Cryptococcus: The Daily PANCE Blueprint
A 32-year-old male with a history of HIV presents to the ER with shortness of breath, cough, fever, altered mentation, and a headache. His last CD4 count is <100/microL. Physical exam demonstrates a positive Kernig sign and scattered crackles across both lung fields. CXR reveals bilateral alveolar infiltrates, small pleural effusions, and a left lower lobe opacity. The first set of blood cultures is positive for Cryptococcus neoformans. Lumbar puncture results are pending. Which of the following is the preferred treatment of choice for this patient?
A. Amphotericin B plus flucytosine for 2 weeks followed by fluconazole for a minimum of 8-10 weeks
B. Amphotericin B plus micafungin for 2 weeks followed by fluconazole for a minimum of 4-8 weeks
C. Fluconazole B plus flucytosine for 2 weeks followed by high-dose steroids for 6-8 weeks
D. Fluconazole B plus flucytosine for 4 weeks
E. Micafungin plus flucytosine for 4-6 weeks
Answer and topic summary
The answer is A. Amphotericin B plus flucytosine for 2 weeks followed by fluconazole for a minimum of 8-10 weeks
People become infected with Cryptococcus neoformans by inhaling the spore form of the fungus or small, encapsulated yeasts. Disseminated cryptococcosis is defined by either a (1) positive blood culture or (2) positive culture from at least two different sites (e.g., lymph nodes, CSF, lungs, etc). Cases normally occur in immunocompromised (e.g, HIV infection — typically with CD4 < 100/microL, organ transplant patients, etc) and are often due to reactive action of a latent infection. It is important to note that dissemination from the lungs to the central nervous system occurs in ~70-95% of HIV-associated pulmonary cryptococcosis. Clinical symptoms depend on the site of infection but may include lethargy, neck pain, photophobia, cough, fever, headache, and dyspnea. In disseminated cryptococcosis, serum cryptococcal antigen is positive in almost all patients and is a great screening tool. Blood and sputum cultures should be sent immediately. Lumbar puncture should be performed if a CNS infection is suspected; the fluid should be sent for culture, microscopy, cryptococcal antigen (CrAg), and/or CSF PCR. Overall, among patients with HIV infection and disseminated cryptococcosis, induction therapy with amphotericin B (0.7–1 mg/kg/d) plus flucytosine (100 mg/kg/d) for 2 weeks followed by fluconazole (400 mg/d) for a minimum of 8-10 weeks is the treatment of choice.
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