A 44-year-old-man with HIV is being discharged from the hospital. He was admitted 2 weeks ago for fever and headache and was diagnosed with cryptococcal meningitis. The patient was treated with amphotericin B and flucytosine, and his symptoms are now resolved. Vital signs are normal. Physical examination shows no abnormalities. Which of the following medications should be prescribed for the patient to take following discharge?
Cryptococcal meningitis is a common AIDS-defining illness in patients with HIV who have CD4 counts <100/mm3. Patients generally present with subacute fever, headache, and altered mental status. Diagnosis is made when encapsulated yeasts (Cryptococcus neoformans) are identified in cerebrospinal fluid.
Patients with cryptococcal meningitis usually require 3 successive phases of treatment, as follows:
Induction therapy with liposomal amphotericin B plus flucytosine is given for ≥2 weeks until acute symptoms resolve and/or cerebrospinal fluid becomes sterile.
Consolidation therapy with high-dose oral fluconazole is given for ≥8 weeks to prevent disease relapse.
Maintenance therapy with low-dose oral fluconazole is given indefinitely or until CD4 counts rise to >100/mm3 for >3 months on antiretroviral therapy (ART).
ART should be initiated in all patients with HIV. However, due to the risk of life-threatening CNS complications from immune reconstitution syndrome, ART initiation is generally delayed for approximately 2 weeks after treatment begins for Cryptococcus.
(Choice A) Caspofungin, an echinocandin, is used to treat some fungal infections (eg, Aspergillus, Candida), but it is not effective against Cryptococcus species.
(Choice C) Itraconazole can be used for consolidation therapy in those unable to take fluconazole. However, it is considered a second-line agent because it is less effective at preventing relapse and has more adverse effects and drug interactions.
(Choice D) Cessation of treatment after induction therapy is associated with a high rate of relapse; patients need to have consolidation therapy to prevent recurrence.
(Choice E) Although corticosteroids are used as an adjuvant treatment to limit inflammation in some opportunistic infections (eg, severe Pneumocystis pneumonia, tuberculous meningitis), corticosteroids do not improve outcomes in patients with cryptococcal meningitis and may slow clearance of the organism from the CNS. Therefore, corticosteroids are not recommended as part of standard treatment.
Educational objective:
Cryptococcal meningitis is an AIDS-defining illness that primarily affects patients with CD4 counts <100/mm3. Three phases of treatment are required to ensure eradication and prevent relapse: induction with amphotericin B and flucytosine for ~2 weeks, consolidation with high-dose oral fluconazole for ~8 weeks, and maintenance with low-dose oral fluconazole until CD4 counts recover to >100/mm3 for >3 months on antiretroviral treatment.