Clinical And Experimental Study Of Cryptococcal Meningitis

The aim of this paper is to develop new parameters for evaluating clinical therapeutic efficacy and design reasonable strategy for the treatment of cryptococcal meningitis. The work included: (1) The susceptibilities of 19 clinical cryptococcus neoformans isolates to amphotericin B, 5-flucytosine and fluconazole were determined by NCCLS M27-A broth microdilution method. The correlation of MICs and clinical outcome was calculated. Amphotericin B MICs ranged from 0.5 to 2(g/ml, 5-flucytosine MICs ranged from 0.25 to 8(g/ml, while fluconazole MICs ranged from 2 to 32(g/ml. The M27-A-derived MICs did not correlate with clinical outcome. (2) A rapid flow cytometric assay for in vitro antifungal drug susceptibility testing was developed. Good agreement was shown between flow cytometric and broth macrodilution MICs. Compared with the M27-A macrodilution procedure, this assay was more rapid (4-5h versus 72h). (3) Using electron microscope examination, animal inoculation and neutral red staining, a method for evaluating the viability of cryptococcus in cerebrospinal fluid was developed. (4) Analysis of peripheral blood immune parameters showed patients with cryptococcal meningitis had lower CD4 counts and CD4/CD8 ratios than that in health volunteers. (5) By comparing the efficacy of three different antifungal regimens in the treatment of cryptococcal meningitis, we suggested that the two-step combination therapeutic regimen be well suited to the treatment of cryptococcal meningitis. Intrathecally administered amphotericin B should be recommended, especially when serious toxicity emerged because of systemic administration. Our study also demonstrated that a negative CSF culture for cryptococci as an endpoint for initial treatment was feasible, while CSF cryptococcal count as the most important parameter evaluating clinical outcome was reasonable. Among 7 cases of Cryptococcal meningitis in children, 4 of them had severe sequelae. Management of impending complication combined medical and surgical treatment modalities.