors?
- Males > females
- Risk factors - obesity, DM, immunodeficiency, sweating
if a pt presents with
Erythematous lesions with scaly, sharp, spreading
margins; may have central clearing
confining to the groin and gluteal cleft
what is it?
Tinea Cruris
can be asx or itchy
how to diagnose tinea cruris
- clinically
- KOH prep and/or culture - usually only in ambiguous/refractory cases
what fungal infection is known to be
Shared showers, locker rooms, floors around public pools
tinea pedis
what other fungal infections can be seen with tinea pedis
tinea cruris, tinea manuum, tinea unguium
Itching, burning, stinging of the toes and feet
Erythematous bullae (acute) → scaling, fissuring, macerated skin, thickened plaques
tinea pedis
how to diagnose tinea pedis
- clinically
- KOH prep and/or culture - usually only in ambiguous/refractory cases
- May be falsely negative if taken from macerated skin
etiology of tinea unguium
dermatophytes
yeasts
molds
risk factors of tinea unguium
elderly, swimming, tinea pedis,
immunocompromised, DM, psoriasis
a pt prsenting with a thickened nail with yellow/brown discoloration, separated from nail bed
what do they have?
Tinea Unguium
how do you diagnose tinea unguium
KOH prep and/or culture
recommended to r/o other nail disorders
tx for tinea capitis
- Systemic
- griseofulvin
- terbinafine
- may consider fluconazole, itraconazole
tx for tinea corporis
- Topical
- azole
- butenafine
- tolnafate
- ciclopirox
- terbinafine
- QD-BID until cleared (1-3 wks) - Systemic - extensive or refractory
- griseofulvin
- terbinafine
- fluconazole
- itraconazole
tx for tinea cruris
- Topical
- azole
- butenafine
- tolnafate
- ciclopirox
- terbinafine
- until cleared (1 wk)
- drying powders - Systemic - extensive or refractory
- griseofulvin
- terbinafine
- fluconazole
- itraconazole
tx for tinea pedis
- Topical
- azole
- butenafine
- tolnafate
- ciclopirox
- terbinafine - Systemic - extensive or refractory
- terbinafine
- itraconazole
- fluconazole
- griseofulvin - If macerated
- aluminum subacetate soaks 20 min BID
tx for tinea unguium
- Topical
- efinaconazole
- tavaborole
- ciclopirox - Systemic
- terbinafine
- itraconazole
what should NOT be given for dermatophyte infections
topical nystatin
presentation of Disseminated Candidiasis
- Varies greatly - minimal fever to septic shock
- May see skin lesions ranging from pustules to nodules
- May involve liver, kidney, spleen, eyes, heart
risk factors: severely immunocompromised state; nosocomial infection
diagnosing disseminated candidiasis
blood cultures only (+) 50% of the time
tx for disseminated candidiasis
- _First-line (especially if critically ill or non-albicans strain) _
- IV echinocandins
- Caspofungin
- Micafungin, anidulafungin -
Mild-Moderate Disease
- fluconazole
Continue for 2 weeks AFTER last positive blood culture
what infection is transmitted via inhaled spores from contaminated bird and bat droppings
Histoplasmosis
- Primarily in river valleys (Ohio and
Mississippi River Valleys in US)
- Begins in lungs, but spreads throughout the body
4 forms of histoplasmosis presentations
- MC
- asx/mild
- accidental findings of pulmonary and/or splenic calcification may see “eggshell” LN calcification - acute pulmonary - after soil with bird or bat droppings is disturbed
- Fever, cough, myalgias, minor chest pain -
- Mild flu-like illness to severe pneumonia - 1 week to 6 months
- CXR - Miliary infiltrates and mediastinal LAN - Progressive disseminated - Immunocompromised pts (HIV+, TNF-blockers)
- Fever, cough, dyspnea, weight loss, prostration, oropharyngeal ulcers
- Multiple organ system involvement - hepatomegaly, splenomegaly, GI inflammation, adrenal insufficiency, bone marrow suppression, CNS infection
- CXR - miliary infiltrates and mediastinal LAN
- Can have fulminant, septic shock-like presentation progressing to death without tx - Chronic pulmonary - older pts with underlying chronic lung disease
- Pts are not necessarily immunosuppressed!
- CXR - apical cavities, chronic infiltrates, pulmonary nodules
complications of histoplasmosis
-
Granulomatous mediastinitis - persistent mediastinal LAN and fibrosis of the mediastinum
- compromises pulmonary vascular structures
- SVC syndrome, esophageal constriction
work up for histoplasmosis
- Labs
- may see anemia of chronic disease elevated LDH, ferritin, and/or AST
- Disseminated - pancytopenia possible - Cultures
- sputum culture (chronic disease)
- blood culture (disseminated) - Bronchoscopy
- with biopsy
tx for histoplasmosis
- Mild-Moderate = itraconazole (Sporanox)
- HIV/AIDS pts - need lifelong suppressive tx - Severe = IV amphotericin B
- Granulomatous/Fibrosing Mediastinitis
- itraconazole, +/- rituximab, +/- corticosteroids
- often need surgical intervention
what infection is transmitted via inhaled spores that grows in arid soil, such as SW US, Mexico, and Central America?
Coccidioidomycosis
“Valley fever”
what infection is transmitted via inhaled spores that grows in arid soil, such as SW US, Mexico, and Central America?
Coccidioidomycosis
“Valley fever”
Coccidioidomycosis is MC in who?
