title: A comparison of the fungicidal activity of amphotericin B and posaconazole against Zygomycetes in vitro.
abstract: Zygomycoses is a rapidly progressive infection associated with high mortality. Although amphotericin B (AMB) has been the only treatment option for years, recent studies have demonstrated that posaconazole (PCZ) has good activity against Zygomycetes. Because rapid onset of antifungal activity is crucial in the management and never studied before, we compared the time for maximum fungicidal activity of AMB versus PCZ using time-kill curves. The MIC of AMB and PCZ against clinical isolates of Mucor spp. and Rhizopus spp. was determined by the Clinical and Laboratory Standards Institute M38-A2 method, and the fungicidal activity was examined by time-kill studies. AMB was rapidly fungicidal, with 95% killing noted as early as 6 h and 99.9% killing at 24 h; PCZ showed <70% killing at 6 h and 99.9% killing at 48 h. In vivo animal studies using AMB in the early phase, followed by a switch to high-dose PCZ later, could provide data that may have clinical implications because there are only a few drugs currently available for the management of zygomycoses.
authors.affiliation: Department of Medicine, Division of Infectious Diseases, Wayne State University, John D Dingell VA Medical Center, Detroit, MI, USA. skrishn@med.wayne.edu
authors.forename: Suganthini
authors.initials: S
authors.lastname: Krishnan-Natesan
authors.forename: Elias K
authors.initials: EK
authors.lastname: Manavathu
authors.forename: George J
authors.initials: GJ
authors.lastname: Alangaden
authors.forename: Pranatharthi H
authors.initials: PH
authors.lastname: Chandrasekar
mesh_terms: D000666:Amphotericin B / Q000494:pharmacology*; D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology*; D006801:Humans; D008826:Microbial Sensitivity Tests; D050296:Microbial Viability; D009089:Mucor / Q000187:drug effects* / Q000302:isolation & purification; D012233:Rhizopus / Q000187:drug effects* / Q000302:isolation & purification; D013997:Time Factors; D014230:Triazoles / Q000494:pharmacology*; D020096:Zygomycosis / Q000382:microbiology*
chemical_list: D000935:Antifungal Agents; D014230:Triazoles; C101425:posaconazole; D000666:Amphotericin B