Cryptococcosis

SOURCE

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

DEFINITION

• Systemic fungal infection.

ETIOLOGY

• Caused by ubiquitous encapsulated soil yeast Cryptococcus neoformans

PATHOPHYSIOLOGY

• 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.

EPIDEMIOLOGY

• 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.

RISK FACTORS

• Immunocompromised patients.

  • Malignancies.

  • Diabetes.

  • Chronic renal failure.

  • Organ transplantation.

  • Receiving immunosuppressive agents.

  • AIDS

CLINICAL PRESENTATION

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

SIGNS AND SYMPTOMS

• 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.

DIAGNOSIS

MEANS OF CONFIRMATION AND DIAGNOSIS

• 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.

LABORATORY TESTS

• Serologic testing: latex agglutination.

• India ink smear of CSF

• Cultures.

• Serum cryptococcal antigen.

IMAGING

• MRI more sensitive than CT to detect CNS abnormalities.

DIAGNOSTIC PROCEDURES

• Lumbar puncture.

  • Elevated opening pressure.

  • CSF pleocytosis (usually lymphocytes)

  • Leukocytosis.

  • Decreased CSF glucose.

  • Elevated CSF protein.

  • Positive cryptococcal antigen.

DIFFERENTIAL DIAGNOSIS

• Tuberculous meningitis.

• Other fungal infection.

• Neurosyphilis.

• Lyme meningitis.

DESIRED OUTCOMES

• Resolution of signs and symptoms of infection.

• Cure infection.

TREATMENT: PHARMACOLOGIC THERAPY

• 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 ...