Fungal Infections

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    Source: MKSAP 16 (2014)

     

    Disseminated Candidiasis

    • Can be disseminated or focal organ involvement.
    • Candida infections (like catheter related candidiasis) can be primary disorder, can lead to disseminated/focal-organ involvement
    • Organism:
      • Candida albicans most common
      • Non-albicans identification increasing.
    • Diagnosis:
      • Any candida isolated in a blood culture should NEVER be treated as a contaminant, always investigate for cause.
      • Routine blood culture for candidemia is gold standard for dx of disseminated disease (bacterial culture is ok, no need to order specificaly fungal, unless old culture system).
        • Blood cultures often negative (does not exclude dx).
      • Organ systems:
        • Obtain biopsies for pathology and culture.
        • Any candida in culture from any sterile site.
    • Risk factors for systemic candidiasis:
      • Medications, Broad spectrum Abx, Chemotherapy, Immunosuppressive agents, Catheter related causes (central venous catheters), parenteral nutrition, hemodialysis, hospitalization (esp, prolongued stay in ICU, malignancies, AKI, neutropenia, severe acute pancreatitis, transplant recipients, recovering from recent surgery.
    • Clinical Presentation:
      • Fever, hypotension, leukocytosis
        • Sepsis syndrome/shock (indistinguishable from severe bacterial infection).
      • Can involve any organ:
        • Eye: lesions (distinctive white retinal exudates).
          • Must get an eye exam if disseminated candidiasis is concerned
        • Skin: papules, pustules on erythematous base. (contain yeast).
        • Kidneys/liver/spleen/brain can be involved:
          • Urinary Tract Infections
          • Peritonitis
          • Bone/Joint Infections
          • Endopthalmitis
          • Meningitis
          • "Hepatosplenic candidiasis" - from heme malignancies who are no longer neutropenic (fever, RUQ abdo pain, nausea, vomiting).
          • NOTE: Can be in sputum but pneumonia is VERY RARE.
    • Treatment:
      • Empiric therapy for suspected candidiasis:
        • fluconazole or echinocandin (Caspofungin, Anidulafungin, Micafungin).
          • (recommended for non-neutropenic pts with candidemia)
          • Previously used Amphotericin B (3 mg/kg/day liposomal), but caspofungin (70mg load + 50mg/day) equally effective. (Mora-Duarte J NEJM 2002)
          • Fluconazole preferred if
            • LESS critically ill.
            • Candida parapsilosis
          • Echinocandin preferred in:
            • moderate to severe disease who recently received azole
            • Candida glabrata (can subtitute oral azole later, test for fluconazole/voraconazole susceptibility)
          • Voriconazole for oral step down due to C. krusei or voriconazole susceptible C. glabrata.
        • Duration: if uncomplicated candidemia: 2 weeks after clearance of the pathogen from blood and resolution of sx.
          • Removal of IV cathers strongly recommended (removal = shorter duration of infection, better pt outcomes), unless neutropenic (b/c GI source).
          • Candidemia from C. parapsilosis is almost always catheter-related.
      • If neutropenic and proven candida infection:
        • Echinocandin or voriconazole, role of cather removal less clear (often from GI tract).
          • If candida persists for more than few days, remove cather.
        • If invasive candidiasis: lipid formulation of amphotericin B, echinocandin or voriconazole.
          • (For mold coverage use voriconazole or echinocandin)
      • NO THERAPY for asymptomatic cystitis caused by Candida unless:
        • - Pt is neutropenic
        • - Undergoing urologic procedure
        • If must treat symptomatic cysitis or pyelonephritis, choice of treatment is fluconazole
      • Focal Infection:
        • Same as candidemia.
        • Do not use echinocandin if meningitis or endopthalmitis (poor penetration).

