Lecture 8: Fungal Diseases Flashcards
What are the classes of antifungals?
Azoles
Polyenes
Echinocandins
Mitotic inhibitors
Allyamines
Flucytosine (Ancobon)
Ibrexafungerp (Brexafemme)
What are the two types of azoles?
Triazoles (for systemic or cutaneous infections)
Imidazoles (topicals mainly)
What falls under triazoles?
Fluconazole
Itraconazole
Voriconazole
Posaconazole
Isavuconazole
FIVPI (No letters overlap with the imidazoles)
What is the MOA of an azole?
Inhibit synthesis of ergosterol
Systemic resistance is increasing!!
Which azole tends to have less DDI than any other?
Fluconazole
What can slow azole metabolism?
Grapefruit juice
Alcohol (binge)
Some abx and some GERD meds
What can increase azole metabolism?
Alcohol (chronic), several anticonvulsants
What are the minor SE of azoles?
GI UPSET (N/V/D, abd pain) HA; taste changes
What are the major SE of azoles?
Hepatotoxicity, QT prolong, seizures, leukopenia, thrombocytopenia
What are the CIs of azoles?
Similar SE drugs
What kind of patients should not take azoles?
Caution in hepatic/renal impairment
Pregnancy (mainly systemic in 1st tri)
What is the prototype of the azoles?
Fluconazole (narrow range but covers the common)
When is fluconazole indicated?
C. albicans
Cryptococcus
The FCC
CSF (superficial or uncomplicated systemic)
What is itraconazole the DOC in?
Histoplasmosis
Sporotrichosis
Blastomycosis
BISH
What is Voriconazole the DOC in?
Invasive aspergillosis (mold)
Vacuum the mold
What are posaconazole and isavuconazole the DOC in?
Invasive infections in immunocomped or resistant infections.
What is the key diff between posa and isavu azoles?
Posa gets into CSF well.
Isavu gets into brain tissue well, not CSF. (i save ur brain)
What azoles are the broadest spectrum?
Posa and Isavu
Which topical azoles can be QD instead of BID?
Eco
Keto
Eko friendly
What are the cheapest OTC topical azoles?
Clotrim
Micon
What is the MOA of a polyene?
Bind to ergosterol in the membrane, creating pores and leaking cell contents.
Polyenes have high affinity for fungal ergosterol.
What should you avoid using nystatin for?
Systemic therapy.
Nystatin has severe SE with systemic administration.
When do we use amphotericin B? Why?
For severe, disseminated mycotic infections. It is often the initial tx while we wait for culture results.
It has very broad spectrum activity.
What are the adverse effects of ampho B?
Infusion-related: fever, chills, N/V, HA
Renal: IMPAIRMENT, NEPHROTOXIC
Electrolytes: HypoK, HypoM, HyperC acidosis
Others: Anemia, hypotension
When do we use nystatin?
Non-invasive candidal infections. (It is topical and oral rinse form)
Oral, vulvovaginal, intertrigo
What are the adverse effects of Nystatin?
Topical: Local irritation
Oral Rinse: Local irritation, GI upset
What are the echinocandins?
Caspofungin
Anidulafungin
Micafungin
All IV.
Echidnas are candid fun guys
What is the MOA of the echinocandins?
Inhibits synthesis of beta-(1,3)-d-glucan, needed in cell walls.
When are echinocandins used?
Invasive fungal infections:
Disseminated candidiasis
Aspergillosis (esp HIV pts)
DEA
What are the adverse effects of echinocandins?
Infusion-related: dyspnea, flushing, hypotension
Common: GI upset, HA, fever, insomnia
Serious: HEPATOTOXICITY, HypoK, anemia
What is the mitotic inhibitor and its MOA?
Griseofulvin.
Acts on cell wall and DNA synthesis, no clear.
What is unique about the admin of griseofulvin?
Greasy griseo.
Oral absorption best with a fatty meal.
When do we use griseo?
Dermatophyte/tinea infections of hair and skin.
Greasy skin, greasy hair
What are the DDIs of griseo to be worried about?
Alcohol (di-sulfiram like)
Contraceptives
Warfarin
Barbs
What are the CIs of griseo?
