Invasive Fungal - Lee Flashcards by Khristine Dinh

Endemic Mycoses

mold in environment; yeast in body
Histoplasmosis
Blastomycosis
Coccidioidomycosis

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Opportunistic Mycoses

Candidiasis
Cryptococcosis
Aspergillosis - multiple forms

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Risk factors for fungal infections

Organ and bone marrow transplantation
Cytotoxic chemotherapy
Indwelling intravenous catheters, burns, surgery, or trauma
Widespread use of potent broad-spectrum antimicrobial agents

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Candida - approximately ___ C. albicans

50%

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C. krusei is resistant to

fluconazole

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C. glabrata is

somewhat resistant to fluconazole, so use high dose

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C. tropicalis

C. parapsilosis

fluconazole susceptible

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Risk factors for invasive candidiasis

Immunocompromised
o Neutropenia
o Lymphoreticular or hematologic malignancies
o Uncontrolled Diabetes
o Immunodeficiency diseases
o High-dose corticosteroids
o Immunosuppressants, antineoplastic agents

Loss of Protective Barrier:
o	Central venous catheters
o	Total parenteral nutrition (TPN)
o	Extensive surgery (especially, surgery of GI tract)
o	Burns
o	Renal failure and hemodialysis

Other:
o Prior fungal colonization
o Receipt of multiple antibiotics

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Clinical Presentation of Candida infection

acut onset of fever, tachycardia/tachypnea. maybe chills and/or hypotension
intermittent fevers. symptomatic when febrile
PROGRESSIVE DETERIORATION +/- FEVER
Hepatosplenic (< 1000 wbc/mm3)

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Not severely ill and treatment naive

Treatment of suspected/documented candidemia or invasive candidiasis.

Fluconazole (FIRST LINE)
other azole (itra, vori)
Echinocandin
Amphotericin B

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Recent azole exposure
OR Severely ill. (severe sepsis or septic shock)
Treatment of suspected/documented candidemia or invasive candidiasis.

Echincocandin (FIRST LINE) -(Caspo/Mica/Anidala-fungin)
Amphotericin B
Other azole (itra, vori)

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Duration of therapy for candidemia or hematogenous candidiasis

2 weeks after last positive blood culture and resolution of signs/symptoms of inf.

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Fluconazole dose for C. albicans, C. parapsilosis, and C. tropicalis

6mg/kg/day dose

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Fluconazole dose of C. glabrata

12 mg/kg/day dose

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Echinocandins

expanded coverage against C. glabrata and C. Krusei (less potent for parapsilosis)
IV only
need for de-escalation after culture results

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Amphotericin B

problems: infusion -toxicity, nephrotoxicity

IV only

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Aspergillosis

A. fumigatus
A. flavus
A. niger

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Aspergillosis Pathopsy

by inhalation of spores (airbone candida) + imparied host defense

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Aspergillosis prediposing factors/risk factors

o prolonged neutropenia (> 7 days) (most important)
o chronic high dose steroid therapy (30-200 mg/day of prednisone)
o cytotoxic agents
o recent and/or concurrent broad-spectrum antimicrobial therapy

Apersgillosis presentation

o	Pleuritic chest pain
o	Fever
o	Hemoptysis
o	friction rubs
other sites of  inf: CNS! liver, spleen, heart. GI tract, pericaridum

Empiric therapy for Aspergillosis

1st line: Voriconazole

2nd line: Amphotericin B

Asperigillosis salvage therapy

if 1st/2nd line didn’t work

Combo:

vori + echinocandin
lipid form amphot. B + echinocandin

Mono: posaconazole

Crytococcus predisposing/risk factors

o HIV infection
o Lymphoproliferative disorders (ex: Hodgkin’s lymphoma)
o Sarcoidosis
o Long-term steroid therapy

primary cypt presentation

o Always in the lungs, usually subclinical infection

o Cough, rales, shortness of breath (resolve spontaneously)

crypt meningitis non- AIDS presentation

o Headaches, fever, vomiting, mental status changes, neck stiffness o Less common: visual disturbances, papilledema, seizures, aphasia

crypt meningitis AIDS presentation

o Fever, headache o Meningismus* and photophobia are less common than non-AIDS patients *Evidence of meningeal infection: nuchal rigidity, Kernig’s sign, brudzinski’s sign

crypt treatment | pulmonary (mild/mod)

o Fluconazole for 6 mos | o Alternatives: itraconazole, amphotericin B

crypt treatment severe pulmonary CNS disease

o Induction: Amphotericin B + flucytosine x 2 wks, then ± fluconazole x 8wks o Alternatives Monotherapy: lipid form amphotericin B

crypt maintenance therapy for AIDS

o Fluconazole until CD4 > 200 /µl

Echinocandins in Cryotococcus therapy

Not used. Modified glucan struct so synthesis is no inh. significantly

Histoplasmosis treatment | for mild/mod disease

Treatment is usually not needed unless | Symptoms > 1 month: itraconazole

Histoplasmosis treatment | for mod severe to severe

Amphotericin B, then itraconazole OR Methylprednisolone for patients with acute respiratory complications (hypoxemia, significant respiratory distress)

Treatment of Blastomycosis pulmonary (non-CNS) mild/mod

Itraconazole

Treatment of Blastomycosis pulmonary (non-CNS) life threatening

Amphotericin B, then itraconazole

Treatment of Blastomycosis | CNS disease

Amphotericin B (Lipid formulation is preferred) x 4-6 weeks, then Azole (fluconazole, itraconazole, or voriconazole) x 12 months OR resolution of CSF abnormalities

Treatment Histoplasmosis/Blastomycosis after initial therapy in AIDS

Lifelong suppressive therapy with oral azoles until CD4 > 200 /µl

Risk factors for severe/disseminated inf of Coccidioidomycosis

o Race (Filipinos > African-American > Native American > Hispanics > Asians) o Pregnancy (especially 2nd or 3rd trimester) o Compromised immune system (AIDS pts, on steroids, immunosuppressive agents, chemotherapy) o Male gender o Neonates o Patients with B or AB blood types

``` Coccidioidomycosis Asymptomatic patients (60%) presentation ```

o Non-specific symptoms (fever, cough, headache, sore throat, myalgias, fatigue) o Fine diffuse rash during the first few days of illness

Coccidioidomycosis primary pneumonia presentation

o Productive cough (+/- blood streaked) | o Dense homogenous hilar or basal infiltrate(s)

Coccidioidomycosis presentation | chronic, persistant pneumonia (>6 wk of primary)

o Hemoptysis o Pulmonary scarring o Necrosis of pulmonary tissue with drainage of cavities or bronchopleural fistulas o Persistent cough, fevers, and weight loss

``` Coccidioidomycosis presentation Valley fever (25%) ```

o Erythema nodosum and erythema multiforme o Diffuse joint aches o Fever o Diffuse, mild erythroderma or macropapular rash o Pleuritic chest pain o Peripheral eosinophilia

Coccidioidomycosis presentation | disseminated (<1%)

o Common sites include skin, lymph nodes, bone, meninges | o Other sites: spleen, liver, kidney, adrenal gland

Coccidioidomycosis treatment | asymptomatic

no treatment

Coccidioidomycosis treatment | Disseminated CNS disease

``` o Fluconazole (for life... first line) o Itraconazole (for life... doesn't work well) o Amphotericin B intrathecal therapy ± fluconazole or itraconazole ```

Coccidioidomycosis treatment | Primary respiratory or disseminated (NON-CNS) infection

o Azole antifungal (usually FIRST LINE is fluconazole, , or itraconazole for bone disease) o Amphotericin B formulation