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

J Infect. 2001 Nov;43(4):226-33. doi: 10.1053/jinf.2001.0916.


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 x 10(7)) and 31,000 (10 to 1.4 x 10(7)) 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.

MeSH terms

  • AIDS-Related Opportunistic Infections / cerebrospinal fluid
  • AIDS-Related Opportunistic Infections / drug therapy*
  • AIDS-Related Opportunistic Infections / microbiology*
  • AIDS-Related Opportunistic Infections / mortality
  • Adult
  • Aged
  • Amphotericin B / administration & dosage
  • Amphotericin B / therapeutic use*
  • Antifungal Agents / administration & dosage
  • Antifungal Agents / therapeutic use*
  • Cryptococcus neoformans / drug effects*
  • Cryptococcus neoformans / isolation & purification*
  • Dose-Response Relationship, Drug
  • Female
  • Humans
  • Male
  • Meningitis, Cryptococcal / cerebrospinal fluid
  • Meningitis, Cryptococcal / drug therapy*
  • Meningitis, Cryptococcal / mortality
  • Middle Aged
  • Predictive Value of Tests
  • Prognosis
  • Prospective Studies
  • Risk Factors
  • Survival Analysis
  • Thailand / epidemiology
  • Time Factors
  • Treatment Outcome


  • Antifungal Agents
  • Amphotericin B