Liver failure
Porphyria
PREGNANCY (Absolute CI)
What are the main AE of griseo?
HA, GI upset, skin rashes, dizziness
Serious: GRANULOCYTOPENIA, hepatotoxicity, teratogenic.
Need weekly CBCs.
What drug is an allylamine? MOA?
Terbinafine
Interferes with ergosterol synthesis.
What is important regarding terbinafine administration?
Irritating to mucous membranes
When is oral terbinafine used?
Onychomycosis
Dermatophyte/tinea infections of hair and skin
DOT
When is topical terbinafine used?
Dermatophyte/tinea infections of hair and skin
What are the DDIs of terbinafine?
BBs
TCAs
Tamoxifen
Tramadol
T and B
What is the main CI for terbinafine use?
Liver disease
What are the AE of terbinafine?
HA, GI upset, rashes, taste disturbances
Serious:
Hepatoxicity
Neutropenia
What is the MOA of flucytosine?
converted to 5-FU upon entering a cell, which is an antimetabolite.
Inhibits fungal RNA and protein synthesis.
When is flucytosine used?
Adjunct for amphotericin B in cryptococcal meningitis
Severe candidal or cryptococcal infections (IC pts)
What are the AE of flucytosine?
BBW: Renal impairment use
Renal: Renal failure, increased need for BMPs
Hepatic: injury, toxicity, GI upset
Heme: Pancytopenia/aplastic anemia
CNS: peripheral neuropathy, confusion, psychosis, dizziness, ataxia
What is ibrexafungerp’s MOA? drug class?
Inhibits glucan synthase, used to make part of cell wall.
New class: triterpenoids
What is ibrexafungerp indicated for?
Vulvovaginal candidiasis (Single day tx)
What is ibrexafungerp CId in?
pregnancy
What are the AE of ibrexa?
GI: Abd pain, N/D
Rare GI: elevated AST/ALT, flatulence, V
GU: vaginal bleeding, dysmenorrhea
Other: Rash, dizziness, back pain
What are the other topical antifungals for tineas only?
Butenafine (OTC)
Tolnaftate (OTC)
Naftifine (RX only)
What are the other topical antifungals for onychomycosis only?
Ciclopirox
Tavaborole
Efinaconazole (not a real azole) (no generic)
What is the main superficial candidiasis strain?
Candida albicans
What increases risk of candidiasis?
Chronic disease: CKD, cancer, HIV, DM
Meds: Steroids, immunosupps, broad-spectrum abx
Vascular access: IVDU, IV catheters
Other: recent abd surgery, prolonged neutropenia, organ transplant.
What is candidiasis of the mouth and esophagus or lower respiratory indicative of?
AIDS-defining conditions.
What kind of pts usually get oral candidiasis?
Infants
Elderly
DM
Immunodef
Post med use
What does oral candidiasis present as?
Beefy red, edematous mucosa of oral cavity.
+/- white plaques on tongue, palate, buccal, oropharynx
SCRAPABLE PLAQUES
How do we Dx oral candidiasis?
Clinically is OK
KOH prep: bud yeasts, pseudohyphae
Culture: checking which species.
How do we Tx oral candidiasis?
Topically:
Nystatin
Clotrimazole
Miconazole
Systemic:
Fluconazole
1-2 weeks for all tx.
What is the alternate tx to oral candidiasis that we avoid?
Gentian violet x3 days
(faster tx but stains everything violet)
How does esophageal candidiasis present?
Odynophagia
Nausea
Reflux
+/- oral thrush
How do we actually Dx esophageal candidiasis?
Endoscopy
How do we Tx esophageal candidiasis?
Systemic only!
Oral:
Fluconazole (2-3 weeks)
Itraconazole (if failed flu)
IV:
Fluconazole (2-3 weeks)
Vori, Posa, Enchinocandin (if failed flu)
What ups the likelihood of vulvovaginal candidiasis?
HIV
Pregnancy
ABX use
Uncontrolled DM
What are the S/S of vulvovaginal candidiasis?
Discomfort: pruritis, burning, pain, dyspareunia
Discharge: thick, white, malodorous, cottage cheese
What PE findings suggest vulvovaginal candidiasis?