- immunocompromised, elderly
- Suspect in patients who live or
work in endemic areas
60% of Coccidioidomycosis cases are ____
asx
presentations of coccidioidomycosis
- Primary Coccidioidomycosis - incubation period of 10-30 d followed by fever, chills, fatigue, HA, cough, myalgia
- arthralgia and joint swelling (knees and ankles)
- Rash (erythema nodosum) - may appear 2-20 days after s/s onset
- CXR - infiltrate, cavities, abscesses, nodules, bronchiectasis - Disseminated coccidioidomycosis - 0.1% of white, 1% of nonwhite patients
- Filipinos, blacks, pregnant women, and immunosuppressed = high risk
- Worsened pulmonary s/s - mediastinal LAD, cough, increased sputum, lung abscesses
- Multiorgan involvement - skin, bones, pericardium/myocardium, meningitis
- Fungemia is possible; usually followed rapidly by death
- CXR - localized infiltrate, thin-walled cavities, pulmonary abscesses, nodules, mediastinal LAD, pleural effusion
how do you diagnose/work up Coccidioidomycosis
- Labs
- may see leukocytosis, eosinophilia
- May test for IgM and IgG complement fixation titer; possible to have false negatives - Cx
- blood cultures rarely positive -
Bronchoscopy
- with biopsy and culture - most reliable method - CXR - patchy, nodular and lobar upper lobe pulmonary infiltrates are MC
tx for coccidioidomycosis
“valley fever”
1. Mild-Moderate
- fluconazole/itraconazole - 4-12 wks
- voriconazole, posiconazole if refractory
2. Severe/Disseminated
- IV amphotericin B x 2-3 weeks, then switched to azole
- Abscesses may need surgical management
3. Prophylactic
- AIDS pts with CD4 count <250 - maintenance therapy with azole to prevent relapse
tx for coccidioidomycosis
- Mild-Moderate
- fluconazole/itraconazole - 4-12 wks
- voriconazole, posiconazole if refractory - Severe/Disseminated
- IV amphotericin B x 2-3 weeks, then switched to azole
- Abscesses may need surgical management - Prophylactic
- AIDS pts with CD4 count <250 - maintenance therapy with azole to prevent relapse
what infection is caused by inhaled spores found in moist soil with decomposing organic matter (wood and leaves)
MC seen in men infected during
outdoor activities for
occupation/recreation
Blastomycosis
presentation for blastomycosis
- Asymptomatic - about 50% of cases
-
MC - chronic pulmonary infection
- Flu-like - cough, moderate fever, dyspnea, chest pain
- Extrapulmonary involvement - nodular, wart-like lesions
- S/S may resolve or progress to pneumonia-like illness - Disseminated - rare; mainly immunocompromised pts
- Bone - ribs, vertebrae MC affected
- GU - epididymitis, prostatitis, bladder irritation
- Skin - may see nodular lesions as above
work up for blastomycosis
- Labs - may see leukocytosis, anemia
- Urine antigen test - cross-reactivity with Histoplasma - Cultures - sputum cultures; blood cultures if disseminated
- Bronchoscopy - with biopsy and culture
- CXR - airspace consolidation or masses are most common
tx for blastomycosis
- Mild-Moderate - itraconazole (Sporanox)
- Severe/CNS involvement - IV amphotericin B
what infection is transmitted by inhaled spores found in soil and pigeon dung
Cryptococcosis
presentation of Cryptococcosis
- Pulmonary disease - ranges from mild to respiratory failure
- May see simple nodules or fever, cough, dyspnea, widespread infiltrates - Meningitis
- HA followed by altered mental status, fever, CN abnormalities
- Meningeal signs - often absent, especially in HIV+ - Skin - mainly in immunocompromised pts
- May see nodular lesions
- May mimic bacterial cellulitis
what is the MC cause of fungal meningitis
Cryptococcosis
work up for Cryptococcosis
- Serum - may test for serum cryptococcal antigens
- Cultures - sputum, blood, and/or urine cultures may be helpful
- Bronchoscopy - with culture of sputum
- CSF - budding, encapsulated yeast; + cryptococcal antigen
tx for Cryptococcosis
- Pneumonia - fluconazole (Diflucan)
- HIV patients need continued suppressive therapy - Meningitis - IV amphotericin B plus flucytosine (if tolerated)
- Followed by 8 wks of fluconazole
- Frequent LP or CSF shunting to relieve high CSF pressure if needed
what infection transmission is believed to have airborne transmission
Most individuals have had asymptomatic infection by a young age
pneumocystosis
major patterns of clinical infection of pneumocystosis
aka who do they affect the most?
- Epidemics among premature or debilitated
infants in underdeveloped countries - Sporadic cases among older children and adults
with impaired immunity
- HIV/AIDS patients
presentation of pneumocystosis
- Pulmonary - abrupt onset of fever, tachypnea, SOB, nonproductive cough
- +/- bibasilar crackles on exam
- Spontaneous pneumothorax is possible
- Rapid deterioration and death if not treated
work up for pneumocystosis
- CXR
- diffuse interstitial infiltration
- may also see consolidation, nodules, cavitations - Bronchoscopy - special testing of respiratory specimens
- Giemsa, methenamine silver, PCR, monoclonal antibody testing
cannot be cultured
tx for pneumocystosis
- First-Line
- TMP-SMZ (Bactrim)
- HIV patients with CD4 <200 need continued suppressive therapy - Second-Line
- primaquine/clindamycin
- trimethoprim-dapsone
