Meningitis cryptococcal, treatment

The combination of amphotericin B with flucytosine for 6 weeks is often used for treatment of cryptococcal meningitis. An alternative is amphotericin B for 2 weeks followed by fluconazole for an additional 8 to 10 weeks. Suppressive therapy with fluconazole 200 mg/day for 6 to 12 months is optional. 

The use of intrathecal amphotericin B is not recommended for the treatment of cryptococcal meningitis except in very ill patients or in those with recurrent or progressive disease despite aggressive IV amphotericin B therapy. The dosage of amphotericin B employed is usually 0.5 mg administered via the lumbar, cisternal, or intraventricular (via an Ommaya reservoir) route two or three times weekly. 

Amphotericin B with flucytosine is the initial treatment of choice for acute therapy of cryptococcal meningitis in AIDS patients. Many clinicians will initiate therapy with amphotericin B, 0.7 mg/kg/day IV (with flucytosine, 100 mg/kg/day). After 2 weeks, consolidation therapy with either itraconazole 400 mg/day orally or fluconazole 400 mg/day orally can be administered for 8 weeks or until CSF cultures are negative. Lifelong therapy with fluconazole is then recommended. 

Cryptococcal meningitis in HIV Treatment of cryptococcal meningitis in HIV-infected patients AmBisome only). 

Cryptococcal meningitis 400 mg on the first day, followed by 200 mg once daily. A dosage of 400 mg once daily may be used, based on the patient s response to therapy. The duration of treatment for initial therapy of cryptococcal meningitis is 10 to 12 weeks after the cerebrospinal fluid becomes culture negative. The dosage of fluconazole for suppression of relapse of cryptococcal meningitis in patients with AIDS is 200 mg once daily. 

Flucytosine is an oral antifungal pro-drug. It has to be enzymatically deaminated by the fungi to the active metabolite, fluorouracil. Fluorouracil inhibits thymidylate synthetase and DNA synthesis. Its indications are treatment of cryptococcal meningitis and serious systemic candidiasis. Resistance develops rapidly, due to altered drug-permeability. For this reason Amphotericin B and flucytosine are often given in combination as they have synergistic effects. 

Intravenous amphotericin plus intravenous or oral flucytosine is the traditional treatment. There is an increasing role for fluconazole, particularly in maintenance therapy in acquired immunodeficiency syndrome (AIDS). The treatment for Cryptococcal meningitis is discussed in Table 15. 

The aim of this study reported by Powderly et al. (1992) was to establish the non-inferiority of a test treatment, fluconazole, compared to an established treatment, amphotericin B, in preventing the relapse of cryptococcal meningitis in HIV-infected patients. It was thought that fluconazole would be less effective than amphotericin B, but would offer other advantages in terms of reduced toxicity and ease of administration fluconazole was an oral treatment while amphotericin B was given intravenously. The non-inferiority margin was set at —15 per cent in terms of relapse rates. 

To decrease dose-related toxicity by using reduced doses of one or more components of the drug regimen. The use of flucytosine in combination with amphotericin for the treatment of cryptococcal meningitis in non-HIV-infected patients allows for a reduction in amphotericin dosage with decreased amphotericin -induced nephrotoxicity. 

Indications Treatment of oropharyngeal and esophageal candidiasis and may be effective for the treatment of serious systemic candidal infections Cryptococcal meningitis c <... 

In the treatment of entero-coccal endocarditis with penicillin and streptomycin or cryptococcal meningitis infections with amphotericin B in combination with flucytosine. 

Torre D, Banfi G, Tambini R, Speranza F, Zeroli C, Martegani R, Airoldi M, Fiori G. A retrospective study on the efficacy and safety of amphotericin B in a lipid emulsion for the treatment of cryptococcal meningitis in AIDS patients. J Infect 1998 37(l) 36-8. 

Bozzette SA, Larsen RA, Chiu J, Leal MA, Jacobsen J, Rothman P, Robinson P, Gilbert G, McCutchan JA, Tilles J, et al. A placebo-controUed trial of maintenance therapy with fluconazole after treatment of cryptococcal meningitis in the acquired immunodeficiency syndrome. California Collaborative Treatment Group. N Engl J Med 1991 324(9) 580-4. 

Sugar AM, Stern JJ, Dupont B. Overview treatment of cryptococcal meningitis. Rev Infect Dis 1990 12(Suppl 3) S338-48. 

Combination therapy with fluconazole (200 mg/day for 2 months) and flucytosine (150 mg/kg/day for the first 2 weeks n = 30) has been compared with fluconazole monotherapy (200 mg/day for 2 months n = 28) in a randomized open trial in Ugandan patients with AIDS-associated cryptococcal meningitis (12). Patients in both groups who survived for 2 months received maintenance therapy with fluconazole (200 mg three times per week for 4 months). There were no serious adverse events in any of the patients. The combination therapy prevented death within 2 weeks and significantly increased the survival rate at 6 months (32 versus 12%). However, the rate of positive cryptococcal antigen titers remained high at 2 months after treatment in both groups. 

L-Amph is also approved for Cryptococcal meningitis in AIDS patients (recommended dose 6 mg/ kg/d), and in the treatment of other fungal infections with patients who were refractory and or intolerant to AmB or with baseline renal impairment (recommended dose 3-5 mg/kg/d) [182,190]. Different dose of ABLC have been compared to AmB in the treatment of cryptococcal meningitis however the risk of nephrotoxicity with ABLC was not convincingly lower than that with AmB [191]. 

Sharkey PK, Graybill JR, Johnson ES, et al. Amphotericin B lipid complex compared with amphotericin B in the treatment of cryptococcal meningitis in patients with AIDS. Clin Infect Dis 1996 22 315-21. 

Leenders AC, Reiss P, Portegies P, et al. Liposomal amphotericin B (AmBisome) compared with amphotericin B both followed by oral fluconazole in the treatment of AIDS-associated cryptococcal meningitis. AIDS 1997 11 1463-1471. 

Saag MS, Powderly WG, Cloud GA, et al. Comparison of amphotericin B with fluconazole in the treatment of acute AIDS-associated cryptococcal meningitis. The NIAID Mycoses Study Group and the AIDS Clinical Trials Group (see comments). N Engl J Med 1992 326 83-89. 

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