A prospective study of AIDS-associated cryptococcal meningitis in Thailand treated with high-dose amphotericin B.
OBJECTIVE
To assess kinetic of cryptococci in the cerebrospinal fluid (CSF) and outcome of AIDS-associated cyptococcal meningitis after high-dose amphotericin B.


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).


CONCLUSIONS
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.
Pitisuttithum
P
P
Clinical Infectious Diseases Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand. tmppt@mahidol.ac.th
Tansuphasawadikul
S
S
Simpson
A J
AJ
Howe
P A
PA
White
N J
NJ
D017088:AIDS-Related Opportunistic Infections / Q000134:cerebrospinal fluid / Q000188:drug therapy* / Q000382:microbiology* / Q000401:mortality; D000328:Adult; D000368:Aged; D000666:Amphotericin B / Q000008:administration & dosage / Q000627:therapeutic use*; D000935:Antifungal Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D003455:Cryptococcus neoformans / Q000187:drug effects* / Q000302:isolation & purification*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D016919:Meningitis, Cryptococcal / Q000134:cerebrospinal fluid / Q000188:drug therapy* / Q000401:mortality; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D011446:Prospective Studies; D012307:Risk Factors; D016019:Survival Analysis; D013785:Thailand / Q000453:epidemiology; D013997:Time Factors; D016896:Treatment Outcome
D000935:Antifungal Agents; D000666:Amphotericin B