    Aspergillosis

    • Aspergillous (mold) is everywhere in the environment.
    • Inhalation of aerosolized spores --> infects lung.
    • Most common:
      • A. fumigatus, A. flavus, A. niger, and A. terreus
    • Syndromes
      • Allergic bronchopulmonary aspergillosis (most often asthma and CF).
        • Dx criteria: Asthma, Central bronchiectasis, fleeting pulmonary infiltrates on CXR, laboratory studies showing eosinophillia (>1000) + elevated serum IgE levels (>1000 U/mL, cutaneous reactivity to aspergillous antigens, presence of aspergillous precipitating antibodies. 
      • Aspergilloma aka "Fungus ball" symptoms:
        • Cough, hemoptysis (life threatening), dyspnea, wt loss, fatigue, fever, chest pain. 
        • CXR: rounded mass in pre-existing pulmonary cavity or cyst or in areas of dead lung.
        • Sputum cultures positive for aspergillous.
      • Invasive sino-pulmonary aspergillosis, disseminated aspergillosis:
        • Occur in immunocompromised patients (lung is most common)
          • Organism invades blood vessels causing distal tissue infarction.
        • Present with fever, cough, chest pain, hemoptysis, lung infilrates or nodules on CXR. (wedge-shaped densities resembling infarcts can be also seen on CXR).
          • CT shows target lesion with necrotic center with a ring of hemorrhage (halo sign).
          • Dissemination to CNS can occur, brain abscess.
    • Diagnosis:
      • Difficult, frequent sputum contaminant.
      • Dx established by tissue bx showing aspergillous in histo and culture specimens esp if samples from normally sterile sites.
        • Blood cultures are rarely positive.
      •  Galactomannan antigen immunoassay - can be useful for serum, CSF, bronchoalveolar lavage fluid
        • Can do serial measurements to monitor therapy.
      • B-D-Glucan assay and PCR also promising dx tests.
    • Treatment:
      • Allergic bronchopulmonary aspergillosis  
        • Oral corticosteroids during acute phase. 
        • itraconazole shown to improve outcomes, and steroid-sparing effect.
      • Aspergilloma: Surgery to resect aspergilloma
      • Invasive:
        • Convetional and lipid formulations of amphotericin B, voriconazole, itraconazole, posticonazole, caspofungin.
          • Voriconazole superior to conventional amphotericin B.
          • Lipid formulations of ampB, echinocandins, or other tri-azole agents indicated for pts that can't take voriconazole.

    Mucormycosis

    • Used to be called Zygomycosis
    • Acute and rapidly progressing infection.
      • Most common in pts with prolongued neutropenia: hematologic malignancies.
        • Also: severe burns, trauma, poorly controlled diabetes, corticosteroids, cytotoxic agents, defuroxamine.
    • Syndromes:
      • Rhinocerebral Mucormycosis
        • Most common.
        • Rapidly fatal infection spreads from sinuses retroorbitally to CNS.
        • Patients present with headache, epistaxis, ocular findings (proptosis, periorbital edema, decreased vision).
          • Examination of nose/pallate shows black necrotic tissue (pathognemonic).
      • Pulmonary, GI, cutaneous, disseminated rarely occur.
        • Pulmonary: thrombosis, infarction (pts with heme malignancies)
        • Cutaneous: rare, burn/trauma pts, or disseminations.
        • GI: rare, pts with GI tract abnormalities, severe malnutrition.
        • CNS isolated: usually hematogenous spread (IVDU).
    • Diagnosis:
      • Tissue biopsy and culture.
        • Histopathology: Broad, irregular ribbon-like, aseptate hyphae that exhibit broad right-angle branching.
        • Blood cultures are usually negative.
    • Treatment:
      • Medical and surgical required.
      • Antifungal: High dose conventional or lipid amphotericin B.
      • Surgery: Immediate aggressive surgical debridement, may need to be repeated.

     

    Cryptococcosis

    • Invasive mycosis worldwide (lungs are primary portal of entry).
    • Immunocompetent host contain pathogen (cell-mediated immunity).
    • Immunocompromised pts can have rapidly-disseminating infection.
    • Syndromes:
      • CNS (most common)
        • Almost always CNS (subacute or chronic meningoencephalitis or meningitis)
        • Most common: Headache and altered mental status
        • Less often: fever, nuchal rigidity.
        • Complications:
          • Hydrocephalus
          • Encephalitis
          • Brainstem vasculitis
          • Optic pathways
          • Cryptococcomas of the brain.
      • Pulmonary (inhaled)
      • Less commonly skin, prostate, bone, eye, urinary tract.
        • If found outside of CNS, must do LP to rule out CNS infection.
    • Diagnosis:
      • Pathology showing cryptococci.
        OR
      • Cryptococcal antigen in tissue, serum of CSF.
        AND:
      • Confirmed by isolation of cryptococci in culture.
    • Treatment:
      • Pulmonary cryptococcosis in asymptomatic immunocompetent host may resolve without treatment.
      • Outside lungs: treat all patients (especially if CNS).
      • Antifungals:
        • For primary cutaneous without dissemination and isolated symptomatic pulmonary disease.
          • Fluconazole
        • For disseminated infection in immunocompromised pt, or meningoencephalitis/meningitis.
          • Amphotericin B + flucytosine as induction x2 weeks (4 weeks for non-HIV non-transplant)
          • Fluconazole as consolidation x8w.
        • Elevated CSF: may need frequent LP, or placement of shunt.

     

    Tinea

    • Foot: Tinea Pedis
      • moccasin distribution on the feet
      • Includes toe web spaces
      • Can cause dystrophic nails
    • Body: Tinea Corporis
    • Scalp: Tinea Capitis
    • Treatment:
      • Antifungal Therapy (2-4 week course)
        • Azole-based (i.e. Clotrimazole (topical))
        • Terbinafine (squalene epoxidase inhibitors)
        • DO NOT use topical nystatin (for Candida only, not dermatophyte)
        • DO NOT use combination topical corticosteroids
      • Remove/wash fomites (footware etc..)
      • Foot powder as a drying agent to prevent maceration
      • Avoidance of occlusive footwear, and treating shoes with antifungal powders before being worn.
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