title: The entry of meropenem into human macrophages and its immunomodulating activity.
abstract: The uptake of meropenem by human macrophages and its consequences upon subsequent phagocytosis and killing of intracellular staphylococci has been studied. The cellular to extracellular concentration ratios (C/E) of meropenem were always high (range 3-12) at extracellular concentrations ranging from 0.125 to 1 mg/L. The uptake was not energy-dependent, being similar when viable and formalin-killed cells were used and was influenced neither by environmental temperature nor by the addition of a metabolic inhibitor. Meropenem at half the MIC caused a significant enhancement of phagocytosis and a reduction in the survival of intracellular Staphylococcus aureus. Pre-exposure of either staphylococci or macrophages to sub-MIC concentrations of meropenem led to an increase in uptake of bacteria and intracellular bactericidal activity by macrophages.
authors.affiliation: Institute of Microbiology, University of Turin, Torino, Italy.
authors.forename: A M
authors.initials: AM
authors.lastname: Cuffini
authors.forename: V
authors.initials: V
authors.lastname: Tullio
authors.forename: A
authors.initials: A
authors.lastname: Allocco
authors.forename: F
authors.initials: F
authors.lastname: Giachino
authors.forename: S
authors.initials: S
authors.lastname: Fazari
authors.forename: N A
authors.initials: NA
authors.lastname: Carlone
mesh_terms: D000276:Adjuvants, Immunologic / Q000493:pharmacokinetics* / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism*; D000077731:Meropenem; D010587:Phagocytosis / Q000187:drug effects; D013211:Staphylococcus aureus / Q000276:immunology; D013845:Thienamycins / Q000493:pharmacokinetics* / Q000494:pharmacology*
chemical_list: D000276:Adjuvants, Immunologic; D013845:Thienamycins; D000077731:Meropenem