A prospective study of AIDS-associated cryptococcal meningitis in Thailand treated with high-dose amphotericin B

Abstract

Objective: To assess kinetic of cryptococci in the cerebrospinal fluid (CSF) and outcome of AIDS-associated cyptococcal meningitis after high-dose amphotericin B. Patients and Methods: A prospective study involving Thai adults (n = 106) with cryptococcal meningitis associated with AIDS was conducted to determine the kinetic of cryptococci in CSF and prognostic factors affecting survival after high-dose amphotericin B (0.7 mg/kg/day) followed by oral azole treatment. Cerebrospinal fluids were collected for cryptococcal count and culture at weekly intervals for at least 2 weeks or until CSF cultures were negative for cryptococci. All patients were followed monthly for 1 year or until death in order to detect relapse or occurrence of any other opportunistic infection. Results: A total of 106 AIDS patients with cryptococcal meningitis were enrolled. The geometric mean (range) total and viable cryptococcal counts in CSF on admission were 430 000 (1000 to 3.4 × 107) and 31 000 (10 to 1.4 × 107) per ml, respectively. Both total and viable cryptococcal counts declined monoexponentially with an elimination half life of 4 days. The cumulative CSF yeast clearance rates were 38% and 56% at 2 and 4 weeks, respectively. Early death was associated significantly with previous history of weight loss [relative risk (RR) = 2.2; 95% CI, 1.2-3.9], Glasgow Coma Score <13 (RR = 2.33; 95% CI, 1.55-3.50), and hypoalbuminaemia (P < 0.001). Later mortality was associated delayed CSF yeast clearance (RR = 3.6; 95% CI, 1.9-6.4) and relapse (RR = 3.9; 95% CI, 1.4-10.8). Conclusion: High-dose amphotericin B was not as effective as previously thought. Cumulative mortality at 2 weeks, 4 weeks and 1 year were 16%, 24% and 76%, respectively. © 2001 The British Infection Society.