A 38-year-old woman comes to the emergency department with a 2-week history of worsening headaches and low-grade fever. She has no weakness or sensory loss. The patient has lost a significant amount of weight over the last 6 months. Her temperature is 38.1 C (100.5 F), blood pressure is 115/70 mm Hg, pulse is 100/min, and respirations are 14/min. BMI is 18.7 kg/m². The patient has neck stiffness and cervical lymphadenopathy. Oropharyngeal examination shows thrush. The neurologic examination is nonfocal, and fundoscopy is within normal limits. CT scan of the head without contrast is normal. Lumbar puncture is performed and results of cerebrospinal fluid analysis are as follows: Cerebrospinal fluid fungal stain shows encapsulated yeast. Which of the following is the most appropriate next step in management of this patient?

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This patient's presentation is consistent with cryptococcal meningoencephalitis, a subacute invasive fungal infection caused by Cryptococcus neoformans. It is typically seen in immunocompromised patients, especially those with advanced HIV disease (CD4 cell count <100/µL). Cryptococcal proteins progressively block cerebrospinal fluid (CSF) flow. Therefore, patients develop progressive fever, lethargy, headache, and altered mentation that may advance to coma if left untreated. An elevated opening pressure on lumbar puncture along with low white blood cell count (<50/µL), low glucose, and elevated protein on CSF analysis is highly suggestive of cryptococcal meningoencephalitis. cryptococcal meningoencephalitis Treatment consists of induction therapy with 2 weeks of intravenous amphotericin B (AmB) and flucytosine, followed by fluconazole for consolidation (8 weeks) and maintenance therapy (≥1 year). Intrathecal AmB may be considered as salvage therapy for patients who have failed systemic therapy or developed significant adverse effects to intravenous medications. Serial lumbar punctures may be required to reduce increased intracranial pressure, which is associated with increased morbidity and mortality. (Choice B) Griseofulvin is used to treat dermatophytosis and onychomycosis. C neoformans is not sensitive to griseofulvin. (Choice C) The presence of thrush and an opportunistic infection such as Cryptococcus suggests that the patient is immunocompromised. HIV is a relatively common and treatable cause of immunosuppression in this patient's age group. She should be tested for HIV, but initiation of antiretroviral therapy in the setting of cryptococcal meningoencephalitis is not recommended due to the risk of immune reconstitution syndrome (characterized by worsening of infections after antiretroviral initiation due to increased inflammation). Antiretroviral therapy should be deferred until at least 2 weeks after antifungal therapy is initiated. (Choice D) Itraconazole can be used as an alternate to fluconazole in the treatment of pulmonary cryptococcal infection. However, compared to fluconazole, it has less reliable drug levels in CSF and is associated with more side effects; it can sometimes be used as a second-line agent for consolidation and maintenance therapy for cryptococcal meningoencephalitis if fluconazole is not tolerated or not available. (Choice E) Sulfadiazine-pyrimethamine is used in the treatment of cerebral toxoplasmosis, which typically presents with headache, focal neurologic deficits, and/or seizures. Neuroimaging shows multiple ring-enhancing brain lesions with edema. Educational objective: Cryptococcal meningoencephalitis usually develops in patients with advanced HIV disease (CD4 cell count <100/µL). Induction therapy includes amphotericin B plus flucytosine followed by fluconazole for consolidation and maintenance therapy. Serial lumbar punctures may be required to reduce increased intracranial pressure. Antiretroviral therapy should be deferred for at least 2 weeks after antifungal therapy is started. References: Guidelines for prevention and treatment of opportunistic infections in HIV-infected adults and adolescents. (http://www.ncbi.nlm.nih.gov/pubmed/19357635) New insights in the prevention, diagnosis, and treatment of cryptococcal meningitis. (http://www.ncbi.nlm.nih.gov/pubmed/22763808)

A 38-Year-Old Woman Comes to the Emergency Department with a 2-Week