Erythematous, edematous mucosa
+/- erythema, edema, excoriations
Thick, white, curdy, cottage cheese easily removed by swab.
How do we Dx vulvovaginal candidiasis?
Clinically.
KOH prep
Culture
How do we Tx vulvovaginal candidiasis topically?
Topical:
1,3,7 day regimens of micon, clotrim, tercon azoles.
How do we tx vulvovaginal candidiasis systemically?
Fluconazole 1 dose
Ibrexafungerp 2 doses 1 day
How do we tx recurrent/prophylaxis for vulvovaginal candidiasis?
Azoles: topical PV or flu x1 week
Probiotics: maybe
What is the alternative tx for vulvovaginal candidiasis?
Gentian violet
Boric acid PV
Where does candidal intertrigo usually appear?
Skin folds
What increases the risk of candidal intertrigo?
Obesity
Tight clothing
Sweating
Incontinence
DM
Immunosupps
Meds
How does candidal intertrigo present?
Erythematous, macerated, well-defined plaques
Satellite erythematous papules and pustules
How do we Dx candidal intertrigo?
Clinically.
KOH prep (skin scrapings)
Culture
How do we tx candidal intertrigo?
Correct underlying factors. use drying agents (talc, nystatin powder)
Topical azoles/nystatin
Systemic fluconazole
What are the 6 tineas?
Tinea capitis (scalp)
Tinea corporis (ringworm/body)
Tinea cruris (Jock itch/groin)
Tinea pedis (Athlete’s foot)
Tinea unguium (Nail/onych)
Tinea versicolor (Body/pityriasis versicolor)
Which tinea is a fake one?
Tinea versicolor
What is the etiology and diagnostic technique for tineas?
Etiology: dermatophytes eat keratin sources.
Species: epidermophyton, trichphyton, microsporum
Diagnostic technique: KOH prep should show segmented hyphae.
How does tinea capitis present?
Single/multiple scaly, circular patches on scalp.
Alopecia, black dots at follicles.
Enlarging patches.
Who is tinea capitis most common in and how do I Dx?
Children primarily, seen in child-to-child contact.
Clinical Dx, KOH prep/culture only for ambiguous/refractory.
How does tinea corporis (ringworm) present?
Early: Pruritic, erythematous, scaling, circular, or oval plaque.
Later: spreads outward. Central clearing with raised, scaly border.
Who is tinea corporis most common in and how do I Dx?
Person to person
Infected animal
Clinical Dx
KOH only for ambiguous/refractory.
How does tinea cruris (Jock itch) present?
Asymptomatic or itchy
GROIN and GLUTEAL CLEFT
Erythematous lesions with scaly, sharp, spreading margins. May have central clearing.
Who is tinea cruris most common in and how do I Dx?
Males
Risk factors: Obesity, DM, immunodeficiency, sweating
Clinical Dx
KOH only for ambiguous/refractory.
How does tinea pedis (athlete’s foot) present?
Itching, burning, stinging of toes and feet.
Erythematous bullae (acute) => scaling, fissuring, macerated skin, thickened papules
Acute exacerbations are self-limiting, often triggered by sweat.
Continues indefinitely without treatment.
Who is tinea pedis most common in and how do I Dx?
Teens and adults, esp. MALES and ATHLETEs.
Contact via shower spores, poools, etc…
Often have cruris, manuum, and unguium also.
Clinical Dx.
KOH only for ambiguous/refractory and can be false-negative if skin was macerated.
How does tinea unguium (onychomycosis) present?
Thickened nail with yellowish or brownish discoloration, may separate from nail bed.
Who is tinea unguium most common in and how do I Dx?
Elderly
Swimmers
Tinea pedis people
Immunocompromised
DM
Psoriasis
KOH prep/culture recommended to r/o other nail disorders. NOT CLINICAL DX.
How do I treat tinea capitis?
Systemic only. Can use griseofulvin.
Terbinafine, fluconazole, itraconazole.
How do I treat tinea corporis, tinea cruris, and tinea pedis?
Topically or systemically.
What can I recommend for tinea cruris besides an oral antifungal?
Drying powder: Talc or nystatin powder.
How do I treat tinea unguium?
Topically or systemically.
Systemic: terbinafine
What topical antifungal is specifically not effective for dermatophyte infections?
