title: Combination therapy of murine invasive candidiasis with fluconazole and amphotericin B.
abstract: A study was performed to assess the in vivo relevance of the in vitro antagonism between fluconazole and amphotericin B against Candida albicans. Combinations of fluconazole and amphotericin B were explored for their efficacies against acute (100% mortality in 2 to 5 days) or less acute (100% mortality in 30 days) invasive candidiasis infections in mice with healthy immune systems and immunocompromised mice. Treatment efficacy was assessed by protection from mortality and/or a reduction in the fungal burden in tissue. In models of acute infection in mice with healthy immune systems or less acute infection in immunocompromised mice, combinations of fluconazole and amphotericin B were superior to fluconazole alone, and the effects were at least additive. Combination therapy was at least as efficacious as amphotericin B alone. In a different model of less acute infection in mice with healthy immune systems, combinations of fluconazole and amphotericin B showed no interactions and were no better than either drug alone. We conclude that combination therapy with fluconazole and amphotericin B is not antagonistic in vivo, in contrast to published in vitro studies, and, consequently, suggest that combination therapy should be considered in the management of clinical candidiasis.
authors.affiliation: Evans Memorial Department of Clinical Research, Boston University Medical Center Hospital, MA 02118, USA.
authors.forename: A M
authors.initials: AM
authors.lastname: Sugar
authors.forename: C A
authors.initials: CA
authors.lastname: Hitchcock
authors.forename: P F
authors.initials: PF
authors.lastname: Troke
authors.forename: M
authors.initials: M
authors.lastname: Picard
mesh_terms: D000666:Amphotericin B / Q000008:administration & dosage / Q000627:therapeutic use*; D000818:Animals; D002177:Candidiasis / Q000188:drug therapy* / Q000276:immunology / Q000382:microbiology; D003520:Cyclophosphamide; D004338:Drug Combinations; D005260:Female; D015725:Fluconazole / Q000008:administration & dosage / Q000627:therapeutic use*; D007668:Kidney / Q000382:microbiology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008815:Mice, Inbred Strains; D009503:Neutropenia / Q000139:chemically induced / Q000382:microbiology
chemical_list: D004338:Drug Combinations; D000666:Amphotericin B; D003520:Cyclophosphamide; D015725:Fluconazole