title: Time-kill studies with micafungin and voriconazole against Candida glabrata intracellularly in human monocyte-derived macrophages and extracellularly in broth.
abstract: The purpose of this study was to determine by time-kill methodology the anticandidal effectiveness and durability of micafungin (MCF) and voriconazole (VRC), singly and in combination, against Candida glabrata (Cgl), intracellularly in human monocyte-derived macrophages and extracellularly in RPMI-MOPS broth with and without fetal calf serum (FCS) or pooled human serum (PHS). The anticandidal activity of MCF was concentration-dependent and durable. Combinations of MCF + VRC both intra- and extracellularly were more effective than single drugs. However, in extracellular experiments, FCS, and even more PHS, significantly decreased the anticandidal activity of MCF and VRC. Our in vitro studies suggest that MCF alone may be adequate where protein concentration is low (intracellular or extravascular sites), while MCF + VRC combinations may be preferred where protein concentration is high such as in the intravascular space.
authors.affiliation: Stratton VA Medical Center, Albany, NY 12208, USA. Aldona.Baltch@med.va.gov
authors.forename: Aldona L
authors.initials: AL
authors.lastname: Baltch
authors.forename: William
authors.initials: W
authors.lastname: Ritz
authors.forename: Lawrence H
authors.initials: LH
authors.lastname: Bopp
authors.forename: Phyllis B
authors.initials: PB
authors.lastname: Michelsen
authors.forename: Raymond P
authors.initials: RP
authors.lastname: Smith
mesh_terms: D000935:Antifungal Agents / Q000494:pharmacology*; D041221:Candida glabrata / Q000187:drug effects*; D004357:Drug Synergism; D054714:Echinocandins / Q000494:pharmacology*; D006801:Humans; D055666:Lipopeptides / Q000494:pharmacology*; D008264:Macrophages / Q000382:microbiology*; D000077551:Micafungin; D008826:Microbial Sensitivity Tests; D050296:Microbial Viability / Q000187:drug effects*; D011743:Pyrimidines / Q000494:pharmacology*; D013997:Time Factors; D014230:Triazoles / Q000494:pharmacology*; D065819:Voriconazole
chemical_list: D000935:Antifungal Agents; D054714:Echinocandins; D055666:Lipopeptides; D011743:Pyrimidines; D014230:Triazoles; D065819:Voriconazole; D000077551:Micafungin