Itraconazole compared with amphotericin B plus flucytosine in AIDS patients with cryptococcal meningitis.

OBJECTIVE: We conducted a comparison of itraconazole versus amphotericin B plus flucytosine in the initial treatment of cryptococcal meningitis in patients with AIDS and established the efficacy of itraconazole as maintenance treatment. DESIGN: The trial was a prospective, randomized, and non-blinded study. SETTING: The study was performed at an academic centre for AIDS, Amsterdam, The Netherlands. PATIENTS, PARTICIPANTS: Twenty-eight HIV-1-seropositive men with a presumptive diagnosis of cryptococcal meningitis, randomized between 5 February 1987 and 1 January 1990, were included for analysis. INTERVENTIONS: Oral itraconazole (200 mg twice daily), versus amphotericin B (0.3 mg/kg daily) intravenously plus oral flucytosine (150 mg/kg daily) was administered for 6 weeks followed by maintenance therapy with oral itraconazole (200 mg daily) to all patients. MAIN OUTCOME MEASURES: Outcome measures were a complete or partial response, recrudescence and relapse. RESULTS: A complete response was observed in five out of the 12 patients who completed 6 weeks of initial treatment with itraconazole versus all 10 patients who completed treatment with amphotericin B plus flucytosine (P = 0.009). A partial response was observed in seven out of the 14 patients assigned to itraconazole. During maintenance therapy, recrudescence (n = 6) or relapse (n = 1) occurred in seven out of the 12 patients initially assigned to itraconazole, whereas two relapses occurred among nine patients initially treated with amphotericin B plus flucytosine (P = 0.22); recurrence of clinical symptoms was significantly related to a positive cerebrospinal fluid culture at 6 weeks (P = 0.003). CONCLUSION: Itraconazole is less effective compared with amphotericin B plus flucytosine in achieving a complete response in initial therapy in AIDS patients with cryptococcal meningitis.

Therapy for cytomegalovirus polyradiculomyelitis in patients with AIDS: treatment with ganciclovir.

Six AIDS patients with progressive cytomegalovirus (CMV) polyradiculomyelitis were treated with ganciclovir in an open study. The diagnosis was based on the presence of a distinct clinical syndrome with progressive flaccid paraparesis, preserved proprioception and urinary retention with specific cerebrospinal fluid (CSF) findings. Ganciclovir therapy, 5-10 mg/kg per day, instituted 3-6.5 weeks after onset of symptoms, was ineffective in four patients with severe paraparesis. One patient developed CMV polyradiculomyelitis while receiving ganciclovir and further deteriorated during foscarnet therapy. One patient however, showing minor paresis of one leg, improved after institution of ganciclovir therapy 1 week after onset of symptoms. It is concluded that a presumptive diagnosis of CMV polyradiculomyelitis can be made on the basis of distinct clinical findings and CSF pleocytosis with predominance of polymorphonuclear leukocytes in patients with AIDS. Ganciclovir therapy does not appear to be beneficial for patients with advanced paresis in the doses used. Further investigations are needed in order to determine if early intervention with ganciclovir, when paresis is mild, or higher doses in advanced paresis, might be of some benefit.

Predominance of polymorphonuclear leukocytes in cerebrospinal fluid of AIDS patients with cytomegalovirus polyradiculomyelitis.

Cytomegalovirus (CMV) polyradiculomyelitis was diagnosed in 4 of 241 consecutive neurologically assessed human immunodeficiency virus type (HIV-1) seropositive patients. CMV-related neurologic disease was suspected on clinical grounds and was subsequently confirmed by CMV culture from cerebrospinal fluid (CSF) and/or CMV in situ hybridization on specific specimens. All four patients showed CSF pleocytosis with predominance of polymorphonuclear leukocytes (PMNs). Retrospective analysis of the results of CSF examination, performed in 143 of 241 patients with neurologic symptoms, showed pleocytosis in 58 of 143 patients. Predominance of PMNs was found in seven patients, including the four with CMV polyradiculomyelitis. It is concluded that in HIV-1 seropositive patients with a clinical diagnosis of polyradiculomyelitis, a predominance of PMNs in CSF could be an indication that the condition is CMV related. This should lead to early diagnosis and institution of specific antiviral therapy.