UNLABELLEDBACKGROUND. Ribavirin is active in vitro against hantaviruses, but the findings of an open trial of the use of intravenous ribavirin for the treatment of hantavirus cardiopulmonary syndrome (HCPS) were inconclusive.METHODSSubjects with suspected HCPS in the prodrome or cardiopulmonary phase but without shock were eligible for randomization to receive either intravenous ribavirin (33 mg/kg [<or=2 g], followed by 16 mg/kg [<or=1 g] given every 6 h for 4 days and by 8 mg/kg [<or=.5 g] given every 8 h for 3 days) or placebo (administered for 7 days or until the initial Sin Nombre virus antibody test result was confirmed to be negative). The primary outcome was survival at day 28 of the study without the need for extracorporeal membrane oxygenation (ECMO).RESULTSThirty-six subjects were enrolled in the trial from March 1996 through July 2001, at which point the study was terminated prematurely because of both the slow rate of accrual of subjects and the findings of a futility analysis. Of the 36 subjects enrolled, 23 (all of whom were enrolled during the cardiopulmonary stage of HCPS) had HCPS confirmed by serologic testing. The severity of illness at entry into the study was similar among the 10 subjects with HCPS who received ribavirin and the 13 subjects with HCPS who received placebo. The proportion of subjects who survived and who did not require ECMO was similar among ribavirin recipients and placebo recipients (70% vs. 62%, respectively); 2 ribavirin recipients and 2 placebo recipients died, including 3 of 7 subjects treated with ECMO. The frequency of adverse events, including anemia, was similar between treatment groups.CONCLUSIONSThe rate of accrual of subjects in the present study was inadequate to clearly assess the safety or efficacy of ribavirin in the treatment of HCPS. However, ribavirin was well tolerated, and the lack of trends supporting the use of intravenous ribavirin suggests that it is probably ineffective in the treatment of HCPS in the cardiopulmonary stage.

This study was undertaken to characterize the laboratory and clinical course of patients with AIDS and cryptococcal meningitis who had normal or elevated cerebrospinal fluid (CSF) pressure. Data were obtained retrospectively from a randomized multicenter quasifactorial phase III study comparing amphotericin B with or without flucytosine in primary treatment of cryptococcal meningitis. CSF pressure was measured before treatment and at 2 weeks. Repeated lumbar punctures were done to drain CSF and to reduce pressure. Patients with the highest baseline opening pressures (> or = 250 mm H2O) were distinguished by higher titers of cryptococcal capsular polysaccharide antigen in CSF; more frequently positive India ink smears of CSF; and more frequent headache, meningismus, papilledema, hearing loss, and pathological reflexes. After receiving antifungal therapy, those patients whose CSF pressure was reduced by >10 mm or did not change had more frequent clinical response at 2 weeks than did those whose pressure increased >10 mm (P<.001). Patients with pretreatment opening pressure <250 mm H2O had increased short-term survival compared with those with higher pressure. We recommend that opening pressures >/=250 mm H2O be treated with large-volume CSF drainage.