title: Activity of three {beta}-lactams (ertapenem, meropenem and ampicillin) against intraphagocytic Listeria monocytogenes and Staphylococcus aureus.
abstract: OBJECTIVE
  Assessment of the activity of three beta-lactams [ertapenem (a carbapenem with a prolonged half-life), meropenem and ampicillin] against intraphagocytic Listeria monocytogenes and Staphylococcus aureus.
  
  
  METHODS
  Quantitative measurements of cfu changes in broth and in THP-1 macrophages (post-phagocytosis) over time (5 and 24 h) at concentrations spanning from sub-MICs to C(max) (maximal concentration typically observed in patients' serum upon administration of conventional doses); morphological studies using an electron microscope; evaluation of drug stability (HPLC), protein binding (equilibrium dialysis) and measurement of drug cellular accumulation (microbiological assay).
  
  
  RESULTS
  Ertapenem was unable to control L. monocytogenes growth in THP-1 macrophages at all concentrations and times tested, even under conditions where ampicillin and meropenem were bactericidal. This behaviour could not be ascribed to drug instability, protein binding or lack of cell accumulation in comparison with ampicillin or meropenem. Ertapenem, ampicillin and meropenem were equally effective at reducing the post-phagocytosis inoculum of S. aureus ( approximately 1 log cfu), and caused conspicuous changes in the morphology of intracellular bacteria consistent with their lysis. These effects were obtained, however, only at large multiples (100-fold or more) of the MIC maintained over 24 h. Because of the high intrinsic antimicrobial potency of the beta-lactams studied, these concentrations were below the C(max).
  
  
  CONCLUSIONS
  Ertapenem will probably be ineffective against intraphagocytic forms of L. monocytogenes for reasons that remain to be discovered. Conversely, ertapenem could be an alternative to ampicillin and meropenem against intraphagocytic S. aureus since its longer half-life may allow high concentrations to be maintained for more prolonged times.
authors.affiliation: Unité de Pharmacologie cellulaire et moléculaire, Université catholique de Louvain, Brussels, Belgium.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Lemaire
authors.forename: Françoise
authors.initials: F
authors.lastname: Van Bambeke
authors.forename: Marie-Paule
authors.initials: MP
authors.lastname: Mingeot-Leclercq
authors.forename: Paul M
authors.initials: PM
authors.lastname: Tulkens
mesh_terms: D000667:Ampicillin / Q000494:pharmacology*; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001770:Blood Bactericidal Activity; D004305:Dose-Response Relationship, Drug; D000077727:Ertapenem; D007769:Lactams / Q000493:pharmacokinetics / Q000494:pharmacology*; D008089:Listeria monocytogenes / Q000187:drug effects*; D000077731:Meropenem; D008826:Microbial Sensitivity Tests; D013211:Staphylococcus aureus / Q000187:drug effects*; D013845:Thienamycins / Q000494:pharmacology*; D047090:beta-Lactams
chemical_list: D000900:Anti-Bacterial Agents; D007769:Lactams; D013845:Thienamycins; D047090:beta-Lactams; D000667:Ampicillin; D000077731:Meropenem; D000077727:Ertapenem