Topical Nystatin is a nono
What are the main risk factors for disseminated candidiasis?
Severely immunocomped
Nosocomial
How does disseminated candidiasis present?
Minimal fever to septic shock.
Skin lesions from pustules to nodules
May involve liver, kidney, spleen, eyes, and heart.
How do I diagnose disseminated candidiasis?
Blood cultures. Only 50% positive ):
What is first-line treatment for disseminated candidiasis?
IV echinocandins: Caspofungin with loading dose.
(Good for critically ill or non-albicans strain)
What is the other treatment for disseminated candidiasis and how long?
Mild-moderate = fluconazole with loading dose.
2 weeks past the last positive blood culture.
In WV, what are the two main fungal strains to be worried about?
Histoplasmosis
Blastomycosis
How is histoplasmosis transmitted? What is the nickname?
Inhaled spores via bird and bat droppings.
Batman and robin disease
What is the organism that causes histoplasmosis and where does it usually begin in the body?
Histoplasma capsulatum
Lungs, spreading to the body.
What are the 4 major presentations of histoplasmosis?
Asymptomatic
Acute pulmonary histoplasmosis
Progressive disseminated histoplasmosis (HIV+ or TNF-blockers)
Chronic pulmonary histoplasmosis
How does asymptomatic histoplasmosis present?
Incidental CXR showing pulmonary or splenic calcifications.
Often described as EGG SHELL lymph node calcification.
How does acute pulmonary histoplasmosis present?
Fever, cough, myalgia, minor chest pain.
Mild FLS to severe pna for 1 wk to 6 mo.
CXR shows miliary infiltrates and mediastinal LAN.
Often in land development when soil is disturbed that has droppings.
How does progressive disseminated histoplasmosis present?
Fever, cough, dyspnea, weight loss, prostration, oropharyngeal ulcers.
Multiple organ system involvement.
CXR shows miliary infiltrates and mediastinal LAN.
Can also have a fulminant, septic shock presentation.
How does chronic pulmonary histoplasmosis present?
CXR shows apical cavities, chronic infiltrates, and pulmonary nodules.
Often in older pts with chronic underlying disease.
Presents like a chronic lung disease, but complications of granulomatous mediastinitis can occur.
What is granulomatous mediastinitis?
Persistent mediastinal LAN leading to fibrosis.
What are the complications of granulomatous mediastinitis?
SVC syndrome
Esophageal constriction
What diagnostic studies should you order for histoplasmosis and what would they show?
CMP: elevated AST
LDH: elevated
Ferritin: elevated
CBC: Pancytopenia possible
Sputum culture (chronic); Blood culture (Disseminated)
Bronchoscopy + biopsy.
CXR and CT Chest vary depending on presentation
What is the treatment for mild-moderate histoplasmosis?
Itraconazole (HIV/AIDS needs it lifelong)
What is the treatment for severe histoplasmosis?
Amphotericin B
What is the treatment for granulomatous mediastinitis?
Itraconazole +/- rituximab +/- corticosteroids.
Consider surgery
What causes coccidioidomycosis and what is its nickname?
Coccidioides immitis
Coccidioides posadasii
Valley fever
How is valley fever transmitted? MC demographics?
Inhaled spores.
Arid soil in southwest US, mexico, central america.
Immunocomped and elderly and endemic areas.
Responsible for 15-30% of CAP in endemic areas.
What are the 3 possible presentations of valley fever?
Asymptomatic (60%)
Primary
Disseminated
How does primary valley fever present?
INcubation of 10-30 days, followed by FLS.
Arthralgia and joint edema in knees and ankles.
Erythema nodosum may appear (bilateral shin rashes)
CXR shows INFILTRATE, cavities, abscesses, nodules, bronchiecstasis (5%)
How does disseminated valley fever present?
Worsened pulmonary s/s: mediastinal LAN, cough, sputum, abscesses
Multiorgan involvement: skin, bones, pericadium/myocardium, meningitis
Fungemia possible, death imminent.
CXR shows LOCALIZED INFILTRATE, thin-walled cavities, etc
Local valley
What ethnicities are MC for disseminated valley fever?
Non-white:
Filipino
Black
Also pregnant women and immunosuppressed.
