title: Influence of subinhibitory concentrations of loracarbef (LY 163892) and daptomycin (LY 146032) on bacterial phagocytosis, killing and serum sensitivity.
abstract: The aim of this study was to evaluate whether pre-exposure of bacteria to a subinhibitory concentration (sub-MIC) of loracarbef (LY 163892) or daptomycin (LY 146032) could modify bacterial susceptibility to serum bactericidal activity and to phagocytosis and killing by murine peritoneal macrophages and by human polymorphonuclear leucocytes. Escherichia coli, Haemophilus influenzae type b and Staphylococcus aureus grown in the presence of one quarter the MIC of loracarbef, and S. aureus exposed to one quarter the MIC of daptomycin were phagocytosed and killed in numbers significantly higher than non-exposed bacteria. Pre-exposure to loracarbef resulted in increased susceptibility of E. coli and H. influenzae type b to the bactericidal activity of antiserum, but exposure to loracarbef or daptomycin did not modify serum sensitivity of S. aureus. Loracarbef treatment and antiserum enhanced phagocytosis and killing of E. coli and H. influenzae type b to a greater extent than either antibiotic treatment or antiserum alone. These data indicate that loracarbef and daptomycin at sub-MIC enhance the susceptibility of bacterial pathogens to cellular and host defence mechanisms.
authors.affiliation: Istituto di Terapia Medica, Facoltà di Medicina, Università di Napoli, Italy.
authors.forename: M F
authors.initials: MF
authors.lastname: Tripodi
authors.forename: L E
authors.initials: LE
authors.lastname: Adinolfi
authors.forename: R
authors.initials: R
authors.lastname: Utili
authors.forename: A
authors.initials: A
authors.lastname: Marrone
authors.forename: G
authors.initials: G
authors.lastname: Ruggiero
mesh_terms: D001419:Bacteria / Q000187:drug effects*; D001770:Blood Bactericidal Activity / Q000187:drug effects*; D002511:Cephalosporins / Q000494:pharmacology*; D017576:Daptomycin; D004352:Drug Resistance, Microbial; D006801:Humans; D007106:Immune Sera / Q000276:immunology; D008264:Macrophages / Q000276:immunology; D009504:Neutrophils / Q000276:immunology; D010455:Peptides / Q000494:pharmacology; D010587:Phagocytosis / Q000187:drug effects*
chemical_list: D002511:Cephalosporins; D007106:Immune Sera; D010455:Peptides; C054920:loracarbef; D017576:Daptomycin