title: Liposomal amphotericin B (AmBisome) compared with amphotericin B both followed by oral fluconazole in the treatment of AIDS-associated cryptococcal meningitis.
abstract: OBJECTIVE
  Amphotericin B deoxycholate initial therapy and fluconazole maintenance therapy is the treatment of choice for AIDS-associated cryptococcal meningitis. However, the administration of amphotericin B is associated with considerable toxicity. A potential strategy for reducing the toxicity and increasing the therapeutic index of amphotericin B is the use of lipid formulations of this drug.
  
  
  METHODS
  HIV-infected patients with cryptococcal meningitis were randomized to treatment with either liposomal amphotericin B (AmBisome) 4 mg/kg daily or standard amphotericin B 0.7 mg/kg daily for 3 weeks, each followed by fluconazole 400 mg daily for 7 weeks. During the first 3 weeks, clinical efficacy was assessed daily. Mycological response was primarily evaluated by cerebrospinal fluid (CSF) cultures at days 7, 14, 21 and 70.
  
  
  RESULTS
  Of the 28 evaluable patients, 15 were assigned to receive AmBisome and 13 to receive amphotericin B. Baseline characteristics were comparable. The time to and the rate of clinical response were the same in both arms. AmBisome therapy resulted in a CSF culture conversion within 7 days in six out of 15 patients versus one out of 12 amphotericin B-treated patients (P = 0.09), within 14 days in 10 out of 15 AmBisome patients versus one out of nine amphotericin B patients (P = 0.01), and within 21 days in 11 out of 15 AmBisome patients versus three out of eight amphotericin B patients (P = 0.19). When Kaplan-Meier estimates were used to compare time to CSF culture conversion, AmBisome was more effective (P < 0.05; median time between 7 and 14 days for AmBisome versus > 21 days for amphotericin B). AmBisome was significantly less nephrotoxic.
  
  
  CONCLUSIONS
  A 3-week course of 4 mg/kg AmBisome resulted in a significantly earlier CSF culture conversion than 0.7 mg/kg amphotericin B, had equal clinical efficacy and was significantly less nephrotoxic when used for the treatment of primary episodes of AIDS-associated cryptococcal meningitis.
authors.affiliation: University Hospital Rotterdam, The Netherlands.
authors.forename: A C
authors.initials: AC
authors.lastname: Leenders
authors.forename: P
authors.initials: P
authors.lastname: Reiss
authors.forename: P
authors.initials: P
authors.lastname: Portegies
authors.forename: K
authors.initials: K
authors.lastname: Clezy
authors.forename: W C
authors.initials: WC
authors.lastname: Hop
authors.forename: J
authors.initials: J
authors.lastname: Hoy
authors.forename: J C
authors.initials: JC
authors.lastname: Borleffs
authors.forename: T
authors.initials: T
authors.lastname: Allworth
authors.forename: R H
authors.initials: RH
authors.lastname: Kauffmann
authors.forename: P
authors.initials: P
authors.lastname: Jones
authors.forename: F P
authors.initials: FP
authors.lastname: Kroon
authors.forename: H A
authors.initials: HA
authors.lastname: Verbrugh
authors.forename: S
authors.initials: S
authors.lastname: de Marie
mesh_terms: D017088:AIDS-Related Opportunistic Infections / Q000188:drug therapy*; D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000666:Amphotericin B / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000935:Antifungal Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016503:Drug Delivery Systems; D004359:Drug Therapy, Combination; D015725:Fluconazole / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D008081:Liposomes; D016919:Meningitis, Cryptococcal / Q000150:complications / Q000188:drug therapy*; D017063:Outcome Assessment, Health Care
chemical_list: D000935:Antifungal Agents; D008081:Liposomes; C068538:liposomal amphotericin B; D000666:Amphotericin B; D015725:Fluconazole