Comparison of 2 doses of liposomal amphotericin B and conventional amphotericin B deoxycholate for treatment of AIDS-associated acute cryptococcal meningitis: a randomized, double-blind clinical trial of efficacy and safety.
BACKGROUND. It is generally acknowledged that amphotericin B is the most effective treatment for cryptococcal meningitis. However, administration of this drug is accompanied by substantial adverse effects. This double-blind study, performed before the routine availability of highly active antiretroviral therapy, was designed to compare the efficacy and safety of liposomal amphotericin B to conventional amphotericin deoxycholate in patients with acquired immunodeficiency syndrome (AIDS) and acute cryptococcal meningitis. METHODS. Patients were randomized (ratio, 1:1:1) from multiple sites in the United States and Canada to receive either amphotericin B at 0.7 mg/kg/day (n = 87), liposomal amphotericin B at 3 mg/kg/day (n = 86), or liposomal amphotericin B at 6 mg/kg/day (n = 94). RESULTS. Efficacy was similar among all 3 treatment groups. The overall incidence of infusion-related reactions was significantly lower for both the 3 mg/kg/day and 6 mg/kg/day dosages of liposomal amphotericin B, compared with conventional amphotericin B (P < .001). Significantly fewer patients who received the 3 mg/kg/day dosage of liposomal amphotericin B developed nephrotoxicity, indicated by a doubling of the serum creatinine value, compared with recipients of conventional amphotericin B (P = .004). Overall mortality at 10 weeks was 11.6%, with no significant differences among the treatment groups. CONCLUSIONS. Liposomal amphotericin B provides an equally efficacious alternative to conventional amphotericin B deoxycholate in patients with AIDS and acute cryptococcal meningitis. Liposomal amphotericin B at a dosage of 3 mg/kg/day is accompanied by significantly fewer adverse effects.
Section of Infectious Diseases, Michael E. DeBakey Veterans Affairs Medical Center and Baylor College of Medicine, San Antonio, Texas, USA. rhamill@bcm.edu
Richard J
RJ
Hamill
Jack D
JD
Sobel
Wafaa
W
El-Sadr
Philip C
PC
Johnson
John R
JR
Graybill
Kedarnath
K
Javaly
David E
DE
Barker
D017088:AIDS-Related Opportunistic Infections / Q000188:drug therapy*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000666:Amphotericin B / Q000008:administration & dosage* / Q000009:adverse effects; D000935:Antifungal Agents / Q000008:administration & dosage* / Q000009:adverse effects; D002170:Canada; D002648:Child; D003404:Creatinine / Q000097:blood; D003840:Deoxycholic Acid / Q000008:administration & dosage* / Q000009:adverse effects; D004311:Double-Blind Method; D004338:Drug Combinations; D005260:Female; D006801:Humans; D007674:Kidney Diseases / Q000139:chemically induced; D008297:Male; D016919:Meningitis, Cryptococcal / Q000188:drug therapy* / Q000401:mortality; D008875:Middle Aged; D016896:Treatment Outcome; D014481:United States; D055815:Young Adult
D000935:Antifungal Agents; D004338:Drug Combinations; C068538:liposomal amphotericin B; D003840:Deoxycholic Acid; D000666:Amphotericin B; C059765:amphotericin B, deoxycholate drug combination; D003404:Creatinine