Abstract

BackgroundThis study aimed to evaluate the prevalence and predictors of AIDS-related complicated cryptococcal meningitis. The outcome was complicated cryptococcal meningitis: prolonged (≥ 14 days) altered mental status, persistent (≥ 14 days) focal neurologic findings, cerebrospinal fluid (CSF) shunt placement or death. Predictor variable operating characteristics were estimated using receiver operating characteristic curve (ROC) analysis. Multivariate analysis identified independent predictors of the outcome.ResultsFrom 1990-2009, 82 patients with first episode of cryptococcal meningitis were identified. Of these, 14 (17%) met criteria for complicated forms of cryptococcal meningitis (prolonged altered mental status 6, persistent focal neurologic findings 7, CSF surgical shunt placement 8, and death 5). Patients with complicated cryptococcal meningitis had higher frequency of baseline focal neurological findings, head computed tomography (CT) abnormalities, mean CSF opening pressure, and cryptococcal antigen (CRAG) titers in serum and CSF. ROC area of log2 serum and CSF CRAG titers to predict complicated forms of cryptococcal meningitis were comparable, 0.78 (95%CI: 0.66 to 0.90) vs. 0.78 (95% CI: 0.67 to 0.89), respectively (χ2, p = 0.95). The ROC areas to predict the outcomes were similar for CSF pressure and CSF CRAG titers. In a multiple logistic regression model, the following were significant predictors of the outcome: baseline focal neurologic findings, head CT abnormalities and log2 CSF CRAG titer.ConclusionsDuring initial clinical evaluation, a focal neurologic exam, abnormal head CT and large cryptococcal burden measured by CRAG titer are associated with the outcome of complicated cryptococcal meningitis following 2 weeks from antifungal therapy initiation.

Highlights

  • This study aimed to evaluate the prevalence and predictors of AIDS-related complicated cryptococcal meningitis

  • Over the last twenty years at the University of California, San Diego (UCSD), we occasionally cared for patients with minimal or no symptoms related to the central nervous system, high serum cryptococcal antigen (CRAG) titer and fatal HIV-associated cryptococcal meningitis

  • All patients with complicated cryptococcal meningitis were treated with Amphotericin B deoxycholate (AmpBd) and 5-Fluorocytosine (5-FC) during the induction phase followed by oral fluconazole 800 mg during the consolidation phase

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Summary

Introduction

This study aimed to evaluate the prevalence and predictors of AIDS-related complicated cryptococcal meningitis. Over the last twenty years at the University of California, San Diego (UCSD), we occasionally cared for patients with minimal or no symptoms related to the central nervous system, high serum CRAG titer (as high as 1:65,536) and fatal HIV-associated cryptococcal meningitis. This observation prompted us to study whether serum and/ or CSF CRAG titers alone or in combination with other baseline clinical parameters could be used to identify AIDS patients at risk for complicated forms of cryptococcal meningitis. The study aims were to (1) establish the prevalence of complicated cryptococcal meningitis in our clinical cohort, (2) identify a parsimonious set of clinical and laboratory predictors of complicated cryptococcal meningitis, and (3) to examine the operating characteristics of quantitative predictors of complicated cryptococcal meningitis

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