title: Macrophage killing of bacterial and fungal pathogens is not inhibited by intense intracellular accumulation of the lipoglycopeptide antibiotic oritavancin.
abstract: Intact phagocytic effector function is fundamental to host defense against microbial pathogens. Concern has been raised regarding the potential that accumulation of certain agents, including cationic amphiphilic antibiotics, within macrophages could cause a mixed-lipid storage disorder, resulting in macrophage dysfunction in recipients. The ability of 2 macrophage cell lines (HL-60; RAW 264.7) to kill archetypal Gram-positive (Staphylococcus aureus), Gram-negative (Acinetobacter baumannii), and fungal (Candida albicans) pathogens was tested following exposure of the macrophages to the lipoglycopeptide antibiotic oritavancin. Oritavancin did not affect killing of C. albicans but markedly enhanced killing of S. aureus by both macrophages. Oritavancin modestly reduced killing of A. baumannii by HL-60 cells but not by RAW 264.7 cells. Thus, macrophage killing of microbes remains intact despite substantial intracellular accumulation with a lipoglycopeptide antibiotic.
authors.affiliation: Division of General Internal Medicine, Los Angeles Biomedical Research Institute at Harbor-University of California at Los Angeles (UCLA) Medical Center, Torrance, CA 90502, USA.
authors.forename: Beverlie
authors.initials: B
authors.lastname: Baquir
authors.forename: Sandrine
authors.initials: S
authors.lastname: Lemaire
authors.forename: Françoise
authors.initials: F
authors.lastname: Van Bambeke
authors.forename: Paul M
authors.initials: PM
authors.lastname: Tulkens
authors.forename: Lin
authors.initials: L
authors.lastname: Lin
authors.forename: Brad
authors.initials: B
authors.lastname: Spellberg
mesh_terms: D040981:Acinetobacter baumannii / Q000187:drug effects; D000818:Animals; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics / Q000494:pharmacology; D002176:Candida albicans / Q000187:drug effects; D002460:Cell Line; D006020:Glycopeptides / Q000493:pharmacokinetics* / Q000494:pharmacology*; D006801:Humans; D000077427:Lipoglycopeptides; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism*; D051379:Mice; D050296:Microbial Viability / Q000187:drug effects; D010587:Phagocytosis / Q000187:drug effects; D013211:Staphylococcus aureus / Q000187:drug effects; D014640:Vancomycin / Q000031:analogs & derivatives
chemical_list: D000900:Anti-Bacterial Agents; D006020:Glycopeptides; D000077427:Lipoglycopeptides; C100708:oritavancin; D014640:Vancomycin