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SOURCE

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Source: Carver PL. Invasive fungal infections. In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM. Pharmacotherapy: A Pathophysiologic Approach. 10th ed. New York, NY: McGraw-Hill; 2017. http://accesspharmacy.mhmedical.com/content.aspx?bookid=1861&sectionid=146073167. Accessed March 14, 2017

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DEFINITION

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  • Systemic fungal infection.

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ETIOLOGY

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  • Caused by ubiquitous encapsulated soil yeast Cryptococcus neoformans

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PATHOPHYSIOLOGY

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  • Acquired by inhalation.

  • Stimulates minimal inflammatory response in tissue.

  • Polysaccharide capsule appears to allow resistance to host phagocytosis.

  • Four serotypes of C. neoformans

  • Cell-mediated immunity plays major role in host defense.

    • 29–55% of patients with cryptococcal meningitis have predisposing condition.

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EPIDEMIOLOGY

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  • C. neoformans found in soil, particularly in pigeon droppings.

  • Incidence has risen; increased numbers of immunocompromised patients, including those with malignancies, diabetes mellitus, chronic renal failure, and organ transplants receiving immunosuppressive agents.

  • No geographic area of endemic focus.

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RISK FACTORS

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  • Immunocompromised patients.

    • Malignancies.

    • Diabetes.

    • Chronic renal failure.

    • Organ transplantation.

    • Receiving immunosuppressive agents.

    • AIDS

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CLINICAL PRESENTATION

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  • Disease may remain localized in lungs or disseminate to other tissues, particularly CNS, although skin can also be affected.

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SIGNS AND SYMPTOMS

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  • Primary cryptococcosis almost always occurs in lungs.

    • Usually subclinical infection.

    • Symptomatic infections resolve spontaneously.

      • Cough.

      • Rales.

      • Shortness of breath.

  • Cryptococcal meningitis.

    • Asymptomatic in 10–12% of all patients.

      • Non-AIDS patient.

        • Fever.

        • Headache.

        • Nausea.

        • Vomiting.

        • Mental status changes.

        • Neck stiffness.

        • Photophobia.

      • AIDS patient.

        • Fever.

        • Headache.

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DIAGNOSIS

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MEANS OF CONFIRMATION AND DIAGNOSIS
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  • Examination of cerebrospinal fluid (CSF)

    • Latex agglutination to detect antigens to C. neoformans.

    • India ink smear of CSF detects ~60% of C. neoformans.

    • C. neoformans can be cultured in 96% of patients.

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LABORATORY TESTS
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  • Serologic testing: latex agglutination.

  • India ink smear of CSF

  • Cultures.

  • Serum cryptococcal antigen.

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IMAGING
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  • MRI more sensitive than CT to detect CNS abnormalities.

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DIAGNOSTIC PROCEDURES
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  • Lumbar puncture.

    • Elevated opening pressure.

    • CSF pleocytosis (usually lymphocytes)

    • Leukocytosis.

    • Decreased CSF glucose.

    • Elevated CSF protein.

    • Positive cryptococcal antigen.

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DIFFERENTIAL DIAGNOSIS
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  • Tuberculous meningitis.

  • Other fungal infection.

  • Neurosyphilis.

  • Lyme meningitis.

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DESIRED OUTCOMES

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  • Resolution of signs and symptoms of infection.

  • Cure infection.

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TREATMENT: PHARMACOLOGIC THERAPY

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  • Nonimmunocompromised patients.

    • Careful observation is an option with asymptomatic, isolated pulmonary disease, and no evidence of CNS disease.

    • Management of symptomatic infection in Table 1

      • Combination of amphotericin B with flucytosine for 6 weeks.

      • Alternative regimen: amphotericin B for 2 weeks, followed by fluconazole for additional 8–10 weeks.

      • Optional: suppressive therapy with fluconazole for 6–12 months after completion of induction and consolidation therapy.

  • Immunocompromised patients.

    • Amphotericin B with flucytosine initial ...

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