How is CNS cryptococcosis treated in HIV infection?

Updated: Jan 08, 2020
  • Author: Felicia J Gliksman, DO, MPH; Chief Editor: Niranjan N Singh, MBBS, MD, DM, FAHS, FAANEM  more...
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Answer

Answer

If left untreated, cryptococcal CNS infections are fatal. Treatment with amphotericin B, flucytosine, fluconazole, and other antifungal agents greatly improves the prognosis, but a mortality rate of 6%, despite therapy, has been reported.

Per the Infectious Diseases Society of America (IDSA), for induction therapy of cryptococcal meningitis in HIV-infected patients, the following regimen is preferred:

  1. Liposomal amphotericin B 3-4 mg/kg IV daily PLUS flucytosine 25mg/kg PO in 4 divided doses at 6 hour intervals OR
  2. Amphotericin B deoxycholate 0.7-1.0 mg/kg IV daily PLUS flucytosine 25mg/kg PO in 4 divided doses at 6 hour intervals, for at least 2 weeks. [12]  

Flucytosine should be adjusted in renal impairment. Serum flucytosine levels should be monitored 2 hours post-dose, after 3-5 doses. The drug concentration should be between 25-100 mg/L. Patients on amphotericin B should be monitored for dose-dependent nephrotoxicity and electrolyte disturbance.

Consolidation therapy can begin 2 weeks after successful induction therapy, which occurs with clinical improvement and negative CSF culture. The IDSA preferred regimen is fluconazole 400mg PO or IV once daily for at least 8 weeks. Alternatively, can use itraconazole 200mg PO twice daily.

Liposomal amphotericin B may lead to quicker improvement with less renal toxicity. Flucytosine may be given intravenously in severe cases and in patients without oral intake. [12]

In a randomized study that compared 1 mg/kg versus 0.7 mg/kg of amphotericin B in HIV-infected patients with cryptococcal meningitis, the higher dose was more rapidly fungicidal; side effects were comparable. [13] Patients in both arms of the study also received flucytosine, 25 mg/kg 4 times daily.

Because amphotericin B treatment is not available in many centers in developing countries, oral therapy is an important alternative. Results of a randomized trial suggest that a 2-week course of high-dose fluconazole (1200 mg/day) combined with flucytosine (100 mg/kg/day) is the optimal oral therapy for cryptococcal meningitis. The combination proved more fungicidal than fluconazole alone and had a tolerable side-effect profile. [10]

When flucytosine is unavailable, amphotericin B in combination with fluconazole (800-1200 mg/day). or voriconazole (300 mg twice daily) is an effective alternative in patients not receiving interacting medications. [11]

A double-blind, placebo-controlled phase II study suggested that adjunctive recombinant interferon-gamma 1b (rIFN- gamma 1b) may induce more rapid early sterilization of CSF in patients with HIV-associated Cryptococcus meningitis. [3] Patients in the treatment arm of this study received 100 or 200 µg 3 times weekly for 10 weeks, plus standard antifungal therapy. IDSA guidelines suggest considering adjunctive rIFN- gamma 1b (100 µg/m2 3 times weekly for 10 weeks) along with standard antifungal therapy, in cases of refractory infection. For patients weighing less than 50 kg, consider giving 50 µg/m2. [12]


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