Multicenter randomized trial of fluconazole versus amphotericin B for treatment of candidemia in non-neutropenic patients. Canadian Candidemia Study Group.
A randomized trial was conducted to compare the efficacy and safety of fluconazole versus that of amphotericin B in the treatment of candidemia in non-neutropenic adults. Enrollment was stratified by disease severity (APACHE II score). Patients were randomized (1:1) to receive amphotericin B 0.6 mg/kg/day (cumulative dose 8 mg/kg) or fluconazole 800 mg intravenous loading dose, then 400 mg daily for four weeks (intravenous for at least 10 days). Patients were monitored for six months. A total of 106 patients were enrolled. A protocol amendment implemented midway through the trial required patients to be removed from the study and treated with amphotericin B if species identification indicated candidemia due to Candida glabrata or Candida krusei. Baseline characteristics were similar for the two groups; 103 patients (fluconazole, 50; amphotericin B, 53) met the major enrollment criteria. The intention-to-treat analysis indicated successful therapy in 50% of fluconazole recipients compared to 58% of the amphotericin B group (p = 0.39; one-sided 95% CI, -8 to 24%). The efficacy analysis included 84 patients (fluconazole, 42; amphotericin B, 42); successful outcomes were observed in 57% and 62% of cases in the fluconazole and amphotericin B groups, respectively (p = 0.66: one-sided 95% CI, -12 to 22%). The mortality at day 14 for the fluconazole group was 26% and for the amphotericin B group 21% (p = 0.52; chi-square test) and remained similar throughout the course of follow-up, Drug-related adverse events were more frequent with amphotericin B than with fluconazole and prompted switching of therapy for two (4%) and zero cases, respectively. Fluconazole and amphotericin B were associated with similar clinical response rates and survival in the treatment of candidemia among non-neutropenic patients; however, drug-related adverse events were more frequent with amphotericin B.
Phillips
P
P
Division of Infectious Diseases, St. Paul's Hospital, Vancouver, British Columbia, Canada.
Shafran
S
S
Garber
G
G
Rotstein
C
C
Smaill
F
F
Fong
I
I
Salit
I
I
Miller
M
M
Williams
K
K
Conly
J M
JM
Singer
J
J
Ioannou
S
S
D000328:Adult; D000368:Aged; D000666:Amphotericin B / Q000627:therapeutic use*; D000935:Antifungal Agents / Q000627:therapeutic use*; D002177:Candidiasis / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality; D016001:Confidence Intervals; D005260:Female; D015725:Fluconazole / Q000627:therapeutic use*; D016469:Fungemia / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality; D006801:Humans; D007121:Immunocompetence; D008297:Male; D008875:Middle Aged; D015996:Survival Rate; D016896:Treatment Outcome
D000935:Antifungal Agents; D000666:Amphotericin B; D015725:Fluconazole