What will I see in diagnostic studies for valley fever?
CBC: Leukocytosis, eosinophilia (you can test for IgM and IgG complement fixation titer (sometimes neg)
Cultures: Blood cultures are rarely positive
Bronchoscopy: with biopsy and culture. MOST RELIABLE.
CXR: patchy, nodular, upper lobe infiltrates are MC.
How do I treat mild-moderate valley fever?
Fluconazole or itraconazole
How do I treat severe/disseminated valley fever?
Amphotericin B followed by an azole.
When do AIDS pts get prophylaxis for valley fever?
CD4 < 250 with azole.
What causes blastomycosis? What is the nickname?
Blastomyces dermatitidis
Woodsman disease
How is woodsman disease transmitted and where is it most common?
Inhaled spores found in moist soil with decomposing organic matter.
MC in outdoors men.
South central and midwestern US + Canada
Often occurs in immunoCOMPETENT pts.
What are the 3 presentations of woodsman disease?
Asymptomatic
MC: Chronic pulmonary infection
Disseminated
How does chronic woodsman disease present?
FLS
Wart-like skin lesions
S/S may become pneumonia like.
How does disseminated woodsman disease present?
Rare, only immunocompromised generally.
Bone pain: ribs and vertebrae MC
GU: epididymitis, prostatitis, bladder irritation
Skin: nodular lesions.
Often a DDx for UTI in men.
Morning wood => epididymitis
How do diagnostic studies present for woodsman disease?
CBC: Leukocytosis, anemia
Urine antigen: cross-reacts with histoplasma
Cultures: sputum or blood.
Bronchoscopy: with biopsy and culture (most specific?)
CXR: Consolidation or masses (a forest consolidates)
urine antigen: his wood
How do I treat mild-moderate woodsman disease?
Itraconazole (2-3 months)
How do I treat Severe/CNS involvement woodsman disease?
Amphotericin B
What causes cryptococcosis?
Crytococcus neoformans (worldwide)
Cryptococcus gattii (tropical regions and pacific NW)
How is cryptococcosis transmitted?
Inhaled spores via soil and PIGEON dung.
Clinically significant in immunocompromised pts.
C. gattii is more likely to infect regular people and cause severe disease.
How does pulmonary cryptococcosis present?
Mild to resp failure.
Simple nodules or fever, infiltrates, dyspnea
How does Cryptococcal meningitis present?
MC cause of Fungal meningitis
HA followed by AMS, fever, CN abnormalities.
Often NO MENINGEAL SIGNS in HIV+ esp.
How does skin cryptococcosis present?
Nodular lesions
Mimics bacterial cellulitis
Mainly in immunocompromised pts
What diagnostic study results would I expect in cryptococcosis?
Serum: cryptococcal antigens
Cultures: Sputum, blood, urine
Bronchoscopy: Sputum
CSF: Budding, encapsulated yeast; + cryptococcal antigen
What is the treatment for pneumonia cryptococcosis?
Fluconazole for 6-12 months.
What is the treatment for cryptococcal meningitis?
Amphotericin B + Flucytosine (2 weeks
Followed by 8 weeks of fluconazole
Possible LP or CSF shunting for high CSF pressure
What is the main cause of pneumocystosis?
Pneumocystis jirovecii (previously named carinii)
PJP or PCP
How is PCP transmitted?
Airborne.
Most pts had an asymptomatic infection when younger.
Epidemics occur among preemies or debilitated infants in underdeveloped countries.
Sporadic in older people with impaired immunity, esp AIDS.
How does PCP/PJP present?
Abrupt onset of fever, tachypnea, SOB, non-productive cough
+/- bibasilar crackles on exam
Spontaneous pneumothorax possible.
Rapid deterioration and death if not treated.
What do diagnostic studies show for PCP?
CXR: diffuse interstitial infiltration. (5-10% normal CXR)
Cultures: CANNOT CULTURE
Bronchoscopy: special testing of respiratory specimens required (giemsa, methenamine silver, PCR, MAB testing)
What is the treatment for PCP?
TMP-SMZ first line. CD4 < 200 need prophylaxis.
Second: primaquine/clindamycin, trimethoprim-dapsone
