invasive fungal infections - dr sheemer

define mycosis

fungal infection

define clinical resistance

failure of an antifungal agent in an infection due to factors other than microbial resistance

define microbial resistance

resistance to a therapeutic agent due to intrinsic or acquired mechanisms

define primary microbial resistance

intrinsic

recorded prior to drug exposure

define second microbial resistance

acquired

develops over time due to exposure, transient adaptation, or genetic alteratioon

mycoses are most commonly caused by ________

inhalation of airborne conidia

often soil

list risk factors for invasive fungal infections

immunosuppression

ANC ≤ 500

what is the gold standard for diagnosis?

histopathological examination and culture of clinical specimens

systemic mycoses caused by primary or pathogenic fungi:

histoplasmosis

blastomycosis

coccidiomycosis

cryptococcosis

mycoses can be caused by what opportunistic fungi?

generally in immunocompromised pts

candida albicans

aspergillus

what is early empiric therapy used for?

fever

neutropenia

what is empiric therapy used for?

granulocytopenia with persistent fever despite antibiotics

what is secondary prophylaxis/suppression used for?

prevent relapse during an episode of granulocytopenia

pt has history of invasive fungal infections with granulocytopenia

histoplasmosis is caused by ________

inhaling dust-borne microconidia of H. capsulatum

what factors affect the risk of a histoplasmosis infection?

immunosuppression

immunity due to prior infection

pathogen

inoculum size

exposure in enclosed area

duration of exposure

how does histoplasmosis present?

differentiate between low and high inoculum

low inoculum: asymptomatic or mild disease

high inoculum: flu-like pulmonary symptoms, chills, HA, fever, nonproductive cough

how do you treat asymptomatic or mild histoplasmosis?

no treatment unless persistent symptoms

how do you treat mild, self-limited, chronic disseminated, or chronic pulmonary histoplasmosis?

oral itraconazole

IV amphotericin B

how do you treat HIV patients in the hospital with histoplasmosis?

amphotericin B

transition to oral itraconazole when ready

how do you treat HIV patients in the outpatient setting with histoplasmosis?

itraconazole

what is the duration of treatment for histoplasmosis in HIV pts?

12-weeks

then lifelong suppressioon

T/F fluconazole is recommended to be used in histoplasmosis

FALSE

not recommended: relapse, resistance, lower efficacy, inferior coverage

blastomycosis is caused by _________

inhalation of blastomyces dermatitidis conidia

what kind of symptoms do you see with blastomycosis?

pulmonary or extrapulmonary

describe each of the following:

acute pulmonary blastomycosis:

sporadic (nonepidemic) pulmonary blastomycosis:

chronic pulmonary blastomycosis:

acute pulmonary blastomycosis: generally asymptomatic or self-limited; does NOT colonize

sporadic (nonepidemic) pulmonary blastomycosis: chronic or subacute disease; resembles TB

chronic pulmonary blastomycosis: can have disseminated disease that appears 1-3 years after original infection

when do you treat blastomycosis with antifungal therapy?

moderate-severe pneumonia

disseminated infection

immunocompromised

how do you treat mild-moderate blastomycosis?

itraconazole x 6 months

how do you treat moderate-severe, disseminated, or CNS blastomycosis?

amphotericin B, followed by itraconazole

x 6-12 months

coccidiodomycosis is caused by ___________

coccidioides immitts

inhalation of arhroconidia from contaminated soil

what percent of patients with coccidioidomycosis are asymptomatic with self-limiting disease?

a. < 1%

b. 20%

c. 40%

d. 60%

d.

what percent of patients with coccidioidomycosis develop symptoms?

a. < 1%

b. 20%

c. 40%

d. 60%

c.

what are nonspecific symptoms of coccidioidomycosis?

fever

cough

headache

sore throat

myalgias

fatigue

what are common and specific symptoms of coccidioidomycosis?

maculopapular rash

pulmonary necrosis

cavity formation

what percent of patients with coccidioidomycosis have disseminated disease?

a. < 1%

b. 20%

c. 40%

d. 60%

a.

T/F coccidiodomycosis is difficult to treat and difficult to prevent relapse after discontinuing therapy

TRUE

what is the first line treatment for invasive coccidoidomycosis fungal infections?

fluconazole

itraconazole

cryptococcosis is caused by __________

inhaling encapsulated soil yeast

c. neoformans

found in soil and PIGEON DROPPINGS

cryptococcosis almost always occurs in the ______

lungs

how does cryptococcosis present?

cough, rales, SOB

w/o AIDS: nonspecific: HA, fever, N/V, neck stiffness

with AIDS: fever and HA

how is cryptococcosis diagnosed?

meningitis: elevated CSF opening pressure and CSF pleocytosis

CSF abnormalities

positive cryptococcal antigen

what are the three methods of managing cryptococcosis?

systemic antifungal therapy

control of elevated ICP

supportive care

how do you treat cryptococcosis in HIV pts?

induction: amphotericin B + flucytosine x ≥ 2 weeks

consolidation: fluconazole x ≥ 8 weeks

suppression: fluconazole, itraconazole, or amphotericin B x ≥ 1 year

how do you treat cryptococcosis in transplant recipients?

mild-mod: fluconazole x 6-12 months

CNS or mod-severe:

-induction: amphotericin B + flucytosine x ≥ 2 weeks

-consolidation/maintenance: fluconazole x 8 weeks/6-12 months

how do you treat cryptococcosis? (non-HIV and non-transplant)

asymptomatic: careful observation

mild-mod: fluconazole x 6-12 months

mod-severe, CNS: amphotericin B + flucytosine followed by fluconazole

what are predictors for poor outcomes in patients with cryptococcal CNS infection?

AIDS

corticosteroids

immunosuppressive therapy

c. albicans is normal flora of ___________

skin

female GU tract

GI tract

list risk factors for candidiasis

colonization

antibiotic use

surgery

foreign devices

renal failure

dialysis

underlying disease/baseline characteristics

what is the duration of treatment for hematogenous candidiasis?

2 weeks following negative blood cultures and resolution of signs and symptoms of infection

list tx options for known candidemia without speciation

fluconazole or voriconazole

echinocandins

amphotericin B

list tx options for empiric therapy for hematogenous candidiasis

echinocandins

fluconazole

what is candiduria?

candida growing in the urine

often follows catheterization

T/F aspergillosis has extremely high mortality rates

TRUE

aspergillosis has varying degrees of pathogenicity due to what?

relative geographic prevalence

conidial size and shape

thermotolerance

production of mycotoxins

what tx is used for superficial aspergillosis?

topical antifungal ointment

how does aspergillosis present?

symptoms often mimic those of an acute pulmonary embolism

-pleuritic chest pain

-fever

-hemoptysis

-frictions rubs

how is invasive aspergillosis definitively diagnosed?

biopsy of lung tissue

list tx options for invasive aspergillosis

what is the drug of choice?

DOC: voriconazole

amphotericin B

echinocandins

azoles

what class of antifungals needs to be avoided in pregnant women?

azoles

what drugs can have interactions with azoles?

remember: azoles are metabolized CYP3A4

CYP3A4 inducers

-rifampin

-rifabutin

-isoniazid

-phenytoin

-carbamazepine