Practice guidelines for the management of cryptococcal disease

An 8-person subcommittee of the National Institute of Allergy and Infectiou s Diseases (NIAID) Mycoses Study Group evaluated available data on the trea tment of cryptococcal disease. Opinion regarding optimal treatment was base d on personal experience and information in the literature. The relative st rength of each recommendation was graded according to the type and degree o f evidence available to support the recommendation, in keeping with previou sly published guidelines by the Infectious Diseases Society of America (IDS A). The panel conferred in person (on 2 occasions), by conference call, and through written reviews of each draft of the manuscript. The choice of treatment for disease caused by Cryptococcus neoformans depen ds on both the anatomic sites of involvement and the host's immune status. For immunocompetent hosts with isolated pulmonary disease, careful observat ion may be wan-anted: in the case of symptomatic infection, indicated treat ment is fluconazole, 200-400 mg/day for 3-6 months. For those individuals w ith non-CNS-isolated cryptococcemia, a positive serum cryptococcal antigen titer >1 : 8, or urinary tract or cutaneous disease, recommended treatment is oral azole therapy (fluconazole) for 3-6 months. Tn each case, careful a ssessment of the CNS is required to rule out occult meningitis. For those i ndividuals who are unable to tolerate fluconazole, itraconazole (200-400 mg /day for 6-12 months) is an acceptable alternative. For patients with more severe disease, treatment with amphotericin B (0.5-1 mg/kg/d) may be necess ary for 6-10 weeks. For otherwise healthy hosts with CNS disease, standard therapy consists of amphotericin B, 0.7-1 mg/kg/d, plus flucytosine, 100 mg /kg/d, for 6-10 weeks. An alternative to this regimen is amphotericin B (0. 7-1 mg/kg/d) plus 5-flucytosine (100 mg/kg/d) for 2 weeks, followed by fluc onazole (400 mg/day) for a minimum of 10 weeks. Fluconazole "consolidation" therapy may be continued for as along as 6-12 months, depending on the cli nical status of the patient. HIV-negative, immunocompromised hosts should b e treated in the same fashion as those with CNS disease, regardless of the site of involvement. Cryptococcal disease that develops in patients with HIV infection always wa rrants therapy. For those patients with HIV who present with isolated pulmo nary or urinary tract disease, fluconazole at 200-400 mg/d is indicated. Al though the ultimate impact from highly active antiretroviral therapy (HAART ) is currently unclear it is recommended that all HIV-infected individuals continue maintenance therapy For lift. Among those individuals who are unab le to tolerate fluconazole, itraconazole (200-400 mg/d) is an acceptable al ternative. For patients with more severe disease, a combination of fluconaz ole (400 mg/d) plus flucytosine (100 150 mg/d) may be used for 10 weeks, fo llowed by fluconazole maintenance therapy. Among patients with HIV infectio n and cryptococcal meningitis, induction therapy with amphotericin B (0.7-1 mg/kg/d) plus flucytosine (100 mg/kg/d for 2 weeks) followed by fluconazol e (400 mg/d) for a minimum of 10 weeks is the treatment of choice. After 10 weeks of therapy, the fluconazole dosage may be reduced to 100 mg/d, depen ding on the patient's clinical status. Fluconazole should be continued for life. An alternative regimen for AIDS-associated cryptococcal meningitis is amphotericin B (0.7-1 mg/kg/d) plus 5-flucytosine (100 mg/kg/d) for 6-10 w eeks, followed by fluconazole maintenance therapy. Induction therapy beginn ing with an azole alone is generally discouraged. Lipid formulations of amp hotericin B can be substituted for amphotericin B for patients whose renal function is impaired. Fluconazole (400 800 mg/d) plus flucytosine (100-150 mg/kg/d) for 6 weeks is an alternative to the use of amphotericin B, althou gh toxicity with this regimen is high. In all cases of cryptococcal meningi tis, careful attention to the management of intracranial pressure is impera tive to assure optimal clinical outcome.